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Effect of Aqueous Extracts of Black and Green Teas in Arsenic-induced Toxicity in Rabbits
Abstract
Arsenic causes oxidative stress in the body. Its administration (3 mg/kg/day) for 14 days in rabbits resulted in a significant reduction of whole blood glutathione (GSH), and elevation of thiobarbituric acid reactive substances (TBARS) and the index of nitrite/nitrate (NOx) levels. These are the markers of oxidative stress. Both black tea (BT) and green tea (GT) (Camellia sinensis), when administered to the arsenic-treated rabbits for 14 days, caused a significant elevation of the depleted GSH level to 53.12% and 57.47%, respectively. On the contrary, in the placebo group the level was 26.59%. The BT and GT reduced the elevated TBARS level to 43.27% and 62.28%, respectively, whereas the corresponding level in the placebo groups was 21.24%. The NOx levels were also reduced to 63.62%, 67.67% and 58.94% in BT, GT and the placebo groups, respectively. When arsenic and black tea were given concurrently to another group the results were even more pronounced. The polyphenol components of black and green tea were 27.69% and 29.71% of the dry weight of the total extracts, respectively. These results indicated that arsenic-induced toxicities in rabbits were significantly reversed by the black and green tea polyphenols. The greater activity of green tea than that of black tea correlates with the slightly higher content of polyphenols in green tea.
... Several plant species have medicinal value with great antioxidant potency (Krishnaiah, Sarbatly, & Nithyanandam, 2011), like black tea (BTE) (Łuczaj & Skrzydlewska, 2005) and curcumin (CMN) (Zhang et al., 2016). BTE derived from Camellia sinensis, was used as antioxidant (Raihan et al., 2009) for its polyphenols constituents (Jha, Krithika, Manjeet, & Verma, 2013), it was found to reduce the thiobarbituric acid reactive substance (TBARS) elevated in AFB1-renal intoxication (Choudhary & Verma, 2006), and also normalize the elevated creatinine, urea, and uric acid in blood as a result of other toxic factors like lindane (Prasad, Srilatha, Sailaja, Raju, & Jayasree, 2016). ...
The study aimed to clarify the characteristics of black tea (BTE) and/or curcumin (CMN) against aflatoxin‐B1 (AFB1). Forty eight adult male Sprague–Dawley rats were divided into eight groups. G1 was non‐treated control. G2, G3, and G4 were olive oil, BTE, and CMN, respectively. G5 was olive oil‐dissolved AFB1 (25 µg/kg b.w). G6, G7, and G8 were AFB1 along with BTE (2%), CMN (200 mg/kg b.w.), and BTE plus CMN, respectively. All treatments were orally given for consecutive 90 days. After treatment period, rats were sacrificed. Serobiochemical analysis and histopathology showed hepatorenal dysfunction in response to AFB1. Glutathione‐antioxidants were significantly decreased versus increased lipid peroxides (p < .05–.001). AFB1 significantly increased the expression of the antitumor p53, but decreased that of antiapoptotic Bcl2 in liver or kidney tissue, either (p < .05). BTE or CMN ameliorated those changes induced by AFB1 in both liver and kidney with highly pronounced improvement when combined BTE/CMN was used.
Practical applications
Black tea (BTE) and curcumin (CMN) were known for their antioxidant effects, and several studies reported their independent effects against different toxicities including aflatoxicosis. The current study clarifies the ameliorative characteristics of both agents; BTE and/or CMN, against the toxicity resulted from the chronic exposure to aflatoxin‐B1 (AFB1) (25 µg/kg b.w. for consecutive 90 days). The dose of either agents, BTE or CMN, was 200 mg/kg b.w. along with AFB1. The pathologic changes, serobiochemical parameters, oxidative stress, histological changes, and the molecular disruption, induced by AFB1 in both liver and kidney were obviously and significantly ameliorated after BTE and/or CMN treatments in variable potencies where both agents showed the most effective antitoxic capacities.
... The null effect of sulfasalazine on nitrite levels agrees with the recent findings byCetin, Erdogan, Dincel, Bakar, and Kisa (2017), who observed a null effect displayed by sulfasalazine on nitrite production. In actuality, the downregulation of nitrite levels induced by the extracts is consistent with their total phenol and flavonoid contents(Raihan et al., 2009), with a particular regard to the levels of epicatechin and rutin(Machawal & Kumar, 2014).Consistent with these antioxidant effects, we observed that alcoholic P. fruticosa and P. herba-venti extracts displayed a significant reduction of LPS-induced increase in MDA levels(Figure 9), a recognized biomarker of lipid peroxidation and tissue damageMancuso et al., 2012). Alcoholic P. fruticosa and P. herba-venti extracts were as effective as sulfasalazine in restoring basal MDA levels in isolated rat colon challenged with LPS. ...
Phlomis fruticosa L. and P. herba‐venti are species belonging to the Lamiaceae family, which have been traditionally used to prepare tonic and digestive drinks. Multiple studies also demonstrated the inhibitory effects of P. fruticosa extracts and essential oil against oxidative/proinflammatory pathways and bacterial strains deeply involved in ulcerative colitis. Considering these findings, the present study evaluated the effects of alcoholic P. fruticosa and P. herba‐venti leaf extracts in isolated rat colon challenged with Escherichia coli lipopolysaccharide (LPS), an ex vivo experimental paradigm of ulcerative colitis. In this context, we assayed colon levels of pro‐oxidant and proinflammatory biomarkers, including nitrites, malondialdehyde (MDA), lactate dehydrogenase (LDH), and serotonin (5‐HT). Additionally, the extracts have been tested in order to evaluate possible inhibitory effects on specific bacterial and fungal strains involved in ulcerative colitis. Alcoholic P. fruticosa and P. herba‐venti extracts were able to blunt LPS‐induced nitrite, MDA, 5‐HT, and LDH levels in isolated rat colon. The same extracts also inhibited the growth of Pseudomonas aeruginosa, E. coli, Staphylococcus aureus, Candida albicans and Candida tropicalis. In conclusion, our findings show a potential role exerted by alcoholic P. fruticosa and P. herba‐venti in managing the clinical symptoms related to ulcerative colitis. We evaluated antioxidant/anti‐inflammatory effects of alcoholic P. fruticosa and P. herba‐venti leaf extracts in isolated rat colon challenged with lipopolysaccharide (LPS). We also investigated the inhibitory effects of P. fruticosa and P. herba‐venti extracts on specific bacterial and fungi strains involved in ulcerative colitis. P. fruticosa and P. herba‐venti extracts were able to blunt LPS‐induced colon nitrite, MDA, 5‐HT, and LDH level and to inhibit the growth of P. aeruginosa, E. coli, S. aureus, C. albicans, and C. tropicalis.
... LDH could be considered a predictive marker of tissue damage, especially in the gut, and reduced LDH activity following extracts treatment was related to protective effects in IBDs (Kannan and Guruvayoorappan, 2013;Nagarjun et al., 2017). Actually, the downregulation of nitrite, MDA and LDH level induced by the extracts is consistent with their total phenol and flavonoid content (Raihan et al., 2009). The relative abundance in kaempferol could explain, albeit partially, the major blunting effect exerted by R. sanctus methanol extract on LPS-induced nitrite, MDA and LDH level, in isolated rat colon.. 5-HT pro-inflammatory role in ulcerative colitis has been previously suggested (Regmi et al., 2014), possibly involving the activation of 5-HT3 receptors (Mousavizadeh et al., 2009). ...
In the present study, the biological properties, including, the enzyme inhibitory and antioxidant activities, as well as, the phytochemical profile of the ethyl acetate, methanol, and water extracts of Rubus sanctus Schreb. and Rubus ibericus Juz. leaves were determined using in vitro bioassays. Wide range of phytochemicals, including, hydroxybenzoic acids, hydroxycinnamic acids, acylquinic acids, ellagitannins, flavonoids, and triterpenoid saponins were determined using UHPLC-ESI/HRMS technique. The ethyl acetate and methanol extracts of the studied Rubus species effectively inhibited acetyl and butyryl cholinesterase. On the other hand, R. sanctus water extract showed low inhibition against α-amylase and prominent inhibitory action against α-glucosidase. Data collected from this study reported the radical scavenging and reducing potential of the studied Rubus species. Investigation of the protective effects of the different extracts of R. sanctus and R. ibericus in experimental model of ulcerative colitis was performed. The extracts were also tested on spontaneous migration of human colon cancer cells (HCT116) in wound healing experimental paradigm. Only R. sanctus methanol extract inhibited spontaneous HCT116 migration in the wound healing test. Our results suggested that R. sanctus and R. ibericus may be potential candidates as sources of biologically-active compounds for the development of nutraceuticals, pharmaceuticals, and/or cosmetics.
... We observed that all the extracts were able to reduce LPS-induced nitrite level, in isolated rat colon (Fig. 7). Actually, the downregulation of nitrite level induced by the extracts is consistent with their total phenolic and flavonoid content (Raihan et al., 2009). This could explain, albeit partially, the minor efficacy exerted by Carmagnola Cs extract, which displayed a total phenolic and flavonoid content significantly lower than the other extracts. ...
One of the most promising economic perspectives of hemp production chain is female inflorescence valorization, despite there being actually no chemical composition or biological data from water fraction. In this context, the focus of this study is the evaluation of protective effects related to hemp water flower extracts from four commercial cultivars (Futura 75, Kc virtus, Carmagnola Cs and Villanova). We evaluated the phytochemical profile through validated spectrophotometric and HPLC methods. Then, we studied the biological activity on C2C12 and HCT116 cell lines, and in an ex vivo experimental model of ulcerative colitis, constituted by isolated LPS-stimulated colon. Particularly, we assayed the blunting effects induced by hemp water extract treatment on LPS-induced levels of nitrites, malondialdehyde (MDA), prostaglandin (PG)E2 and serotonin (5-HT). All tested cultivars displayed similar total phenolic and flavonoid profile. However, Futura 75 water extract displayed a better antioxidant and anti-inflammatory profile. Considering this, Futura 75 extract activity has been subsequently assayed on bacterial and fungal species involved in ulcerative colitis, finding a significant inhibition on C. albicans and selected Gram positive and negative bacterial strains.
