Abstract
The aim of this study was to examine the effect of ACS14, a hydrogen sulfide (H2S)-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, H2S 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 PGE2 level. ACS14 reversed the decreased H2S 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, p47phox and p67phox. In conclusion, ACS14 protects Asp induced gastric mucosal injury by inhibiting oxidative stress in the gastric tissue.
Highlights
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed drugs due to their high efficacy in reducing of pain, fever, inflammation and protection against stroke and myocardial infarction [1]
We found that intragastric administration of ACS14 at 430 mg/kg did not cause any damage in the gastric mucosa
Asp at 200 mg/kg induced severe mucosal damage. These data suggest that H2S released from ACS14 may protect against Asp-induced gastric damage (Fig. 1)
Summary
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed drugs due to their high efficacy in reducing of pain, fever, inflammation and protection against stroke and myocardial infarction [1] Their clinical use is commonly associated with the occurrence of adverse effects at the level of digestive tract, ranging from dyspeptic symptoms, gastrointestinal erosions and peptic ulcers to more serious complications, such as overt bleeding or perforation [2]. To overcome the adverse effects related to NSAID-induced gastrointestinal toxicity, different therapeutic strategies have been evaluated [4,5,6] This may include reducing the risk of gastrointestinal damage induced by NSAIDs and enhancing the protective function of the gastric mucosa. H2S and H2S-releasing molecules are able to enhance intracellular antioxidant activities by means of several mechanisms, including stimulation of glutathione and induction of the antioxidant and tissue protective protein heme oxygenase-1 [12,13,14]
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