Effect of L-arginine on the course of experimental colitis

Background and aims: L-Arg is the substrate for nitric oxide, and also for L-ornithine which, in turn, is the precursor for the synthesis of collagen and polyamines. By these different metabolic pathways, L-Arg is involved in the mechanisms of inflammation, tissue repair and fibrosis. Thus, the aim of this study was to assess the effect of both different amounts of L-Arg s upplementation and L-Arg-free diets upon colonic inflammatory damage and fi brosis in experimental colitis. Methods: Sprague-Dawley rats with trinitrobenzene sulphonic acid (TNBS)-ind uced colitis received increasing doses of L-Arg (30,100, 500 mg/day), or D- Arg (500 mg/day). In a second experiment, two L-Arg-free diets (one supplem ented with L-Gly) were compared to a L-Arg diet. Nitrite/nitrate release in the lumen of the colon and colonic damage were evaluated. In the first exp eriment, tissue collagen levels and colonic mucosal proliferation were also assessed. Results: In the acute phase of colitis, intracolonic nitrite/nitrate levels were significantly higher in the 100 and 500 mg supplemented L-Arg groups than in D-Arg group. However, only rats treated with 500 mg of L-Arg showed moderately higher inflammatory and fibrosis colonic scores than the D-Arg treated rats. There was no significant influence of L-Arg-free diets on the course of TNBS-induced colitis. However, L-Arg diet accelerated weight gai n both pre- and post-TNBS. Conclusions: These results suggest that normal amounts of L-Arg in the diet are not harmful, whereas both absence of L-Arg or supplementation with hig h doses of this amino acid may be deleterious. In the former this might be due to a decrease of nitrogen retention in injured rats, whereas in the lat ter it may result from both nitric oxide-mediated tissue damage and collage n deposition. (C) 2001 Harcourt Publishers Ltd.