title: Treatment with Mesna and n-3 polyunsaturated fatty acids ameliorates experimental ulcerative colitis in rats.
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.
authors: Department of Surgery, Veria General Hospital, Veria, Greece.
authors: Ioannis
authors: I
authors: Triantafyllidis
authors: Laboratory of Pathology, Faculty of Health Sciences, School of Veterinary Medicine, Aristotle University, Thessaloniki, Greece.
authors: Theofilos
authors: T
authors: Poutahidis
authors: Laboratory of Physiology, Faculty of Health Sciences, School of Veterinary Medicine, Aristotle University, Thessaloniki, Greece.
authors: Ioannis
authors: I
authors: Taitzoglou
authors: 3rd Department of Surgery, AHEPA University Hospital, Faculty of Health Sciences, School of Medicine, Aristotle University, Thessaloniki, Greece.
authors: Isaak
authors: I
authors: Kesisoglou
authors: 4th Department of Surgery, Papanikolaou University Hospital, Faculty of Health Sciences, School of Medicine, Aristotle University, Thessaloniki, Greece.
authors: Charalampos
authors: C
authors: Lazaridis
authors: 4th Department of Surgery, Papanikolaou University Hospital, Faculty of Health Sciences, School of Medicine, Aristotle University, Thessaloniki, Greece.
authors: Dimitrios
authors: D
authors: Botsios
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019610:Cytoprotection; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D015080:Mesna / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D017208:Rats, Wistar; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D015525:Fatty Acids, Omega-3; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D016264:Dextran Sulfate; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C505410:Casp3 protein, rat; D053148:Caspase 3; D015080:Mesna
keywords: NF-κΒ; dextran sodium sulphate; iNOS; mesna; n-3 PUFAs; ulcerative colitis