Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas 79106, USA.
Free Radic Res. 2010 Apr;44(4):441-53. doi: 10.3109/10715761003610729.
Recent studies have shown that cytochrome P450 inhibitors reduce oxidative stress and injury to the liver following warm ischemia-reperfusion (IR). The aim here was to test the effect of P450 induction by phenobarbital on the IR injury in rat livers. Rats were pre-treated with saline or phenobarbital and subjected to IR or sham operation. IR significantly increased the plasma alanine aminotransferase concentrations. Phenobarbital further exacerbated the injury by an additional 50% increase in the alanine aminotransferase levels. Phenobarbital also caused an approximately 40% increase in the total P450 content of the liver, which was also associated with a 75% increase in the reactive oxygen species (ROS) generation in the IR group. There was a strong correlation between the microsomal ROS generation and total P450 content, CYP3A2 activity or CYP2B1 activity. It is concluded that the induction of P450 by phenobarbital significantly increases hepatic production of ROS, leading to significantly higher hepatic IR injury.
最近的研究表明，细胞色素 P450 抑制剂可减少热缺血再灌注（IR）后肝脏的氧化应激和损伤。本研究旨在测试苯巴比妥诱导 P450 对大鼠肝脏 IR 损伤的影响。大鼠用生理盐水或苯巴比妥预处理，然后进行 IR 或假手术。IR 显著增加了血浆丙氨酸氨基转移酶浓度。苯巴比妥通过丙氨酸氨基转移酶水平进一步增加 50%，使损伤恶化。苯巴比妥还使肝脏的总 P450 含量增加了约 40%，这与 IR 组中活性氧 (ROS) 的生成增加了 75%有关。微粒体 ROS 的生成与总 P450 含量、CYP3A2 活性或 CYP2B1 活性之间存在很强的相关性。结论：苯巴比妥诱导的 P450 显著增加了 ROS 的肝脏生成，导致肝 IR 损伤显著增加。
