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 supplementation and L-Arg-free diets upon colonic inflammatory damage and fibrosis in experimental colitis. METHODS: Sprague-Dawley rats with trinitrobenzene sulphonic acid (TNBS)-induced 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 supplemented 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 experiment, 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 gain 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 high 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 latter it may result from both nitric oxide-mediated tissue damage and collagen deposition. Copyright 2001 Harcourt Publishers Ltd.
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 supplementation and L-Arg-free diets upon colonic inflammatory damage and fibrosis in experimental colitis. METHODS:Sprague-Dawley rats with trinitrobenzene sulphonic acid (TNBS)-induced 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 supplemented 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 experiment, 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 gain 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 high 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 latter it may result from both nitric oxide-mediated tissue damage and collagen deposition. Copyright 2001 Harcourt Publishers Ltd.
Authors: R C Dutra; M Cola; D F P Leite; A F Bento; R F Claudino; A F Z Nascimento; P C Leal; J B Calixto Journal: Br J Pharmacol Date: 2011-05 Impact factor: 8.739