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.
Li
Li
L
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, P.R. China.
Luo
Xiu-Ju
XJ
Liu
Ying-Zi
YZ
Zhang
Yi-Shuai
YS
Yuan
Qiong
Q
Tan
Na
N
Xiang
Da-Xiong
DX
Peng
Jun
J
D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity; D017665:Hydroxyl Radical / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D013481:Superoxides / Q000378:metabolism
C497286:3,4',5-trimethoxystilbene; D000897:Anti-Ulcer Agents; D013267:Stilbenes; D013481:Superoxides; D009569:Nitric Oxide; D017665:Hydroxyl Radical; D000431:Ethanol; C018524:N,N-dimethylarginine; D001120:Arginine; D000581:Amidohydrolases; C059999:dimethylargininase; D000077185:Resveratrol