Zingiber officinale and 6-gingerol alleviate liver and kidney dysfunctions and oxidative stress induced by mercuric chloride in male rats: A protective approach.

Mercury toxicity is an emerging problem in the world as its concentration is rising continuously due to increased industrial, medicinal and domestic uses. Exposure to mercury represents a serious challenge to humans and other living biomes. The aim of the present study was to assess the protective effect of natural products as Zingiber officinale extract and its active compound (6-gingerol) against mercuric chloride-induced hepatorenal toxicity and oxidative stress in male rats. Male Sprague-Dawley rats (150±10g, n=6 per group) were administered HgCl2 (12µmol/kg, ip; once only) the treatment of Zingiber officinale Rosc. extract (ZO: 125mg/kg, po) and 6-gingerol (GG: 50mg/kg, po) for three days after 24h of HgCl2 administration. Acute HgCl2 administration altered various biochemical parameters, including transaminases, alkaline phosphatase, lactate dehydrogenase, bilirubin, gamma-glutamyl transferase, triglycerides and cholesterol, urea, creatinine, uric acid and blood urea nitrogen contents with a concomitant decline in protein and albumin concentration in serum. In addition, a significant rise in lipid peroxidation level with concomitant decrease in reduced glutathione content and the antioxidant enzymes activities of superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and glutathione-S-transferase after acute HgCl2 exposure. Results of the present investigation clearly showed that both treatments as Zingiber officinale extract and 6-gingerol provide protection against acute mercuric chloride-intoxication by preventing oxidative degradation of a biological membrane from metal mediated free radical attacks. Biochemical data were well supported by histopathological findings. In conclusion, natural products may be an ideal choice against oxidative damage induced by mercury poisoning.

Curcuma longa Linn. extract and curcumin protect CYP 2E1 enzymatic activity against mercuric chloride-induced hepatotoxicity and oxidative stress: A protective approach.

The present investigation has been conducted to evaluate the therapeutic potential of Curcuma longa (200mgkg-1, po) and curcumin (80mgkg-1, po) for their hepatoprotective efficacy against mercuric chloride (HgCl2: 12µmolkg-1, ip; once only) hepatotoxicity. The HgCl2 administration altered various biochemical parameters, including transaminases, alkaline phosphatase, lactate dehydrogenase, bilirubin, gamma-glutamyl transferase, triglycerides and cholesterol contents with a concomitant decline in protein and albumin concentration in serum which were restored towards control by therapy of Curcuma longa or curcumin. On the other hand, both treatments showed a protective effect on drug metabolizing enzymes viz. aniline hydroxylase (AH) and amidopyrine-N-demethylase (AND), hexobarbitone induced sleep time and BSP retention. Choleretic, 1,1-diphenyl-2-picryl-hydrazil (DPPH)-free radical scavenging activities and histological studies also supported the biochemical findings. The present study concludes that Curcuma longa extract or curcumin has the ability to alleviate the hepatotoxic effects caused by HgCl2 in rats.

Reversal of methylmercury-induced oxidative stress, lipid peroxidation, and DNA damage by the treatment of N-acetyl cysteine: a protective approach.

This study was designed to evaluate the protective effect of N-acetyl cysteine in reducing methylmercury (MeHg)-induced oxidative stress, lipid peroxidation, DNA damage in liver, kidney, and brain, and their ability to restore altered hepatic, renal, and other biochemical variables. Male Sprague-Dawley rats (150±10 g) were randomly divided into three groups. Group 1 served as the control. Groups 2 and 3 were administered methylmercury (1 mg kg⁻¹ orally, 5 days/week) for 12 weeks, and group 2 served as the experimental control. Group 3 received N-acetyl cysteine (0.6 mg kg⁻¹ intraperitoneally, two days/week) for 12 weeks after methylmercury exposure. Methylmercury exposure caused a significant rise in bilirubin, gamma-glutamyl transpeptidase, protein, triglycerides, cholesterol, urea, creatinine, uric acid, and blood urea nitrogen, with a concomitant decrease in albumin content, reduced glutathione level and acetyl cholinesterase activity, antioxidant enzymes such as glutathione reductase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, and adenosine triphosphatase. However, lipid peroxidation level, metallothionein expression, and DNA damage with increment of tail length were observed after methylmercury intoxication. N-acetyl cysteine, a widely available, nontoxic amino acid derivative, is a promising antioxidant with a wide spectrum of biological functions. The ability of N-acetyl cysteine to enhance mercury excretion and its wide availability in clinical use indicate that it may be an ideal therapeutic agent against methylmercury poisoning.

