Summary 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 (IR) and intraperitoneal (IP) appli- cation of N(G)-nitro-L-arginine methyl ester (L-NAME), a non-specific nitric oxide synthase inhibitor, in experimen- tal acute colitis in the rats . Acute colitis was induced in rats by 2,4,6-trinitroben- zenesulfonic acid (TNBS) and ethanol. Twenty-eight rats were divided into four groups. L-NAME (50 mg/kg/day) was administered IP (Group 1) and IR (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 IR instead of TNBS. The presence of hyperemia, inflammation and ulcer was evaluated to score of macroscopic morphologic dam- age. The severity of colitis was assessed by microscopic criteria including ulceration, mucus cell depletion, crypt abscesses, inflammatory cysts, mucosal atrophy, edema, in- flammatory 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 IP and IR L-NAME treatment significantly re- duced serum and rectal tissue nitrite levels, but no effect on MPO activity and histologic damage score was observed. Under the present conditions we concluded IR and IP L- NAME treatment, applied at the dosage of 50 mg/kg/day, does not have any protective effect on the colonic injury. Exp Toxic Pathol 2003; 55: 271–276 URBAN & FISCHER http://www.elsevier-deutschland.de 0940-2993/03/55/04-271 $ 15.00/0 271 Department of Gastroenterology 1 , Pathology 2 , and Biochemistry 3 Osmangazi University Faculty of Medicine, Eskisehir, Turkey Effects of intrarectal and intraperitoneal N(G)-nitro-L-arginine methyl ester treatment in 2,4,6-Trinitrobenzenesulfonic acid induced colitis in rats ESER V ARDARELI 1 , EMINE DUNDAR 2 , KEMAL ANGIN 3 , TULAY SARICAM 1 , and MINE INAL 3 With 5 figures and 2 tables Received: June 20, 2003; Revised: August 11, 2003; Accepted: August 21, 2003 Address for correspondence: Dr. EMINE DUNDAR, Osmangazi Universitesi Tip Fakultesi Patoloji Anabilim Dali, 26480 Eskisehir, Turkey; Tel.: 90-222-2392979-4538, Fax: 90-222-2393772, e-mail: edundar_99@yahoo.com Key words: Nitric oxide; L-NAME; 2,4,6-Trinitrobenzenesulfonic Acid induced colitis; rats. Introduction Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation. Although the precise ae- tiology and pathogenesis of the disease remains to be elucidated, there has been increasing interest in the pathogenic role of the nitric oxide (NO) in IBD (KIMURA et al. 1997; LUNDBERG et al. 1994; RACHMILEWITZ et al. 1995; SINGER et al. 1996; MACNAUGHTON et al. 1998; MILLER et al. 1995). NO is formed from L-arginin by the enzyme nitric oxide synthase (NOS) and there are two major classes of NOS isoenzymes. Constitutive NOS (calcium depen- dent, cNOS) is present primarily in endothelial cells and neuronal cells. It produces a small amount of NO which acts as a vasodilatator and neurotransmittor. Inducible NOS (calcium-independent, iNOS) is present in various types of cells. iNOS produces much more NO and it’s production can be triggered by injury, inflammation and infection (MONCADA and HIGGS 1993). NO contributes to the modulation of several key physio- logical functions in the digestive system. It is showed that if NO is produced in small amounts it generally exerts benefi- cal effects in gastrointestinal tract, whereas production of high amounts of NO can be detrimental (WALLACE and MILLER 2000). Therefore, NO may have bipolar function. It has been identified both in the studies held on pa- tients with IBD and in experimental colitis models that iNOS is activated in the colon and the levels of citruline, nitrate and nitrite of the end metabolites of NO pathway