The CYP inhibitor 1-aminobenzotriazole does not prevent oxidative stress associated with alcohol-induced liver injury in rats and mice
The CYP inhibitor 1-aminobenzotriazole does not prevent oxidative stress associated with alcohol-induced liver injury in rats and mice
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DOI：
10.1016/j.freeradbiomed.2003.09.007
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发表时间：
2003-12-15
影响因子：
7.4
通讯作者：
Arteel, GE
中科院分区：
文献类型：
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作者：
Isayama, F;Froh, MR;Arteel, GE
细胞色素 P450 (CYP) 2E1 由乙醇诱导，被认为是酒精性肝病期间活性氧的来源。然而，饲喂乙醇的野生型和 CYP2E1 敲除小鼠的肝脏病理学和自由基形成没有差异。如果 CYP2E1 受到抑制或缺失，其他 CYP 同工型可能会产生这些效应。因此，本研究的目的是确定用 1-氨基苯并三唑（ABT；100 mg/kg i.g.）阻断大部分 P450 亚型是否对大鼠和小鼠酒精引起的肝损伤和氧化应激有影响。雄性 C57BL/6 小鼠和 Wistar 大鼠喂食高脂肪对照或含乙醇肠内饮食 4 周。 ABT 对许多 P450 异构体具有显着的抑制作用，与同时服用酒精无关。然而，ABT 并不能防止这两个物种因酒精引起的肝损伤。饲喂乙醇的媒介物处理和 ABT 处理动物的肝脏氧化应激和炎症指数也相似。总之，用 ABT 抑制 P450 活性对大鼠和小鼠酒精引起的氧化应激没有明显影响。这些数据支持这样的假设：在早期酒精引起的肝损伤期间，大鼠和小鼠的氧化应激和肝损伤可以独立于 CYP 活性而发生。 (C) 2003 爱思唯尔公司。
Cytochrome P450 (CYP) 2E1 is induced by ethanol and is postulated to be a source of reactive oxygen species during alcoholic liver disease. However, there was no difference in liver pathology and radical formation between wild-type and CYP2E1 knockout mice fed ethanol. Other CYP isoforms may contribute these effects if CYP2E1 is inhibited or absent. The purpose of this study was, therefore, to determine if blocking most of the P450 isoforms with 1-aminobenzotriazole (ABT; 100 mg/kg i.g.), has any effect on liver damage and oxidative stress due to alcohol in rats and mice. Male C57BL/6 mice and Wistar rats were fed either high-fat control or ethanol-containing enteral diet for 4 weeks. ABT had a significant inhibitory effect on many P450 isoforms independent of concomitant alcohol administration. However, ABT did not protect against liver damage due to alcohol in either species. Indices of oxidative stress and inflammation were also similar in livers from vehicle-treated and ABT-treated animals fed ethanol. In summary, suppression of P450 activity with ABT had no apparent effect on oxidative stress caused by alcohol in both rats and mice. These data support the hypothesis that oxidative stress and liver damage can occur independently of CYP activities in both rats and mice during early alcohol-induced liver injury. (C) 2003 Elsevier Inc.