The Effect of Nitric Oxide Synthases Inhibitors on Inflammatory Bowel Disease in a Rat Model

Background/Aims: Overexpression of nitric oxide (NO) has been implicated in the pathogenesis of experimental and clinical inflammatory bowel disease (IBD). NO is produced by two types of enzymes: constitutively expressed and inducible NO synthases (NOS). This study assessed N w -nitro-L-arginine methyl ester (L-NAME) and aminoguanidine (AMG), the most studied inhibitors of nitric oxide synthases, with regard to their effectiveness as modulators of inflammation in trinitrobenzene sulfonic acid (TNBS)-induced colitis in the rat. Materials and Methods: Colitis was induced in Wistar rats. The colitis was treated everyday for 10 days with L-NAME and AMG. To assess the severity of the colitis, clinical (body weight), hematological (hematocrit and erythrocytes sedimentation rate-ESR) and morphological (gross and microscopic) criteria were used. Results: The administration of both nitric oxide synthases inhibitors L-NAME and AMG proved to be beneficial in all the examined parameters compared with the control group. A statistically significant difference between the L-NAME and the AMG groups was observed only in macroscopic and histological grading. Conclusion: NOS inhibitors may be promising agents in preventing the onset, or mediating the symptoms, of inflammatory bowel disease. Over the last decade the pathophysiological role of nitric oxide (NO) in the pathogenesis of inflammatory bowel disease (IBD) has been well documented in both patients (1) and animal models with experimentally-induced colitis (2). Nitric oxide is synthesized by various cell types, via the so-called "L-arginine-NO pathway" (3) .The main catalyzing enzyme in this metabolic pathway (nitric oxide synthase- NOS) is present, in the gut, in two isoforms: the first, Ca 2+ - dependent isoform, is called constant NOS (c-NOS) and catalyses the production of minimal amounts of NO which are necessary for maintaining the physiological gut functions (motility, absorption and secretion); the second isoform is called inducible-NOS (i-NOS), is Ca 2+ -independent and, once stimulated, synthesizes excessive amounts of NO, leading to severe intestinal injury. This is considered to be a mechanism of major importance in the pathogenesis of colonic inflammation (4-6).