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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. Une étude récente a montré que le resvératrol, un polyphénol trouvé dans de nombreuses espèces végétales, exerce un double effet sur la lésion de la muqueuse gastrique. Dans la présente étude, nous avons utilisé le modèle de lésion induite par l’éthanol, pour examiner l’effet du trans-3,5,4′-triméthoxystilbène (BTM-0512), un nouvel analogue du resvératrol, sur la lésion de la muqueuse gastrique et les mécanismes sous-jacents potentiels. Nous avons induit le modèle de lésion de la muqueuse gastrique chez le rat par l’administration orale d’éthanol acidifié, et nous avons prélevé les tissus gastriques pour analyser l’indice d’ulcère gastrique, la teneur en diméthylarginine asymétrique (ADMA) et en monoxyde d’azote (NO), l’activité de la diméthylarginine diméthylaminohydrolase (DDAH) et la formation d’anion superoxyde (O2-) et de radical hydroxyl (OH·). Les résultats ont montré que l’administration aiguë d’éthanol a significativement augmenté l’indice d’ulcère gastrique en même temps qu’elle a diminué l’activité de la DDAH et la teneur en NO, et augmenté les teneurs en ADMA, effets qui ont été renversés par un prétraitement 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’O2- et de OH·. Les résultats donnent à penser que le BTM-0512 pourrait protéger la muqueuse gastrique contre la lésion induite par l’éthanol, qui est principalement associée à une augmentation de l’activité de la DDAH et une diminution de la teneur en ADMA. [ABSTRACT FROM AUTHOR]

Our recent study has shown that asymmetric dimethylarginine (ADMA) plays an important role in facilitating gastric mucosal injury by multiple factors. To explore whether the protection of rutaecarpine against gastric mucosal injury is related to reduction of ADMA content, a model of ethanol-induced gastric mucosal injury in rats was selected for this study. The ulcer index, the content of ADMA and NO, and the activity of dimethylarginine dimethylaminohydrolase (DDAH) in gastric tissues were measured in vivo after pretreatment with rutaecarpine. The in vitro effect of rutaecarpine on the release of calcitonin gene-related peptide (CGRP) and NO from isolated gastric tissues was also determined. The results showed that ethanol significantly increased the ulcer index, decreased the DDAH activity and the NO level, and elevated the ADMA level, which was attenuated by pretreatment with rutaecarpine (0.6 mg/kg or 1.2 mg/kg). In the isolated gastric tissues, rutaecarpine significantly increased the release of both CGRP and NO; the release of NO, but not CGRP, was abolished in the presence of l-NAME (10-4 mol/L). The present results suggest that rutaecarpine protects the gastric mucosa against injury induced by ethanol and that the gastroprotection of rutaecarpine is related to reduction of ADMA levels through stimulating the release of CGRP. [ABSTRACT FROM AUTHOR]