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Hydrogen peroxide-induced alterations in prostaglandin secretion in the rat colon in vitro

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Abstract

Although the specific cause(s) of inflammatory bowel diseases (IBD) has not been identified, one theory suggests ischemia as the early event that occurs in IBD and reperfusion causes sustained release of oxyradicals, leading to inflammation and ulceration. In this study, we have confirmed that H2O2 in the concentration seen during ischemia/reperfusion is primarily responsible for cellular membrane damage in the rat colonic fragments in vitro. Hydrogen peroxide caused a time and dose-dependent increase in 6-keto-PGF1α and TXB2 release. Hydrogen peroxide-stimulated 6-keto-PGF1α release was blocked (50%) by phospholipase A2 (PLA2) inhibitors quinacrine and dimethyleicosodienoic acid at 5 min. Hydrogen peroxide-stimulated 6-keto-PGF1α release was completely blocked by idomethacin, significantly blocked (69%) by nordihydroguiaretic acid, and completely blocked by catalase. superoxide dismutase and uric acid failed to inhibit H2O2-stimulated 6-keto-PGF1α release. Endogenous catalase inhibitors 3-aminotriazole and sodium azide further enhanced the release of 6-keto-PGF1α stimulated by H2O2 by 29% and 73%, respectively. Xanthine-xanthine oxidase also increased 6-keto-PGF1α release from the fragments by 110%. This release was not inhibited by superoxide dismutase and uric acid, but was completely inhibited by catalase. These studies suggest a direct effect of H2O2 on colonic fragments leading to submicroscopic cellular membrane damage and excess prostanoid production utilizing a PLA2/cyclooxygenase and catalase-sensitive pathway without the formation of toxic hydroxyl ions. The quick release of 6-keto-PGF1α also suggests an early manifestation of H2O2-induced damage in rat colonic fragments.

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Authors and Affiliations

  1. Division of Gastroenterology Krancer Center for Inflammatory Bowel Disease Research, Hahnemann University, Philadelphia, Pennsylvania

    S. N. S. Murthy, Christopher G. Cooney & Harris R. Clearfield

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  1. S. N. S. Murthy
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  3. Harris R. Clearfield
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Murthy, S.N.S., Cooney, C.G. & Clearfield, H.R. Hydrogen peroxide-induced alterations in prostaglandin secretion in the rat colon in vitro. Inflammation 14, 645–661 (1990). https://doi.org/10.1007/BF00916368

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