Azathioprine induced hepatotoxicity due to oxidative stress, protective aspect of Quercetin in rats

Mitochondrion plays the most prominent role in the production of energy and cell cycle regulation. Administration of immunosuppressant drug AZA (azathioprine)adversely affects the hepatic mitochondria, which may culminate in hepatotoxicity. The present study is aimed at evaluating the role of QE (quercetin) in AZA provoked hepatic injury. Male Wister rats were used for the experimentation. AZA was administered as a single intraperitoneal injection (50 mg/kg body weight) on the 7th day of the experiment. A prominent depletion in the levels of mitochondrial antioxidants such as MnSOD (manganese Superoxide dismutase), GPx (glutathione peroxidase) and GSH (reduced glutathione) was observed in AZA induced rats. There was a poignant deterioration noticed in mitochondrial membrane, which was observed by measuring levels of MDA (malondialdehyde). Simultaneous decrease in the levels of TCA (tricarboxylic acid) enzymes such as ICDH (isocitrate dehydrogenase) α-KGDH (α-ketoglutarate dehydrogenase) SDH (succinate dehydrogenase) and MDH (malate dehydrogenase) were observed. Decrease in the levels of these enzymes suggests a loss in mitochondrial function and integrity. The supplementation of QE (50 mg/kg body weight) restored the depleted levels of enzymes and above hepatic mitochondrial abnormalities to near normalcy. Thus,our study emphasizes on antioxidant property of QE in improving the mitochondrial functions in AZA induced hepatic degradation.