Figure 1 - uploaded by Swaran Flora
Content may be subject to copyright.
Source publication
Arsenic is a naturally occurring element that is ubiquitously present in the environment. High concentration of naturally occurring arsenic in drinking water is a major health problem in different parts of the world. Despite arsenic being a health hazard and a well documented carcinogen, no safe, effective and specific preventive or therapeutic mea...
Contexts in source publication
Context 1
... is a naturally occurring antioxidant and a drug used for the treatment of diabetic polyneuropathy (structure shown in Fig. 1). 25 It has a thiol group and found naturally in plants and animals. Taurine is a sulphur containing δ-amino acid found in millimolar concentrations especially in tissues that are excitable, rich in membranes and generates oxidants. 26 The sulfonate group in taurine is a strong acid that makes it completely zwitterionic alone provided most effective reversal in GSH and GSSG levels compared to individual treatment with taurine. Co-administration of taurine (particularly at the higher dose) and MiADMSA, on the other hand, provided more pronounced recovery in these variables compared to all other treatments (Table ...
Context 2
... 100 mg/kg were noted when it was administered along with MiADMSA on biochemical variables suggestive of oxida- tive stress. The reversal in the inhibited ALAD activity following treatment with MiADMSA might be attributed to the availability of thiol groups (Fig. 1). Co-administration of MiADMSA with taurine (100 mg/ kg) led to a more pronounced recovery in arsenic-induced oxida- tive injury compared to the individual effects of these drugs. These beneficial effects might be due to (i) depletion of body arsenic burden by MiADMSA and/or (ii) antioxidant action of taurine. 28 Increased catalase activity and decreased SOD activity in liver was also noted following arsenic exposure. Role of taurine in maintaining GSH levels and increasing the status of antioxidant enzymes (SOD, Catalase and GP X ) by directly scavenging superoxide radicals and reducing cellular damage caused by free radicals have been reported earlier in lead exposed animals. 46 It has been demonstrated that taurine acts as an antioxidant in vivo and in vitro studies. 47 The mechanism of the possible antioxidative effects of taurine is unclear, but it has been suggested that the same is related to free radical scavenging activity of taurine. 48 The free sulphydryl group in taurine seems to play a significant role as a ROS scavenger. Taurine is neither metabolized nor incorporated into cellular proteins in mammals suggesting ready availability of sulfhydryl moiety in cytosol. 27,49 Antioxidant potential of taurine has also attributed to its ability to restore metal induced depletion of membrane Na + , K + -ATPase activity. 50 Besides the above, mechanism for the antioxidant effect of taurine can also be explained as its direct action to quench and detoxify some reactive intermediate such as hypochlorous acid gener- ated by myeloperoxidase, 50 nitric oxide, 51 and H 2 O 2 52 and indirectly via protecting cells through intercalating into the membrane and stabilizing it. 53 The membrane protecting activity of taurine is suggested to be related to its action on permeability to ions and water. 47 In this exposure including depletion of intracellular arsenic. 38 Few recent studies reported the superior efficacy of monoisoamyl DMSA (MiADMSA) and mono-n-amyl DMSA in protecting the mice from the lethal effects of arsenic and in reducing body arsenic burden. 38,39 Reactive oxygen species are thought to contribute to the patho- genesis of arsenic toxicity. 40,41 Results from the present study also suggest that some of the toxic effects of arsenic could be attributed to the arsenic induced oxidative stress. A significant inhibition of blood ALAD and GSH level and an increase in ZPP level was noted in the present study. It is well known that arsenic affects the haematopoi- etic system by inhibiting the haem bio-synthesis. The enzyme that is sensitive to the toxic effects of arsenic is probably δ-aminolevulinic acid dehydratase (ALAD). ALAD is a sulfhydryl-containing enzyme involved in the heme synthesis pathway, and its inhibition can be attributed to the binding of arsenic with sulfhydryl groups. Arsenic has got a high affinity for -SH group and it binds with reduced glutathione (GSH). Inhibition of ALAD enzyme by arsenic led to decreased heme synthesis and ultimately anemia. ALAD inactiva- tion may also led to the accumulation of δ-aminolevulinic acid that can cause an overproduction of ROS, which in part could explain arsenic induced oxidative stress. 