N-acetyl cysteine and selenium protects mercuric chloride-induced oxidative stress and antioxidant defense system in liver and kidney of rats: a histopathological approach.

Mercury exposure is second-most common cause of metal poisoning which is quite stable and biotransformed to highly toxic metabolites thus eliciting biochemical alterations and oxidative stress. The aim of present study describes the protective effect of selenium either alone or in combination with N-acetyl cysteine (NAC) against acute mercuric chloride poisoning. The experiment was carried out in male albino Sprague Dawley rats (n=30) which was divided into five groups. Group 1 served as control. Groups 2-5 were administered mercuric chloride (HgCl2: 12mol/kg, i.p.) once only, group 2 served as experimental control. Animals of groups 3, 4 and 5 were received N-acetyl cysteine (NAC: 0.6mg/kg, i.p.) and selenium (Se: 0.5mg/kg, p.o.) and NAC with Se in combination. Acute HgCl2 toxicity caused significant rise in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, albumin, bilirubin, γ-glutamyl transpeptidase, cholesterol, triglycerides, protein, urea, creatinine, uric acid and blood urea nitrogen content. Animals also showed significantly higher mercury content in liver and kidney, significant rise in lipid peroxidation level with concomitant decrease in reduced glutathione content and the antioxidant enzyme activities of superoxide dismutase and catalase after HgCl2 exposure. Results of the present investigation clearly showed that combination therapy with NAC+Se provide maximum protection against mercury toxicity than monotherapy (alone treated groups) by preventing oxidative degradation of biological membrane from metal mediated free radical attacks.

Methylmercury toxicity: amelioration by selenium and water-soluble chelators as N-acetyl cysteine and dithiothreitol.

The protective potential of chelators, i.e. N-acetyl cysteine (0.6 mg /kg, intraperitoneally) and dithiothreitol (15.4 mg kg(-1) , intraperitoneally) with selenium (0.5 mg kg(-1) , pre-oral) were evaluated individually and in combination against methylmercury-induced biochemical alterations and oxidative stress consequences. Forty-two male Sprague-Dawley rats were exposed with methylmercury (1.5 mg kg(-1) , pre-oral) daily for 21 days followed by different treatments for five consecutive days. Administration of methylmercury caused significant enhancement in the release of transaminases, alkaline phosphatases and lactate dehydrogenases in serum. A significant increased was observed in lipid peroxidation level with a concomitant decreased in glutathione content after methylmercury exposure in liver, kidney and brain. Hepatic microsomal drug metabolizing enzymes (aniline hydroxylase and amidopyrine N-demethylase) of cytochrome p4502E1 showed sharp depletion after methylmercury exposure. Alterations in histological changes in liver, kidney and brain were also noted in methylmercury administered group. All treated groups showed recovery pattern, but the combined treatments with N-acetyl cysteine and dithiothreitol in combination with selenium were more effective than that with either alone treatments in recovering blood biochemical changes after methylmercury toxicity. In conclusion, the results demonstrated that combination therapy may recover all blood biochemical alterations and offer maximum protection against methylmercury-induced toxicity.

Therapeutic potential of N-acetyl cysteine with antioxidants (Zn and Se) supplementation against dimethylmercury toxicity in male albino rats.

