Azri S, Renton K W
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Int J Immunopharmacol. 1991;13(2-3):197-204. doi: 10.1016/0192-0561(91)90099-s.
A number of infections are capable of depressing the capacity of the liver to metabolize drugs. We have studied a number of factors which could be involved in the depression of cytochrome P-450 and related drug biotransformation enzymes during infections with Listeria monocytogenes. During the course of the infection, drug metabolism and heme content of hepatic microsomes were depressed but heme oxygenase was elevated. A free radical scavenger alpha-tocopherol did not prevent the loss and xanthine oxidase activities did not correlate with the time course of the loss. Infections in susceptible (balb/c) mice produced a larger loss in drug metabolism than in resistant (C57BL/6) mice, and an avirulent strain of the bacteria was without effect. A preparation of hemolysin isolated from Listeria monocytogenes produced a dose-dependent loss of cytochrome P-450 in isolated hepatocytes. These experiments indicate that the loss of drug metabolism during Listeria infections is most likely due to hemolysin released by the bacteria.
许多感染能够抑制肝脏代谢药物的能力。我们研究了在单核细胞增生李斯特菌感染期间可能参与细胞色素P - 450及相关药物生物转化酶抑制的多种因素。在感染过程中，肝脏微粒体的药物代谢和血红素含量降低，但血红素加氧酶升高。自由基清除剂α-生育酚不能阻止这种损失，且黄嘌呤氧化酶活性与损失的时间进程无关。易感（balb/c）小鼠的感染比抗性（C57BL/6）小鼠的药物代谢损失更大，且该细菌的无毒菌株没有影响。从单核细胞增生李斯特菌分离出的溶血素制剂在分离的肝细胞中产生了剂量依赖性的细胞色素P - 450损失。这些实验表明，李斯特菌感染期间药物代谢的损失很可能是由于细菌释放的溶血素所致。