42 It has been reported earlier that this significant increase in ALA level might be a contributing factor in the induction of reactive oxygen species (ROS) generation. [43][44][45] Considerable beneficial effects of taurine particularly at a dose Figure 2. Effects of MiADMSA and taurine co-administration on some biochemical variables suggestive of renal oxidative stress in arsenic exposed rats. Figure shows oxidative stress condition by the depletion of GSH level and elevation of GSSG level and significant recovery by co-administration of higher dose of taurine (100 mg/kg) and MiADMSA. GSH, reduced glutathione; GSSG, oxidized glutathione. Values are mean ± SE; n = 5. *, †, ‡ Means with matching symbol notations in each column are not signifi- cant at 5% level of significance Figure 3. Effects of MiADMSA and taurine co-administration on arsenic concentration in blood and soft tissues. Figure shows significantly elevated level of arsenic in arsenic exposed animals which depleted more favorably during combined administration of taurine (100 mg/kg) and MiADMSA. MiA, monoisoamyl dimercap- tosuccinic acid; As, arsenic. Values are mean ± SE; n = 5. *, †, ‡, § Means with matching symbol notations in each column are not significant at 5% level of significance. study, a direct correlation between arsenic concentration and tissue oxidative injury was noted. Depletion in tissue oxidative stress was accompanied by a decrease in tissue arsenic level. Similar obser- vations were noted where taurine administration protected lead induced oxidative stress in rats. 28 Taurine supplementation also provided significant recovery in depleted SOD activity. SOD, a metalloprotein accomplishes its antioxidant function by protecting the cells against the toxic effects of O 2-by catalyzing its dismutation reactions. A significant effect of taurine on liver and kidney GSSG was observed, while only a marginal protection was noticed on liver and kidney GSH after taurine administration. Although, it has been reported recently that taurine has a protective effect against thioacet- amide hepatotoxicity in rats. 54 and also decreases oxidative stress. 55 Another new and interesting observation in the present study was that taurine at the dose of 100 mg/kg when administered along with MiADMSA provided more pronounced depletion of arsenic concentration in blood, liver and kidneys. This suggests that the antioxidative capacity of taurine becomes most effective only when it is administered along with the thiol chelators or taurine might be facilitating the entry of chelator to the intracellular sites thereby reducing arsenic ...
Context 3
... indicative of alterations in heme biosynthesis pathway and oxidative stress in arsenic exposed rats and after treatment with taurine, MiADMSA either individually or in combination, is shown in Table 1. Exposure to arsenic significantly decreased blood ALAD activity and increased ZPP level while, GSH concentration showed marginal depletion. Administration of taurine (100 mg/ kg) and MiADMSA individually, had no effect on inhibited blood ALAD activity, ZPP and GSH levels except for a moderate beneficial effect of MiADMSA when administered alone on blood ZPP levels. Combined administration of lower dose of taurine (50 mg/kg) with MiADMSA was effective in increasing blood ALAD and depleting ZPP level although the effects were statistically non significant. On the other hand, combined administration of a higher dose of taurine (100 mg/kg) with MiADMSA led to a more pronounced beneficial effects on ALAD activity and GSH levels compared to all other treatments. Neither MiADMSA nor the combination treatments with taurine were effective in reducing ZPP level towards the normal value. particularly after it was approved for the clinical use against child- hood lead poisoning by US Food and Drug Administration (FDA). 14 DMSA is one of the least toxic drugs that could be given orally; a less obvious benefit may also be derived as a result of DMSA's structural potential to serve as an antioxidant in vivo 15 however, use of DMSA is compromised with some limitations. Hydrophilic and lipophobic properties of DMSA do not allow it to pass through cell membrane. It was recently reported that the monoesters of DMSA might be more effective chelating agent for metal poisoning than DMSA. 16,17 Mono isoamyl ester of DMSA (MiADMSA) is a C5 branched chain ester (Fig. 1) that has been found to be more effective than DMSA in reducing lead, mercury and cadmium burden. 