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表没食子儿茶素没食子酸酯对微囊藻毒素LR诱导的小鼠肝细胞氧化损伤及细胞色素P450 2E1表达的拮抗作用

[The antagonistic action of epigallocatechin-3-gallate on microcystin LR-induced oxidative damage on hepatocytes of mice and the expression of cytochrome P450 2E1].

作者信息

Han Zhi-Xia, Yang Lan, Zhang Liang, Xu Chuan, Shu Wei-Qun

机构信息

Department of Environmental Hygiene, School of Military Preventive Medicine, The Third Military Medical University, Chongqing 400038, China.

出版信息

Zhonghua Yu Fang Yi Xue Za Zhi. 2010 Jan;44(1):24-9.

PMID:20388359
Abstract

OBJECTIVE

To evaluate the effects of antagonistic action of epigallocatechin-3-gallate (EGCG) on microcystin LR (MC-LR) induced oxidative damage on mice and the expression of cytochrome P450 2E1 (CYP2E1) which was one of phase Iota detoxification enzymes.

METHODS

A total of 24 specific pathogen free (SPF) male BALB/c mice were randomly divided into four groups, including control group, MC-LR group, low concentration EGCG group, and high concentration EGCG group. Mice were sacrificed on the 15th day, body weight, and the relative organ weight, liver antioxidant enzyme level and lipid peroxidation product, liver histopathology and CYP2E1 gene and protein expression were detected and analyzed respectively.

RESULTS

(1) EGCG could antagonise the liver injury which had been damaged by MC-LR. (2) The malonaldehyde (MDA) level ((2.87 +/- 0.03) nmol/mg prot) and superoxide dismutase (SOD) level ((168.18 +/- 2.86) U/mg prot) in MC-LR group were significantly different when compared with the two EGCG treatment groups (the MDA values of the low and high concentration EGCG group were (2.37 +/- 0.05) nmol/mg prot and (1.44 +/- 0.05) nmol/mg prot, F = 906.63, P < 0.01; the SOD values were (176.55 +/- 2.98) U/mg prot and (184.89 +/- 1.53) U/mg prot, F = 32.32, P < 0.01). (3) MC-LR up-regulated the mRNA and protein expression of CYP2E1 (the mRNA values of MC-LR group and control were 1.41 +/- 0.26, 0.86 +/- 0.13, t = -4.22, P = 0.003; the protein values of MC-LR group and control were 0.24 +/- 0.03, 0.12 +/- 0.02, t = -9.21, P < 0.05). EGCG down-regulated the mRNA (the values of the low and high concentration EGCG group were 1.09 +/- 0.08, 0.99 +/- 0.09, F = 9.03, P = 0.004) and protein expression (the values of the low and high concentration EGCG group were 0.21 +/- 0.03, 0.14 +/- 0.02, F = 24.76, P < 0.05) of CYP2E1 which activated by MC-LR.

CONCLUSION

The up-regulation of CYP2E1 which induced by MC-LR was inhibited by EGCG intervention. EGCG might antagonize the oxidation damage of hepatocytes in a certain degree.

摘要

目的

评估表没食子儿茶素-3-没食子酸酯(EGCG)对微囊藻毒素LR(MC-LR)诱导的小鼠氧化损伤的拮抗作用,以及对Ⅰ相解毒酶之一的细胞色素P450 2E1(CYP2E1)表达的影响。

方法

将24只无特定病原体(SPF)雄性BALB/c小鼠随机分为四组,包括对照组、MC-LR组、低浓度EGCG组和高浓度EGCG组。于第15天处死小鼠,分别检测并分析体重、相对脏器重量、肝脏抗氧化酶水平和脂质过氧化产物、肝脏组织病理学以及CYP2E1基因和蛋白表达。

结果

(1)EGCG可拮抗MC-LR所致的肝脏损伤。(2)MC-LR组的丙二醛(MDA)水平((2.87±0.03)nmol/mg蛋白)和超氧化物歧化酶(SOD)水平((168.18±2.86)U/mg蛋白)与两个EGCG治疗组相比有显著差异(低、高浓度EGCG组的MDA值分别为(2.37±0.05)nmol/mg蛋白和(1.44±0.05)nmol/mg蛋白,F = 906.63,P < 0.01;SOD值分别为(176.55±2.98)U/mg蛋白和(184.89±1.53)U/mg蛋白,F = 32.32,P < 0.01)。(3)MC-LR上调CYP2E1的mRNA和蛋白表达(MC-LR组和对照组的mRNA值分别为1.41±0.26、0.86±0.13,t = -4.22,P = 0.003;蛋白值分别为0.24±0.03、0.12±0.02,t = -9.21,P < 0.05)。EGCG下调MC-LR激活的CYP2E1的mRNA(低、高浓度EGCG组的值分别为1.09±0.08、0.99±0.09,F = 9.03,P = 0.004)和蛋白表达(低、高浓度EGCG组的值分别为0.21±0.03、0.14±0.02,F = 24.76,P < 0.05)。

结论

EGCG干预可抑制MC-LR诱导的CYP2E1上调。EGCG可能在一定程度上拮抗肝细胞的氧化损伤。

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