title: Beneficial effects of mycophenolate mofetil on cardiotoxicity induced by tacrolimus in wistar rats.
abstract: The immunosuppressive drug tacrolimus (TAC) is used clinically to reduce the rejection rate in transplant patients. TAC has contributed to an increased prevalence of cardiovascular disease in patients receiving solid organ transplantation. Mycophenolate mofetil (MMF), a potent inhibitor of de novo purine synthesis, is known to prevent ongoing rejection in combination with TAC. In the present study, we investigated the antioxidant and antigenotoxic effect of MMF on TAC-induced cardiotoxicity in rats. Oral administration of TAC at 2.4, 24, and 60 mg/kg b.w. corresponding, respectively, to 1, 10, and 25% of LD50for 24 h caused cardiac toxicity in a dose-dependant manner. TAC increased significantly DNA damage level in hearts of treated rats. Furthermore, it increased malondialdehyde (MDA) and protein carbonyl (PC) levels and decreased catalase (CAT) and superoxide dismutase (SOD) activities. The oral administration of MMF at 50 mg/kg b.w. simultaneously with TAC at 60 mg/kg b.w. proved a significant cardiac protection by decreasing DNA damage, MDA, and PC levels, and by increasing the antioxidant activities of CAT and SOD. Thus, our study showed, for the first time, the protective effect of MMF against cardiac toxicity induced by TAC. This protective effect was mediated via an antioxidant process.
authors.affiliation: 1 Laboratory of Research on Biologically Compatible Compounds, Dental Medicine Faculty, University of Monastir, 5019 Monastir, Tunisia.
authors.forename: Hanen
authors.initials: H
authors.lastname: Ferjani
authors.affiliation: 1 Laboratory of Research on Biologically Compatible Compounds, Dental Medicine Faculty, University of Monastir, 5019 Monastir, Tunisia.
authors.forename: Rim
authors.initials: R
authors.lastname: Timoumi
authors.affiliation: 1 Laboratory of Research on Biologically Compatible Compounds, Dental Medicine Faculty, University of Monastir, 5019 Monastir, Tunisia.
authors.forename: Ines
authors.initials: I
authors.lastname: Amara
authors.affiliation: 1 Laboratory of Research on Biologically Compatible Compounds, Dental Medicine Faculty, University of Monastir, 5019 Monastir, Tunisia.
authors.forename: Salwa
authors.initials: S
authors.lastname: Abid
authors.affiliation: 2 Department of Nephrology, Dialysis and Transplant, University Hospital of Sahloul, 4021 Sousse, Tunisia.
authors.forename: Abedellatif
authors.initials: A
authors.lastname: Achour
authors.affiliation: 1 Laboratory of Research on Biologically Compatible Compounds, Dental Medicine Faculty, University of Monastir, 5019 Monastir, Tunisia.
authors.forename: Hassen
authors.initials: H
authors.lastname: Bacha
authors.affiliation: 1 Laboratory of Research on Biologically Compatible Compounds, Dental Medicine Faculty, University of Monastir, 5019 Monastir, Tunisia.
authors.forename: Imen
authors.initials: I
authors.lastname: Boussema-Ayed
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D066126:Cardiotoxicity / Q000188:drug therapy; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000188:drug therapy*; D002374:Catalase / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D006084:Graft Rejection / Q000517:prevention & control; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009173:Mycophenolic Acid / Q000627:therapeutic use*; D016377:Organ Transplantation / Q000009:adverse effects; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D016559:Tacrolimus / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; D009173:Mycophenolic Acid; D016559:Tacrolimus
keywords: Tacrolimus; antigenotoxic propriety; antioxidant effect; cardiotoxicity; mycophenolate mofetil; rats