Protection against carbon tetrachloride hepatotoxicity by oleanolic acid is not mediated through metallothionein
Protection against carbon tetrachloride hepatotoxicity by oleanolic acid is not mediated through metallothionein
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DOI：
10.1016/s0378-4274(98)00009-5
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发表时间：
1998-03-31
影响因子：
3.5
通讯作者：
Liu, J
中科院分区：
文献类型：
--
作者：
Liu, YP;Hartley, DP;Liu, J
油酸是一种三萜类化合物，已被证明可以防止某些肝毒物引起的肝损伤。本研究旨在探讨油酸对四氯化碳肝毒性的保护作用，以及金属硫蛋白在其中的作用。油酸预处理（100 - 400 μ mol/kg，sc）以剂量和时间依赖性方式保护Sprague-Dawley大鼠和小鼠免受四氯化碳诱导的肝损伤，血清丙氨酸转氨酶和山梨醇脱氢酶活性以及组织病理学证明了这一点。对四氯化碳肝毒性的保护作用不明显，直到动物与油酸预处理12小时，并持续72小时后，单次注射。这表明，这种保护作用可能是由于诱导了某些适应机制。金属硫蛋白（MT），急性时相蛋白提出减少四氯化碳诱导的肝损伤，显着诱导油酸治疗后。为了检查油酸保护是否通过MT介导，使用MT-1和II敲除（MT-无效）小鼠。油酸预处理增加MT水平在对照组小鼠（20倍），但不是在MT-null小鼠，然而，它同样保护对四氯化碳诱导的肝毒性在对照组和MT-null小鼠。这些数据表明，油酸是有效的保护大鼠和小鼠免受四氯化碳产生的肝毒性，和保护不是通过诱导MT介导的。(C)1998爱思唯尔科学爱尔兰有限公司保留所有权利。
Oleanolic acid is a triterpenoid compound that has been shown to protect against liver injury produced by some hepatotoxicants. This study was designed to characterize the protective effects of oleanolic acid on carbon tetrachloride-induced hepatotoxicity, and the role of metallothionein in the protection. Oleanolic acid pretreatment (100-400 mu mol/kg, sc) protected Sprague-Dawley rats and mice from carbon tetrachloride-induced liver injury in a dose-and time-dependent manner, as evidenced by serum alanine aminotransferase and sorbitol dehydrogenase activities, as well as by histopathology. The protection against carbon tetrachloride hepatotoxicity was not evident until animals were pretreated with oleanolic acid 12 h, and lasted for 72 h after a single injection. This suggests that the protection might be due to induction of some adaptive mechanisms. Metallothionein (MT), an acute-phase protein proposed to decrease carbon tetrachloride-induced liver injury, was dramatically induced following oleanolic acid treatment. To examine whether oleanolic acid protection is mediated through MT, MT-I and II knock-out (MT-null) mice were utilized. Oleanolic acid pretreatment increased MT levels in control mice (20-fold), but not in MT-null mice, however, it protected equally against carbon tetrachloride-induced hepatotoxicity in both control and MT-null mice. These data indicate that oleanolic acid is effective in protecting rats and mice from the hepatotoxicity produced by carbon tetrachloride, and the protection is not mediated through induction of MT. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.