Concluding, our results support the potential efficacy of hemp inflorescence water extracts in managing the clinical symptoms related to ulcerative colitis.
... El β-caroteno y la naringina (flavonoide cítrico) son capaces de normalizar el perfil hematológico y bioquímico del suero en ratones, además de modular los parámetros hepáticos y renales modificados por el As(III) (Roy et al., 2014;Das et al., 2015). Raihan et al. (2009) evidencian que extractos de té negro y verde, ricos en polifenoles, son capaces de contrarrestar el estrés oxidativo causado por la administración de As(III), normalizando los niveles séricos de GSH, peróxidos lipídicos y óxido nítrico en conejos. ...
El arsénico es un metaloide tóxico ampliamente distribuido en el medioambiente.Su forma inorgánica [As(III) y As(V)] es la más tóxica encontrada en agua y alimentos. La exposición a arsénico inorgánico, descrita en numerosas zonas del planeta y que en la actualidad se estima que afecta a 200 millones de personas, aumenta la incidencia de determinados tipos de cáncer y otras patologías no cancerígenas. Teniendo en cuenta que la principal vía de exposición es la oral, el
tracto gastrointestinal se considera la puerta de entrada de este tóxico al organismo; sin embargo, los estudios para determinar los efectos tóxicos del arsénico inorgánico a nivel intestinal son escasos. Esta tesis doctoral tiene como objetivo evaluar la toxicidad del arsénico inorgánico sobre el epitelio intestinal en diferentes tipos de exposición in vitro e in vivo, así como la búsqueda de componentes de la dieta que puedan contrarrestar este efecto tóxico. Para tal fin se han empleado modelos celulares de colon (Caco-2, células
procedentes de un adenocarcinoma y NCM460, línea celular no transformada) y ratones BALB/c. Como posibles estrategias de reducción de la toxicidad intestinal de este metaloide se han ensayado cepas de bacterias lácticas y suplementos dietéticos.
Los estudios in vitro ponen de manifiesto que las exposiciones de corta duración a arsénico inorgánico (2-24 h) generan un aumento de la liberación de la citoquina pro-inflamatoria IL-8 y de la generación de especies reactivas de oxígeno y/o nitrógeno en células Caco-2 y NCM460. Esta respuesta pro-inflamatoria puede ser la responsable de las modificaciones estructurales que cursan con cambios en los patrones de distribución de la zonula occludens 1 y de expresión de la claudina 1, proteínas de las uniones intercelulares que interviene en el mantenimiento de la estructura del epitelio. Paralelamente a estos efectos se evidencia una pérdida de la función barrera de las monocapas intestinales.
En las exposiciones subcrónicas in vitro (7-21 días), también se pone de manifiesto una respuesta pro-inflamatoria que se mantiene durante todo el tratamiento. Esta respuesta viene acompañada de cambios en el programa de proliferación celular y diferenciación, lo que conduce a un detrimento del proceso de reparación celular. Además, la exposición subcrónica afecta igualmente a la estructura epitelial, causando la pérdida de microvellosidades, y a la función de barrera del epitelio intestinal. Estos datos evidencian que la exposición aguda y subcrónica a arsénico inorgánico puede alterar la homeostasis intestinal, afectando la capa de la mucosa, que realiza las funciones más importantes de la pared intestinal.
Adicionalmente se ha evidenciado in vitro que exposiciones más prolongadas (6 meses) favorecen la adquisición de características tumorogénicas en células NCM460, en parte debido al mantenimiento de la respuesta pro-inflamatoria. En las células expuestas crónicamente se observa un aumento de la expresión de CD133, disminución de la expresión de CDX1 y CDX2, mayor secreción de la
metaloproteínasa de matrix MMP-2, modificaciones en el perfil de acetilación de la histona H3, aumento de la hiperproliferación y la formación de esferas flotantes. En general, estos datos sugieren que la exposición de células epiteliales de colon humano a As(III) provoca la adquisición de características de células transformadas.
Los resultados obtenidos en la exposición subcrónica in vivo confirman los datos obtenidos in vitro. Esta exposición genera estrés oxidativo y una respuesta pro-inflamatoria, evidenciada por una mayor expresión génica y proteica de las citoquinas IL-1β, IL-2 e IL-6 en el intestino grueso de animales tratados con As(III). Asimismo, se observa un efecto sobre la morfología del epitelio, con evidencias de hiperplasia en las criptas. Los tratamientos con arsénico también
reducen la expresión de la mucina 2 y posiblemente la formación de mucus. Estos efectos tóxicos pueden ser los causantes del aumento de permeabilidad observado en los animales tratados con arsénico. Este es el primer estudio que evidencia la pérdida de la función barrera del epitelio intestinal in vivo debido a una exposición a arsénico inorgánico.
Finalmente, los ensayos in vitro para evaluar el papel protector de componentes de la dieta ponen de manifiesto que determinadas cepas de Lactobacillus y ciertos suplementos dietéticos modulan la toxicidad que el arsénico inorgánico ejerce sobre el epitelio intestinal. La recuperación de la función barrera y/o de la capacidad de regeneración celular tras los tratamientos indica que estas estrategias, cuya seguridad alimentaria está probada, podrían emplearse para aminorar los efectos que ejerce el arsénico inorgánico a nivel intestinal, y posiblemente a nivel sistémico, en poblaciones afectadas.
... To overcome this handicap, curcumin nano-encapsulated in chitosan has been employed, achieving reductions in As(III) toxicity at a much lower dose than with free curcumin (Yadav et al., 2012). Other plant antioxidants that have demonstrated their usefulness in the reduction of As(III)-induced oxidative stress are b-carotene (Das et al., 2015), naringenin (Roy et al., 2014), and tea polyphenols (Raihan et al., 2009). ...
A large part of the population is exposed to metals and metalloids through the diet. Most of the in vivo studies on its toxicokinetics and toxicity are conducted by means of exposure through drinking water or by intragastric or intraperitoneal administration of aqueous standards, and therefore they do not consider the effect of the food matrix on the exposure. Numerous studies show that some components of the diet can modulate the toxicity of these food contaminants, reducing their effect on a systemic level. Part of this protective role may be due to a reduction of intestinal absorption and subsequent tissue accumulation of the toxic element, although it may also be a consequence of their ability to counteract the toxicity directly by their antioxidant and/or anti-inflammatory activity, among other factors. The present review provides a compilation of existing information about the effect that certain components of the diet have on the toxicokinetics and toxicity of the metals and metalloids of greatest toxicological importance that are present in food (arsenic, cadmium, lead, and mercury), and of their most toxic chemical species.
... In relation to arsenic therapeutics, recently, some herbal and phytochemical remediation of arsenic-induced tissue toxicity has been shown [13][14][15], but none has conclusive and satisfactory level of efficacy. Green tea polyphenols show antioxidant and anticancer effects [16]. ...
Green tea (Camellia sinensis; CS) strongly reverses/prevents arsenic-induced apoptotic hepatic degeneration/micronecrosis and mutagenic DNA damage in in vitro oxidant stress model and in rat as shown by comet assay and histoarchitecture (HE and PAS staining) results. Earlier, we demonstrated a link between carcinogenesis and impaired antioxidant system-associated mutagenic DNA damage in arsenic-exposed human. In this study, arsenic-induced (0.6 ppm/100 g body weight/day for 28 days) impairment of cytosolic superoxide-dismutase (SOD1), catalase, xanthine-oxidase, thiol, and urate activities/levels led to increase in tissue levels of damaging malondialdehyde, conjugated dienes, serum necrotic-marker lactate-dehydrogenase, and metabolic inflammatory-marker c-reactive protein suggesting dysregulation at the transcriptional/signal-transduction level. These are decisively restrained by CS-extract (≥10 mg/ml aqueous) with a restoration of DNA/tissue structure. The structural/functional impairment of dialyzed and centrifugally concentrated (6-8 kd cutoff) hepatic SOD1 via its important Cys modifications by H2O2/arsenite redox-stress and that protection by CS/2-mercaptoethanol are shown in in vitro/in situ studies paralleling the present Swiss-Model-generated rSOD1 structural data. Here, arsenite(3+) incubation (≥10(-8) μM + 10 mM H2O2, 2 hr) is shown for the first time with this low-concentration to initiate breakage in rat hepatic-DNA in vitro whereas, arsenite/H2O2/UV-radiation does not affect DNA separately. Arsenic initiates Fe and Cu ion-associated free-radical reaction cascade in vivo. Here, 10 μM of Cu(2+)/Fe(3+)/As(3+) +H2O2-induced in vitro DNA fragmentation is prevented by CS (≥1 mg/ml), greater than the prevention of ascorbate or tocopherol or DMSO or their combination. Moreover, CS incubation for various time with differentially and already degraded DNA resulted from pre-incubation in 10 μM As(3+)-H2O2 system markedly recovers broken DNA. Present results decisively suggest for the first time that CS and its mixed polyphenols have potent SOD1 protecting, diverse radical-scavenging and antimutagenic activities furthering to DNA protection/therapy in arsenic-induced tissue necrosis/apoptosis.
... In many countries, the levels of arsenic As in the environment have turned out to be one of concern and many studies have recognized various adverse health effects on populations 1 . In modern days, exposure to sufficiently high concentrations of inorganic As in natural environments such as in water, sediment and soil has proved to be harmful to the organisms 2, 3 . ...