13,18 Structure of MiADMSA comprises of straight and branched chain amyl group which helps in increasing its lipophilicity. Lipophilicity and molecular size of this new drug might be an important factors for the removal of arsenic from both intra-cellular sites possibly leading to better therapeutic efficacy. 19 It has been observed that MiADMSA is more efficient in mobilizing brain lead than DMSA. 20 It is believed that DMSA being relatively efficient and non-toxic chelator, MiADMSA should also be of greater interest particularly as a potential drug for chelation therapy in arsenic poisoning. One of the major drawbacks of chelation therapy is related to redistribution of toxic metals to other tissues, especially to the brain. 5 No such redistribution was however, observed with MiADMSA administration. 21 Mehta and Flora 22 reported that administration of MiADMSA may lead to copper loss and also mild hepatotoxicity. It indicates greater complexing poten- tial of DMSA monoester compared to DMSA. The depletion of essential metals does not necessarily result in the pronounced excre- tion of the metal in the urine. A number of previous reports have indicated an increased uptake of zinc and copper with no alteration in urinary copper and zinc following DMSA administration. 23 It has also been reported that chelator is relatively safe during late gesta- tion and it does not cause any major alteration in the mothers and the developing pups. 24 Despite a few drawbacks/side effects associ- ated with MiADMSA, MiADMSA is being considered recently as a future drug of choice owing to its specificity, accessibility to intra- cellular spaces and the absence of essential metal redistribution. [22][23][24] Moderate toxicity followed by administration of MiADMSA may be reversible after withdrawal of chelating ...
Citations
... It prevents enzyme activity at the mitochondrial level with inhibition of dehydrogenase; at the same time, it stimulates adenosine triphosphatase activity, deactivating oxidative phosphorylation, which causes deterioration of tissue respiration and consequently causes toxicity (Maity et al. 2020;Gakidou et al. 2017). Exposure to arsenic at the cellular level generates nitric oxide and superoxide anions that cause the formation of hydroxyl radicals and with this comes oxidative stress, lipid peroxidation and DNA damage (Flora et al. 2008;Lai et al. 2008;Obinaju 2009). With regard to the possible role of haematological parameters, assessed in the Sicilian Barbaresca sheep, as blood biomarkers in response to the bioaccumulation of heavy metals in the different matrices studied (blood, milk and fleece), it emerges that no significant correlation was found between haematological parameters and the concentration of each metal (arsenic, cadmium, lead and mercury) present in the biological matrices studied (Figs. 1 and 2). ...
The health of humans, animals and the environment is interconnected. Adopting a One Health approach means intervening promptly to prevent the main diseases that affect animal health to guarantee the safety of livestock production. Exposure to toxic trace elements in sheep can lead to increased accumulation in different biological substrate, developing both acute and chronic diseases in humans and livestock. The aim of this study was to evaluate the bioaccumulation of arsenic (As), cadmium (Cd), lead (Pb) and mercury (Hg) in Sicilian Barbaresca sheep using the following biological substrates: milk, blood and fleece. An inductively coupled plasma mass spectrometer (ICP-MS) was used for As, Cd and Pb, and a direct mercury analyser (DMA-80) was used for Hg determination. In addition, the role of the haematological parameters as possible indicators of different biodistribution was evaluated. A statistically significant value was observed from our analysed metals in the substrates: arsenic (p < 0.001), cadmium (p < 0.01), lead (p < 0.001) and mercury (p < 0.0001). The correlation analysis showed a relationship between milk and blood for arsenic (p < 0.0001) and lead (p < 0.0001), and no correlation for the metals was observed between milk/blood and the haematological parameters analysed for the low concentration observed in the present study comforting the final consumer.
