CYP450代谢酶和一些抗氧化信号参与调控了绿原酸抑制对乙酰氨基酚的肝毒性
目的：本研究旨在观察绿原酸对乙酰氨基酚诱导肝损伤的解毒作用及其机理。创新点：发现CYP450代谢酶和一些重要的抗氧化信号分子（如Prx家族蛋白等）参与调控了绿原酸抑制对乙酰氨基酚的肝毒性。方法：检测小鼠血清转氨酶含量,检测体外CYP2E1、CYP3A4和CYP1A2酶活性,检测肝组织中丙二醛（MDA）、谷胱甘肽（GSH）和活性氧（ROS）含量,用实时聚合酶链反应（real-time PCR）检测肝组织中Prx1-6、Ephx2、Polr2k、Fmo5、Nrf2等的m RNA表达情况。结论：绿原酸可以明显抑制对乙酰氨基酚造成的急性肝损伤。给药组小鼠血清中的转氨酶与模型组相比均有显著下降,绿原酸在...
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| Published in: | 浙江大学学报：B卷英文版 Vol. 16; no. 7; pp. 602 - 610 |
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| Main Author: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2015
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | 目的：本研究旨在观察绿原酸对乙酰氨基酚诱导肝损伤的解毒作用及其机理。创新点：发现CYP450代谢酶和一些重要的抗氧化信号分子（如Prx家族蛋白等）参与调控了绿原酸抑制对乙酰氨基酚的肝毒性。方法：检测小鼠血清转氨酶含量,检测体外CYP2E1、CYP3A4和CYP1A2酶活性,检测肝组织中丙二醛（MDA）、谷胱甘肽（GSH）和活性氧（ROS）含量,用实时聚合酶链反应（real-time PCR）检测肝组织中Prx1-6、Ephx2、Polr2k、Fmo5、Nrf2等的m RNA表达情况。结论：绿原酸可以明显抑制对乙酰氨基酚造成的急性肝损伤。给药组小鼠血清中的转氨酶与模型组相比均有显著下降,绿原酸在体外可以微弱抑制CYP2E1和CYP1A2代谢酶的活性,通过MDA、GSH和ROS分析发现绿原酸可以抑制对乙酰氨基酚造成的氧化应激损伤。通过real-time PCR分析发现对乙酰氨基酚降低了抗氧化酶Prx家族、Ephx2、Polr2k和Nrf2的基因表达,而绿原酸可以逆转对乙酰氨基酚降低的这些基因的表达。 |
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| Bibliography: | Chlorogenic acid（CGA）, a polyphenolic compound, is abundant in fruits, dietary vegetables, and some medicinal herbs. This study investigated the prevention of CGA against acetaminophen（AP）-induced hepatotoxicity and its engaged mechanisms. CGA reversed the decreased cell viability induced by AP in L-02 cells in vitro. In addition, CGA reduced the AP-induced increased serum levels of alanine/aspartate aminotransferase（ALT/AST） in vivo. The effect of CGA on cytochrome P450（CYP） enzymatic（CYP2E1, CYP1A2, and CYP3A4） activities showed that CGA caused very little inhibition on CYP2E1 and CYP1A2 enzymatic activities, but not CYP3A4. The measurement of liver malondialdehyde（MDA）, reactive oxygen species（ROS）, and glutathione（GSH） levels showed that CGA prevented AP-induced liver oxidative stress injury. Further, CGA increased the AP-induced decreased m RNA expression of peroxiredoxin（Prx） 1, 2, 3, 5, 6, epoxide hydrolase（Ephx） 2, and polymerase（RNA） II（DNA directed） polypeptide K（Polr2k）, and nuclear factor erythroid-2-related factor 2（Nrf2）. In summary, CGA ameliorates the AP-induced liver injury probably by slightly inhibiting CYP2E1 and CYP1A2 enzymatic properties. In addition, cellular important antioxidant signals such as Prx1, 2, 3, 5, 6, Ephx2, Polr2 k, and Nrf2 also contributed to the protection of CGA against AP-induced oxidative stress injury. Chlorogenic acid; Acetaminophen; CYP450; Oxidative stress injury 33-1356/Q |
| ISSN: | 1673-1581 1862-1783 |