Aims: We investigated the effect of n–3 polyunsaturated fatty acids (PUFAs) on mucosal levels of leukotrienes (LTs) and lipid peroxide (LPO), and on mucosal microcirculation, in rats with experimental colitis induced by dextran sulfate sodium (DSS). Methods: We fed Wistar rats a perilla oil-enriched diet containing α-linolenic acid (63.2% of total fatty acids) with various doses of vitamin E for 4 weeks, with 4% DSS added to the drinking water during the last week. Control rats were fed a diet produced from soybean oil containing α-linolenic acid (5.1% of total fatty acids). Colonic mucosal blood flow was measured with a laser Doppler flowmeter. Results: The mucosal level of arachidonic acid was significantly lower and that of eicosapentaenoic acid was significantly higher in the experimental group. The mucosal level of LPO in the experimental group fed a trace or ordinary dose of vitamin E was significantly higher than that of the controls. The production of LTB4 and LTC4 from the colonic mucosa in the experimental group was significantly lower than that in controls. However, only the experimental group fed a vitamin E dose 4-fold higher than that given to the controls showed a significant increase in mucosal blood flow. Conclusion: These results suggest that n–3 PUFAs increase mucosal blood flow by inhibiting LT production when there is sufficient vitamin E to inhibit lipid peroxidation in rats with experimental colitis.

1.
Stenson WF, Cort D, Rodgers J, Burakoff R, DeSchryver-Kecskemeti K, Gramlich TL, Beeken W: Dietary supplementation with fish oil in ulcerative colitis. Ann Intern Med 1992;116:609–614.
[PubMed]
2.
Belluzzi A, Brignola C, Campieri M, Pera A, Boschi S, Miglioli M: Effect of enteric-coated fish-oil preparation on relapses in Crohn’s disease. N Engl J Med 1996;334:1557–1560.
[PubMed]
3.
Hawthorne AB, Daneshmend TK, Hawkey CJ, Belluzzi A, Holmes GKT, Malkinson C, Shaheen MZ, Wilars JE: Treatment of ulcerative colitis with fish oil supplementation: A prospective 12 month randomized controlled trial. Gut 1992;33:922–928.
[PubMed]
4.
Ikehata A, Hiwatashi N, Kinouchi Y, Yamazaki H, Kumagai Y, Ito K, Kayaba Y, Toyota T: Effect of intravenously infused eicosapentaenoic acid on the leukotriene generation in patients with active Crohn’s disease. Ann J Clin Nutr 1992;56:938–942.
5.
Kinsella JE: Dietary n–3 polyunsaturated fatty acids of fish oils, autoxidation ex vivo and peroxidation in vivo: Implications; in Friedman M (ed): Nutritional and Toxicological Consequences of Food Processing. New York, Plenum Press, 1991, pp 225–268.
6.
Sedghi S, Keshavarzian A, Klamut M, Eiznhamer D, Zarling E: Elevated breath ethane levels in active ulcerative colitis: Evidence for excessive lipid peroxidation. Am J Gastroenterol 1994;89:2217–2221.
[PubMed]
7.
Guslandi M, Polli D, Sorghi M, Tittobello A: Rectal blood flow in ulcerative colitis. Am J Gastroenterol 1995;90:579–580.
[PubMed]
8.
Tateishi S, Arima S, Futami K: Assessment of blood flow in the small intestine by laser Doppler flowmetry: Comparison of healthy small intestine and small intestine in Crohn’s disease. J Gastroenterol 1997;32:457–463.
[PubMed]
9.
Wallace JL, Mcknight GW, Keenan CM, Byles NIA, MacNaughton WK: Effects of leukotrienes on susceptibility of the rat stomach to damage and investigation of the mechanism of action. Gastroenterology 1990;98:1178–1186.
[PubMed]
10.
Takemura T, Yoshikawa T, Naito Y, Ueda S, Tanigawa T, Sugino S, Kondo M: Role of xanthine oxidase system and polymorphonuclear leukocytes in lipid peroxidation in compound 48/80-induced gastric mucosal injury in rats. Adv Exp Med Biol 1990;264:415–418.
[PubMed]
11.
