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 ([O.sub.2-]) or hydroxyl radical (OHx) 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 [O.sub.2.sup.-] or OHx 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. Key words: trans-3,5,4'-trimethoxystilbene (BTM-0512), resveratrol, gastric ulcer, asymmetric dimethylarginine (ADMA), dimethylarginine dimethylaminohydrolase (DDAH). Une etude recente a montre que le resveratrol, un polyphenol trouve dans de nombreuses especes vegetales, exerce un double effet sur la lesion de la muqueuse gastrique. Dans la presente etude, nous avons utilise le modele de lesion induite par l'ethanol. pour examiner l'effet du trans-3,5,4'-trimethoxystilbene (BTM-0512), un nouvel analogue du resveratrol, sur la lesion de la muqueuse gastrique et les mecanismes sous-jacents potentiels. Nous avons induit le modele de lesion de la muqueuse gastrique chez le rat par l'administration orale d'ethanol acidifie, et nous avons preleve les tissues gastriques pour analyser l'indice d'ulcere gastrique, la teneur en dimethylarginine asymetrique (ADMA) et en monoxyde d'azote (NO), l'activite de la dimethylarginine dimethylaminohydrolase (DDAH) et la formation d'anion superoxyde ([O.sub.2-]) et de radical hydroxyl (OHx). Les resultats ont montre que l'administration aigue d'ethanol a significative ment augmente l'indice d'ulcere gastrique en meme temps qu'elle a diminue l'activite de la DDAH et la teneur en NO, et augmente les teneurs en ADMA, effets qui ont ete renverses par un pretraitement avec le BTM-0512 (100 mg/kg) ou la L-arginine (300 mg/kg). L'administration de BTM-0512 n'a pas eu d'effet significatif sur la formation d'[O.sub.2-] et de OHx. Les resultants donnent a penser que le BTM-0512 pourrait proteger la muqueuse gastrique contre la lesion induite par l'ethanol, qui est principalement associee a une augmentation de l'activite de la DDAH et une diminution de la teneur en ADMA. Mots-cles : trans-3,5,4'-trimethoxystilbene (BTM-0512), resveratrol, ulcere gastrique, dimethylarginine asymetrique (ADMA), dimethylarginine dimethylaminohydrolase (DDAH). [Traduit par la Redaction]
Introduction Gastric mucosal ulcer is a common gastrointestinal disease in humans. Despite intensive research, the pathogenesis underlying gastric mucosal injury is not fully understood. It has been shown that a [...]