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


CONCLUSIONS
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.
Mostafavi-Pour
Zohreh
Z
Department of Biochemistry, and Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Zal
Fatemeh
F
Monabati
Ahmad
A
Vessal
Mahmood
M