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Protective effect of mycophenolate mofetil against nephrotoxicity and hepatotoxicity induced by tacrolimus in Wistar rats

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Abstract

Tacrolimus (TAC), a calcineurin inhibitor (CNI), is clinically used as an immunosuppressive agent in the transplant recipient; however, the use of TAC is greatly limited by its nephrotoxicity and hepatotoxicity. Mycophenolate mofetil (MMF), an inhibitor of the purine synthesis, has been used in combination with many immunosuppressive drugs such as TAC. The association TAC/MMF was used in organ transplantation to increase the efficiency and reduce acute rejection rates, but the effects of MMF on TAC-induced kidney and liver injuries are still not well investigated. The aims of this study are to explore whether MMF co-administration with TAC has a renoprotective and hepatoprotective effect against TAC-induced renal and hepatic injuries and to check the implication of oxidative stress in the MMF’s possible protective effect. Our results showed that MMF (at 50 mg kg−1 body weight (b.w.)) restored creatinine, in addition to increased AST and ALT levels by TAC (at 60 mg kg−1 b.w.). Furthermore, MMF decreased DNA damage induced by TAC in the kidney and liver of rats as assessed by comet assay. This renoprotective and hepatoprotective effect of MMF was associated with an antioxidant effect. In fact, MMF co-treatment with TAC decreased oxidative damage induced by TAC. It reduced malondialdehyde (MDA) and protein carbonyl (PC) levels as well as catalase and superoxide dismutase (SOD) activities. We conclude that the co-administration MMF with TAC protect liver and kidney against TAC toxicity via an antioxidant process.

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Acknowledgments

This research was supported by the “Ministère Tunisien de l’enseignement Supérieur, de la Recherche Scientifique et des Technologies de l’Information et de la Communication” through the “Laboratoire de Recherche sur les Substances Biologiquement Compatibles” (LRSBC).

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Authors and Affiliations

  1. Laboratory of Research on Biologically Compatible Compounds, Dental Medicine Faculty, 5019, Monastir, Tunisia

    Hanen Ferjani, Aicha Bouraoui, Salwa Abid, Hassen Bacha & Imen Boussema-Ayed

  2. Department of Nephrology, Dialysis and Transplant, University Hospital of Sahloul, 4021, Sousse, Tunisia

    Abedellatif Achour

  3. Laboratory of Bioresources, Biology Integrative and Valorization, Higher Institute of Biotechnology of Monastir, Avenue Tahar Hadded, BP 74, 5000, Monastir, Tunisia

    Amira El Arem

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  1. Hanen Ferjani
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Correspondence to Hassen Bacha.

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Ferjani, H., El Arem, A., Bouraoui, A. et al. Protective effect of mycophenolate mofetil against nephrotoxicity and hepatotoxicity induced by tacrolimus in Wistar rats. J Physiol Biochem 72, 133–144 (2016). https://doi.org/10.1007/s13105-015-0451-7

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