Vascular mechanism in the formation of diclophenac induced gastrotoxicity: the association with the level of hydrogen sulfide

Abstract

Background: Non-steroid anti-inflammatory drugs (NSAIDs)-induced gastrotoxicity arises as a result of imbalance between vasodilator and vasoconstrictor bioregulators. The influence of deficiency and excess of hydrogen sulfide on vascular mechanisms in the formation of NSAIDs-induced gastrotoxicity was investigated. Material and methods: Male nonlinear rats underwent preconditioning with donor of H2S (NaHS) and inhibitor of its synthesis (propargilglycine). Diclophenac sodium was introduced orally (8 mg/kg). In homogenates of rats’ gastric mucosa was evaluated the activity of prostaglandin-H-synthase (PgH-synthase), NO-synthase, content of nitrites and nitrates, H2S and the activity of cystathionine-γ-lyase. In vitro H2S-induced relaxation of mesenteric arteries was measured. Results: Diclophenac sodium decreased cystathionine-γ-lyase enzyme activity, NO-synthase and PGH-synthase (by 17-24%), content of their H2S metabolites and nitrites/nitrates (by 20-22%) in gastric mucosa, and accompanied with the decrease of mesenteric artery sensitivity to vasodilatory action of H2S (EC50 increased to 27.5%). H2S deficiency – increases and excess of H2S – inhibits the negative influence of diclophenac on the production of vasoactive molecules and H2S-induced relaxation of mesenteric arteries. Conclusions: Excess of H2S in organism increases the content of vasoligating molecules and thus can prevent vascular disturbances caused by NSAIDs in rat stomach mucosa.