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The imbalance between nitric oxide (NO) and reactive oxygen species (ROS) production appears to be a common feature of experimental and human hypertension. Previously, different antioxidants and/or scavengers of oxygen free radicals were shown to activate nitric oxide synthase (NO synthase, NOS) and to increase the expression of both endothelial an...
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... The increased level of NO could further upregulate the p21 expression in vivo independent of p53 and cGMP leading to G1 cell cycle arrest [58]. Our data showed that AECIR regulated the production of NO, which could lead to cell cycle arrest either by activating the p53 pathway or p21 gene expression and also an alternative mechanism could be involved such as NOS expression as described in several research studies [65]. Furthermore, NO generates reactive nitrogen species, enhancing cellular oxidative stress leading to apoptotic cell death [66]. ...
Objective:
Clerodendrum infortunatum L. has long been used in traditional medicine in Sri Lanka for tumours, cancer, and certain skin diseases. The present study aimed to assess the anticancer properties of the aqueous extract of C. infortunatum L. root (AECIR) through the activation of the apoptotic pathway on hepatocellular carcinoma (HepG2) and thus give it a scientific validation. Further, the contribution of polyphenols in antioxidant activity and cell cytotoxicity was investigated.
Methods:
Powdered plant material was boiled with water (100°C) to obtained AECIR. The DPPH assay was used to determine the antioxidant potential. The activity of AECIR on HepG2 and normal rat fibroblast (CC1) cell growth was determined using MTT assay. The morphological changes related to apoptotic pathway was examined by Ethidium Bromide/Acridine Orange (EB/AO), Rhodamine 123 (Rh123) and DNA fragmentation assay.
Results:
The AECIR demonstrated antioxidant potential with an EC50 of 350.2 ± 1.5 ug/mL for DPPH assay. The HO•, H2O2 and •NO free radical scavenging activity was observed with EC50 of 19.7 ± 2.3, 11.7 ± 0.1 and 273.1 ± 0.9 ug/mL, respectively. The antiproliferative effect of AECIR on HepG2 cells was observed in a time and dose dependent manner with an EC50 of 239.1 ± 1.3 μg/mL while CC1 cells showed a nontoxic effect with an EC50 1062.7 ± 3.4 μg/mL after 24hrs treatment. A significant decrease in antioxidant activity (p<0.001) and 90% HepG2 cell viability was observed with polyphenol removed AECIR compared to the polyphenol present AECIR. The EB/AO uptake, depletion of mitochondrial transmembrane potential, and DNA fragmentation assay results revealed that the apoptosis was induced by AECIR.
Conclusion:
The obtained result of the present study demonstrates that the antioxidant potential and antiproliferative activity of AECIR is attributed to the presence of polyphenols. Furthermore, the findings provide the scientific base for anti-cancer potential of AECIR.
... However, as the effects of melatonin are highly variable depending on the vasculature, the mechanisms explored in the mesenteric artery may not be translated to other vascular beds. It is hypothesised that melatonin, via its receptors, changes calcium and potassium channel regulation, and may also directly activate guanylate cyclase [132]. This is supported by an in vitro study that demonstrated melatonin-induced relaxation was only partially inhibited when NOS, the enzyme responsible for NO production, and guanylate cyclase were blocked [133]. ...
Preeclampsia is a disease specific to pregnancy characterised by new-onset hypertension with maternal organ dysfunction and/or fetal growth restriction. It remains a major cause of maternal and perinatal morbidity and mortality. For sixty years, antihypertensives have been the mainstay of treating preeclampsia and only recently have insights into the pathogenesis of the disease opened new avenues for novel therapies. Melatonin is one such option, an endogenous and safe antioxidant, that may improve the maternal condition in preeclampsia while protecting the fetus from a hostile intrauterine environment. Here we review the evidence for melatonin as a possible adjuvant therapy for preeclampsia, including in vitro evidence supporting a role for melatonin in protecting the human placenta, preclinical models, vascular studies, and clinical studies in hypertension and pregnancy.
... There are many causes for the development of hypertension. The increased level of free radicals and vasoconstrictor agents like endothelin and endoperoxides appears to be a significant cause of endothelial dysfunction, which leads to hypertension [1]. ...
