Protective effect of Sharbat-e-Deenar against acetaminophen-induced hepatotoxicity in experimental animals.

OBJECTIVE: To investigate the effect of Sharbat-e-Deenar (SD) on acetaminophen (APAP)-induced hepatotoxicity in rat model. METHODS: Albino rats were treated with SD at the doses of 1, 2 and 4 mL/kg, p.o. against hepatotoxicity after APAP (2 g/kg, p.o. once only) intoxication. The blood, tissue biochemical parameters and histopathological observation were performed. RESULTS: APAP exposure in rats significantly increased the level of biochemical parameters such as aspartate aminotransaminase, alanine aminotransaminase, lactate dehydrogenase, serum alkaline phosphatase, bilirubin, urea and creatinine into blood circulation which were reversed towards normal by SD therapy at all doses. The tissue biochemical parameters such as lipid peroxidation, reduced glutathione, adenosine tri-phosphatase and glucose-6-phosphatase were significantly restored after SD treatment against hepatotoxity. Histological analysis confirmed that SD-treated rats significantly alleviated of liver damage and reduced lesions caused by APAP intoxication. The biochemical changes are in good correlation with the histopathological observations. CONCLUSION: On the basis of these results, it can be concluded that SD exerts hepatoprotective activity against APAP-induced liver injury.

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.

Protective effect of combined therapy with dithiothreitol, zinc and selenium protects acute mercury induced oxidative injury in rats.

The present study was undertaken to establish mode of action, comparative therapeutic efficacy and safety evaluation of dithiothreitol (DTT) supplemented with Zn and Se against dimethylmercury in rats. Adult male albino rats of Sprague-Dawley strain (150±10 g, n=6 per group) were exposed a bolus dose of dimethylmercury (10 mg/kg, p.o.) for once only followed by DTT (15.4 mg/kg, i.p.) along with the combination of antioxidants Zn and Se (2 mmol/kg and 0.5 mg/kg, p.o.) after 72 h of toxicant administration for three days. The results showed a significant (P≤0.05) increase in the activities of AST, ALT, alkaline phosphatase, lactate dehydrogenase, in serum after toxicant administration. This was accompanied by histopathological observations. A significant rise was observed in lipid peroxidation level and mercury ion concentration however reduced glutathione content decreased in liver, kidney and brain. A significant (P≤0.05) decrease in the activity of acetyl cholinesterase was also seen in different regions of brain. Combined treatment of DTT along with Zn and Se significantly (P≤0.05) recouped the alterations in the enzymatic activities of serum and reversed the tissue biochemical and histopathological changes of liver, kidney and brain. Our results demonstrate that combined treatment of thiol chelator (DTT) along with antioxidants (Zn and Se) plays an important role against dimethylmercury induced tissue damage and hepatic, nephro and neurotoxicity.