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The aim of this study was to examine the effect of ACS14, a hydrogen sulfide (H 2 S)-releasing derivative of aspirin (Asp), on Asp-induced gastric injury. Gastric hemorrhagic lesions were induced by intragastric administration of Asp (200 mg/kg, suspended in 0.5% carboxymethyl cellulose solutions) in a volume of 1 ml/100 g body weight. ACS14 (1, 5 or 10 mg/kg) was given 30 min before the Asp administration. The total area of gastric erosions, H 2 S concentration and oxidative stress in gastric tissues were measured three hours after administration of Asp. Treatment with Asp (200 mg/kg), but not ACS14 (430 mg/kg, at equimolar doses to 200 mg/kg Asp), for 3 h significantly increased gastric mucosal injury. The damage caused by Asp was reversed by ACS14 at 1–10 mg/kg in a concentration-dependent manner. ACS14 abrogated Asp-induced upregulation of COX-2 expression, but had no effect on the reduced PGE 2  level. ACS14 reversed the decreased H 2 S concentrations and blood flow in the gastric tissue in Asp-treated rats. Moreover, ACS14 attenuated Asp-suppressed superoxide dismutase-1 (SOD-1) expression and GSH activity, suggesting that ACS14 may stimulate antioxidants in the gastric tissue. ACS14 also obviously inhibited Asp-induced upregulation of protein expression of oxidases including XOD, p47 phox  and p67 phox . In conclusion, ACS14 protects Asp induced gastric mucosal injury by inhibiting oxidative stress in the gastric tissue.

H(2)S-Releasing Aspirin Protects against Aspirin-Induced Gastric Injury via Reducing Oxidative Stress