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Title: Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice

Abstract

Excessive alcohol consumption can lead to gastric ulcer and the present work was aimed to examine the protective effect of tetrahydrocoptisine (THC) in the model of ethanol-induced gastric ulcer in mice. Fasted mice treated with ethanol 75% (0.5 ml/100 g) were pre-treated with THC (10 or 20 mg/kg, ip), cimetidine (100 mg/kg, ip) or saline in different experimental sets for a period of 3 days, and animals were euthanized 4 h after ethanol ingestion. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that ethanol induced gastric damage, improving nitric oxide (NO) level, increased pro-inflammatory cytokine (TNF-α and IL-6) levels and myeloperoxidase (MPO) activity, as well as the expression of nuclear factor-κB (NF-κB) in the ethanol group. Pretreatment of THC at doses of 10 and 20 mg/kg bodyweight significantly attenuated the gastric lesions as compared to the ethanol group. These results suggest that the gastroprotective activity of THC is attributed to reducing NO production and adjusting the pro-inflammatory cytokine, inhibited neutrophil accumulation and NF-κB expression. - Highlights: • THC decreased ethanol-induced pro-inflammatory cytokine release. • THC inhibited the production of NO in serum and gastric tissue. • THC reduced NF-κB expression and MPO accumulationmore » in ethanol-induced gastric tissue.« less

Authors:
; ; ; ; ;
Publication Date:
OSTI Identifier:
22285391
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 272; Journal Issue: 1; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AMINOBUTYRIC ACID; ENZYME IMMUNOASSAY; ETHANOL; INFLAMMATION; INGESTION; MICE; NITRIC OXIDE; PROSTAGLANDINS; RECEPTORS

Citation Formats

Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn, Huang, Huimin, Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn, Fan, Ting, Mu, Qingli, and Li, Huani. Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice. United States: N. p., 2013. Web. doi:10.1016/J.TAAP.2013.05.035.
Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn, Huang, Huimin, Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn, Fan, Ting, Mu, Qingli, & Li, Huani. Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice. United States. doi:10.1016/J.TAAP.2013.05.035.
Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn, Huang, Huimin, Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn, Fan, Ting, Mu, Qingli, and Li, Huani. 2013. "Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice". United States. doi:10.1016/J.TAAP.2013.05.035.
@article{osti_22285391,
title = {Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice},
author = {Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn and Huang, Huimin and Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn and Fan, Ting and Mu, Qingli and Li, Huani},
abstractNote = {Excessive alcohol consumption can lead to gastric ulcer and the present work was aimed to examine the protective effect of tetrahydrocoptisine (THC) in the model of ethanol-induced gastric ulcer in mice. Fasted mice treated with ethanol 75% (0.5 ml/100 g) were pre-treated with THC (10 or 20 mg/kg, ip), cimetidine (100 mg/kg, ip) or saline in different experimental sets for a period of 3 days, and animals were euthanized 4 h after ethanol ingestion. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that ethanol induced gastric damage, improving nitric oxide (NO) level, increased pro-inflammatory cytokine (TNF-α and IL-6) levels and myeloperoxidase (MPO) activity, as well as the expression of nuclear factor-κB (NF-κB) in the ethanol group. Pretreatment of THC at doses of 10 and 20 mg/kg bodyweight significantly attenuated the gastric lesions as compared to the ethanol group. These results suggest that the gastroprotective activity of THC is attributed to reducing NO production and adjusting the pro-inflammatory cytokine, inhibited neutrophil accumulation and NF-κB expression. - Highlights: • THC decreased ethanol-induced pro-inflammatory cytokine release. • THC inhibited the production of NO in serum and gastric tissue. • THC reduced NF-κB expression and MPO accumulation in ethanol-induced gastric tissue.},
doi = {10.1016/J.TAAP.2013.05.035},
journal = {Toxicology and Applied Pharmacology},
number = 1,
volume = 272,
place = {United States},
year = 2013,
month =
}
  • This study investigated whether intracellular glutathione is cytoprotective against ethanol-induced injury to cultured rat gastric mucosal cells in vitro. Secondly, it investigated whether reduced glutathione or oxidized glutathione is responsible for this cytoprotection. Cytolysis was quantified by measuring 51Cr release from prelabeled cells. Concentrations of ethanol greater than 12% caused cell damage and increased 51Cr release in a dose-dependent and time-related fashion. When a substrate for glutathione synthesis, N-acetyl-L-cysteine, was provided to cultured cells for 4 h before challenge with ethanol, cytolysis was significantly decreased corresponding with an increase in cellular glutathione content. Pretreatment with diethyl maleate, which depletes reducedmore » glutathione without forming oxidized glutathione, potentiated ethanol-induced cell damage in a dose-dependent manner with the decrease of cellular glutathione content. The administration of tert-butyl hydroperoxide (which is specifically reduced by glutathione peroxidase to generate oxidized glutathione from reduced glutathione) or diamide (which nonenzymatically oxidizes reduced glutathione to oxidized glutathione) enhanced ethanol injury. We conclude that in cultured gastric mucosal cells, (a) intracellular glutathione maintains integrity of gastric mucosal cells against ethanol in vitro; and (b) reduced glutathione rather than oxidized glutathione is responsible for this cytoprotection. We postulate that the presence of reduced glutathione is essential to allow glutathione peroxidase to catalyze the ethanol-generated toxic oxygen radical, hydrogen peroxide.« less
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  • Colloids of Au/sup 198/, NaI/sup 131/, and Lu/sup 177/ Cl/sub 3/ in small viny l tubes, diluted to provide a wide range of radiation activities, were implanted at various locations along the gastrointestinal tract. The radiosensitivity of the various segments of the gastrointestinal tract was determined in animals sacrificed at various intervals after the implantations were made. The protective effects of cortisone, ACTH, insulin, atrophine, and chloropromazine against lesions induced by implants of colloidal Au/sup 198/ were evaluated. The physiological effects of the 5 compounds are reviewed. The possible relation of the effects of the compounds on control of gastricmore » secretion of HCl and their protective effects against radiation injury to the gastrointestinal tract is considered. (C.H.)« less