Modulatory Effect of a-tocopherol in Simvastatin and Gemfibrozil Induced Rhabdomyolysis in Rats

The present study was aimed to evaluate the protective effect of α-tocopherol in simvastatin and gemfibrozil induced rhabdomyolysis in rats. HMG-Coenzyme A reductase inhibitors are the most widely used drug for the treatment of hyperlipidemias but their long term use is associated with rhabdomyolysis. Administration of simvastatin (80 mg/kg, p.o.) and gemfibrozil (600mg/kg, p.o. twice) for 30 days produced significant increase in the level of various serum parameters (creatine Phospho kinase, urea and blood urea nitrogen) indicating development of rhabdomyolysis in rats as well as development of renal complications. Administration of simvastatin + gemfibrozil also caused significant increase in the level of lipid peroxidation and decrease in the antioxidant enzymes (reduced glutathione, superoxide dismutase and catalase) level in rats. α-tocopherol (1gm/kg, p.o) was given to prevent rhabdomyolysis caused by simvastatin + gemfibrozil combination.

Administration of α-tocopherol caused increase in the level of antioxidant enzymes and decrease in the level of lipid peroxidation. α-tocopherol also caused improvement in the serum parameters of rhabdomyolysis in the rats. Histopathology of the kidney from simvastatin + gemfibrozil treated rats showed no significant renal damage. Improvement in the level of biochemical parameters and decrease in the level of oxidative stress indicates that α-tocopherol due to its antioxidant activity modifies the biochemical changes occurred during rhabdomyolysis and thus had a potential protective effect in rhabdomyolysis.