Silymarin attenuates mycophenolate mofetil-induced duodenal disorders in rats.

Abstract

The protective effect of silymarin (SMN) on mycophenolate mofetil (MMF)-induced duodenal disorders was investigated. Forty-two Wistar rats were assigned to seven groups including control and test groups. The control animals received saline and the test animals were treated with MMF (30 mg/kg, orally) and saline, MMF and SMN (25, 50, and 100 mg/kg, orally), MMF and Celecoxib (CLX, 50 mg/kg, orally), and MMF and SMN plus CLX for 14 consecutive days. The antioxidant status and myeloperoxidase activity were determined and the histopathological examinations on duodenal section also were performed. Biochemical analyses revealed that SMN and CLX individually and in combination therapy could reduce the MMF-increased nitric oxide (NO) content, myeloperoxidase (MPA) activity, and malondialdehyde (MDA) level, while the MMF-reduced level of total thiol molecules (TTM) was increased significantly (p<0.05) by given compounds. Concurrent administration of SMN and CLX resulted in a synergistic effect on the reduction of MDA level and MPO activity. SMN and CLX were able to improve the MMF-induced histopathological damages including the villus atrophy and inflammatory cells infiltration. Our data suggest that the MMF-induced duodenal disorders may attribute to the elevated NO and MDA levels and myeloperoxidase activity that resulted in pathological injuries. Moreover, the biochemical alterations and histopathological injuries due to MMF administration were reduced by SMN alone or in combination with CLX indicating its protective effect.