title: Tacrolimus and mycophenolate mofetil associations: Induction of oxidative stress or antioxidant effect?
abstract: Gastrointestinal risk factors after organ transplantation are prevalent, due to the chronic use of immunosuppressant. The immunosuppressive drugs such as tacrolimus/mycophenolate mofetil (TAC/MMF) association are the most commonly used therapy. TAC and MMF have been implicated in gastrotoxicity, but their direct effects, alone and combined, on intestinal cells are not completely elucidated. This study investigated the effect of TAC and MMF alone and combined on human colon carcinoma cells. Our results demonstrated that TAC and MMF individually inhibit clearly cells proliferation, enhanced free radicals, lipid peroxidation production, induced DNA lesions and reduced mitochondrial membrane potential. In this study, we also showed that the two molecules TAC and MMF combined at high concentrations amplified the cell damage. Furthermore, the TAC (5 µM) prevented cell death induced by MMF (half maximal inhibitory concentration (IC(50))). Also, MMF (50 µM) induced cytoprotection in HCT116 cells against TAC (IC(50)) toxicity. Our findings provide additional evidence that oxidative damage is the major contribution of TAC and MMF combined toxicities. In fact, MMF and TAC exert a gastroprotective effect by modulating reactive oxygen species production. These data underscore the pleiotropic effect of TAC and MMF on HCT116 cells that play a preventive and critical role on intestinal function.
authors: Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Monastir, Tunisia.
authors: H
authors: H
authors: Ferjani
authors: Department of Nephrology, Dialysis and Transplant, University Hospital of Sahloul, Sousse, Tunisia.
authors: A
authors: A
authors: Achour
authors: Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Monastir, Tunisia hassen.bacha@fmdm.rnu.tn.
authors: H
authors: H
authors: Bacha
authors: Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Monastir, Tunisia.
authors: S
authors: S
authors: Abid
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D004347:Drug Interactions; D045325:HCT116 Cells; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D007166:Immunosuppressive Agents; D017382:Reactive Oxygen Species; D009173:Mycophenolic Acid; D016559:Tacrolimus
keywords: Tacrolimus; combination; free radicals; genotoxicity; lipid peroxidation; mycophenolate mofetil