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Acta Biochimica et Biophysica Sinica Advance Access originally published online on March 18, 2009
Acta Biochimica et Biophysica Sinica 2009 41(4):301-308; doi:10.1093/abbs/gmp014
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© The Author 2009. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

Protective effects of DIDS against ethanol-induced gastric mucosal injury in rats

Wei Zhao, Feng Zhu, Weiwei Shen, Aifen Fu, Lin Zheng, Zhaowen Yan, Lingzi Zhao and Guohui Fu*

Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Institutes of Medical Sciences, Department of Pathology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China

* Correspondence address. Tel: +86-21-63846590-776601; E-mail: fuguhu{at}263.net


  Abstract

The compound 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) is an efficient anion exchanger inhibitor that can block the activities of anion exchanger 2 (AE2), which plays an indispensable role in gastric acid secretion. DIDS also has potent anti-oxidative and anti-apoptosis activities. This study aimed to investigate the effect of DIDS on ethanol-induced mucosal damage in rats and to evaluate the underlying mechanisms that mediate the action of the compound. The rats received 1 ml of absolute ethanol or saline orally. DIDS [50 mg/kg intravenous (i.v.)] was given 5 min before ethanol administration. Gastric lesions were evaluated macroscopically, microscopically, and electron microscopically at 60 min after ethanol challenge. Gastric myeloperoxidase (MPO) activity, malonyldialdehyde (MDA) level, prostaglandin E2 (PGE2) synthesis, and cyclooxygenase-2 (COX-2) expression were assessed. For the evaluation of the effect of DIDS on gastric acid secretion, histamine-stimulatory gastric acid secretion was examined with or without pretreatment of DIDS (50 mg/kg; i.v.). Ethanol-induced gastric lesions were characterized by increasing gastric MDA level, MPO activity, and COX-2 expression, and decreasing PGE2 synthesis. It was found that DIDS significantly reduced the extent of gastric mucosal damage and reversed tissue MDA level and MPO activity. DIDS further enhanced the expression of COX-2 and reversed the decrease of PGE2. Our results suggested that DIDS is beneficial in rat model of gastric injury through mechanisms that involve inhibiting inflammatory cell infiltration and lipid peroxidation and up-regulating the COX-2/PGE2 pathway.

Keywords    DIDS; gastric injury; MPO; MDA; COX-2; PGE2

Received: October 8, 2008; Accepted: February 16, 2009
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