Abstract
The ability of leukotrienes derived from eicosapentaenoic acid were compared with counterpart leukotrienes derived from arachidonic acid in terms of their ability to affect susceptibility of the stomach to injury induced by a topical irritant and their ability to alter gastric blood flow. Intra-arterial infusion of leukotriene C4 (LTC4) and LTD4 (0.1-3 micrograms/kg/min for 5 min) produced dose-dependent increases in gastric mucosal damage induced by topically applied 20% ethanol, as assessed macroscopically, by changes in transmucosal potential difference and by measurement of efflux of protein into the gastric lumen. Similar doses of LTC5 or LTD5 did not produce significant changes in any of these three parameters, when compared with control rats receiving the vehicle. With a higher dose of LTC5 or LTD5 (5 micrograms/kg/min), significant damage was observed. LTC4 and LTD4 were also found to be more potent at reducing gastric blood flow than LTC5 and LTD5. These results demonstrate that the peptido-leukotrienes derived from eicosapentaenoic acid (LTC5 and LTD5) are on the order of five times less potent than the leukotrienes derived from arachidonic acid (LTC4 and LTD4), in terms of increasing the susceptibility of the gastric mucosa to damage and reducing gastric blood flow. These results may have important implications in terms of the hypothesis that fish oil diets may be protective or may accelerate healing in ulcerative diseases of the gastrointestinal tract.
Full Text
The Full Text of this article is available as a PDF (406.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
- Charleson S., Evans J. F., Zamboni R. J., Leblanc Y., Fitzsimmons B. J., Leveillé C., Dupuis P., Ford-Hutchinson A. W. Leukotriene B3, leukotriene B4 and leukotriene B5; binding to leukotriene B4 receptors on rat and human leukocyte membranes. Prostaglandins. 1986 Oct;32(4):503–516. doi: 10.1016/0090-6980(86)90033-x. [DOI] [PubMed] [Google Scholar]
- Faust T. W., Lee E., Redfern J. S., Feldman M. Effect of prostaglandin F3 alpha on gastric mucosal injury by ethanol in rats: comparison with prostaglandin F2 alpha. Prostaglandins. 1989 Apr;37(4):493–504. doi: 10.1016/0090-6980(89)90098-1. [DOI] [PubMed] [Google Scholar]
- Goldman D. W., Pickett W. C., Goetzl E. J. Human neutrophil chemotactic and degranulating activities of leukotriene B5 (LTB5) derived from eicosapentaenoic acid. Biochem Biophys Res Commun. 1983 Nov 30;117(1):282–288. doi: 10.1016/0006-291x(83)91572-3. [DOI] [PubMed] [Google Scholar]
- Hammarström S. Leukotriene C5: a slow reacting substance derived from eicosapentaenoic acid. J Biol Chem. 1980 Aug 10;255(15):7093–7094. [PubMed] [Google Scholar]
- Kiel J. W., Riedel G. L., DiResta G. R., Shepherd A. P. Gastric mucosal blood flow measured by laser-Doppler velocimetry. Am J Physiol. 1985 Oct;249(4 Pt 1):G539–G545. doi: 10.1152/ajpgi.1985.249.4.G539. [DOI] [PubMed] [Google Scholar]
- Pihan G., Rogers C., Szabo S. Vascular injury in acute gastric mucosal damage. Mediatory role of leukotrienes. Dig Dis Sci. 1988 May;33(5):625–632. doi: 10.1007/BF01798368. [DOI] [PubMed] [Google Scholar]
- Terano T., Salmon J. A., Moncada S. Biosynthesis and biological activity of leukotriene B5. Prostaglandins. 1984 Feb;27(2):217–232. doi: 10.1016/0090-6980(84)90075-3. [DOI] [PubMed] [Google Scholar]
- Wallace J. L., Morris G. P., Krausse E. J., Greaves S. E. Reduction by cytoprotective agents of ethanol-induced damage to the rat gastric mucosa: a correlated morphological and physiological study. Can J Physiol Pharmacol. 1982 Dec;60(12):1686–1699. doi: 10.1139/y82-247. [DOI] [PubMed] [Google Scholar]