title: Protective effect of mycophenolate mofetil against nephrotoxicity and hepatotoxicity induced by tacrolimus in Wistar rats.
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.
authors.affiliation: Laboratory of Research on Biologically Compatible Compounds, Dental Medicine Faculty, 5019, Monastir, Tunisia.
authors.forename: Hanen
authors.initials: H
authors.lastname: Ferjani
authors.affiliation: Laboratory of Bioresources, Biology Integrative and Valorization, Higher Institute of Biotechnology of Monastir, Avenue Tahar Hadded, BP 74, 5000, Monastir, Tunisia.
authors.forename: Amira
authors.initials: A
authors.lastname: El Arem
authors.affiliation: Laboratory of Research on Biologically Compatible Compounds, Dental Medicine Faculty, 5019, Monastir, Tunisia.
authors.forename: Aicha
authors.initials: A
authors.lastname: Bouraoui
authors.affiliation: Department of Nephrology, Dialysis and Transplant, University Hospital of Sahloul, 4021, Sousse, Tunisia.
authors.forename: Abedellatif
authors.initials: A
authors.lastname: Achour
authors.affiliation: Laboratory of Research on Biologically Compatible Compounds, Dental Medicine Faculty, 5019, Monastir, Tunisia.
authors.forename: Salwa
authors.initials: S
authors.lastname: Abid
authors.affiliation: Laboratory of Research on Biologically Compatible Compounds, Dental Medicine Faculty, 5019, Monastir, Tunisia. hassen.bacha@fmdm.rnu.tn.
authors.forename: Hassen
authors.initials: H
authors.lastname: Bacha
authors.affiliation: Laboratory of Research on Biologically Compatible Compounds, Dental Medicine Faculty, 5019, Monastir, Tunisia.
authors.forename: Imen
authors.initials: I
authors.lastname: Boussema-Ayed
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D065095:Calcineurin Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009173:Mycophenolic Acid / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D050050:Protein Carbonylation / Q000187:drug effects; D011897:Random Allocation; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects* / Q000037:antagonists & inhibitors
chemical_list: D015415:Biomarkers; D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D020011:Protective Agents; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid; D016559:Tacrolimus
keywords: Antioxidant activity; Hepatoprotection; Mycophenolate mofetil; Nephroprotection; Tacrolimus