Mercury (Hg) is currently one of the most prevalent pollutants in the environment. Many studies have examined its effects on the health of both humans and animals. Experimental studies have shown that sulfur-containing nutrients play an important role as detoxification and protecting cell against the detrimental properties of mercury. The present study was undertaken to elucidate the toxicity induced by dimethylmercury in male rats through the activities of transaminases, alkaline phosphatase, lactate dehydrogenase in serum and oxidative damage as acetyl cholinesterase activity in different regions of brain and lipid peroxidation, reduced glutathione content, mean DNA damage in liver, kidney and brain of rats given dimethylmercury (10 mg/kg, p.o., once only) along with combination therapy of N-acetyl cysteine (2 mM/kg, i.p.), zinc (2 mM/kg, p.o.) and selenium (0.5 mg/kg, p.o.) for 3 days. In the dimethylmercury group, activities of transaminases, alkaline phosphatase, lactate dehydrogenase in serum, level of lipid peroxidation, mean DNA damage and mercury ion concentration were significantly higher whereas reduced glutathione content and the activity of acetyl cholinesterase were significantly lower compared to controls (P≤0.05). Combined treatment of zinc and selenium with N-acetyl cysteine to dimethylmercury-exposed rats showed a substantial reduction in the levels of DMM-induced oxidative damage and comet tail length. In conclusion, the results of this study support that the supplementation of zinc and selenium with N-acetyl cysteine can improve the DMM induced blood and tissue biochemical oxidative stress and molecular alterations by recoupment in mean DNA damage.

Combined effect of N-acetyl cysteine, zinc, and selenium against chronic dimethylmercury-induced oxidative stress: a biochemical and histopathological approach.

Mercury (Hg), widely used in industry, is a great environmental health problem for humans and animals. Despite several reports regarding Hg toxicity, there is scarcity of data on its toxic manifestations on Sprague Dawley rats under realistic exposure conditions. Experimental studies have shown that sulphur-containing antioxidants have beneficial effects against the detrimental properties of Hg. The present work was aimed to study the therapeutic potential of combined administration of N-acetyl cysteine (NAC; 2 mmol/kg ip), zinc (Zn; 2 mmol/kg po), and selenium (Se; 0.5 mg/kg po) against dimethylmercury (DMM; 1 mg/kg po)-intoxicated male rats for 12 weeks. Exposure to DMM caused significant alterations in cytochrome P450 (CYP) activity, microsomal lipid peroxidation, and proteins. Activities of transaminases (aspartate aminotransferase/alanine aminotransferase), alkaline phosphatase, and lactate dehydrogenase in serum, as well as activities of CYP enzymes aniline hydroxylase (AH), amidopyrine-N-demethylase (AND) in liver microsomes and activities of acid phosphatase, alkaline phosphatase, glucose-6-phophatase, and succinic dehydrogenase in the liver and kidney, were significantly altered after DMM administration. DMM exposure also induced severe hepato-renal alterations at the histopathological level. NAC, along with Zn and Se, dramatically reversed the alterations in all of the variables more toward control. The study results conclude that protective intervention of combined treatment of NAC, along with Zn and Se, is beneficial in attenuating DMM-induced systemic toxicity.

Cotherapy of Tiron and selenium against vanadium induced toxic effects in lactating rats.

BACKGROUND: Vanadium is an important environmental and industrial pollutant. It has a status of reproductive toxicant and is reported to cross placental barrier. OBJECTIVE: The current study was performed to assess the therapeutic efficacy of Tiron and its combination with selenium against vanadium induced toxicity in lactating and suckling rats. MATERIALS AND METHODS: Rats were exposed to vanadium at a dose of 7.5 mg/kg/day (p.o.) for 20 days from 0 day of post partom (p.p.). Tiron (606 mg/kg/day, i.p.) and selenium (0.5 mg/kg/day, p.o.) were administered for 5 days on 21-25 day PP. RESULTS: Vanadium exposure decreased blood sugar level while serum transaminases and serum alkaline phosphatase showed increased values significantly (p<0.01). Elevation in glycogen content of liver and kidney of suckling and kidney of lactating rats was found after toxicant administration. Toxicant intoxication increased the enzymatic activity of acid phosphatase in liver of suckling and lactating and kidney of suckling rats. On the contrary alkaline phosphatase and adenosine triphosphatase activities were inhibited significantly (p<0.01) in all the organs. Lipid peroxidation was enhanced whereas glutathione was reduced significantly in liver of suckling and lactating rats (p<0.01). Vanadium also caused histopathological lesions. Therapies of Tiron per se and Tiron along with selenium maintained almost all blood and tissue biochemical parameters towards normal. Tiron along with selenium reduced vanadium induced lesions in lactating and sucklings rats. CONCLUSION: Tiron along with selenium is more effective than Tiron alone against vanadium induced toxic effect on lactating and suckling rats.