The present study was adopted to evaluate the antioxidant efficacy of medium chain fatty acid (caprylic, capric and lauric) rich rice bran oils in comparison to rice bran oil in terms of altered biochemical parameters of oxidative stress following sodium arsenite treatment in rats. Animals were divided into ten groups; five normal groups and five arsenite treated groups. Results showed that activities of antioxidant enzymes in liver, brain and erythrocyte membrane increased with the administration of rice bran oil and MCFA rich rice bran oils both in normal and arsenite treated cases. Lipid peroxidation increased with the administration of sodium arsenite, but again administration of rice bran oil and MCFA rich rice bran oils decreased the lipid peroxidation. Caprylic acid rich rice bran oil showed the best ameliorative effects.
... In many countries, the levels of As in the environment have turned out to be one of concern and many studies have recognized various adverse health effects on populations. [1] In modern days, exposure to sufficiently high concentrations of inorganic As in natural environments such as in water, sediment and soil has proved to be harmful to the organisms. [2,3] The main pathways of exposure to the human beings include ingestion of drinking water and consumption of foods and to a lesser extent, inhalation of air. ...
Contamination of the environment with arsenic (As) from both human and natural sources is known as a global problem. This study investigated the chemoprotective potential of Vernonia amygdalina leave extract against sodium arsenite-induced genotoxicity and hepatotoxicity.
Genotoxic effects were evaluated in the rat bone marrow using micronuclei. The gamma glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP) activities were assayed in rat serum.
Pre-treatment with extract of V. amygdalina at doses 5 mg/kg and 10 mg/kg significantly decreased the frequency of micronucleated polychromatic erythrocytes (PCEs). The GGT and ALP activities were elevated more than fourfold, in the liver of rats treated with sodium arsenite, while it was reduced almost to half when the sodium arsenit-treated rats were fed fresh V. amgdalina leave extracts The phytochemical constituents of V. amygdalina assayed in this study may be responsible for high radical scavenging of the DPPH free radical observed.
The present results indicate that V. amygdalina extract is capable of suppressing the chromosomal aberration induced by sodium arsenite in rat. Thus, V. amygdalina may be a potent chemoprotective agent against the toxicity of sodium arsenite in rats.
... Although there have been a number of studies on the antitoxic effects of catechins [31][32][33][34][35], only a few studies of Fig. 2 Final body weight of mice. Body weight did not decreased with DXR treatment, with or without GTE exposure (G2, G3 and G4). ...
The aim of this study was to investigate the protective effect of green tea extracts against doxorubicin-induced damage in the mouse testes correlating with telomerase activity.
Green tea extracts were administered orally. Doxorubicin was coadministered intraperitoneally. These testes were evaluated histologically and the telomerase activity was analyzed. Additional immunostaining was carried out.
Both the sperm density and sperm motility were significantly increased in green tea extracts coadministration groups as compared to the doxorubicin-treated groups. By histological analysis, germ cell damage was greatly attenuated by green tea extracts coadministration. Telomerase activity significantly increased in association with the coadministration of green tea extracts as compared to that of doxorubicin-only groups. In all groups, human telomerase reverse transcriptase signals were mainly observed in the spermatocytes and spermatids.
These findings suggest that green tea extracts exert protective effects against doxorubicin-induced spermatogenic disorders in conjunction with higher telomerase activity levels.
Chronic exposure to arsenic (As) compounds leads to its accumulation in the body, with skin lesions and cancer being the most typical outcomes. Treating As-induced diseases continues to be challenging as there is no specific, safe, and efficacious therapeutic management. Therapeutic and preventive measures available to combat As toxicity refer to chelation therapy, antioxidant therapy, and the intake of natural dietary compounds. Although chelation therapy is the most commonly used method for detoxifying As, it has several side effects resulting in various toxicities such as hepatotoxicity, neurotoxicity, and other adverse consequences. Drugs of plant origin and natural dietary compounds show efficient and progressive relief from As-mediated toxicity without any particular side effects. These natural compounds have also been found to aid the elimination of As from the body and, therefore, can be more effective than conventional therapeutic agents in ameliorating As toxicity. This review provides an overview of the recently updated knowledge on treating As poisoning through natural dietary compounds. This updated information may serve as a basis for defining novel prophylactic and therapeutic formulations.
Arsenic toxicity, caused mainly by arsenic-contaminated groundwater, is considered as a critical threat to global communal health, as there is no specific and proven conventional therapy for chronic arsenic toxicity i.e., arsenicosis. Therefore, alternative herbal options should be explored for its mitigation. Literature survey reveals several medicinal plants to possess significant protective efficacy against arsenic toxicity in chiefly pre-clinical and few clinical investigations. In this chapter, the medicinal herbs that have arsenic toxicity ameliorative properties are collated as preclinical and clinical evidences which may be useful develop a potential nutraceutical or therapeutic candidate against arsenicosis in humans along with extant therapies.KeywordsArsenic toxicityArsenicosisMedicinal plants
Spirulina
Chronic exposure to arsenic (As) compounds leads to its accumulation in the body, with skin lesions and cancer being the most typical outcomes. Treating As-induced diseases continues to be challenging as there is no specific, safe, and efficacious therapeutic management. Therapeutic and preventive measures available to combat As toxicity refer to chelation therapy, antioxidant therapy, and the intake of natural dietary compounds. Although chelation therapy is the most commonly used method for detoxifying As, it has several side effects resulting in various toxicities such as hepatotoxicity, neurotoxicity, and other adverse consequences. Drugs of plant origin and natural dietary compounds show efficient and progressive relief from As-mediated toxicity without any particular side effects. These natural compounds have also been found to aid the elimination of As from the body and, therefore, can be more effective than conventional therapeutic agents in ameliorating As toxicity. This review provides an overview of the recently updated knowledge on treating As poisoning through natural dietary compounds. This updated information may serve as a basis for defining novel prophylactic and therapeutic formulations.
Context: Chronic arsenic toxicity (arsenicosis) is considered a serious public health menace worldwide, as there is no specific, safe, and efficacious therapeutic management of arsenicosis.
Objectives: To collate the studies on medicinal plants and natural products with arsenic toxicity ameliorative effect, active pre-clinically and/or clinically.
Methods: Literature survey was carried out by using Google, Scholar Google and Pub-Med. Only the scientific journal articles found on the internet for last two decades were considered. Minerals and semi-synthetic or synthetic analogs of natural products were excluded.
Results: Literature study revealed that 34 medicinal plants and 14 natural products exhibited significant protection from arsenic toxicity, mostly in preclinical trials and a few in clinical studies.
Conclusion: This research could lead to development of a potentially useful agent in clinical management of arsenicosis in humans.
Pesticides, smoke, mycotoxins, polychlorinated biphenyls, and arsenic are the most common environmental toxins and toxicants to humans. These toxins and toxicants may impact on human health at the molecular (DNA, RNA, or protein), organelle (mitochondria, lysosome, or membranes), cellular (growth inhibition or cell death), tissue, organ, and systemic levels. Formation of reactive radicals, lipid peroxidation, inflammation, genotoxicity, hepatotoxicity, embryotoxicity, neurological alterations, apoptosis, and carcinogenic events are some of the mechanisms mediating the toxic effects of the environmental toxins and toxicants. Green tea, the non-oxidized and non-fermented form of tea that contains several polyphenols, including green tea catechins, exhibits protective effects against these environmental toxins and toxicants in preclinical studies and to a much-limited extent, in clinical trials. The protective effects are collectively mediated by antioxidant, anti-inflammatory, anti-mutagenic, hepato- and neuro-protective, and anti-carcinogenic activities. In addition, green tea modulates signaling pathway including NFκB and ERK pathways, preserves mitochondrial membrane potential, inhibits caspase-3 activity, down-regulates pro-apoptotic proteins, and induces the phase II detoxifying pathway. The bioavailability and metabolism of green tea and its protective effects against environmental insults induced by pesticides, smoke, mycotoxins, polychlorinated biphenyls, and arsenic are reviewed in this paper. Future studies with emphasis on clinical trials should identify biomarkers of green tea intake, examine the mechanisms of action of green tea polyphenols, and investigate potential interactions of green tea with other toxicant-modulating dietary factors.
Health risk of arsenic (As) has received increasing attention. Acute and chronic exposure to As could cause several detrimental effects on human health. As toxicity is closely related to its bioaccessibility and metabolism. In real environment, many factors, such as diet and nutrition, can influence As bioaccessibility, metabolism and toxicity. This paper mainly reviews the influences of diets and elements on As bioaccessibility, metabolism and toxicity and their underlying mechanisms to provide suggestions for future investigations. Vitamins, jaggery, fruit, tea, glutathione, N-acetylcysteine and zinc could reduce the As-induced toxicity by increasing antioxidative enzymes to antagonize oxidative stress caused by As and/or increasing As methylation. However, bean and betel nut could increase risk of skin lesions caused by As. Interestingly, high-fat diet, selenium and iron have incompatible effects on As bioaccessibility, metabolism and toxicity in different experimental conditions. Based on current literatures, the As methylation and As-induced oxidative damage might be two main ways that the diets and elements influence As toxicity. Combined application of in vitro human cell lines and gastrointestinal models might be useful tools to simultaneously characterize the changes in As bioaccessibility and toxicity in the future research.
Consumption of fruits and the other dietary antioxidants are considered beneficial due to the protection they afford in the pathogenesis associated with oxidative stress. The aim of this study was to evaluate the antioxidative effects of selected fruit extracts (Plums, Apples, Grapes and Cranberries) on human lung fibroblasts (CCD-25LU) exposed to tert-butyl hydroperoxide (tBHP) oxidative stress. Lactate Dehydrogenase (LDH) was used to assess cytotoxicity (cell integrity) and antioxidant enzymes catalase (CAT), glutathione-s-transferase (GST), glutathione peroxidases (GPx) and concentrations of reduced glutathione (GSH) were determined. Results showed that LDH release by cells pretreated with fruits extracts were significantly (p<0.05) lower compared to cells treated with tBHP alone. Antioxidant enzymes (CAT, GST and GPx) in cells pretreated with fruit extracts were increased by 2-4 folds compared to cell exposed to tBHP alone. GSH levels which were significantly (p<0.05) reduced after exposure to tBHP were restored by pretreatment with fruit extracts. Fruits extracts used in this study protected CCD-25LU against oxidative stress induced by tBHP and reduced cell damage. Consumption of fruits may therefore play a significant role in protection against oxidative induced lung diseases.