... As exposure in rats significantly reduced blood δ-aminolevulinic acid dehydratase (ALAD) activity, as an important enzyme involved in heme biosynthesis, improved zinc protoporphyrin (ZPP) level and reduced white blood cell (WBC), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC) with significant elevation of platelet (PLT) count and depression in SOD and CAT activities and level of GSH; however, taurine treatment reversed these changes [34,93]. Ghosh et al. revealed that As decreased viability of cardiomyocytes through the mitochondrial apoptotic pathway is associated with increased IKK and NF-κB (p65) phosphorylation. ...
Taurine is a non-proteinogenic amino acid derived from cysteine. It is involved in several phenomena such as the regulation of growth and differentiation, osmoregulation, neurohormonal modulation, and lipid metabolism. Taurine is important because of its high levels in several tissues such as the central nervous system (CNS), heart, skeletal muscles, retinal membranes, and platelets. In this report, we present the functional properties of taurine indicating that it has potential effects on various metal toxicities. Therefore, a comprehensive literature review was performed using the Scopus, PubMed, and Web of Science databases. According to the search keywords, 61 articles were included in the study. The results indicate that taurine protects tissues against metal toxicity through enhancement of enzymatic and non-enzymatic antioxidant capacity, modulation of oxidative stress, anti-inflammatory and anti-apoptotic effects, involvement in different molecular pathways, and interference with the activity of various enzymes. Taken together, taurine is a natural supplement that presents antitoxic effects against many types of compounds, especially metals, suggesting public consumption of this amino acid as a prophylactic agent against the incidence of metal toxicity.
... When they accumulate in living systems, they can cause severe damage to vital organs such as the nervous system, reproductive systems, gastrointestinal tract, and mucous tissues. Although the precise mechanism of their ability to cause disease is not yet understood, there have been reports from multiple laboratories suggesting that the presence of these heavy metals or their excessive buildup in bodily tissues can trigger the production of free radicals, specifically reactive oxygen species (ROS) and reactive nitrogen species (RNS), which ultimately lead to the development of oxidative stress [1,2]. Free radicals have been linked to DNA damage, oxidation of thiol group(s) of proteins, and lipid peroxidation, which is connected to the development of different diseases. ...
... Mediated neurotoxicity is linked to the generation of an excessive amount of free radical species and oxidative stress, which can potentially disrupt normal brain function [1,22]. Lead efficiently traverses the blood-brain barrier (BBB) and readily replaces calcium ions, thereby interfering with calcium's regulatory effects on brain cells and disrupting its intracellular functions. ...
... Arsenic is a toxic element responsible for a multitude of diseases if found in food or beverages [1][2][3][4][5][6][7][8][9][10][11]. According to the World Health Organization (WHO) a concentration as low as 10 ppb (μg L − 1 ) in drinking water may be dangerous to humans [1,12]. However, arsenic-contaminated water is often used, e.g., for irrigation, and arsenite anions can spread and accumulate in the crops. ...
Arsenic of natural or industrial origin often occurs in water and makes it impotable. Due to its high toxicity, very sensitive detection is required. In the present study an ultra-sensitive arsenite (As³⁺) sensing is reported, based on aggregation-aided surface-enhanced Raman scattering (AA-SERS) of modified silver colloids. SERS intensity of mercapto-compounds attached to the colloidal silver nanoparticles surface is greatly increased in the presence of arsenic. Colloid aggregation is facilitated by cross-linking; a meshwork consisting of arsenic atoms and glutathione bridges is formed, as indicated by UV–Vis absorption spectroscopy, TEM and Raman imaging. The best 2-mercaptopyridine reporter molecule makes it possible to directly detect As³⁺ at concentrations as low as 0.5 ppb, which is better than achieved by the SERS technique so far.
... Importantly, arsenic may also exert toxic effects by inducing oxidative stress. Flora et al. [36] demonstrated that chronic exposure to arsenic (25 ppm) through drinking water for 24 weeks could significantly reduce blood ALAD levels, enhance zinc protoporphyrin (ZPP), and alter various clinical hematological variables, such as WBC, MCH, MCHC, and platelet counts in rats. Furthermore, these changes were accompanied by decreased SOD and increased catalase activities. ...
