四氯化碳诱导大鼠肝微粒体脂质过氧化过程中的关键稳态缺氧条件。

The critical steady-state hypoxic conditions in carbon tetrachloride-induced lipid peroxidation in rat liver microsomes.

作者信息

Noll T, De Groot H

出版信息

Biochim Biophys Acta. 1984 Sep 12;795(2):356-62. doi: 10.1016/0005-2760(84)90086-9.

Abstract

Defined steady-state oxygen partial pressures (PO2) were maintained constant with an oxystat system to study carbon tetrachloride (CCl4)-induced lipid peroxidation and oxygen uptake in rat liver microsomes. The initial rates of oxygen uptake and malondialdehyde formation indicated drastically increasing lipid peroxidation by decreasing PO2, attaining a maximum between 1-10 mmHg (0.1-1.3 kPa). Under these conditions, at the hypoxic end of the physiological PO2 in liver, CCl4 caused a 5-fold increase in the oxygen uptake rate and a 20-fold increase in the malondialdehyde formation rate while, at 80 mmHg (10.7 kPa) the haloalkane caused only an increase of 2- and 4-fold, respectively; in comparison, there was only a slight increase in NADPH-induced lipid peroxidation with increasing PO2. These data clearly demonstrate the critical role of low steady-state PO2 in CCl4-induced lipid peroxidation and support lipid peroxidation as a key factor in CCl4 hepatotoxicity.

摘要

使用氧稳系统维持特定的稳态氧分压（PO2）恒定，以研究四氯化碳（CCl4）诱导的大鼠肝微粒体脂质过氧化和氧摄取。氧摄取和丙二醛形成的初始速率表明，通过降低PO2，脂质过氧化急剧增加，在1-10 mmHg（0.1-1.3 kPa）之间达到最大值。在这些条件下，在肝脏生理PO2的低氧端，CCl4使氧摄取速率增加5倍，丙二醛形成速率增加20倍，而在80 mmHg（10.7 kPa）时，卤代烷仅分别使氧摄取速率和丙二醛形成速率增加2倍和4倍；相比之下，随着PO2升高，NADPH诱导的脂质过氧化仅有轻微增加。这些数据清楚地证明了低稳态PO2在CCl4诱导的脂质过氧化中的关键作用，并支持脂质过氧化是CCl4肝毒性的关键因素。