Background: The aim of this research was to examine the effects of green tea supplementation on plasma total antioxidant capacity (TAC) and lipid peroxidation in young women after a resistance training session.
Methods: Forty young women were randomly divided into four equal groups of green tea supplementation, green tea supplementation and resistance training, resistance training, and control. After supplementation period (14 days, 600 ml/day), subjects performed an intensive resistance training session with 85% of one repetition maximum (1RM). Blood samples were taken at baseline, at the end of supplementation period, and after the exercise protocol. TAC and malondialdehyde (MDA) were measured using Ferric Reducing Antioxidant Power (FRAP) assay and thiobarbituric acid (TBA), respectively.
Findings: After 14 days, the TAC significantly increased (P < 0.001) and MDA significantly decreased (P < 0.01) in the green tea supplementation and resistance training group. However, intensive resistance training decreased TAC (P < 0.04) and increased MDA (P < 0.01) significantly in the resistance training group.
Conclusion: Our results suggested that green tea supplementation will be useful for improving TAC and thereby inhibiting exercise-induced lipid peroxidation after intensive resistance training.
Keywords: Lipid peroxidation, Green tea, Total antioxidant capacity, Resistance training
Background and Objectives: There are many problems in treatment of different kinds of tumors. Many studies were carried out for finding suitable antitumor materials in different countries. The aim of this study is to evaluate the antitumor effects of olive and green tea extracts on human breast tumor cell line (BT474).
Methods: Water and ethanol extracts of green tea and olive were prepared. BT474 cells were treated with determinded concentration of extracts at different incubation times and cell lysis was measured using the lactate dehydrogenase enzyme assay. Experiments were repeated 3 times and the results expressed as means ± standard deviation. Statistical analysis were performed by t-test and p £ 0.05 considered as significant.
Results: Increasing the concentration of green tea in 8 and 24 h exposures decreased cell lysis or killing percentage of treated cells. Olive extract in 1mg/dL concentration showed highest percent (85%) of cell lysis. Cell lysis effect of olive extract treatments was dose-dependent and increased in higher concentrations. There were no significant difference in killing effect of olive extract between 8 and 24 h incubation time (consequently 83% and 85%). But at the same incubation periods the difference between percent of cell lysis in the presence of green tea extracts (0.01 and 0.1 mg/dL) was significant. (p=0.000).
Conclusions: Our results indicated that crude olive and green tea extractions have exerted lytic effects on BT 474 lines. Olive extract have higher cytotoxicity than green tea. Cytotoxicity of olive extract was dose-dependent.
A new automated system for the analysis of nitrate via reduction with a high-pressure cadmium column is described. Samples of urine, saliva, deproteinized plasma, gastric juice, and milk can be analyzed for nitrate, nitrite, or both with a lower limit of detection of 1.0 nmol NO3− or NO2−/ml. The system allows quantitative reduction of nitrate and automatically eliminates interference from other compounds normally present in urine and other biological fluids. Analysis rate is 30 samples per hour, with preparation for most samples limited to simple dilution with distilled water. The application of gas chromatography/mass spectrometry for the analysis of 15NO3− in urine after derivatization to 15NO2-benzene is also described.
Nitric oxide and superoxide, which are produced by several cell types, rapidly combine to form peroxynitrite. This reaction can result in nitric oxide scavenging, and thus mitigation of the biological effects of superoxide. Also, superoxide can trap and hence modulate the effects of nitric oxide; superoxide dismutase, by controlling superoxide levels, therefore can influence the reaction pathways open to nitric oxide. The production of peroxynitrite, however, causes its own sequelae of events: Although neither .NO nor superoxide is a strong oxidant, peroxynitrite is a potent and versatile oxidant that can attack a wide range of biological targets. The peroxynitrite anion is relatively stable, but its acid, peroxynitrous acid (HOONO), rearranges to form nitrate with a half-life of approximately 1 s at pH 7, 37 degrees C. HOONO exists as a Boltzmann distribution of rotamers; at 5-37 degrees C HOONO has an apparent acidity constant, pKa,app, of 6.8. Oxidation reactions of HOONO can involve two-electron processes (such as an SN2 displacement) or a one-electron transfer (ET) reaction in which the substrate is oxidized by one electron and peroxynitrite is reduced. These oxidation reactions could involve one of two mechanisms. The first mechanism is homolysis of HOONO to give HO. and .NO2, which initially are held together in a solvent cage. This caged pair of radicals (the "geminate" pair) can either diffuse apart, giving free radicals that can perform oxidations, or react together either to form nitrate or to reform HOONO (a process called cage return). A large amount of cage return can explain the small entropy of activation (Arrhenius A-factor) observed for the decomposition of HOONO. A cage mechanism also can explain the residual yield of nitrate that appears to be formed even in the presence of high concentrations of all of the scavengers studied to date, since scavengers capture only free HO. and .NO2 and not caged radicals. If the cage mechanism is correct, the rate of disappearance of peroxynitrite be slower in solvents of higher viscosity, and we do not find this to be the case. The second mechanism is that an activated isomer of peroxynitrous acid, HOONO*, can be formed in a steady state. The HOONO* mechanism can explain the inability of hydroxyl radical scavengers to completely block either nitrate formation or the oxidation of substrates such as methionine, since HOONO* would be less reactive, and therefore more selective, than the hydroxyl radical itself.(ABSTRACT TRUNCATED AT 400 WORDS)
To investigate the effect of black and green tea consumption, with and without milk, on the plasma antioxidant activity in humans.
In a complete cross-over design, 21 healthy volunteers (10 male, 11 female) received a single dose of black tea, green tea (2 g tea solids in 300 ml water) or water with or without milk. Blood samples were obtained at baseline and at several time points up to 2 h post-tea drinking. Plasma was analysed for total catechins and antioxidant activity, using the ferric reducing ability of plasma (FRAP) assay.
Consumption of black tea resulted in a significant increase in plasma antioxidant activity reaching maximal levels at about 60 min. A larger increase was observed after consumption of green tea. As anticipated from the higher catechin concentration in green tea, the rise in plasma total catechins was significantly higher after consumption of green tea when compared to black tea. Addition of milk to black or green tea did not affect the observed increases in plasma antioxidant activity.
Consumption of a single dose of black or green tea induces a significant rise in plasma antioxidant activity in vivo. Addition of milk to tea does not abolish this increase. Whether the observed increases in plasma antioxidant activity after a single dose of tea prevent in vivo oxidative damage remains to be established. European Journal of Clinical Nutrition (2000) 54, 87-92
The contamination of groundwater by arsenic in Bangladesh is the largest poisoning of a population in history, with millions of people exposed. This paper describes the history of the discovery of arsenic in drinking-water in Bangladesh and recommends intervention strategies. Tube-wells were installed to provide "pure water" to prevent morbidity and mortality from gastrointestinal disease. The water from the millions of tube-wells that were installed was not tested for arsenic contamination. Studies in other countries where the population has had long-term exposure to arsenic in groundwater indicate that 1 in 10 people who drink water containing 500 micrograms of arsenic per litre may ultimately die from cancers caused by arsenic, including lung, bladder and skin cancers. The rapid allocation of funding and prompt expansion of current interventions to address this contamination should be facilitated. The fundamental intervention is the identification and provision of arsenic-free drinking water. Arsenic is rapidly excreted in urine, and for early or mild cases, no specific treatment is required. Community education and participation are essential to ensure that interventions are successful; these should be coupled with follow-up monitoring to confirm that exposure has ended. Taken together with the discovery of arsenic in groundwater in other countries, the experience in Bangladesh shows that groundwater sources throughout the world that are used for drinking-water should be tested for arsenic.
The purpose of the present study was to investigate the mechanism of cross-tolerance to nickel in arsenic-transformed cells. Chronic arsenite-exposed (CAsE) cells (TRL 1215 cells, which had been continuously exposed to 0.5 microM arsenite for 20 or more weeks) and control TRL 1215 cells were both exposed to nickel for 24 h, and cell viability was determined by metabolic integrity. The LC(50) for nickel was 608 +/- 32 microM in CAsE cells as compared to 232 +/- 16 microM in control cells, a 2.6-fold increase. CAsE and control cells were treated with 200 microM nickel for 4 h and cellular-free radical production was measured using ESR spectrometry. Hydroxyl radical generation was decreased in CAsE cells. Thiobarbituric acid reactive substances, indicative of lipid peroxidation, and 8-oxo-2'-deoxyguanosine, indicative of oxidative DNA damage, were reduced in CAsE cells. Flow cytometric analysis using Annexin/FITC revealed that nickel-induced apoptosis was reduced in CAsE cells. CAsE cells showed generalized resistance to oxidant-induced toxicity as evidenced by a marked reduction in sensitivity to hydrogen peroxide. Interestingly, intracellular reduced glutathione (GSH) levels were significantly increased in CAsE cells, and when GSH was depleted, CAsE cells lost their nickel resistance. The mechanism of arsenic-induced cross-tolerance to cytotoxicity, genotoxicity, and apoptosis induced by nickel appears related to a generalized resistance to oxidant-induced injury, probably based, at least in part, in increased cellular GSH levels.
