The role of the DDAH–ADMA pathway in the protective effect of resveratrol analog BTM-0512 on gastric mucosal injury

A recent study showed that resveratrol, a polyphenol found in many plant species, exerts dual effects on gastric mucosal injury. By using the model of ethanol-induced gastric mucosal injury in the present study, we explored the effect of trans-3,5,4′-trimethoxystilbene (BTM-0512), a novel analog of resveratrol, on gastric mucosal injury and the possible underlying mechanisms. Gastric mucosal injury in the rat was induced by oral administration of acidified ethanol. The gastric tissues were collected for determination of the gastric ulcer index, asymmetric dimethylarginine (ADMA) and nitric oxide (NO) contents, the activity of dimethylarginine dimethylaminohydrolase (DDAH) and superoxide anion (O2–) or hydroxyl radical (OH·) formation. The results showed that acute administration of ethanol significantly increased the gastric ulcer index concomitantly with the decrease in DDAH activity and NO content as well as the increase in ADMA content, effects that were reversed by pretreatment with BTM-0512 (100 mg/kg) or l-arginine (300 mg/kg). Administration of BTM-0512 did not show a significant effect on O2–or OH· formation. The results suggest that BTM-0512 could protect the gastric mucosa against ethanol-induced injury, which is mainly related to an increase in DDAH activity and subsequent decrease in ADMA content.