Root of Chrysopogon zizanioides (L.) Roberty has been used in Siddha system of medicine to treat hypertension. The present study was therefore to investigate the vasorelaxation effect of root essential oil of C. zizanioides using rat isolated thoracic aortic rings. Chemical characterization of root essential oil was carried out using Gas Chromatography-Flame Ionization Detector (GC-FID) and Gas Chromatography-Mass Spectrometry (GC-MS). Essential oil nanoemulsion (EONE) was prepared and characterized. Vasorelaxant effect of EONE in endothelium-intact aortic rings precontracted with phenylephrine (PE) (1 µM) or KCl (80 mM) was investigated. Role of Ca2+, nitric oxide and K+ channels in precontracted aortic rings were investigated to elucidate the mechanism of action of the essential oil. Further, the role of muscarinic and prostacyclin receptors in EONE induced relaxation was studied. The EONE significantly induced relaxation (Emax 77.1 ± 4.87%) in PE precontracted aortic rings. The nitric oxide synthase, and cyclooxygenase inhibitors and potassium channel blockers have not significantly inhibited the vasorelaxation induced by EONE. However, EONE induced relaxation in precontracted endothelium-intact aortic rings was significantly inhibited by muscarinic receptor and calcium channel. The root essential oil of C. zizanioides possesses vasorelaxant effect through muscarinic pathway as well as acts as calcium channel blocker.
... Captopril has the ability to scavenge free radicals due to the presence of a sulfhydryl group; thus, it is capable of preventing oxidant-induced cell injury. [28] HESS may also have been capable of preventing oxidation of NO to peroxynitrite or oxidation of BH 4 by ROS, thus preventing eNOS uncoupling and oxidative stress. The HESS extract was found to prevent proteinuria and increase creatinine clearance, urea excretion, and GFR. ...
Background: Oxidative stress is implicated in the pathogenesis of many diseases. Proper management of oxidative stress requires antioxidants from external sources to supplement that of the body. Plants are considered as a major source of antioxidants because of their natural origin and therapeutic benefits. Objectives: This study was aimed at investigating the renoprotective and antioxidant capacity of hydroethanolic extract of Senecio serratuloides (HESS). Materials and Methods: In vitro and ex vivo antioxidant capacity of the extract was investigated. Female Wistar rats were treated with N w-nitro L-arginine methyl ester (L-NAME) (40 mg/kg) for 4 weeks and then cotreating with L-NAME (20 mg/kg) and extract (HESS150 or HESS300 mg/kg) for 2 weeks and finally with plant extract or normal saline only for 2 weeks making a total of 8 weeks. Twenty-four-hour urine samples were collected during the study, and at the end of the study; blood and kidneys were harvested for biochemical and histological assays. Results: HESS exhibited high antiradical activity against 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) radicals with IC 50 values of 0.1 and 0.4 mg/ml, respectively. HESS significantly (P < 0.01) augmented L-NAME-induced decrease in creatinine clearance, glomerular filtration rate, and serum calcium concentration. HESS significantly increased in vivo antioxidant capacity (P < 0.01), decreased malondialdehyde (P < 0.01), and Bax (P < 0.001) concentration. It showed renoprotection and significantly (P < 0.01) prevented collagen deposition in the kidneys. Conclusion: S. serratuloides has renoprotective and free radical-scavenging properties and therefore maybe important in combating oxidative stress-mediated diseases in the kidneys and other parts of the body.
... NAC is a low molecular weight thiol derived from cysteine amino acid and due to antioxidant, anti-aging and anti-inflammatory activities, it has an important role in reducing oxidative stress, eliminating ROS and improving nitric oxide activity (20,21). Some studies confirm the protective and positive effects of NAC on various tissues of the body, including the liver, kidney, intestine and ovary (22)(23)(24)(25). ...
... NO is synthesized by nitric oxide synthase (NOS) and AA can exert its toxic effects through NOS pathway on the female reproductive system (10). Nevertheless, it appears that NAC can modulate the toxic effects of AA on the ovary by affecting the NOS activity (21,28). ...
