Inhibition of hydrogen sulfide generation contributes to gastric injury caused by anti-inflammatory nonsteroidal drugs

Abstract

Background & Aims: Hydrogen sulfide (H2S), an endogenous gaseous mediator that causes vasodilation, is generated in mammalian tissues by cystathionine β-synthase (CBS) and cystathionine-γ-lyase (CSE). Here, we have investigated the role of H2S in a rodent model of nonsteroidal anti-inflammatory drug (NSAID) gastropathy. Methods: Rats were given acetyl salycilic acid (ASA) or an NSAID alone or in combination with NaHS, an H2S donor, and killed 3 hours later. Gastric blood flow was measured by laser-Doppler flowmetry, whereas intravital microscopy was used to quantify adhesion of leukocytes to mesenteric postcapillary endothelium. Results: At a dose of 100 μmol/kg, NaHS attenuated by 60%-70% the gastric mucosal injury, and tumor necrosis factor (TNF)-α, intercellular adhesion molecule (ICAM)-1, and lymphocyte function-associated antigen (LFA)-1 mRNA up-regulation induced by NSAIDs (P < .05) NaHS administration prevented the associated reduction of gastric mucosal blood flow (P