Takizawa H, Sasakawa T, Nakazawa T, Boku S, Nomoto M, Yamashita A, Asakura H: Dynamics of immunocompetent cells in colitis mucosa induced by dextran sulfate in rats; in Tsuchiya M, Nagura H, Hibi T, Mori I (eds): Frontiers of Mucosal Immunology. Amsterdam, Excerpa Medica, 1991, vol 1, pp 853–854.
12.
Marotta F, Chui DH, Safran P, Rezakovic I, Zhong GG, Ideo G: Shark fin enriched diet prevents mucosal lipid abnormalities in experimental acute colitis. Digestion 1995;56:46–51.
[PubMed]
13.
Folch J, Lees M, Sloane Stanley GH: A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 1957;226:497–509.
14.
Chapkin RS, Haberstroh B, Liu T, Holub BJ: Characterization of the individual phospholipids and their fatty acids in serum and high-density lipoprotein of the renal patient on long-term maintenance hemodialysis. J Lab Clin Med 1983;101:726–735.
[PubMed]
15.
Ohkawa H, Ohnishi N, Yagi K: Assay for lipid peroxides for animal tissues by thiobarbituric acid reaction. Anal Biochem 1986;95:351–358.
16.
Shimizu T, Beijer E, Ryd W, Strandvik B: Leukotriene B4 and C4 generation by small intestinal mucosa in children with coeliac disease. Digestion 1994;55:239–242.
[PubMed]
17.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265–275.
[PubMed]
18.
Shepherd AP, Riedel GL: Continuous measurements of intestinal mucosal blood flow by laser-Doppler velocimetry. Am J Physiol 1982;242:G668–G672.
[PubMed]
19.
Böjrck S, Jennische E, Dahlström A, Ahlman H: Influence of topical rectal application of drugs on dextran sulfate-induced colitis in rats. Dig Dis Sci 1997;41:824–832.
20.
Samuelsson B, Dahlen S-E, Lindgren JA, Rouzer CA, Serhan CN: Leukotrienes and lipoxins: Structures, biosynthesis, and biological effects. Science 1987;237:1171–1176.
[PubMed]
21.
Sharon P, Stenson WF: Enhanced synthesis of leukotriene B4 by colonic mucosa in inflammatory bowel disease. Gastroenterology 1984;86:453–460.
[PubMed]
22.
Kim JH, Tagari P, Griffiths AM, Ford-Hutchinson A, Smith C, Sherman PM: Levels of peptidoleukotriene E4 are elevated in active Crohn’s disease. J Pediatr Gastroenterol Nutr 1995;20:403–407.
[PubMed]
23.
Shimizu T: The future potential of eicosanoids and their inhibitors in paediatric practice. Drugs 1998;56:169–176.
[PubMed]
24.
Shoda R, Matsueda K, Yamato S, Umeda N: Therapeutic efficacy of n–3 polyunsaturated fatty acid in experimental Crohn’s disease. J Gastroenterol 1995;30(suppl VIII):89–101.
25.
Inui K, Fukuta Y, Ikeda A, Kameda H, Kokubo Y, Sato M: The nutritional effect of α-linolenic acid-rich emulsion with total parenteral nutrition in a rat model with inflammatory bowel disease. Ann Nutr Metab 1996;40:227–233.
[PubMed]
26.
Krawisz JE, Sharon P, Stenson WF: Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment inflammation in rat and hamster models. Gastroenterology 1984;87:1344–1350.
[PubMed]
27.
Muggli R: Dietary fish oils increase the requirement for vitamin E in humans; in Chandra RK (ed): Health Effects of Fish Oils. St Johns, ARTS Press, 1989, pp 201–210.
28.
Ahn H, Lindhagen J, Lundgren O: Measurement of colonic blood flow with laser Doppler flowmetry. Scand J Gastroenterol 1986;21:871–880.
[PubMed]
29.
Sato N, Kamada T, Shichiri M, Kawano S, Abe H, Hagihara B: Measurement of hemoperfusion and oxygen sufficiency in gastric mucosa in vivo. Gastroenterology 1979;76:814–819.
[PubMed]
30.
Granger DN, Höllwarth ME, Parks DA: Ischemia-reperfusion injury: Role of oxygen-derived free radicals. Acta Physiol Scand 1986;126:47–63.
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