... Interestingly, As can affect the integrity of the mitochondrial membrane potential and negatively affect ATP formation during glycolysis and induction of apoptosis in various cells (Obinaju 2009). There are plethora of reports on As oxidative-DNA damaged based on iron release from ferritin accompanied with ROS production (Colognato et al. 2007;Flora et al. 2008;Lai et al. 2008;Obinaju 2009). For example, Shen et al. (2001) documented that ROS-induced oxidative stress is caused by a mitochondria-dependent apoptotic pathway. ...
Arsenic (As) is one of the human carcinogens with a global peril to human health through direct or indirect exposure to contaminated water, food, air and skin contact. As a result, research on arsenic remediation has surged. However, no report evaluating the trends of studies on the subject has been documented. Therefore, the present study was conducted to examine global research trends on arsenic removal and remediation. Web of Science and Scopus were explored to retrieve published papers on the subject between 1929 and 2020. In all, 2605 articles were published within the survey period, with annual mean and growth rate of 28.63 and 11.11%, respectively. Research productivity raised consistently and peaked in 2019 (9.9%) and 2020 (9.2%). China (n = 574, 22%) ranked first followed by India (n = 361, 10%) and the United States (n = 239, 9.2%). The top 20 productive authors published articles between 19 and 49 with total citations of 442 to 511. The highest recurrent Keywords were arsenic (n = 992, 38.08%), adsorption (n = 519, 19.2%) and arsenic removal (n = 435, 16.72%). This study revealed an improved global research on Arsenic removal with greater research outputs from both developed and developing countries; however, the global collaboration appears to be low (collaboration index of 2.5), hence, the policymakers, governments and researchers should encourage international collaborations and establish research programs that can monitor arsenic contamination globally.
... Increased LPO can be the consequence of oxidative stress in these organs which occurred due to the imbalance between the ROS concentration and the antioxidant capacity of that cell (Flora et al., 2008). An increase in the levels of MDA enhanced lipid peroxidation leading to tissue injury and failure of antioxidant defense mechanisms which prevent the formation of excess free radicals (Kasapoglu and Ozben, 2001). ...
... Autopsy studies of arsenic-exposed animals have shown that among soft tissues, the liver is the largest repository followed by the kidney (Flora et al. 2008). Various studies have correlated acute and chronic arsenic exposure to the genesis of numerous pathologies including diabetes (Sung et al. 2015), vascular diseases (Prozialeck et al. 2008), blackfoot disease (Tseng 2005), and deleterious effects on the kidney, liver, and nervous and cardiovascular systems (Singh et al. 2011). ...
Arsenic, an omnipresent environmental contaminant, is regarded as a potent hepatotoxin. Nigella sativa oil (NSO) consumption has been shown to improve hepatic functions in various in vivo models of acute hepatic injury. The present study evaluates the protective efficacy of NSO against sodium arsenate (As)–induced deleterious alterations in the liver. Male Wistar rats were divided into four groups, namely, control, As, NSO, and AsNSO. After pre-treating rats in AsNSO and NSO groups with NSO (2 mL/kg bwt, orally) for 14 days, NSO treatment was further extended for 30 days, with and without As treatment (5 mg/kg bwt, orally), respectively. As induced an upsurge in serum ALT and AST activities indicating liver injury, as also confirmed by the histopathological findings. As caused significant alterations in the activities of membrane marker enzymes and carbohydrate metabolic enzymes, and in the vital components of antioxidant defense system. Marked DNA damage and hepatic arsenic accumulation were also observed in As-treated rats. Oral NSO administration ameliorated these deleterious alterations and improved overall hepatic antioxidant and metabolic status in As-treated rats. Prevention of oxidative damage could be the underlying mechanism of NSO-mediated protective effects. The results suggest that NSO could be a useful dietary supplement in the management of arsenic hepatotoxicity.