Toxic metals (lead, cadmium, mercury and arsenic) are widely found in our environment. Humans are exposed to these metals from numerous sources, including contaminated air, water, soil and food. Recent studies indicate that transition metals act as catalysts in the oxidative reactions of biological macromolecules therefore the toxicities associated with these metals might be due to oxidative tissue damage. Redox-active metals, such as iron, copper and chromium, undergo redox cycling whereas redox-inactive metals, such as lead, cadmium, mercury and others deplete cells' major antioxidants, particularly thiol-containing antioxidants and enzymes. Either redox-active or redox-inactive metals may cause an increase in production of reactive oxygen species (ROS) such as hydroxyl radical (HO.), superoxide radical (O2.-) or hydrogen peroxide (H2O2). Enhanced generation of ROS can overwhelm cells' intrinsic antioxidant defenses, and result in a condition known as "oxidative stress". Cells under oxidative stress display various dysfunctions due to lesions caused by ROS to lipids, proteins and DNA. Consequently, it is suggested that metal-induced oxidative stress in cells can be partially responsible for the toxic effects of heavy metals. Several studies are underway to determine the effect of antioxidant supplementation following heavy metal exposure. Data suggest that antioxidants may play an important role in abating some hazards of heavy metals. In order to prove the importance of using antioxidants in heavy metal poisoning, pertinent biochemical mechanisms for metal-induced oxidative stress should be reviewed.
Although arsenic is a well-established human carcinogen, the underlying carcinogenic mechanism(s) is not known. Using the human-hamster hybrid (A(L)) cell mutagenic assay that is sensitive in detecting mutagens that induce predominately multilocus deletions, we showed previously that arsenite is indeed a potent gene and chromosomal mutagen and that oxyradicals may be involved in the mutagenic process. In the present study, the effects of free radical scavenging enzymes on the cytotoxic and mutagenic potential of arsenic were examined using the AL cells. Concurrent treatment of cells with either superoxide dismutase or catalase reduced both the cytotoxicity and mutagenicity of arsenite by an average of 2-3 fold, respectively. Using immunoperoxidase staining with a monoclonal antibody specific for 8-hydroxy-2'-deoxyguanosine (8-OHdG), we demonstrated that arsenic induced oxidative DNA damage in A(L) cells. This induction was significantly reduced in the presence of the antioxidant enzymes. Furthermore, reducing the intracellular levels of non-protein sulfhydryls (mainly glutathione) using buthionine S-R-Sulfoximine increased the total mutant yield by more than 3-fold as well as the proportion of mutants with multilocus deletions. Taken together, our data provide clear evidence that reactive oxygen species play an important causal role in the genotoxicity of arsenic in mammalian cells.
Previous research has shown that cell membranes of potato (Solanum tuberosum L. cv Russet Burbank) seed-tubers lose integrity between 7 and 26 months of storage (4[deg]C, 95% relative humidity), and this loss coincides with a significant decrease in growth potential. The age-induced decline in membrane integrity is apparently due to increased peroxidative damage of membrane lipids. Malondialdehyde (MDA) and ethane concentrations (sensitive markers of lipid peroxidation and membrane damage) increased in seed-tuber tissues with advancing age. Moreover, in vivo ethane production from discs of cortex tissue from 13- and 25-month-old seed-tubers was 87% greater (on average) than that from discs from 1-month-old tubers. Calcium suppressed ethane production from all ages of tissue discs, and the effect was concentration dependent. Linoleic acid enhanced ethane production from 5- and 17-month-old tubers by 61 and 228%, respectively, suggesting that older tissue may contain a higher free-radical (FR) titer and/or lower free polyunsaturated fatty acid content. In addition, throughout plant establishment, the internal ethane concentration of older seed-tubers was 54% higher than that of younger seed-tubers. MDA concentration of tuber tissue declined by about 65% during the initial 7 months of storage and then increased 267% as tuber age advanced to 30 months. The age-induced trend in tuber reducing sugar concentration was similar to that of MDA, and the two were linearly correlated. The age-dependent increase in reducing sugars may thus reflect peroxidative degeneration of the amyloplast membrane, leading to increased starch hydrolysis. Compared with 5-month-old seed tubers, 17- and 29-month-old seed-tubers had significantly higher levels of lipofuscin-like fluorescent compounds (FCs), which are produced when MDA reacts with free amino acids. Age-dependent increases in MDA, ethane, and FCs were not associated with higher activities of phospholipase and lipoxygenase in tissue from older tubers. In fact, 8-month-old seed-tubers had significantly higher activities of these enzymes than 20-month-old seed-tubers. However, the activities of superoxide dismutase, peroxidase, and catalase in 20-month-old tubers were substantially higher out of storage, and increased at a faster rate during plant establishment, than in 8-month-old seed-tubers. Collectively, these results suggest that a gradual build-up of FRs leads to peroxidative damage of membrane lipids during aging of potato seed-tubers.
Exposure to toxic metals has become an increasingly recognized source of illness worldwide. Both cadmium and arsenic are ubiquitous in the environment, and exposure through food and water as well as occupational sources can contribute to a well-defined spectrum of disease. The symptom picture of arsenic toxicity is characterized by dermal lesions, anemia, and an increased risk for cardiovascular disease, diabetes, and liver damage. Cadmium has a significant effect on renal function, and as a result alters bone metabolism, leading to osteoporosis and osteomalacia. Cadmium-induced genotoxicity also increases risk for several cancers. The mechanisms of arsenic- and cadmium-induced damage include the production of free radicals that alter mitochondrial activity and genetic information. The metabolism and excretion of these heavy metals depend on the presence of antioxidants and thiols that aid arsenic methylation and both arsenic and cadmium metallothionein-binding. S-adenosylmethionine, lipoic acid, glutathione, selenium, zinc, N-acetylcysteine (NAC), methionine, cysteine, alpha-tocopherol, and ascorbic acid have specific roles in the mitigation of heavy metal toxicity. Several antioxidants including NAC, zinc, methionine, and cysteine, when used in conjunction with standard chelating agents, can improve the mobilization and excretion of arsenic and cadmium.
Recently, considerable attention has been focused on dietary and medicinal phytochemicals that inhibit, reverse, or retard diseases caused by oxidative and inflammatory processes. Green tea polyphenols have both antioxidant and antiinflammatory properties.
We examined the effects of green tea polyphenols in carbon tetrachloride-treated mice, a model of liver injury in which oxidant stress and cytokine production are intimately linked. We tested the effect of a pure form of epigallocatechin gallate (EGCG), the major polyphenol in green tea, in mice treated with carbon tetrachloride.
Eight-week-old ICR mice were administered 20 microL/CCl(4) kg dissolved in olive oil. Two different doses of EGCG, 50 and 75 mg/kg, were tested. Control mice were treated with saline and olive oil. We analyzed liver histopathology, lipid peroxidation, and messenger RNA and protein concentrations of inducible nitric oxide synthase. Additionally, nitric oxide-generated radicals were assessed by electron paramagnetic resonance spectroscopy, and protein concentrations were measured by immunohistochemistry and Western blot analysis.
Carbon tetrachloride administration caused an intense degree of liver necrosis associated with increases in lipid peroxidation, inducible nitric oxide synthase messenger RNA and protein, nitrotyrosine, and nitric oxide radicals. EGCG administration led to a dose-dependent decrease in all of the histologic and biochemical variables of liver injury observed in the carbon tetrachloride-treated mice.
Green tea polyphenols reduce the severity of liver injury in association with lower concentrations of lipid peroxidation and proinflammatory nitric oxide-generated mediators. Green tea polyphenols can be a useful supplement in the treatment of liver disease and should be considered for liver conditions in which proinflammatory and oxidant stress responses are dominant.
Arsenite was shown to inhibit pyruvate dehydrogenase (PDH) activity through binding to vicinal dithiols in pure enzyme and tissue extract. However, no data are available on how arsenite inhibits PDH activity in human cells. The IC(50) values for arsenic trioxide (As(2)O(3)) to inhibit the PDH activity in porcine heart pure enzyme preparation and in human leukemia cell line HL60 cells were estimated to be 182 and 2 microM, respectively. Thus, As(2)O(3) inactivation of PDH activity was about 90 times more potent in HL60 cells than in purified enzyme preparation. The IC(50) values for As(2)O(3) and phenylarsine oxide to reduce the vicinal thiol content in HL60 cells were estimated to be 81.7 and 1.9 microM, respectively. Thus, As(2)O(3) is a potent PDH inhibitor but a weak vicinal thiol reacting agent in HL60 cells. Antioxidants but not dithiol compounds suppressed As(2)O(3) inhibition of PDH activity in HL60 cells. Conversely, dithiol compounds but not antioxidants suppressed the inhibition of PDH activity by phenylarsine oxide. As(2)O(3) increased H(2)O(2) level in HL60 cells, but this was not observed for phenylarsine oxide. Mitochondrial respiration inhibitors suppressed the As(2)O(3)-induced H(2)O(2) production and As(2)O(3) inhibition of PDH activity. Moreover, metal chelators ameliorated whereas Fenton metals aggravated As(2)O(3) inhibition of PDH activity. Treatment with H(2)O(2) plus Fenton metals also decreased the PDH activity in HL60 cells. Therefore, it seems that As(2)O(3) elevates H(2)O(2) production in mitochondria and this may produce hydroxyl through the Fenton reaction and result in oxidative damage to the protein of PDH. The present results suggest that arsenite may cause protein oxidation to inactivate an enzyme and this can occur at a much lower concentration than arsenite binding directly to the critical thiols.
