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.
ABSTRACT
OBJECTIVE: To establish the method for determinating the activity of [poly(2-ethyl-2-oxazoline), PEOZ]-modified liposomes encapsulated superoxide dismutase (SOD) mimic (PEOZ-L-SOD). METHODS: PEOZ-L-SOD was prepared by film dispersion method, and the activities of the SOD mimic and PEOZ-L-SOD were determined by NBT-Illumination method. RESULTS: The fitted equation of the inhibition rate curve of the SOD mimic was IR%=33.4211nρ + 49.715 (r2=0.9992) and the IC50 was 1.0086 × 10-3 μmol · L-1; the fitted equation of the inhibition rate curve of PEOZ-L-SOD was IR%=33.5211nρ + 49.671 (r2=0.9991) and the IC50 was 1.0099 × 10-3 μmol · L-1. CONCLUSION: The NBT-Illumination method is simple, reliable, economic and practical, and can be used as an efficient method to determine the activity of SOD mimic liposomes. The experiment proves that the activity of SOD mimic did not change after it was encapsulated in the liposomes.