1. Treatment with Mesna and n-3 polyunsaturated fatty acids ameliorates experimental ulcerative colitis in rats.
- Author
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Triantafyllidis I, Poutahidis T, Taitzoglou I, Kesisoglou I, Lazaridis C, and Botsios D
- Subjects
- Animals, Apoptosis drug effects, Biomarkers metabolism, Caspase 3 metabolism, Colitis, Ulcerative chemically induced, Colitis, Ulcerative metabolism, Colitis, Ulcerative pathology, Colon metabolism, Colon pathology, Cytoprotection, Dextran Sulfate, Disease Models, Animal, Intestinal Mucosa metabolism, Intestinal Mucosa pathology, Male, Nitric Oxide Synthase Type II metabolism, Oxidative Stress drug effects, Peroxidase metabolism, Rats, Wistar, Time Factors, Transcription Factor RelA metabolism, Antioxidants pharmacology, Colitis, Ulcerative prevention & control, Colon drug effects, Fatty Acids, Omega-3 pharmacology, Intestinal Mucosa drug effects, Mesna pharmacology
- Abstract
Oxidative damage is a central feature of ulcerative colitis. Here, we tested whether the antioxidant Mesna, when administered alone or in combination with n-3 polyunsaturated fatty acids (n-3 PUFAs), affects the outcome of dextran sodium sulphate (DSS)-induced ulcerative colitis in rats. After the induction of colitis, DSS-treated rats were further treated orally (p.o), intraperitoneally (i.p) or intrarectally (i.r) for either 7 or 14 days with Mesna, n-3 PUFAs or both. Rats were euthanized at the end of each treatment period. Clinical disease activity index was recorded throughout the experiment. At necropsy colorectal gross lesions were scored. Colitis was scored histologically, and the expression of myeloperoxidase (MPO), caspase-3, inducible nitric oxide synthase (iNOS) and nuclear factor κB (NF-κΒ) in colonic tissue was assessed by immunohistochemistry. Mesna alone was sufficient to significantly reduce colorectal tissue damage when administered orally or intraperitoneally. Orally coadministered n-3 PUFAs enhanced this effect, resulting in the significant suppression of DSS colitis after 7 days, and a remarkable recovery of colorectal mucosa was evident after 14 days of treatment. The amelioration of colon pathology co-existed with a significant decrease in MPO expression, overexpression of iNOS and reduction of nuclear NF-κB p65 in inflammatory cells, and the suppression of apoptosis in colonic epithelial cells. The simultaneous administration of Mesna and n-3 PUFAs is particularly effective in ameliorating DSS colitis in rats, by reducing oxidative stress, inflammation and apoptosis, probably through a mechanism that involves the inhibition of NF-κB and overexpression of iNOS., (© 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.)
- Published
- 2015
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