Metal-induced toxicity and carcinogenicity, with an emphasis on the generation and role of reactive oxygen and nitrogen species, is reviewed. Metal-mediated formation of free radicals causes various modifications to DNA bases, enhanced lipid peroxidation, and altered calcium and sulfhydryl homeostasis. Lipid peroxides, formed by the attack of radicals on polyunsaturated fatty acid residues of phospholipids, can further react with redox metals finally producing mutagenic and carcinogenic malondialdehyde, 4-hydroxynonenal and other exocyclic DNA adducts (etheno and/or propano adducts). Whilst iron (Fe), copper (Cu), chromium (Cr), vanadium (V) and cobalt (Co) undergo redox-cycling reactions, for a second group of metals, mercury (Hg), cadmium (Cd) and nickel (Ni), the primary route for their toxicity is depletion of glutathione and bonding to sulfhydryl groups of proteins. Arsenic (As) is thought to bind directly to critical thiols, however, other mechanisms, involving formation of hydrogen peroxide under physiological conditions, have been proposed. The unifying factor in determining toxicity and carcinogenicity for all these metals is the generation of reactive oxygen and nitrogen species. Common mechanisms involving the Fenton reaction, generation of the superoxide radical and the hydroxyl radical appear to be involved for iron, copper, chromium, vanadium and cobalt primarily associated with mitochondria, microsomes and peroxisomes. However, a recent discovery that the upper limit of "free pools" of copper is far less than a single atom per cell casts serious doubt on the in vivo role of copper in Fenton-like generation of free radicals. Nitric oxide (NO) seems to be involved in arsenite-induced DNA damage and pyrimidine excision inhibition. Various studies have confirmed that metals activate signalling pathways and the carcinogenic effect of metals has been related to activation of mainly redox-sensitive transcription factors, involving NF-kappaB, AP-1 and p53. Antioxidants (both enzymatic and non-enzymatic) provide protection against deleterious metal-mediated free radical attacks. Vitamin E and melatonin can prevent the majority of metal-mediated (iron, copper, cadmium) damage both in vitro systems and in metal-loaded animals. Toxicity studies involving chromium have shown that the protective effect of vitamin E against lipid peroxidation may be associated rather with the level of non-enzymatic antioxidants than the activity of enzymatic antioxidants. However, a very recent epidemiological study has shown that a daily intake of vitamin E of more than 400 IU increases the risk of death and should be avoided. While previous studies have proposed a deleterious pro-oxidant effect of vitamin C (ascorbate) in the presence of iron (or copper), recent results have shown that even in the presence of redox-active iron (or copper) and hydrogen peroxide, ascorbate acts as an antioxidant that prevents lipid peroxidation and does not promote protein oxidation in humans in vitro. Experimental results have also shown a link between vanadium and oxidative stress in the etiology of diabetes. The impact of zinc (Zn) on the immune system, the ability of zinc to act as an antioxidant in order to reduce oxidative stress and the neuroprotective and neurodegenerative role of zinc (and copper) in the etiology of Alzheimer's disease is also discussed. This review summarizes recent findings in the metal-induced formation of free radicals and the role of oxidative stress in the carcinogenicity and toxicity of metals.
The contamination of groundwater by arsenic in Bangladesh is the largest poisoning of a population in history, with millions of people exposed. This paper describes the history of the discovery of arsenic in drinking-water in Bangladesh and recommends intervention strategies. Tube-wells were installed to provide "pure water" to prevent morbidity and mortality from gastrointestinal disease. The water from the millions of tube-wells that were installed was not tested for arsenic contamination. Studies in other countries where the population has had long-term exposure to arsenic in groundwater indicate that 1 in 10 people who drink water containing 500 mu g of arsenic per litre may ultimately die from cancers caused by arsenic, including lung, bladder and skin cancers. The rapid allocation of funding and prompt expansion of current interventions to address this contamination should be facilitated. The fundamental intervention is the identification and provision of arsenic-free drinking water. Arsenic is rapidly excreted in urine, and for early or mild cases, no specific treatment is required. Community education and participation are essential to ensure that interventions are successful; these should be coupled with follow-up monitoring to confirm that exposure has ended. Taken together with the discovery of arsenic in groundwater in other countries, the experience in Bangladesh shows that groundwater sources throughout the world that are used for drinking-water should be tested for arsenic.
The purpose of the present study was to investigate the mechanism of cross-tolerance to nickel in arsenic-transformed cells. Chronic arsenite-exposed (CAsE) cells (TRL 1215 cells, which had been continuously exposed to 0.5 μM arsenite for 20 or more weeks) and control TRL 1215 cells were both exposed to nickel for 24 h, and cell viability was determined by metabolic integrity. The LC 50 for nickel was 608 ± 32 pM in CAsE cells as compared to 232 ± 16 μM in control cells, a 2.6-fold increase. CAsE and control cells were treated with 200 μM nickel for 4 h and cellular-free radical production was measured using ESR spectrometry. Hydroxyl radical generation was decreased in CAsE cells. Thiobarbituric acid reactive substances, indicative of lipid peroxidation, and 8-oxo-2'-deoxyguanosine, indicative of oxidative DNA damage, were reduced in CAsE cells. Flow cytometric analysis using Annexin/FITC revealed that nickel-induced apoptosis was reduced in CAsE cells. CAsE cells showed generalized resistance to oxidant-induced toxicity as evidenced by a marked reduction in sensitivity to hydrogen peroxide. Interestingly, intracellular reduced glutathione (GSH) levels were significantly increased in CAsE cells, and when GSH was depleted, CAsE cells lost their nickel resistance. The mechanism of arsenic-induced cross-tolerance to cytotoxicity, genotoxicity, and apoptosis induced by nickel appears related to a generalized resistance to oxidant-induced injury, probably based, at least in part, in increased cellular GSH levels.
The extractability of tannin from fresh, lyophilized, and dried leaves collected at various times in the growing season was determined using the radial diffusion assay for protein-precipitating phenolics. The amount of tannin extracted depended on the method of leaf preservation and on the maturity of the leaf. Early in the season, more tannin was extracted from lyophilized leaves than from fresh leaves, but late in the season more tannin was extracted from fresh leaves. At all times, more tannin was extracted with aqueous acetone than with aqueous or acidic methanol.
Accumulating evidence supports the hypothesis that brain iron misregulation and oxidative stress (OS), resulting in reactive oxygen species (ROS) generation from H2O2 and inflammatory processes, trigger a cascade of events leading to apoptotic/necrotic cell death in neurodegenerative disorders, such as Parkinson's (PD), Alzheimer's (AD) and Huntington's diseases, and amyotrophic lateral sclerosis (ALS). Thus, novel therapeutic approaches aimed at neutralization of OS-induced neurotoxicity, support the application of ROS scavengers, transition metals (e.g. iron and copper) chelators and non-vitamin natural antioxidant polyphenols, in monotherapy, or as part of antioxidant cocktail formulation for these diseases. Both experimental and epidemiological evidence demonstrate that flavonoid polyphenols, particularly from green tea and blueberries, improve age-related cognitive decline and are neuroprotective in models of PD, AD and cerebral ischemia/reperfusion injuries. However, recent studies indicate that the radical scavenger property of green tea polyphenols is unlikely to be the sole explanation for their neuroprotective capacity and in fact, a wide spectrum of cellular signaling events may well account for their biological actions. In this article, the currently established mechanisms involved in the beneficial health action and emerging studies concerning the putative novel molecular neuroprotective activity of green tea and its major polyphenol (-)-epigallocatechin-3-gallate (EGCG), will be reviewed and discussed.
The range of As concentrations found in natural waters is large, ranging from less than 0.5 m gl 1 to more than 5000 m gl 1. Typical concentrations in freshwater are less than 10 m gl 1 and frequently less than 1 m gl 1. Rarely, much higher concentrations are found, particularly in groundwater. In such areas, more than 10% of wells may be 'affected' (defined as those exceeding 50 m gl 1) and in the worst cases, this figure may exceed 90%. Well-known high-As groundwater areas have been found in Argentina, Chile, Mexico, China and Hungary, and more recently in West Bengal (India), Bangladesh and Vietnam. The scale of the problem in terms of population exposed to high As con- centrations is greatest in the Bengal Basin with more than 40 million people drinking water containing 'excessive' As. These large-scale 'natural' As groundwater problem areas tend to be found in two types of environment: firstly, inland or closed basins in arid or semi-arid areas, and secondly, strongly reducing aquifers often derived from alluvium. Both environments tend to contain geologically young sediments and to be in flat, low-lying areas where groundwater flow is sluggish. Historically, these are poorly flushed aquifers and any As released from the sediments following burial has been able to accumulate in the groundwater. Arsenic-rich groundwaters are also found in geothermal areas and, on a more localised scale, in areas of mining activity and where oxidation of sulphide minerals has occurred. The As content of the aquifer materials in major problem aquifers does not appear to be exceptionally high, being normally in the range 1-20 mg kg1. There appear to be two distinct 'triggers' that can lead to the release of As on a large scale. The first is the development of high pH (> 8.5) conditions in semi-arid or arid environments usually as a result of the combined effects of mineral weathering and high evaporation rates. This pH change leads either to the desorption of adsorbed As (especially As(V) species) and a range of other anion-forming elements (V, B, F, Mo, Se and U) from mineral oxides, especially Fe oxides, or it prevents them from being adsorbed. The second trigger is the development of strongly reducing conditions at near-neutral pH values, leading to the desorption of As from mineral oxides and to the reductive dissolution of Fe and Mn oxides, also leading to As release. Iron (II) and As(III) are relatively abundant in these groundwaters and SO4 concentrations are small (typically 1mg l 1 or less). Large concentrations of phosphate, bicarbonate, silicate and possibly organic matter can enhance the desorption of As because of competition for adsorption sites. A characteristic feature of high groundwater As areas is the large degree of spatial variability in As concentrations in the groundwaters. This means that it may be difficult, or impossible, to predict reliably the likely concentration of As in a particular well from the results of neighbouring wells and means that there is little alternative but to analyse each well. Arsenic-affected aquifers are restricted to certain environments and appear to be the exception rather than the rule. In most aquifers, the majority of wells are likely to be unaffected, even when, for example, they contain high concentrations of dissolved Fe. # 2002 Published by Elsevier Science Ltd. All rights reserved.
The cell employs several lines of defense against the toxic products of oxygen reduction. The first is systemic protection against high oxygen tensions at the cellular level. The second is the intracellular localization of the enzymes appropriate to the decomposition of the toxic intermediates at or near the site where they are generated, together with steep gradients of the reactive species themselves. A third line of defense is provided by radical scavengers such as α-tocopherol and β-carotene, which also have the advantage of being appropriately distributed in the membranes where lipid peroxidation might occur. A fourth level of protection is provided by glutathione peroxidase, which reacts directly with lipid peroxides. Finally, recent understanding of the beneficial action of H(2)O(2) in phagocytosis and in ethanol oxidation suggests caution in condemning any metabolite as useless until its functions in toto are thoroughly understood.
