Possible protective effects of vitamin E, alfa-lipoic acid and lycopene in mercuric chloride-induced nephrotoxjcity and hepatotoxjcity in rats

ABSTRACT

Mercury [Hg] is a commonly encountered environmental contaminant. It causes severe nephrotoxicity and hepatotoxicity. Although the mechanism underlying Hg toxicity is not clearly understood, several hypotheses encouraging the role of oxidative stress have been proposed. Consequently, the possible protective effects of three natural antioxidants namely vitamin E [VE, 100 mg/kg], alfa-lpoic acid [ALA, 50 mg/kg] and lycopene [LYC, 6 mg/kg] against nephrotoxicity and hepatotoxicity induced by a single i.p. administration of HgCl[2] [3.75 mg/kg] were examined in rats. Test agents were administered orally for 14 consecutive days prior to acute HG intoxication. Nephrotoxicity was assessed by measuring serum levels of urea, creatinine and uric acid, while hepatotoxicity was assessed by measuring serum activities of ALT and AST as well as histological examination of both kidney and liver tissue sections. Tissue reduced glutathione [GSH] and total thiols [SHs] contents were determined. The contents of thiobarbituric acid reactive substances [TBARS], as an index of lipid peroxidation, and total nitrate/nitrite [NO[x]], which reflects nitric oxide output, were also estimated. Acute Hg intoxication resulted in marked nephrotoxicity and hepatotoxicity accompanied by significant reduction in tissue GSH and SHs contents. Interestingly, Hg significantly reduced renal TBARS content, while significantly elevated that of liver. On the other hand, it significantly reduced hepatic NO[x] while did not affect that of kidney. Prior administration of VE, ALA or LYC did not prevent Hg-induced elevations in serum creatinine and urea nitrogen levels. However, pretreatment with ALA or LYC significantly increased Hg-induced decrease in serum uric acid. VE or ALA protected against elevation of both serum ALT and AST. LYC protected only against elevation of serum ALT. VE and ALA provided a significant protection against renal GSH depletion and hepatic THARS elevation, while LYC protected against only hepatic TBARS elevation. None of the test agents produced any significant protection against Hg-induced alterations in renal contents of SHs, TBARS and NO[x] and on hepatic contents of GSH, SHs and NO[x] It could be concluded that the use of antioxidants might protect against Hg toxicity, although mechanisms other than oxidative damage might also contribute to both renal and hepatic cellular injury induced by Hg