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Protective effects of 5-methoxypsoralen against acetaminophen-induced hepatotoxicity in mice
Liu, Wei-Xia; Jia, Feng-Lan; He, Yue-Ying; Zhang, Bao-Xu
关键词5-Methoxypsoralen Protection Acetaminophen Hepatotoxicity Antioxidation
刊名WORLD JOURNAL OF GASTROENTEROLOGY
2012-05-14
DOI10.3748/wjg.v18.i18.2197
18期:18页:2197-2202
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Gastroenterology & Hepatology
研究领域[WOS]Gastroenterology & Hepatology
关键词[WOS]ACUTE LIVER-FAILURE ; MELATONIN SECRETION ; HUMANS ; INDUCTION ; INCREASES ; PSORALENS ; APOPTOSIS ; INJURY ; 5-MOP ; CELLS
英文摘要

AIM: To investigate the hepatic protective effects of 5-methoxypsoralen (5-MOP) and to learn if 5-MOP causes hepatotoxicity at protective doses.

METHODS: C57BL/6J mice were administrated orally with 5-MOP at doses of 12.5, 25 and 50 mg/kg body weight respectively every morning for 4 d before given acetaminophen (APAP) subcutaneously at a dose of 500 mg/kg. The 5-MOP alone group was treated with 5-MOP orally at a dose of 50 mg/kg body weight for 4 d without APAP. Twenty-four hours after APAP administration, blood samples of mice were analyzed for serum enzyme alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH) levels, and malondialdehyde (MDA), reduced glutathione (GSH) and oxidized glutathione (GSSG) of liver tissues were measured and histopathologic changes of the liver were observed.

RESULTS: Compared with the vehicle control group, the serum levels (IU/L) of ALT, AST and LDH were all increased significantly in APAP group (8355 +/- 3940 vs 30 +/- 21, P < 0.05; 6482 +/- 4018 vs 146 +/- 58, P < 0.05; 24627 +/- 10975 vs 1504 +/- 410, P < 0.05). Compared with APAP group, the serum ALT levels (IU/L) (1674 +/- 1810 vs 8355 +/- 3940, P < 0.05; 54 +/- 39 vs 8355 +/- 3940, P < 0.05; 19 +/- 9 vs 8355 +/- 3940, P < 0.05), AST levels (IU/L) (729 +/- 685 vs 6482 +/- 4108, P < 0.05; 187 +/- 149 vs 6482 +/- 4108, P < 0.05; 141 +/- 12 vs 6482 +/- 4108, P < 0.05) and LDH levels (IU/L) (7220 +/- 6317 vs 24 627 +/- 10 975, P < 0.05; 1618 +/- 719 vs 24 627 +/- 10 975, P < 0.05; 1394 +/- 469 vs 24 627 +/- 10 975, P < 0.05) were all decreased drastically in the three-dosage 5-MOP pretreatment groups. Pretreatment of 5-MOP could attenuate histopathologic changes induced by APAP, including hepatocellular necrosis and infiltration of inflammatory cells, and the effect was dose-dependent. MDA levels (nmol/mg) were decreased by 5-MOP in a dose-dependent manner (0.98 +/- 0.45 vs 2.15 +/- 1.07, P > 0.05; 0.59 +/- 0.07 vs 2.15 +/- 1.07, P < 0.05; 0.47 +/- 0.06 vs 2.15 +/- 1.07, P < 0.05). The pretreatment of 5-MOP could also increase the GSH/GSSG ratio (3.834 +/- 0.340 vs 3.306 +/- 0.282, P > 0.05; 5.330 +/- 0.421 vs 3.306 +/- 0.282, P < 0.05; 6.180 +/- 0.212 vs 3.306 +/- 0.282, P < 0.05). In the group treated with 5-MOP but without APAP, the serum enzyme levels, the liver histopathologic manifestation, and the values of MDA and GSH/GSSG ratio were all normal.

CONCLUSION: 5-MOP can effectively protect C57BL/63 mice from APAP-induced hepatotoxicity and possesses an antioxidative activity, and does not cause liver injury at the protective doses. (C) 2012 Baishideng. All rights reserved.

语种英语
WOS记录号WOS:000304222300006
项目编号2009ZX09103-007
资助机构Drug Innovation Program of National Science and Technology Project
引用统计
被引频次:18[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59885
专题北京大学公共卫生学院_毒理学系
北京大学公共卫生学院_公共卫生学院
作者单位Peking Univ, Sch Publ Hlth, Dept Toxicol, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Liu, Wei-Xia,Jia, Feng-Lan,He, Yue-Ying,et al. Protective effects of 5-methoxypsoralen against acetaminophen-induced hepatotoxicity in mice[J]. WORLD JOURNAL OF GASTROENTEROLOGY,2012,18(18):2197-2202.
APA Liu, Wei-Xia,Jia, Feng-Lan,He, Yue-Ying,&Zhang, Bao-Xu.(2012).Protective effects of 5-methoxypsoralen against acetaminophen-induced hepatotoxicity in mice.WORLD JOURNAL OF GASTROENTEROLOGY,18(18),2197-2202.
MLA Liu, Wei-Xia,et al."Protective effects of 5-methoxypsoralen against acetaminophen-induced hepatotoxicity in mice".WORLD JOURNAL OF GASTROENTEROLOGY 18.18(2012):2197-2202.
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