Protective Role of Vitamin E and Acetazolamide in Cisplatin-Induced Changes in Lipid Peroxidation and Antioxidant Enzyme Levels in Albino Rats.

Abstract

SummaryCisplatin, an antitumor chemotherapeutic agent with doselimiting nephrotoxic side effects, was administered i.p, to male albino rats at a concentration of 6 mg/kg body wt. The antioxidant vitamin E (400 mg/kg body wt., orally) and the diuretic acetazolamide (ACZ) (20 mg/ kg body wt., i.p.) were co-administered as modulators. The effect of cisplatin on lipid peroxidation and antioxidant enzyme levels was then examined. The agent increased the level of lipid peroxidation and significantly decreased the activities of antioxidant enzymes. These effects may have been due to the formation of free radicals and were considered to be one of the reasons for cisplatin-induced nephrotoxicity. Interestingly, these changes were found to be very much counteracted by vitamin E and acetazolamide when they were co-administered along with the cisplatin. Hence, we suggest that co-administration of vitamin E and acetazolamide along with cisplatin will be clinically advantageous in attenuating cisplatin-induced nephrotoxicity during chemotherapy. Cisplatin (cis-diammine dichloro platinum-II), a platinum containing coordination complex, is an antitumor agent with proven efficacy as a single agent against a wide spectrum of malignancies [1]. Toxicological studies in humans and animals indicate that higher doses produce enzyme inhibition and histological changes in liver, kidney, gastrointestinal tract, and bone marrow [2]. However, the chief dose-limiting side effect of cisplatin is its pronounced nephrotoxicity, which occurs at doses lower than those that damage other organs [3]. The underlying molecular mechanism of the nephrotoxicity induced by cisplatin remains unclear

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