OXIDATIVE STRESS MEDIATED HEPATOTOXICITY PRODUCED BY SIMVASTATIN

Summary The main objective of present study was to in vivo evaluation of Simvastatin hepatotoxicity. Hepatotoxicity in rat was induced by Simvastatin (20mg/kg/p.o. for 30 days) and evaluation was carried out by estimating oxidative stress markers like lipid peroxidation, reduced glutathione, super oxide dismutase and catalase along with marker enzymes for liver function like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and γ glutamic transpeptidase (GTP) and lactate dehydrogenase (LDH), protein profile likes total bilirubin (TB), direct bilirubin (DB), total albumin (TA) and total protein (TP) and histopathological study to confirm hepatotoxicity. Simvastatin significantly (P<0.001) increased lipid peroxidation compared to control. Tissue levels of reduced glutathione, superoxide dismutase and catalase were significantly (P<0.001) decreased after treatment with Simvastatin compared to control. Serum levels of ALT, AST, γGTP, ALP and LDH were significantly (P<0.001) increased after treatment with Simvastatin compared to control. Simvastatin caused significant (P<0.001) increase in serum total bilirubin and indirect bilirubin and significant (P<0.01) decrease in direct bilirubin and total protein compared to control. Simvastatin hepatotoxicity was characterized by significant increase in oxidative stress markers along with marker enzymes of liver function and depletion of proteins indicated oxidative stress mediated hepatotoxicity produced by Simvastatin.