Effects of n-3 polyunsaturated fatty acids on indomethacin-induced changes in eicosanoid production and blood flow in the gastric mucosa of rats.
We investigated the effects of n-3 polyunsaturated fatty acids (PUFAs) on non-steroidal anti-inflammatory drug (NSAID)-induced changes in microcirculation and eicosanoid production in the gastrointestinal mucosa. We measured gastric mucosal blood flow using laser Doppler flowmetry, assessed the fatty acid composition in the mucosal phospholipids, and quantified the production of prostaglandin E2 (PGE2), leukotriene B4, and leukotriene C4 (LTB4 and C4) from the mucosa with the stimulation of calcium ionophore 20 min after an injection of indomethacin or vehicle in rats fed a diet containing different compositions of alpha-linolenic acid. Four weeks after the initiation of the test diet the arachidonic acid level in gastric mucosal phospholipids was significantly lower in the perilla group than in the other three groups. Conversely, alpha-linolenic acid and eicosapentaenoic acid (EPA) were significantly higher in the perilla group than in the other three groups. The percent of gastric mucosal blood flow in the three groups administered indomethacin were significantly lower than that in the control group injected with vehicle alone. The percent of gastric mucosal blood flow in the perilla group was significantly higher than that in the corn group. LTB4 and LTC4 production from the gastric mucosa in the soybean and corn groups were significantly higher than those in the control group, and the LTC4 production in the perilla group was significantly lower than that in the corn group. There were no significant differences in PGE2 production among the four groups. Our results suggest that alpha-linolenic acid affectively suppressed the indomethacin-induced decreases in gastric mucosal blood flow by increasing EPA and decreasing the levels of arachidonic acid and LTC4 in the gastric mucosa.
Shimizu
T
T
Department of Pediatrics, School of Medicine, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. tsimizut@aol.com
Suzuki
M
M
Lee
T
T
Igarashi
J
J
Kaneko
K
K
Yamashiro
Y
Y
D000818:Animals; D016718:Arachidonic Acid / Q000032:analysis / Q000494:pharmacology; D015232:Dinoprostone / Q000032:analysis / Q000096:biosynthesis; D015777:Eicosanoids / Q000032:analysis / Q000096:biosynthesis*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000032:analysis / Q000096:biosynthesis; D017997:Leukotriene C4 / Q000032:analysis / Q000096:biosynthesis; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects*
D015777:Eicosanoids; D005231:Fatty Acids, Unsaturated; D007975:Leukotriene B4; D016718:Arachidonic Acid; D017997:Leukotriene C4; D015232:Dinoprostone; D007213:Indomethacin