Oxidative and nitrosative stress damage induced by Tacrolimus in brain of rat: Protective effect of Mycophenolate mofetil

Tacrolimus (TAC) and mycophenolate mofetil (MMF) are used effectively to prevent immunologic rejection after solid-organ transplantation. Some immunosuppressive drugs contribute to the pathophysiology of cerebral injury. In this study, we investigate the efficacy of MMF against TAC induced neurotoxicity in the brains of rats. Statistical analyses showed that rats treated with TAC by oral gavage at a dose of 60 mg/kg b.w. caused an alteration of acetylcholinesterase (AChE) activity, a potential induction of oxidative/nitrosative stress mediated by an increase of malondialdehyde (MDA), protein carbonyls (P.C.) and a decrease of the nitric oxide (NO). In addition, TAC provoked significantly caspase-3 activity in brains of rats. A significant correlation between caspase-3 levels and oxidative/nitrosative markers was observed. However, the co-treatment with MMF at a dose of 50 mg/kg is able to restore the AChE activity and all stress markers and regulated apoptosis in brains. These data indicated that MMF plays a neuroprotective role in brain tissue damage.