Supplementation with Terminalia chebula attenuates the tacrolimus induced nephrotoxicity in experimental models

[Speaker] Surender Singh:1
1:Pharmacology, All India Institute of Medical Sciences, New Delhi, India

Background: Tacrolimus, a calcineurin inhibitor, is clinically used as an immunosuppressive agent in the transplant patients; however its use is greatly limited by its nephrotoxicity. Terminalia chebula Retz. commonly known as Black Myrobalan in English, has been reported to possess antioxidant and anti-inflammatory properties. It has been shown to be effective in cadmium and gentamicin induced nephrotoxicity. Therefore, the present investigation was designed to evaluate the ameliorative effect of standardized hydroalcoholic fruit extract of Terminalia chebula (TCE) on tacrolimus induced nephrotoxicity.
Methods: The present study consisted of six groups of Wistar albino rats, normal control, tacrolimus-induced, TCE (50, 100 and 200 mg/kg orally and per se group). Subcutaneous injection of tacrolimus (3 mg/kg) was administered daily to all groups for 28 days, except normal control and per se group. On day 28th, blood was withdrawn from retro orbital plexus and various biochemical and antioxidant parameters were evaluated. The kidneys were excised for performing histopathological and immunohistochemical analysis.
Results: Rats administered with tacrolimus alone showed significant (p<0.001) increase in the level of serum creatinine, blood urea nitrogen, MDA levels and a significant decrease GSH and SOD levels, as compared with the normal group. Pretreatment with TCE significantly (p<0.001) decreased the level of MDA and increase in the activities of GSH and SOD, as compared with the tacrolimus control group. In histopathological evaluation, the kidneys of tacrolimus treated rats showed tubular necrosis, denudation of epithelium and infiltration of inflammatory cells. TCE treatment tubules appeared normal and there was no inflammation. Tacrolimus administration increased expression of the pro-apoptotic Bax and caspase-3, and decreased expression of the anti-apoptotic Bcl-2 in renal tubules. However, treatment with TCE (200 mg/kg) attenuated apoptosis by decreasing the expression of Bax, caspase-3 and increasing the expression of Bcl-2 in renal tubules.
Conclusion: The present findings demonstrated that TCE produced a significant protective effect against tacrolimus induced nephrotoxicity and found to be effective in modulation of oxidative stress and apoptosis induced by tacrolimus administration. It may be concluded that TCE can be used as a renoprotective agent in tacrolimus induced nephrotoxicity.

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