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Cytorpotective effect of alpha-melanocyte stimulating hormone and met-enkephalin on murine model of inflammatory bowel disease

Objectives and Study: Met-enkephalin (MET) and alpha-melanocyte stimulating hormone (-MSH) are endogenous opioid peptides with cytokine properties. The therapeutic potential of -MSH on inflammatory bowel disease (IBD) has been demonstrated in a few studies, but the efficacy of MET and the -MSH+MET mixture on colonic lesions has not yet been tested. Methods: Colitis was induced in male Wistar rats by inracolonic adminisration of 2, 4, 6- trinitrobenzene sulphonic acid (TNBS). The peptides were given i.p. 1 h before the TNBS/40% ethanol enema. Five progressive doses of -MSH (0.25 - 4 mg/kg) and MET (0.625 - 10 mg/kg) ; and two doses of -MSH + MET mixtures (1mg/kg + 2.5 mg/kg and 1 mg/kg + 5 mg/kg) were tested. Animals were sacrificed after 72 h and area of mucosal lesions involving the distal 10 cm of colon was assessed in mm2 by means of image analysis software. Statistical analysis was performed with the ANOVA and subsequent post hoc analysis with Tukey HSD. Results: The results of measurements implicate a dose-related (U-shaped) modulatory effect of peptides on the tissue lesions induced by TNBS. The area of colonic damage was significantly reduced following pretreatment with a single dose of 1 mg/kg -MSH, as compared to control animals (p=0.022). Other doses of -MSH or any dose of MET did not have significant effects. Best cytoprotection was achieved by the mixture 1 mg/kg -MSH + 5 mg/kg MET (p=0.005 ; vs. control). Conclusion: This study confirms the pharmacologically relevant cytoprotection of - MSH on TNBS colitis in rats. The protective effect of the -MSH+MET mixture was even stronger, indicating that the peptides have additive effects. The doses correspond to the single daily human therapeutic doses of 1 mg - MSH and 5 mg of MET. These results are in line with others showing that the -MSH+MET mixture is effective in controlling inflammatory/immunological disorders (i.e. asthma, multiple sclerosis). So far, neither peptide exhibited toxicity or side effects when given in pharmacological doses. Therefore, the combination of -MSH and MET could be further investigated in experimental protocols for IBD.

Met-enkephalin; Alpha MSH; inflammatory bowel disease

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