Adult male rats were treated orally with sodium arsenate (10 mg As/kd/day) for 2 days, and in increase in hepatic glutathione level was seen. Ascorbic acid content increased in both liver and plasma of intoxicated animals. Hepatic activities of superoxide dismutase and glutathione peroxidase did not change with the treatment and there was no increase in the level of lipid peroxidation measured as thiobarbituric acid-reacting substances (TBARS). Arsenic decreased the plasma level of uric acid and increased the plasma triglycerides content without modifying vitamin E levels. Both total lipoproteins and very low density lipoprotein plus low density lipoprotein (VLDL + LDL) fractions demonstrated greater propensity for in vitro oxidation than the corresponding untreated rats. The last finding might be a useful parameter for determining the degree of oxidative stress in the initial steps of intoxication with arsenic.
Nitric oxide (NO.) is produced from L-arginine, as result of a reaction catalyzed by the enzyme nitric oxide synthase (NOS). The reaction is the sole source of NO. in animal tissues. NO. can control physiological processes (or systems) such as (a) blood pressure; (b) relaxation of arterial smooth muscle; (c) platelet aggregation and adhesion; (d) neurotransmission; (e) neuroendocrine secretion. NO. contributes to the killing of pathogenic microorganisms and tumoral cells by phagocytes. NO. reacts with superoxide anion thus producing peroxynitrite, a cytotoxic ion capable of destroying many biological targets. The superoxide/peroxinitrite balance determines the ONOO- production and, accordingly, is essential for the development of hypertension, atherosclerosis, neurodegenerative diseases, viral infections, ischemia-reperfusion injury, and cancer.
Tea is the most highly consumed beverage in the world, other than water. However, unlike water, tea contains substantial amounts of polyphenols that have unique biological activities and may be responsible for many of the health benefits of tea. As a result, it is essential to be able to measure the various tea-associated polyphenols. Total polyphenol content is currently measured by using methodology based on reducing activity. Several HPLC systems with detectors that, collectively, have wide ranges in sensitivity have been developed for analysis of individual flavonoids in tea and biological samples, and for theaflavins in tea. Catechins also have been measured in plasma by solid phase extraction, addition of a chromophore, and colorimetric quantification. Except for theaflavins in tea, routine and robust methods for the measurement of polyphenol condensation products (dimers and thearubigens) in tea and biological samples have not been developed. Although in vitro and animal studies suggest substantial metabolism of flavonoids in the gastrointestinal tract, only a single HPLC procedure has been assembled for monitoring the metabolic products of quercetin in urine of human subjects.
Aqueous extracts of green and black teas have been shown to inhibit a variety of experimentally induced animal tumors, particularly ultraviolet (UV) B light-induced skin carcinogenesis. In the present study, we compared the effects of different extractable fractions of green and black teas on scavenging hydrogen peroxide (H2O2), and UV irradiation-induced formation of 8-hydroxy 2'-deoxyguanosine (8-OHdG) in vitro. Green and black teas have been extracted by serial chloroform, ethyl acetate and n-butanol, and divided into four subfractions designated as GT1-4 for green tea and BT1-4 for black tea, respectively. The total extracts from green and black teas exhibited a potent scavenging capacity of exogenous H2O2 in a dose-dependent manner. It appeared that the total extracts from black tea scavenged H2O2 more potently than those from green tea. When tested individually, the potency of scavenging H2O2 by green tea subfractions was: GT2 > GT3 > GT1 > GT4, whereas the order of efficacy for black tea was: BT2 > BT3 > BT4 > BT1. In addition, we demonstrated that total fractions of green and black teas substantially inhibited the induction of 8-OHdG in calf thymus by all three portions of UV spectrum (UVA, B and C). Consistent with the capacity of scavenging H2O2, the subfractions from black tea showed a greater inhibition of UV-induced 8-OHdG than those from green tea. At low concentrations, the order of potency of quenching of 8-OHdG by green tea subfractions was: GT2 > GT3 > GT4 > GT1 and the efficacy of all subfractions became similar at high concentrations. All subfractions of the black tea except BT1 strongly inhibited UV-induced 8-OHdG and the order of potency was: BT2 > BT3 > BT4 > BT1. Addition of (-)-epigallocatechin gallate (EGCG), an ingredient of green tea extract, to low concentration of green and black tea extracts substantially enhanced the scavenging of H2O2 and quenching of 8-OHdG, suggesting the important role of EGCG in the antioxidant activities of tea extracts. The potent scavenging of oxygen species and blocking of UV-induced oxidative DNA damage may, at least in part, explain the mechanism(s) by which green/black teas inhibit photocarcinogenesis.
This study examined the effects of black tea (Camellia sinensis L.) on lipid peroxidation and glutathione levels in carbon tetrachloride (CCl4)-treated male Wistar rats. Three groups of rats formed two control groups and one treatment group. The control groups were fed with a standard diet, while the black tea group were fed the standard diet plus 6% by weight dried black tea leaves. After two months, the rats in the black tea group and in one control group were administered a single dose of CCl4 (1 ml/kg, i.p.) and sacrificed two hours later. Rats in the other control group were administered olive oil in a similar fashion. Lipid peroxide levels in liver and plasma, glutathione (GSH) levels in liver and alanine transaminase (ALT) and aspartate transaminase (AST) activities in plasma were measured. Rats in the black tea group were found to have significantly decreased liver lipid peroxide levels, and ALT and AST activities compared with the rats in the CCl4-treated control group. In addition, liver glutathione levels were decreased in the black tea group. These data suggest that black tea attenuates CCl4-induced hepatic injury.
Production of black tea [BT] results in biotransformation of catechins of green tea [GT] to theaflavins and thearubigins. BT was found to be more efficient than GT and its individual catechin constituents in proportionate amounts in abrogating production of NO and O2(-) in activated murine peritoneal macrophages. In a reconstitution system of BT that is free of all catechins, stepwise addition of catechins showed that though all the constituents contributed to the overall effect of BT, theaflavin was the most powerful in abrogating NO production. RT-PCR analysis also showed theaflavin to be the most important constituent in down-regulating synthesis of iNOS. Clearly, BT containing theaflavin is an excellent chemopreventor against reactive oxygen and nitrogen species.
Aqueous extracts of green and black tea are shown to quench reactive oxygen species such as singlet oxygen, superoxide and hydroxyl radicals, prevent the oxidative cross-linking of test proteins and inhibit single strand breakage of DNA in whole cells. They are also seen to be able to counteract the oxidative insult mounted by cigarette smoke. In rats in which cataract was induced by subcutaneous injection of selenite, administration of green or black tea extracts led to a retardation of the progression of lens opacity, suggesting the potential cataracto-static ability of tea.
To assess the oxidative injuries caused by arsenic toxicity in rabbits and evaluate the detoxifying effects of exogenous antioxidants, we administered arsenic trioxide (3-5 mg/kg/day) in rabbits through a feeding tube for seven days. These rabbits were then treated with a recipe of vitamins, zinc, selenium (VZS) or a plant polyphenol or a placebo for the next seven days. Blood samples were collected from ear vein for spectrophotometric assay of reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), and nitrite/nitrate (NOx; index of nitric oxide formation) before arsenic administration, seven days after arsenic administration, and seven days after antioxidant treatment. The total arsenic concentrations in hair and spot urine samples of rabbits before arsenic administration were 0.6 +/- 0.21 microg/g and 34.0 +/- 5.9 microg/L, respectively. Administration of arsenic trioxide significantly increased arsenic concentrations in hair and in urine to 2.8 +/- 0.40 microg/g (p<0.001) and 7372 +/- 1392.0 microg/L (p<0.001), respectively. Arsenic administration to rabbits significantly reduced GSH concentration (post-arsenic, 17.5 +/- 0.81 mg/dL vs. pre-arsenic, 32.0 +/- 0.76 mg/dL, p<0.001), increased TBARS concentration (post-arsenic, 8 +/- 1.1 microM vs. pre-arsenic, 5 +/- 0.7 microM, p<0.05), and NOx concentration (post-arsenic, 465 +/- 38.5 microM vs. pre-arsenic, 320 +/- 24.7 microM, p<0.001) as compared to the pre-arsenic levels. There was a negative correlation between TBARS and GSH concentrations (r=-0.464, p<0.01) and between NOx and GSH concentrations (r=-0.381, p<0.05) of intoxicated rabbits. The recovery of the depleted GSH was significantly greater in the polyphenols (77.0 +/- 12.0%) or VZS (67.0 +/- 17.0%) treatment groups compared with the placebo group (36.0 +/- 7.0%). The decrease in NOx level of arsenic-treated rabbits was significantly greater in polyphenols treatment group than the placebo group (60.0 +/- 9.0% vs. 17.0 +/- 6.0%, p<0.001). These results indicate that arsenic induces toxicity in rabbits associated with an increase in lipid peroxidation. Arsenic toxicity increases nitric oxide production in the body. Exogenous antioxidants such as polyphenols and recipe of vitamins, zinc, and selenium are useful for arsenic detoxification.
Chinese Beiqishen tea was studied in an in vitro test system.
Phytochemical screening, trace element analysis, and the analysis of antioxidant properties were carried out. Characteristic constituents were determined by chromatographic (capillary gas chromatography and GCQ Ion Trap mass spectrometry) and spectrometric (ultraviolet and UV-VIS) methods. Element concentrations were determined by inductively coupled plasma optical emission spectrometry. Antioxidant capacity was studied by spectrophotometric and luminometric techniques using a Berthold Lumat 9501 luminometer. Hydrogen-donating activity, reducing power, and total scavenger capacity were measured.
