Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2005; 11(47): 7450-7456
Published online Dec 21, 2005. doi: 10.3748/wjg.v11.i47.7450
Increased susceptibility of ethanol-treated gastric mucosa to naproxen and its inhibition by DA-9601, an Artemisia asiatica extract
Tae Young Oh, Gook Jun Ahn, Seul Min Choi, Byoung Ok Ahn, Won Bae Kim
Tae Young Oh, Gook Jun Ahn, Seul Min Choi, Byoung Ok Ahn, Won Bae Kim, Research Laboratories, Dong-A Pharm. Co., Ltd., 47-5, Sanggal, Kiheung, Yongin, Kyunggi, 449-905, South Korea
Author contributions: All authors contributed equally to the work.
Supported by the National Ministry of Health and Welfare
Correspondence to: Gook Jun Ahn, Research Laboratories, Dong-A Pharm. Co., Ltd., 47-5, Sanggal, Kiheung, Yongin, Kyunggi, 449-905, South Korea. ahnsnu2@donga.co.kr
Telephone: +82-31-280-1359 Fax: +82-31-282-8564
Received: April 7, 2005
Revised: July 1, 2005
Accepted: July 5, 2005
Published online: December 21, 2005
Abstract

AIM: 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.

CONCLUSION: 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.

Keywords: DA-9601; Alcohol; Naproxen; Gastric damage; Malondialdehyde; Prostaglandin E2; Glutathione; Myeloperoxidase; NSAIDs