... Interestingly, taurine's activity can be amplified when used in combination with other anti-oxidant drugs. For example, when taurine is combined with dimercaptosuccinate, it appears to significantly enhance the activity of anti-oxidant enzymes in the liver (253). Elsewhere, taurine has been shown to alleviate liver injury caused by carbon tetrachloride (CCL 4 ) and to reverse the characteristic symptoms of liver fibrosis such as portal inflammation, severe centrilobular necrosis, and excessive deposition of collagen (254). ...
Taurine is a fundamental mediator of homeostasis that exerts multiple roles to confer protection against oxidant stress. The development of hypertension, muscle/neuro‑ associated disorders, hepatic cirrhosis, cardiac dysfunction and ischemia/reperfusion are examples of some injuries that are linked with oxidative stress. The present review gives a comprehensive description of all the underlying mechanisms of taurine, with the aim to explain its anti‑oxidant actions. Taurine is regarded as a cytoprotective molecule due to its ability to sustain normal electron transport chain, maintain glutathione stores, upregulate anti‑oxidant responses, increase membrane stability, eliminate inflammation and prevent calcium accumulation. In parallel, the synergistic effect of taurine with other potential therapeutic modalities in multiple disorders are highlighted. Apart from the results derived from research findings, the current review bridges the gap between bench and bedside, providing mechanistic insights into the biological activity of taurine that supports its potential therapeutic efficacy in clinic. In the future, further clinical studies are required to support the ameliorative effect of taurine against oxidative stress.
... In all tissues examined via histology, it was evident that DMSA did not provide the desired protection from arsenite toxicity. This can be attributed to the inability of DMSA to be well distributed in intracellular spaces due to its lipophobic and hydrophilic properties [72]. Notably, CoQ 10 independently and when combined with DMSA, assuaged arsenic-induced tissue injury as per the histology results. ...
Background
Arsenic poisoning affects millions of people. The inorganic forms of arsenic are more toxic. Treatment for arsenic poisoning relies on chelation of extracellularly circulating arsenic molecules by 2,3-dimecaptosuccinic acid (DMSA). As a pharmacological intervention, DMSA is unable to chelate arsenic molecules from intracellular spaces. The consequence is continued toxicity and cell damage in the presence of DMSA. A two-pronged approach that removes extracellular arsenic, while protecting from the intracellular arsenic would provide a better pharmacotherapeutic outcome. In this study, Coenzyme Q 10 (CoQ 10 ), which has been shown to protect from intracellular organic arsenic, was administered separately or with DMSA; following oral exposure to sodium meta-arsenite (NaAsO 2 ) – a very toxic trivalent form of inorganic arsenic. The aim was to determine if CoQ 10 alone or when co-administered with DMSA would nullify arsenite-induced toxicity in mice.
Methods
Group one represented the control; the second group was treated with NaAsO 2 (15 mg/kg) daily for 30 days, the third, fourth and fifth groups of mice were given NaAsO 2 and treated with 200 mg/kg CoQ 10 (30 days) and 50 mg/kg DMSA (5 days) either alone or in combination.
Results
Administration of CoQ 10 and DMSA resulted in protection from arsenic-induced suppression of RBCs, haematocrit and hemoglobin levels. CoQ 10 and DMSA protected from arsenic-induced alteration of WBCs, basophils, neutrophils, monocytes, eosinophils and platelets. Arsenite-induced dyslipidemia was nullified by administration of CoQ 10 alone or in combination with DMSA. Arsenite induced a drastic depletion of the liver and brain GSH; that was significantly blocked by CoQ 10 and DMSA alone or in combination. Exposure to arsenite resulted in significant elevation of liver and kidney damage markers. The histological analysis of respective organs confirmed arsenic-induced organ damage, which was ameliorated by CoQ 10 alone or when co-administered with DMSA. When administered alone, DMSA did not prevent arsenic-driven tissue damage.
Conclusions
Findings from this study demonstrate that CoQ 10 and DMSA separately or in a combination, significantly protect against arsenic-driven toxicity in mice. It is evident that with further pre-clinical and clinical studies, an adjunct therapy that incorporates CoQ 10 alongside DMSA may find applications in nullifying arsenic-driven toxicity.
