Increased susceptibility of ethanol-treated gastric mucosa to naproxen and its inhibition by DA-9601, an Artemisia asiatica extract.
OBJECTIVE
To examine the effect of DA-9601, a new gastroprotective agent, on the vulnerability of ethanol-treated rat's stomach to naproxen (NAP).


METHODS
Male Sprague-Dawley rats were pretreated with 1 mL of 50% ethanol twice a day for 5 d and then NAP (50 mg/kg) was administered. DA-9601 was administered 1 h before NAP. Four hours after NAP, the rats were killed to examine gross injury index (mm2), histologic change and to determine mucosal levels of malondialdehyde (MDA), prostaglandin E2 (PGE2), glutathione (GSH) and myeloperoxidase (MPO).


RESULTS
Pretreatment of ethanol significantly increased NAP-induced gastric lesions, as well as an increase in MDA and MPO. On the contrary, mucosal PGE2 and GSH contents were decreased dramatically by ethanol pretreatment, which were aggravated by NAP. DA-9601 significantly reduced NAP-induced gastric injury grossly and microscopically, regardless of pretreatment with ethanol. DA-9601 preserved, or rather, increased mucosal PGE2 and GSH in NAP-treated rats (P<0.05), with reduction in mucosal MDA and MPO levels.


CONCLUSIONS
These results suggest that repeated alcohol consumption renders gastric mucosa more susceptible to NSAIDs though, at least in part, reduction of endogenous cytoprotectants including PGE2 and GSH, and increase in MPO activation, and that DA-9601, a new gastroprotectant, can reduce the increased vulnerability of ethanol consumers to NSAIDs-induced gastric damage via the mechanism in which PGE2 and GSH are involved.
Oh
Tae Young
TY
Research Laboratories, Dong-A Pharm. Co., Ltd., 47-5, Sanggal, Kiheung, Yongin, Kyunggi, 449-905, South Korea.
Ahn
Gook Jun
GJ
Choi
Seul Min
SM
Ahn
Byoung Ok
BO
Kim
Won Bae
WB
D000428:Alcohol Drinking; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D019306:Artemisia; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D005756:Gastritis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009288:Naproxen / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002492:Central Nervous System Depressants; C116959:DA 9601; D010936:Plant Extracts; D000431:Ethanol; D009288:Naproxen