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茶多酚对小鼠扑热息痛诱导的肝毒性的保护作用与细胞色素P450抑制显著相关。

Protective effect of tea polyphenols against paracetamol-induced hepatotoxicity in mice is significantly correlated with cytochrome P450 suppression.

作者信息

Chen Xia, Sun Chang-Kai, Han Guo-Zhu, Peng Jin-Yong, Li Ying, Liu Yan-Xia, Lv Yuan-Yuan, Liu Ke-Xin, Zhou Qin, Sun Hui-Jun

机构信息

Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Lvshunkou District, Dalian, Liaoning Province, China.

出版信息

World J Gastroenterol. 2009 Apr 21;15(15):1829-35. doi: 10.3748/wjg.15.1829.

Abstract

AIM

To investigate the hepatoprotective activity of tea polyphenols (TP) and its relation with cytochrome P450 (CYP450) expression in mice.

METHODS

Hepatic CYP450 and CYPb(5) levels were measured by UV-spectrophotometry in mice 2 d after intraperitoneal TP (25, 50 and 100 mg/kg per day). Then the mice were intragastricly pre-treated with TP (100, 200 and 400 mg/kg per day) for six days before paracetamol (1000 mg/kg) was given. Their acute mortality was compared with that of control mice. The mice were pre-treated with TP (100, 200, and 400 mg/kg per day) for five days before paracetamol (500 mg/kg) was given. Hepatic CYP2E1 and CYP1A2 protein and mRNA expression levels were evaluated by Western blotting, immunohistochemical staining and transcriptase-polymerase chain reaction.

RESULTS

The hepatic CYP450 and CYPb(5) levels in mice of TP-treated groups (100, 200 and 400 mg/kg per day) were decreased in a dose-dependent manner compared with those in the negative control mice. TP significantly attenuated the paracetamol-induced hepatic injury and dramatically reduced the mortality of paracetamol-treated mice. Furthermore, TP reduced CYP2E1 and CYP1A2 expression at both protein and mRNA levels in a dose-dependent manner.

CONCLUSION

TP possess potential hepatoprotective properties and can suppress CYP450 expression.

摘要

目的

研究茶多酚(TP)对小鼠的肝脏保护活性及其与细胞色素P450(CYP450)表达的关系。

方法

对小鼠腹腔注射TP(每天25、50和100mg/kg)2天后,采用紫外分光光度法测定肝脏CYP450和CYPb(5)水平。然后在给予对乙酰氨基酚(1000mg/kg)前,小鼠连续6天经口给予TP(每天100、200和400mg/kg)进行预处理。将其急性死亡率与对照小鼠进行比较。在给予对乙酰氨基酚(500mg/kg)前,小鼠连续5天经口给予TP(每天100、200和400mg/kg)进行预处理。通过蛋白质印迹法、免疫组织化学染色和转录酶-聚合酶链反应评估肝脏CYP2E1和CYP1A2蛋白及mRNA表达水平。

结果

与阴性对照小鼠相比,TP处理组(每天100、200和400mg/kg)小鼠的肝脏CYP450和CYPb(5)水平呈剂量依赖性降低。TP显著减轻了对乙酰氨基酚诱导的肝损伤,并显著降低了对乙酰氨基酚处理小鼠的死亡率。此外,TP以剂量依赖性方式降低了CYP2E1和CYP1A2在蛋白和mRNA水平的表达。

结论

TP具有潜在的肝脏保护特性,并且可以抑制CYP450表达。

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