Protective effects of a combination of quercetin and vitamin E against cyclosporine A-induced oxidative stress and hepatotoxicity in rats

Aim: Cyclosporine A (CsA) is the most widely used immunosuppressive drug in transplant surgery. It is able to generate reactive oxygen species (ROS) and cause lipid peroxidation (thiobarbituric acid-reacting substances [TBARS]), which will directly result in CsA hepatotoxicity. Methods: In this study, the potential of quercetin (Q) and vitamin E (E), in attenuating CsA-induced liver dysfunction in rats was investigated. Male Sprague-Dawley rats were divided into six groups and treated with either olive oil, ethanol + olive oil, CsA, CsA + E, CsA + Q, or CsA + E + Q for both 4 and 8 weeks. Hepatotoxicity was assessed by morphological alterations in tissue architecture and by reduced serum total protein and increased serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Results: The results indicated that CsA treatment increases TBARS and decreases activities of catalase (CAT) and glutathione peroxidase (GPx) in the rat liver. The co-administration of E and Q with CsA treatment improved both liver morphology changes and function. A combination of these antioxidants significantly reduced TBARS and increased CAT and GPx activities in the hepatic tissue. Conclusion: Our data demonstrates that E + Q plays a protective role against the imbalance elicited by CsA between the production of free radicals and antioxidant defence systems, and suggests that a combination of these two antioxidants may find clinical application where cellular damage is a consequence of ROS.