Nitric oxide and acute phase proteins are involved in pathogenesis of mycophenolate mofetil-induced gastrointestinal disorders in rats

Abstract

This study was designed to clarify the molecular mechanism(s) of mycophenolate mofetil (MMF)- induced gastrointestinal (GI) disorders. Forty-two adult Wistar rats were assigned to 7 groups including control and test hosts. The control animals received normal saline and the test animals various doses of MMF (10, 20, or 40 mg/kg) for 14 days, or MMF, aspirin, or lipopolysaccharide as single high doses (40, 200, and 1 mg/kg, respectively). To evaluate the GI disorders, are determined body weight gain, serum level of alkaline phosphatase (ALP), nitric oxide (NO), and acute phase proteins (APP). Additionally, we measured the duodenal NO content and myeloperoxidase activity. MMF administration resulted in a significant (P < .05) body weight loss and elevation of serum levels of ALP and NO. The duodenal NO content increased in the test groups with the highest levels among the aspirin-treated cohort. The myeloperoxidase activity and the serum level of APP were elevated among MMF- and aspirin-treated animals. Histopathologic examinations showed villous atrophy and inflammatory cells infiltration among MMF-treated animals. Our data suggested that the MMF-induced GI disorders were likely related to local inflammatory reactions, which may be attributed to elevated NO and myeloperoxidase activities that result in pathological injuries. Moreover, the biochemical alterations and histopathologic injuries due to MMF administration were similar to aspirin-induced local disorders rather than to lipopolysaccharide-induced systemic damage.