Molecular Mechanisms of the Modulatory Effect of Vitamin E on Tacrolimus (FK506)-Induced Renal Injury in Rats

Abstract

Aim: This study was designed to evaluate the possible modulatory effect of vitamine E on tacrolimus (FK506)-induced renal injury in rats. Methods: Twenty-four male Wistar rats (6 animals in each group) were used in this study. The first group (Control) received normal saline intraperitoneal (i.p.) daily for 21 days. The second group received FK506 (1 mg/kg/day i.p.) daily for 21 days. The third group was administered Vitamin E (250 mg/kg/day by oral gavage) 5 days before and concurrently during FK506 administration daily for 21 days. The fourth group received Vitamin E alone (as previously described in the third group). Results: Administration of FK506 significantly increased blood urea nitrogen and serum creatinine levels. In addition, FK506 has also reduced the renal content of reduced glutathione, as well as the enzymatic activities of superoxide dismutase and catalase. Furthermore, these effects were associated with an increase in lipid peroxidation, inducible NO-synthase (iNOS), and NF-kB expression. Moreover, histopathological examinations showed severe damage of the renal tissues in animals treated with FK506. Interestingly, it was found that concomitant administration of vitamin E along with FK506 ameliorated all these parameters and improved renal function. Furthermore, the immunosuppressive effect of FK506 was not affected by vitamin E. Conclusion: The findings of the present study suggest that concomitant use of vitamin E might be useful in reducing nephrotoxicity induced by FK506.