Protective Effect of Taurine on Indomethacin-Induced Gastric Mucosal Injury
It has been suggested that oxygen-derived free radicals play an important role in the pathophysiology of acute gastric ulceration induced by NSAIDs and ischemia-reperfusion. Taurine is hypothesized to exert its protective effect on NSAIDs-induced gastric injury by its antioxidant properties. The protective effect of taurine on indomethacin-induced gastric mucosal lesion and its protective mechanism were investigated. Intragastric administration of 25 mg/kg of indomethacin induced hemorrhagic lesions on the glandular stomach in rats. Pretreatment with 0.25 or 0.5 g/kg of taurine one day before or for 3 days significantly reduced gastric lesion formation and inhibited the elevation of lipid peroxide level in gastric mucosa. Both resting and FMLP-induced luminol-dependent chemiluminescence of rat peritoneal neutrophils increased immediately after treatment with indomethacin. Taurine (5–20 mM) inhibited chemiluminescence of neutrophils activated by FMLP. Human neutrophils (polymorphonuclear leukocytes) adhered to the confluent monolayer of human umbilical vein endothelial cells (HUVEC) after coincubation with indomethacin. This neutrophil adhesion induced by indomethacin to HUVEC was prevented by taurine in a dose-dependent manner.
These results indicate that the protective effect of taurine against NSAIDs-induced gastric mucosal injury is due to its antioxidant effect, which inhibits lipid peroxidation and neutrophil activation.
KeywordsHuman Umbilical Vein Endothelial Cell Gastric Mucosal Injury Gastric Mucosal Lesion Gastric Mucosal Blood Flow Indomethacin Administration
Unable to display preview. Download preview PDF.
- 1.Aruoma, O.I., Halliwell, B., Hoey, B.M., and Butler, J. 1988, The antioxidant action of taurine, hypotaurine and their metabolic precursors, Biochem. J. 256:251–255.Google Scholar
- 6.Dahlgren, C. 1991, Effect of different inhibitors on the intracellularly and extracellularly generated chemiluminescence induced by formylmethionyl-leucyl-phenylalanine in polymorphonuclear leukocytes. Cellular response in the presence of mannitol, benzoate, taurine, indomethacin and NDGA, J.Biolum.Chemilum. 6:29–34.CrossRefGoogle Scholar
- 11.Kitahora, T. and Guth, P.H. 1987, Effect of aspirin plus hydrochloric acid on the gastric mucosal microcirculation, Gastroenterology, 93:810–817.Google Scholar
- 12.McGregor, P.E., Agrawal, D.K., and Edwards, J.D. 1994, Technique for assessment of leukocyte adherence to human umbilical vein endothelial cell monolayers, J.Pharm.Mol. 32:73–77.Google Scholar
- 17.Vaananen, P.M., Meddings, J.B., and Wallace, J.L. 1991, Role of oxygen-derived free radicals in indomethacin-induced gastric injury, Am.J.Physiol. 261:G470–G475.Google Scholar
- 19.Wallace, J.L., Keenan, CM., and Granger, D.N. 1990, Gastric ulceration induced by nonsteroidal anti-inflammatory drugs is a neutrophil-dependent process, J.Physiol. 259:G462–G467.Google Scholar
- 20.Wang, Q., Hyde, D.M., and Giri, S.N. 1992, Abatement of bleomycin-induced increases in vascular permeability, inflammatory cell infiltration, and fibrotic lesions in hamster lungs by combined treatment with taurine and niacin, Lab.Invest. 67:234–242.Google Scholar