Protective effects of DIDS against ethanol-induced gastric mucosal injury in rats.
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 antiapoptosis 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.
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.
Wei
W
Zhao
Feng
F
Zhu
Weiwei
W
Shen
Aifen
A
Fu
Lin
L
Zheng
Zhaowen
Z
Yan
Lingzi
L
Zhao
Guohui
G
Fu
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000633:toxicity; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007124:Immunoenzyme Techniques / Q000379:methods; D007150:Immunohistochemistry; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008854:Microscopy, Electron; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013272:Stomach Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*
D002492:Central Nervous System Depressants; D000431:Ethanol; D008315:Malondialdehyde; D009195:Peroxidase; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid