Circadian variation in intestine toxicity of Mycophenolate mofetil in rats: an experimental and histopathologic study

Mycophenolate mofetil (MMF) as an immunosuppressive agent is used to prevent graft rejection. One of the adverse effects of long time administration of MMF is the gastrointestinal (GI) disorder, which has been associated with multiple histological features. There is little data in the literature describing the histological effects of MMF. This histopathological study investigates whether the MMF intestinal toxicity varied according to the circadian dosing-time in rats. MMF (300 mg/kg) was acutely administered by i.p. route in rats at four different circadian stages (1, 7, 13, and 19 hours after light onset, HALO). Histopathological examinations on intestine sections were performed. The results showed that the intestinal toxicity induced by MMF was time related in rats. A severe toxicity in the duodenum jejunum and colon was observed when the drug was administered at 7 HALO compared to controls and to other circadian times. This toxicity appeared in the form of villous and Lieberkühn gland atrophy and nodular inflammation. The obtained data indicate that the maximum of intestinal toxicity is observed when MMF was injected in the middle of the light-rest span of rats.