Total polyphenol content was 20.77 +/- 0.52 g/100 g of drug; total flavonoid content was 0.485 +/- 0.036 g/100 g of drug; and tannin content was 9.063 +/- 0.782 g/100 g of drug. Caffeine content was 1.08 mg/100 g of drug. Essential oils were identified by gas chromatography: (+)-limonene (21%), p-cymene (1.7%), estragol (3.2%), beta-ocimene (1.4%), and thymol (2.6%). Metallic ion analysis showed significantly high concentrations of Al, As, Ba, Cr, Cu, Fe, Mn, Ni, and Ti in the drug. Antioxidant and scavenger properties were identified as a function of concentration.
The tea infusion contained some non-desirable trace elements and caffeine in addition to polyphenols and tannins in high concentrations. Therefore, the consumption of this tea may involve risks.
The present study was designed to investigate the in vivo effects of oral administration of arsenic trioxide (As2O3; 0.5 and 1 mg/kg body weight/day for 45 days) on cerebral hemispheres and cerebellum in male mice, Mus musculus. Arsenic reduced the concentration of glutathione (GSH) in cerebral hemisphere and cerebellum at both the dose levels; while increased lipid peroxidation (LPO) in cerebral hemisphere and cerebellum regions. Further, the activities of antioxidant enzymes viz., superoxide dismutase and catalase also declined in these two regions with dose indicating oxidative stress. This effect is caused by the action of reactive oxygen species (ROS) induced by arsenic exposure.
It is believed that anticancer and apoptosis inducing properties of green tea are mediated by it's polyphenolic constituents particularly catechins. A number of reports have shown that green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) is among the most effective chemopreventive and apoptosis-inducing agents present in the beverage. Plant polyphenols are naturally occurring antioxidants but they also exhibit prooxidant properties. Over the last several years we have shown that various classes of plant polyphenols including flavonoids, curcuminoids and tannins are capable of catalyzing oxidative DNA cleavage particularly in the presence of transition metal ions such as copper and iron. With a view to understand the chemical basis of various pharmacological properties of green tea, in this paper we have compared the prooxidant properties of green tea polyphenols--EGCG and EC ((-)-epicatechin). The rate of oxidative DNA degradation as well as hydroxyl radical and superoxide anion formation was found to be greater in the case of EGCG as compared with EC. It was also shown that copper mediated oxidation of EC and EGCG possibly leads to the formation of polymerized polyphenols. Further, it was indicated that copper oxidized catechins were more efficient prooxidants as compared with their unoxidized forms. These results correlate with the observation by others that EGCG is the most effective apoptosis inducing polyphenol present in green tea. They are also in support of our hypothesis that prooxidant action of plant polyphenols may be an important mechanism of their anticancer properties. A model for binding of Cu(II) to EC has been presented where the formation of quinone and a quinone methide has been proposed.
Arsenic is an environmental and occupational toxin. Dermatologic toxicities due to arsenic exposure are well-documented and include basal cell and squamous cell carcinomas. However, the mechanism of arsenic-induced skin cancer is not well-understood. Recent studies indicate that arsenic exposure results in the generation of reactive oxygen species (ROS) and oxidative stress. Here, we examined the chemical nature of the specific ROS, studied the interrelationship among these species, and identified the specific species that is responsible for the subsequent DNA damage in a spontaneously immortalized keratinocyte cell line. We detected the formation of O(2)(*)(-) and H(2)O(2) in keratinocytes incubated with arsenite [As(III)] but not with arsenate. As(III)-induced DNA damage was detected in a concentration-dependent manner and evident at low micromolar concentrations. Catalase, an H(2)O(2) scavenger, eliminated H(2)O(2) and reduced the As(III)-mediated DNA damage. Superoxide dismutase, by enhancing the production of H(2)O(2) and (*)OH, significantly increased the As(III)-mediated DNA damage. Sodium formate, a competitive scavenger for (*)OH, and deferoxamine, a metal chelator, both reduced the DNA damage. These results suggest that exposure to arsenite generates O(2)(*)(-) and H(2)O(2), and (*)OH, derived from H(2)O(2), is responsible, at least in part, for the observed DNA damage. These findings demonstrate arsenic-induced formation of specific ROS and provide the direct evidence of (*)OH-mediated DNA damage in keratinocytes, which may play an important role in the mechanism for arsenic-induced skin carcinogenicity.
Accumulated epidemiological studies have suggested that prolonged exposure of humans to arsenic in drinking water is associated with vascular diseases. The exact mechanism of how this occurs currently unknown. Nitric oxide (NO), formed by endothelial NO synthase (eNOS), plays a crucial role in the vascular system. Decreased availability of biologically active NO in the endothelium is implicated in the pathophysiology of several vascular diseases and inhibition of eNOS by arsenic is one of the proposed mechanism s for arsenic-induced vascular diseases. In addition, during exposure to arsenic, overproduction of reactive oxygen species (ROS) can occur, resulting in oxidative stress, which is another major risk factor for vascular dysfunction. The molecular basis for decreased NO levels and increased oxidative stress during arsenic exposure is poorly understood. In this article, evidence for arsenic-mediated alteration in NO production and oxidative stress is reviewed. The results of a cross-sectional study in an endemic area of chronic arsenic poisoning and experimental animal studies to elucidate a potential mechanism for the impairment of NO formation and oxidative stress caused by prolonged exposure to arsenate in the drinking water are also reviewed.
Accumulating evidence supports the hypothesis that brain iron misregulation and oxidative stress (OS), resulting in reactive oxygen species (ROS) generation from H2O2 and inflammatory processes, trigger a cascade of events leading to apoptotic/necrotic cell death in neurodegenerative disorders, such as Parkinson's (PD), Alzheimer's (AD) and Huntington's diseases, and amyotrophic lateral sclerosis (ALS). Thus, novel therapeutic approaches aimed at neutralization of OS-induced neurotoxicity, support the application of ROS scavengers, transition metals (e.g. iron and copper) chelators and non-vitamin natural antioxidant polyphenols, in monotherapy, or as part of antioxidant cocktail formulation for these diseases. Both experimental and epidemiological evidence demonstrate that flavonoid polyphenols, particularly from green tea and blueberries, improve age-related cognitive decline and are neuroprotective in models of PD, AD and cerebral ischemia/reperfusion injuries. However, recent studies indicate that the radical scavenger property of green tea polyphenols is unlikely to be the sole explanation for their neuroprotective capacity and in fact, a wide spectrum of cellular signaling events may well account for their biological actions. In this article, the currently established mechanisms involved in the beneficial health action and emerging studies concerning the putative novel molecular neuroprotective activity of green tea and its major polyphenol (-)-epigallocatechin-3-gallate (EGCG), will be reviewed and discussed.
Impaired antioxidant defense mechanisms and oxidative stress are implicated in the pathogenesis of arsenic toxicity. Our study was designed to determine whether alpha-lipoic acid, which has been shown to have substantial antioxidant properties, when administered (70 mg/kg body weight) once daily for 60 days along with arsenic (100 ppm sodium arsenite mixed in drinking water) would prevent arsenic-induced changes in antioxidant defense system, superoxide dismutase (SOD-total SOD, Mn SOD, Cu/Zn SOD), catalase (CAT) and glutathione peroxidase (GSH-PX) in rat brain regions such as cortex, hypothalamus, striatum, cerebellum and hippocampus. The present study also examined the effect of alpha-lipoic acid over arsenic-induced oxidant production and lipid peroxidation level (LPO) in discrete brain regions of rats. The cortex, striatum and hippocampus showed greater decreases in GSH-Px enzyme activity than cerebellum and hypothalamus with arsenic exposure. Striatum had the greatest percentage of decreased activities of total SOD and Mn SOD, whereas cortex had the greatest percentage decrease in the activity of Cu/Zn SOD in arsenic-alone treated rats. Hypothalamus and cerebellum exhibited the lowest catalase activity among all tested regions in arsenic-only treated rats. Rate of dichlorofluorescin oxidation, an indication of reactive oxygen species and other intracellular oxidants production was increased with arsenic exposure in all brain regions studied. Cortex, hippocampus and striatum exhibited greater increase of LPO levels than cerebellum and hypothalamus. SOD, CAT, GSH-Px activities were upregulated in arsenic plus lipoic acid treated versus arsenic-only treated rats. Also, simultaneous lipoic acid treatment along with arsenic proved to be sufficient in reducing oxidant production and LPO level in all rat brain regions. Our results demonstrate that arsenic-induced deficits in antioxidant enzyme activities and increase in oxidant production and lipid peroxidation level in brain regions can be overcome through simultaneous treatment with lipoic acid.
Black tea, obtained by tea leaves fermentation, is an oxidized product and contains mainly multimeric polyphenols, whose biological activity is not well documented. This paper reviews the available literature on the effects of black tea on health with a focus on its antioxidative activity.
A review of the different issues and studies relating to composition, manufacturing, and antioxidative effects of black tea and its components in vitro as well as in vivo is presented.
It is generally believed that polyphenols such as theaflavins and thearubigins as well as catechins as major constituents of black tea are mainly responsible for antioxidant actions. Antioxidative properties of black tea are manifested by its ability to inhibit free radical generation, scavenge free radicals, and chelate transition metal ions. Black tea, as well as individual theaflavins, can influence activation of transcription factors such as NFkappaB or AP-1. Theaflavins have been also proved to inhibit the activity of prooxidative enzymes such as xanthine oxidase or nitric oxide synthase.
Black tea consumed throughout the world is believed to be not only a popular beverage but also an antioxidative agent available in everyday life.
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Fairbanks VF, Klee GG. 1998. Biochemical aspects of hematology. In Tietz Textbook of Clinical Chemistry, Burtis CA,
Ashwood ER (eds). Harcourt Brace and Company Asia:
Singapore, 1642–1710.
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The chemistry of peroxynitrite: a product from reaction of nitric oxide and superoxide
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A single dose of tea with or without milk increases plasma antioxidant activity in humans
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