伯氏疟原虫实验性疟疾感染对大鼠肝微粒体细胞色素P450活性可能存在的同工酶特异性影响。

Possible isozyme-specific effects of experimental malaria infection with Plasmodium berghei on cytochrome P450 activity in rat liver microsomes.

作者信息

Glazier A P, Kokwaro G O, Edwards G

机构信息

Department of Pharmacology and Therapeutics, University of Liverpool, UK.

出版信息

J Pharm Pharmacol. 1994 May;46(5):352-5. doi: 10.1111/j.2042-7158.1994.tb03811.x.

DOI:10.1111/j.2042-7158.1994.tb03811.x

PMID:8083805

Abstract

We have investigated the effect of experimental malaria infection on rat cytochrome P450-mediated drug metabolism using ethoxyresorufin and metoprolol as probe compounds. Malaria infection caused a significant reduction in total intrinsic clearance of ethoxyresorufin in both low and high parasitaemia malaria compared with control (control 18.7 +/- 7.2; low parasitaemia 10.5 +/- 4.1; high parasitaemia 4.3 +/- 1.4 mL min-1). However, clearance of metoprolol was unchanged in malaria infection compared with control (control 2.7 +/- 1.2; malaria 4.0 +/- 1.7 mL min-1). The change in clearance of ethoxyresorufin was the result of a decrease in Vmax, with no apparent change in Km. There was no change in either Vmax or Km of metoprolol. These results indicate a possible isozyme-selective effect of experimental malaria.

摘要

我们使用乙氧试卤灵和美托洛尔作为探针化合物，研究了实验性疟疾感染对大鼠细胞色素P450介导的药物代谢的影响。与对照组相比，疟疾感染导致低寄生虫血症和高寄生虫血症疟疾中乙氧试卤灵的总内在清除率显著降低（对照组18.7±7.2；低寄生虫血症组10.5±4.1；高寄生虫血症组4.3±1.4 mL·min⁻¹）。然而，与对照组相比，疟疾感染中美托洛尔的清除率没有变化（对照组2.7±1.2；疟疾组4.0±1.7 mL·min⁻¹）。乙氧试卤灵清除率的变化是Vmax降低的结果，Km没有明显变化。美托洛尔的Vmax和Km均无变化。这些结果表明实验性疟疾可能具有同工酶选择性效应。