Effect of L-arginine on the course of experimental colitis.
OBJECTIVE
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.
Mañé
J
J
Research Unit, Pathology, Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
Fernández-Bañares
F
F
Ojanguren
I
I
Castellá
E
E
Bertrán
X
X
Bartolí
R
R
Alvarez
M
M
Gassull
M A
MA
D000208:Acute Disease; D000818:Animals; D001120:Arginine / Q000008:administration & dosage* / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000473:pathology*; D003094:Collagen / Q000096:biosynthesis; D003106:Colon / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D007249:Inflammation; D007413:Intestinal Mucosa / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D009569:Nitric Oxide; D003094:Collagen; D001120:Arginine