Protective role of thiol chelators against dimethylmercury induced toxicity in male rats.

The present study was undertaken to establish mode of action, comparative therapeutic efficacy and safety evaluation of N-acetyl cysteine and dithiothreitol against acute dimethylmercury poisoning in rats. Male Sprague-Dawley albino rats (150 +/- 10 g) were randomly divided into six groups. Group 1 served as control. Group 2-4 were administered dimethylmercury (10 mg/kg, p.o.) once only and group 2 served as experimental control. Animals of group 3 and 4 were received N-acetyl cysteine and dithiothreitol. Compared to the control, significant increase (p < or = 0.05) was observed in the activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lipid peroxidation level and mercury ion concentration, however reduced glutathione, catalase, adenosine triphosphatase, acetyl cholinesterase (in brain only) were also decreased. It was concluded that N-acetyl cysteine provided maximum protection when compared with dithiothreitol group.

Role of micronutrients against dimethylmercury intoxication in male rats.

Mercury is one of the most toxic non-radioactive heavy metals. Chelation therapy has been the basis for the medical treatment of mercury poisoning. Male albino rats were administered dimethylmercury (1.5mg/kg) orally for 21 days. Chelation therapy with N-acetyl cysteine along with combination of antioxidants viz. zinc and selenium was given for 5 days after 24h of toxicant administration. All animals were sacrificed after 48h of last treatment and various blood biochemical parameters were performed. Toxicant caused rise in bilirubin, γ-GT, cholesterol, triglycerides, urea, creatinine, the uric acid content with a decline in albumin. A significant elevation was observed in LPO content and mercury concentration, along with concomitant decline in GSH levels after toxicant administration in liver, kidney and brain. Noticeable fall was also observed in AChE enzyme. Histopathological analysis was consistent with the biochemical observations and led to conclude that combination therapy provided protection against mercury toxicity.

Hepatic endogenous defense potential of propolis after mercury intoxication.

Exposure to mercuric chloride (HgCl(2) ; 5 mg kg(-1) body weight; i.p.) induced oxidative stress in mice and substantially increased lipid peroxidation (LPO) and oxidized glutathione (GSSG) levels, decreased the level of reduced glutathione (GSH) and various antioxidant enzymes in liver and also increased the activities of liver marker enzymes in serum. Therapy with propolis extract, a resinous wax-like beehive product (200 mg kg(-1) orally, after mercury administration), for 3 days inhibited LPO and the formation of GSSG and increased the level of GSH in the liver. Release of serum transaminases, alkaline phosphatase, lactate dehydrogenase and γ-glutamyl transpeptidase were significantly restored after propolis treatment. The activities of antioxidant enzymes, that is, superoxide dismutase, catalase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase, were also concomitantly restored towards normal levels after propolis administration. These observations clearly demonstrate that propolis treatment augments antioxidant defense against mercury-induced toxicity and provide evidence that propolis has therapeutic potential as a hepatoprotective agent.

Effect of monothiol along with antioxidant against mercury-induced oxidative stress in rat.

Efficacy of thiol chelators viz. N-acetyl cysteine and D-penicillamine (NAC and DPA) along with nutritional supplements viz. zinc acetate, sodium selenite and magnesium sulphate (Zn, Se and Mg) in the treatment of mercury intoxication was investigated in rats. This is of particular interest since high bonding affinity between mercuric ion and the thiol group exits. The mutual antagonism of mercury and selenium is one of the strongest examples of the interaction in the trace element field. Adult rats of Sprague-Dawley strain were administered a bolus dose of dimethyl mercury (10 mg/kg) orally. A significant rise in the aspartate aminotransferase, alanine aminotransferase, serum alkaline phosphatase, lactate dehydrogenase, gamma glutamyltranspeptidase, bilirubin and creatinine were observed. Single mercury exposure also resulted in a significant increase in lipid peroxides with a concomitant decrease in reduced glutathione level in liver, kidney and brain. A decrease in the enzymatic activities of acetyl cholinesterase in different regions of the brain was observed. These parameters were restored considerably with chelating agents along with nutritional supplementation, but NAC+Se and DPA+Mg offered significant protection in comparison with other combinations.