Deepak Kumar Mittal

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.

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.

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.

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. Copyright

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.

Protective role of Curcuma longa extract and curcumin on mercuric chloride-induced nephrotoxicity in rats: evidence by histological architecture

Mercury (Hg) is a potent nephrotoxin. The aim of this study was to investigate the protective role of Curcuma longa extract and curcumin against HgCl2-induced nephrotoxicity. Male Sprague Dawley rats were administered HgCl2 (12 μmol kg−1, ip; once only) followed by treatment of Curcuma longa extract (200 mg kg−1, po) and curcumin (80 mg kg−1, po) for three days after 24 h of HgCl2 administration. The present results showed that mercuric chloride administration caused an impairment of renal function system which was evident from significant increase in urea, creatinine, uric acid, and blood urea nitrogen concentration in serum. In addition, the swelling in glomerulus and degenerated renal tubules with obstructed lumen was also observed by acute mercuric chloride administration. Treatment with Curcuma longa extract and curcumin was effective in restoring all variables of kidney functions near to control group, which was consistent with kidney histoarchitecture. In conclusion, these results suggest that Curcuma longa extract and curcumin protect against HgCl2-induced nephrotoxicity. This study could be important for the further understanding of mercury toxicity in renal tissues and in the development of better treatments for people and/or animals exposed to the metal.

Mechanism of Polygonum bistorta and Zingiber roseum Against Toxicity

The present study was carried out to observe the hepatoprotective effect and antioxidant activity of the aqueous extract of the roots of Polygonum bistorta (PB) (100 mg/kg) and Zingiber roseum (ZR) (100 mg/kg) in rats treated with carbon tetrachloride (0.15 ml/kg, i.p.). Extract of PB and ZR at the tested doses restored the levels of liver homogenate enzymes (glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase enzymes significantly. The activities of MTT assay significantly recovered the damage towards normal. This study shows that Zingiber roseum has a more liver protective effect in comparison to Polygonum bistorta and against carbon tetrachloride- induced hepatotoxicity and possess antioxidant activities and extracts exhibited moderate anticancer activity towards cell viability at higher concentration.