Tacrolimus and mycophenolate mofetil associations: Induction of oxidative stress or antioxidant effect?

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 (IC50)). Also, MMF (50 µM) induced cytoprotection in HCT116 cells against TAC (IC50) ...