Hepatotoxicity in Rats Induced by Aqueous Extract of Polygoni Multiflori Radix, Root of Polygonum multiflorum Related to the Activity Inhibition of CYP1A2 or CYP2E1.
Hepatotoxicity in Rats Induced by Aqueous Extract of Polygoni Multiflori Radix, Root of Polygonum multiflorum Related to the Activity Inhibition of CYP1A2 or CYP2E1.
复制标题
何首乌水提取物引起的大鼠肝毒性与CYP1A2或CYP2E1活性抑制有关
DOI：
10.1155/2017/9456785
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Sun ZX
中科院分区：
文献类型：
--
作者：
Li DK;Chen J;Ge ZZ;Sun ZX
本研究旨在探讨何首乌（Polygonum multi florum Thunb.，PMR）的肝毒性与其抗氧化作用的关系。和寿武）和大鼠肝脏中的CYP1A2或CYP2E1活性。在实验剂量范围内，PMR水提物对大鼠血清转氨酶ALT和AST水平无明显影响，但对大鼠肝脏CYP1A2和CYP2E1活性有明显抑制作用。但在注射CYP1A2或CYP2E1特异性抑制剂后联合口服PMR水提物后，ALT和AST水平显著升高，CYP1A2或CYP2E1活性显著降低，尤其是在间隔时间内重复给药时。肝组织病理学观察显示，PMR处理组大鼠出现中度肝损伤，且CYP1A2或CYP2E1活性受到抑制，而PMR处理组和CYP2E1抑制剂单独处理组大鼠无明显肝损伤。提示人群中CYP1A2或CYP2E1基因多态性导致的低水平活性可能是PMR肝毒性的重要原因之一。
The objective of this study is to investigate the relationship between the hepatotoxicity induced by Polygoni Multiflori Radix (PMR, root of Polygonum multiflorum Thunb., He Shou Wu) and the activity of CYP1A2 or CYP2E1 in the rat liver. Levels of rat serum transaminases ALT and AST were not altered but the activity of CYP1A2 or CYP2E1 in the rat liver was significantly inhibited after oral administration of aqueous extract of PMR under the experimental dosage. However, levels of ALT and AST were significantly increased and the activity of CYP1A2 or CYP2E1 was significantly decreased after injection of specific inhibitor for CYP1A2 or CYP2E1 combined with oral administration of aqueous extract of PMR, especially under the repeated treatment over interval times. Liver histopathological observation showed that a moderate liver injury occurred in rats receiving PMR treatment with the activity of CYP1A2 or CYP2E1 inhibited, but there was no significant liver damage in rats receiving PMR treatment or CYP inhibitor alone. These suggested that low level activity of CYP1A2 or CYP2E1 from genetic polymorphism among people might be one of the important reasons for the hepatotoxicity induced by PMR in clinical practice.