... NAC, a thiol-containing compound, was suggested to increase gastric NO levels due to reduced glutathione preservation as well as stabilizing the dimeric form of endothelial NO synthase (eNOS), thereby increasing its activity (Kojsová et al. 2006). The significant increase in gastric NO levels in GEN-pretreated rats may be attributed to enhancement of eNOS phosphorylation/activation, which supports the results of previous researchers (R. . ...
The protective effect of N- acetylcysteine (NAC) and genistein (GEN) on an experimental model of indomethacin (IND) - induced gastric injury was investigated. 50 male rats were divided into 5 groups: control (I), IND (II), NAC pretreated (III), GEN Pretreated (IV), NAC+GEN pretreated (V). Rats were orally administered NAC (500 mg/kg), GEN (10 mg/kg) or both once daily for 7 days before the induction of the gastric injury by IND (50 mg/kg). Stomach was removed for biochemical analysis and histopathological examinations. Pretreatment with either NAC or GEN or both significantly improved ulcer indices, increased nitric oxide (NO) level and superoxide dismutase (SOD) activity , while they significantly decreased malondialdehyde (MDA), tumor necrosis factor α (TNF α) levels and myeloperoxidase (MPO) activity, along with down-regulation of MMP-9 gene expression in pretreated groups compared to IND group. NAC alone ameliorated IND-induced apoptosis, while GEN only significantly increased PGE2 level. Further, co-administration of both recorded a better significant gastroprotective effect rather than their single usage. Conclusively, concomitant administration of NAC and GEN have an additive gastroprotective effect in IND- induced gastric injury which may be through interaction of their potential cytoprotective, antioxidant, anti-inflammatory and anti-apoptotic mechanisms together with regulation of MMP-9 expression.
... Reduction the level of Ang II by captopril, an ACEI, is used widely and highly effective in the treatment of HF through suppressing the activation RAS in clinical trials (Yoo et al. 2015). In addition, more and more studies from animal experiment further revealed that one of the protective mechanisms of captopril on CVD was closely related to the reduction of ROS (Kim et al. 2013, Kojsova et al. 2006. Apocynin is extracted from the root of Picrorhiza kurroa, which has been used as an efficient inhibitor of NADPH oxidase in many experimental models involving phagocytic and nonphagocytic cells. ...
Oxidative stress plays an important role in pressure overload-induced cardiac remodeling. The purpose of this study was to determine whether apocynin, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, attenuates pressure overload-induced cardiac remodeling in rats. After abdominal aorta constriction, the surviving rats were randomly divided into four groups: sham group, abdominal aorta constriction group, apocynin group, captopril group. Left ventricular pathological changes were studied using Masson's trichrome staining. Metalloproteinase-2 (MMP-2) levels in the left ventricle were analyzed by western blot and gelatin zymography. Oxidative stress and apoptotic index were also examined in cardiomyocytes using dihydroethidium and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), respectively. Our results showed that abdominal aorta constriction significantly caused excess collagen deposition and cardiac insult. Treatment with apocynin significantly inhibited deposition of collagen and reduced the level of MMP-2. Furthermore, apocynin also decreased the NADPH oxidase activity, reactive oxygen species production and cardiomyocyte apoptotic index. Interestingly, apocynin only inhibited NADPH oxidase activity without affecting its expression or the level of angiotension II in the left ventricle. In conclusion, apocynin reduced collagen deposition, oxidative stress, and inhibited apoptosis, ultimately ameliorating cardiac remodeling by mechanisms that are independent of the renin-angiotensin system.
... Indirect antioxidant actions of melatonin reside in the stimulation of gene expressions and activation of superoxide dismutase, catalase, glutathione peroxidase (Tomas Zapico and Coto-Montes 2005) and improvement of mitochondrial efficiency ( Acuna-Castroviejo et al. 2001). Since attenuation of the free radical burden in the central nervous system (CNS) was shown to attenuate hypertension ( Kojsova et al. 2006), the antioxidant nature S374 Klimentova et al. Vol. ...
