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五味子乙素通过增强 DT- 二氢嘧啶脱氢酶活性来保护细胞免受甲萘醌诱导的肝毒性。

Schisandrin B protects against menadione-induced hepatotoxicity by enhancing DT-diaphorase activity.

作者信息

Ip S P, Yiu H Y, Ko K M

机构信息

Department of Biochemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, P.R. China.

出版信息

Mol Cell Biochem. 2000 May;208(1-2):151-5. doi: 10.1023/a:1007029625406.

DOI:10.1023/a:1007029625406
PMID:10939639
Abstract

Pretreating mice with schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis, at a daily dose of 1 mmol/kg for 3 days protected against menadione-induced hepatic oxidative damage in mice, as evidenced by decreases in plasma alanine aminotransferase activity (78%) and hepatic malondialdehyde level (70%), when compared with the menadione intoxicated control. In order to define the biochemical mechanism involved in the hepatoprotection afforded by Sch B pretreatment, we examined the activity of DT-diaphorase (DTD) in hepatocytes isolated from Sch B pretreated rats. Hepatocytes isolated from Sch B pretreated (a daily dose of 1 mmol/kg for 3 days) rats showed a significant increase (25%) in DTD activity. The increase in DTD activity was associated with the enhanced rate of menadione elimination in the hepatocyte culture. The ensemble of results suggests that the ability of Sch B pretreatment to enhance hepatocellular DTD activity may at least in part be attributed to the protection against menadione hepatotoxicity.

摘要

用五味子醇甲(Sch B)对小鼠进行预处理,Sch B是从五味子果实中分离出的一种二苯并环辛二烯衍生物,每日剂量为1 mmol/kg,连续3天,可保护小鼠免受甲萘醌诱导的肝氧化损伤,与甲萘醌中毒对照组相比,血浆丙氨酸转氨酶活性降低(78%)和肝丙二醛水平降低(70%)证明了这一点。为了确定Sch B预处理提供肝保护作用的生化机制,我们检测了从Sch B预处理大鼠分离的肝细胞中DT-黄递酶(DTD)的活性。从Sch B预处理(每日剂量1 mmol/kg,连续3天)大鼠分离的肝细胞显示DTD活性显著增加(25%)。DTD活性的增加与肝细胞培养中甲萘醌消除率的提高有关。这些结果表明,Sch B预处理增强肝细胞DTD活性的能力可能至少部分归因于对甲萘醌肝毒性的保护作用。

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本文引用的文献

1
Quinone toxicity in DT-diaphorase-efficient and -deficient colon carcinoma cell lines.DT-黄递酶高效和缺陷结肠癌细胞系中的醌毒性
Biochem Pharmacol. 1999 Jan 1;57(1):27-37. doi: 10.1016/s0006-2952(98)00288-3.
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Induction of DT-diaphorase by 1,2-dithiole-3-thiones in human tumour and normal cells and effect on anti-tumour activity of bioreductive agents.1,2-二硫醇-3-硫酮对人肿瘤细胞和正常细胞中DT-黄递酶的诱导作用及其对生物还原药物抗肿瘤活性的影响。
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Disruption of the DT diaphorase (NQO1) gene in mice leads to increased menadione toxicity.
五味子乙素通过诱导大鼠心肌组织中Hsp25和Hsp70的表达,部分保护心肌缺血再灌注损伤。
Mol Cell Biochem. 2004 Nov;266(1-2):139-44. doi: 10.1023/b:mcbi.0000049151.79238.30.
4
Down-modulation of heat shock protein 70 and up-modulation of Caspase-3 during schisandrin B-induced apoptosis in human hepatoma SMMC-7721 cells.五味子乙素诱导人肝癌SMMC - 7721细胞凋亡过程中热休克蛋白70的下调及半胱天冬酶 - 3的上调
World J Gastroenterol. 2004 Oct 15;10(20):2944-8. doi: 10.3748/wjg.v10.i20.2944.
小鼠中DT黄递酶(NQO1)基因的破坏导致甲萘醌毒性增加。
J Biol Chem. 1998 Mar 27;273(13):7382-9. doi: 10.1074/jbc.273.13.7382.
4
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Biochem Pharmacol. 1998 Feb 1;55(3):253-60. doi: 10.1016/s0006-2952(97)00265-7.
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Metabolism and cytotoxicity of menadione and its metabolite in rat platelets.
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6
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7
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8
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