Dietary manipulation in experimental inflammatory bowel disease.
Eicosanoids are major mediators of defensive and inflammatory processes of the gut mucosa. The activity of the eicosanoid system is modulated by neural and hormonal pathways, but local factors acting within the gastrointestinal lumen may also be involved. We have studied the influence of dietary fatty acids on eicosanoid synthesis by the gastrointestinal mucosa. Since omega-3 fatty acids compete with the omega-6 as precursors of eicosanoid synthesis, we compared the effects of dietary supplementation with either sunflower or cod liver oil as sources of omega-6 or omega-3 fatty acids, respectively. Rats fed with the cod-liver-oil-supplemented diet for four weeks showed high omega-3 and low omega-6 plasma fatty acid levels compared to rats fed with the sunflower oil diet. Synthesis of arachidonic-acid-derived eicosanoids (6-keto-PGF1 alpha, PGE2, TXB2, LTB4, and LTC4) by gastric and intestinal mucosa was found to be lower in the cod liver group as compared to the sunflower group. However, significant generation of eicosapentaenoic-acid-derived eicosanoids (PGE3 and LTC5) was observed only in the cod liver group. We used the (trinitrobenzenesulphonic acid) TNBS model of inflammatory colitis to test the effect of the dietary fat on the development of inflammatory lesions of the bowel. A single intracolonic instillation of the hapten TNBS dissolved in 10% ethanol induces chronic granulomatous lesions of the colonic mucosa that persist for up to 8 weeks. Luminal release of eicosanoid mediators, as measured by intracolonic dialysis, was lower in the cod liver group than in the sunflower group, particularly during the chronic stage of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Guarner
F
F
Digestive System Research Unit, Hospital Vall d'Hebron, Barcelona, Spain.
Vilaseca
J
J
Malagelada
J R
JR
D000818:Animals; D016718:Arachidonic Acid / Q000096:biosynthesis; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000178:diet therapy / Q000378:metabolism*; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage* / Q000494:pharmacology; D015777:Eicosanoids / Q000096:biosynthesis*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014302:Trinitrobenzenesulfonic Acid
D004042:Dietary Fats, Unsaturated; D015777:Eicosanoids; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D016718:Arachidonic Acid; D014302:Trinitrobenzenesulfonic Acid