Melatonin, a multitasking indolamine, seems to be involved in a variety of physiological and metabolic processes via both receptor-mediated and receptor-independent mechanisms. The aim of our study was to find out whether melatonin can affect blood pressure (BP), nitric oxide synthase (NOS) activity, eNOS and nNOS protein expressions in rats with metabolic syndrome (SHR/cp). Rats were divided into four groups: 6-week-old male WKY andSHR/cp and age-matched WKY and SHR/cp treated with melatonin (10 mg/kg/day) for 3 weeks. BP was measured by tailcuff plethysmography. NOS activity, eNOS and nNOS protein expressions were determined in the heart, aorta, brain cortex and cerebellum. MT1 receptors were analyzed in the brain cortex and cerebellum. In SHR/cp rats, BP was decreased after melatonin treatment. In the same group, melatonin did not affect NOS activity and eNOS protein expression in the heart and aorta, while it increased both parameters in the brain cortex and cerebellum. Interestingly, melatonin elevated MT1 protein expression in the cerebellum. Neuronal NOS protein expression was not changed within the groups. In conclusion, increased NOS activity/eNOS upregulation in particular brain regions may contribute partially to BP decrease in SHR/cp rats after melatonin treatment. Participation of MT1 receptors in this melatonin action may be supposed. © 2016 Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
... Our study, showed that SPIR (40 and 80 mg/kg/day) treatment, was associated with significant improvement in GSH and SOD and a significant reduction in levels of TBARS and NO, but in MTX treated mice group has not shown any significant change in oxidative markers except NO. Our study results suggested that SPIR may have anti inflammatory and antioxidant potential to treat RA and are in agreement with earlier studies that reported antiinflammatory and antioxidant effect of spironolactone in various diseases [15,16,38,39]. ...
Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by increased inflammation of synovial joint. The collagen-induced arthritis (CIA) is a widely used animal model for RA. Spironolactone possesses potent anti-inflammatory and immune modifying properties that might make it an excellent medical intervention for rheumatic diseases.
Aim of the work: The present study was conducted to evaluate the therapeutic effect of spironolactone (SPIR) in collagen-induced arthritis model in mice.
Materials and methods: DBA/1mice were divided into eight groups and CIA mice treated with SPIR (20, 40 and 80?mg/kg/day), methotrexate (MTX) and vehicle was administered beginning on day 21 (arthritis onset) until day 42. The effects of treatment in the mice were assessed by clinical, oxidative markers, inflammatory cytokines; tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6) as well as histological changes in ankle joints.
Results: Mice immunized with collagen II with complete and incomplete Freund?s adjuvant developed inflammatory arthritis. Spironolactone (40 and 80?mg/kg/day) was effective in bringing significant changes on all the parameters (paw swelling, arthritis score, oxidative markers) studied. Oral administration of SPIR significantly reduced the level of TNF-? and IL-6. The protective effect of SPIR against RA was also evident from the ankle joint histopathology and its effect was found comparable to that of MTX.
Conclusion: Amelioration of paw swelling, antioxidant properties, inflammatory mediators TNF-? and IL-6 and histopathological changes indicates that SPIR can be considered with MTX among the treatment armamentarium of arthritis. Spironolactone may be considered for use as a novel therapeutic treatment against human arthritis.
... Captopril, an inhibitor of angiotensin converting enzyme (ACE), has also been postulated as a free radical scavenger because of its terminal sulfhydryl group (Bagchi et al., 1989;Andreoli, 1993). Some in vitro studies indicate that captopril functions as an antioxidant both by scavenging ROS and by increasing the activities of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase (Westlin and Mullane, 1988;Kojsova et al., 2006). Captopril has been shown to decrease serum lipid peroxide concentrations in diabetic patients (Ha and Kim, 1992). ...
Considering that lead caused a lot of health problems in the world, the present study was carried out to investigate the protective effect of captopril as antioxidants to reduce liver and spleen toxicity induced by lead. Animals were divided into 3 groups, the 1st group served as control group, the 2nd group received 20 mg/kg of lead acetate and the 3rdgroups received 50 mg/kg of captopril one hour prior to lead administration for 5 days. Results showed that lead intake caused severe alterations in liver and spleen manifested by hepatocytes degeneration, leucocytic infiltration, fibrosis in liver and moderate to severe liver pathological score. Spleen showed ill-defined architecture, presence of large macrophages and lymphoid necrosis. Administration of captopril reduced hepatotoxicity, liver fibrosis and decrease in pathological scoring system. Moreover, reduced toxicity in spleen represented by reduction in necrotic areas, more or less healthy lymphoid follicles and decreasing in pathological scoring system.
