Wirkner K, Damme B, Poelchen W, Pankow D
Institute of Pharmacology and Toxicology, University of Leipzig, Germany.
Toxicol Appl Pharmacol. 1997 Mar;143(1):83-8. doi: 10.1006/taap.1996.8077.
The present study investigates the influence of long-term ethanol (ETOH) treatment of rats [10% (v/v) for 4, 12, and 36 weeks] on the metabolism of DCM after its oral and inhalative uptake to CO. Biotransformation of DCM to CO as measured by carboxyhemoglobin (COHb) formation was stimulated after long-term ETOH treatment in rats. A single oral dose of DCM (6.2 mmol/kg body mass) caused a significant increase of COHb, the maximum of about 9% occurring approximately 6 hr after DCM administration. In comparison to this control, in the blood of rats pretreated with ETOH (10% v/v) for 4, 12, and 36 weeks COHb values of 18, 17, and 13%, respectively, were measured. Long-term ETOH treatment followed by inhalation of 100, 500, and 2500 ppm DCM for 4 hr stimulated the formation of COHb, compared to controls. The elevation of COHb level was accompanied by decreased concentrations of DCM in the blood. The reason for the elevated biotransformation of DCM was ascertained by means of the determination of p-nitrophenol and aniline hydroxylation in liver microsomes of rats after long-term ETOH treatment to be an increase in cytochrome P450-dependent enzyme activities.
本研究调查了长期用乙醇（ETOH）处理大鼠（10%（v/v），持续4、12和36周）对二氯甲烷（DCM）经口服和吸入摄取后代谢为一氧化碳（CO）的影响。通过一氧化碳血红蛋白（COHb）形成来衡量，长期用ETOH处理大鼠后，DCM向CO的生物转化受到刺激。单次口服剂量的DCM（6.2 mmol/kg体重）导致COHb显著增加，给药后约6小时达到最大值，约为9%。与该对照组相比，在分别用ETOH（10% v/v）预处理4、12和36周的大鼠血液中，测得的COHb值分别为18%、17%和13%。长期用ETOH处理后，吸入100、500和2500 ppm的DCM 4小时，与对照组相比，刺激了COHb的形成。COHb水平的升高伴随着血液中DCM浓度的降低。长期用ETOH处理大鼠后，通过测定大鼠肝微粒体中对硝基苯酚和苯胺羟化反应，确定DCM生物转化升高的原因是细胞色素P450依赖性酶活性增加。
