Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2005; 11(18): 2739-2743
Published online May 14, 2005. doi: 10.3748/wjg.v11.i18.2739
Protective role of metallothionein in stress-induced gastric ulcer in rats
Ping Jiang, Lin Chang, Chun-Shui Pan, Yong-Fen Qi, Chao-Shu Tang
Ping Jiang, Chun-Shui Pan, Lin Chang, Chao-Shu Tang, Institute of Cardiovascular Diseases Research, Peking University First Hospital, Beijing 100034, China
Ping Jiang, Yong-Fen Qi, Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing 100083, China
Chao-Shu Tang, Yong-Fen Qi, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100083, China
Author contributions: All authors contributed equally to the work.
Supported by the State Major Basic Research Development Program of the People’s Republic of China, No. 2003CCA041
Correspondence to: Professor Chao-Shu Tang, Institute of Cardiovascular Diseases Research, Peking University First Hospital, Beijing 100034, China. tangchaoshu@263.net.cn
Telephone: +86-10-82802183 Fax: +86-10-66551036
Received: October 18, 2004
Revised: October 19, 2004
Accepted: December 3, 2004
Published online: May 14, 2005
Abstract

AIM: To illustrate the pathophysiological role of metallothionein (MT) in gastric ulcer induced by stress.

METHODS: Wistar rats underwent water-immersion-restraint (WIR) stress, ZnSO4 (an MT inducer) treatment, WIR+ZnSO4 or WIR+MT, and the ulcer index (UI) was estimated in excised stomach and liver tissues. The mRNA level of gastric MT was determined by semi-quantitative RT-PCR. The MT content in gastric and hepatic tissues was determined by Cd/hemoglobin affinity assay. The lipid peroxidation products malondialdehyde (MDA) and conjugated dienes (CD) were estimated by use of thiobarbituric acid reactive species and ultraviolet spectrophotometry.

RESULTS: WIR stress induced severe gastric mucosal lesions in rats. Compared with control rats, stressed rats had increased lipid peroxide content in serum and stomach and liver tissues. MDA content was increased by 34%, 21% and 29% and CD level by 270%, 83% and 28%, respectively. MT content in the stomach and liver was increased by 0.74- and 1.8-fold, and the MT-mRNA level in the stomach was increased by 26%. Pretreatment with ZnSO4 prevented gastric lesion development (the UI was 87% lower than that without pretreatment), and the MDA and CD content in serum and tissues was lower. The MT content in the liver was double in rats that were not pretreated, and the MT mRNA level in the stomach was 35% higher. MT administration 1 h before the WIR stress prevented gastric lesion development (the UI decreased by 47% compared with that in rats not pretreated), and the MDA and CD content in serum and tissues was significantly lower.

CONCLUSION: In WIR-stressed rats, the MT level was increased in serum and in stomach and liver tissues. Pre-administration of exogenous MT or pre-induction of endogenous MT can protect the gastric mucosa against stress-induced ulcers and inhibits the formation of stress-induced lipid peroxide. MT could have a gastroprotective effect and might be a new interventive and therapeutic target in stress-induced gastric ulcers.

Keywords: Metallothionein; Gastric ulcer