Effects of intrarectal and intraperitoneal N(G)-nitro-L-arginine methyl ester treatment in 2,4,6-trinitrobenzenesulfonic acid induced colitis in rats.
Inflammatory bowel disease (IBD) has been associated with an increased generation of nitric oxide (NO). Different authors have shown that NO in IBD can be either harmful or protective. The aim of this study was to investigate the efficiency of intrarectal (i.r.) and intraperitoneal (i.p.) application of N(G)-nitro-L-arginine methyl ester (L-NAME), a non-specific nitric oxide synthase inhibitor, in experimental acute colitis in the rats. Acute colitis was induced in rats by 2,4,6-trinitrobenzenesulfonic acid (TNBS) and ethanol. Twenty-eight rats were divided into four groups. L-NAME (50 mg/kg/day) was administered i.p. (Group 1) and i.r. (Group 2) for 7 days following the day when colitis was induced. Group 3 rats were not given any treatment after induction of colitis. Control group rats were given saline solution i.r. instead of TNBS. The presence of hyperemia, inflammation and ulcer was evaluated to score of macroscopic morphologic damage. The severity of colitis was assessed by microscopic criteria including ulceration, mucus cell depletion, crypt abscesses, inflammatory cysts, mucosal atrophy, edema, inflammatory cell infiltration, and vascular dilatation. Rectal tissue myeloperoxidase (MPO) activity and serum-rectal tissue nitrite levels were measured. Serum and rectal tissue nitrite levels increased in Group 3 rats. Both i.p. and i.r. L-NAME treatment significantly reduced serum and rectal tissue nitrite levels, but no effect on MPO activity and histologic damage score was observed. Under the present conditions we concluded i.r. and i.p. L-NAME treatment, applied at the dosage of 50 mg/kg/day, does not have any protective effect on the colonic injury.
Vardareli
Eser
E
Department of Gastroenterology, Osmangazi University Faculty of Medicine, Eskisehir, Turkey.
Dundar
Emine
E
Angin
Kemal
K
Saricam
Tulay
T
Inal
Mine
M
D000208:Acute Disease; D000285:Administration, Rectal; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000431:Ethanol / Q000633:toxicity; D007274:Injections, Intraperitoneal; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000627:therapeutic use*; D009573:Nitrites / Q000097:blood / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012007:Rectum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
D004791:Enzyme Inhibitors; D009573:Nitrites; D000431:Ethanol; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D019331:NG-Nitroarginine Methyl Ester