Protective effect of mycophenolate mofetil against nephrotoxicity and hepatotoxicity induced by tacrolimus in Wistar rat
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ORIGINAL PAPER
Protective effect of mycophenolate mofetil against nephrotoxicity and hepatotoxicity induced by tacrolimus in Wistar rats Hanen Ferjani & Amira El Arem & Aicha Bouraoui & Abedellatif Achour & Salwa Abid & Hassen Bacha & Imen Boussema-Ayed Received: 16 May 2015 / Accepted: 20 November 2015 / Published online: 9 January 2016 # University of Navarra 2016
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 coadministration 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.). H. Ferjani : A. Bouraoui : S. Abid : H. Bacha (*) : I. Boussema-Ayed Laboratory of Research on Biologically Compatible Compounds, Dental Medicine Faculty, 5019 Monastir, Tunisia e-mail: [email protected] A. Achour Department of Nephrology, Dialysis and Transplant, University Hospital of Sahloul, 4021 Sousse, Tunisia A. El Arem Laboratory of Bioresources, Biology Integrative and Valorization, Higher Institute of Biotechnology of Monastir, Avenue Tahar Hadded, BP 74, 5000 Monastir, Tunisia
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 coadministration MMF with TAC protect liver and kidney against TAC toxicity via an antioxidant process. Keywords Tacrolimus . Mycophenolate mofetil . Nephroprotection . Hepatoprotection . Antioxidant activity
Introduction Tacrolimus (TAC) is a macrolide compound isolated from Streptomyces tsukubaensis [30] with a potent immunosuppressive property that is effective in the prevention of rejection of a transplanted solid organ [42, 49]. The immunosuppressive property of TAC results from inhibition of calcineurin, a calcium- and calmodulin-dependent phosphatase [46]. Several adverse effects have been reported following TAC administration. Among its secondary effects are nephrotoxicity and hepatotoxicity that remain to be a serious problem [16, 45]. Indee
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