Protective effect and mechanism of manganese superoxide dismutase mimic on ulcerative colitis induced by trinitrobenzene sulfonic acid in rats / 中国临床药理学与治疗学

ABSTRACT

AIM: To investigate the effects of manganese superoxide dismutase mimic (MnSODm) on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) induced ulcerative colitis (UC) in rats and to probe into its underlying mechanism. METHODS: Wistar rats were randomly divided into blank group, model group, sulfasalazine (SASP, 500 mg/kg) group, and different doses of MnSODm (10, 20 and 40 mg/kg) groups. Ulcerative colitis was induced in rats by rectal administration of 100 mg/kg TNBS dissolved in 50% ethanol. Rats were killed after SASP and different doses of MnSODm treatment 7 days. The disease activity index (DAI) was recorded, and then the colonic injury and inflammation were assessed by the colon weight/length ratio and microscopic damage scores. The serum and colon tissues activities myeloperoxidase (MPO) were detected by biochemistry method. The activities of glutathione peroxidase (GSH-Px), inducible nitric oxide synthase (iNOS), and the levels of glutathione (GSH) and NO in colon tissues were also detected. The levels of TNF-α, IL-4 and IL-10 in the colon tissues were measure by ELISA. Western blot was undertaken to determine the phosphorylation levels of AKT and PI3K. RESULTS: Compared with the model group, the colonic weight/length ratios, microscopic damage scores and colon tissues and serum MPO activity were significantly decreased in MnSODm groups (P<0.05 or P<0.01). INOS, NO, TNF-α, PI3K, p-AKT levels in colon tissues were also significantly decreased in MnSODm treatment groups; while the activity of GSH-Px and the concentration of GSH, IL-4 and IL-10 obviously increased (P<0.05, P<0.01). CONCLUSION: MnSODm is protective against colitis via antioxidant activity and by inhibiting inflammatory mediators and then down-regulating PI3K/AKT signaling pathways.