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

Abstract

Defined steady-state oxygen partial pressures ( p O 2) were maintained constant with an oxystat system to study carbon tetrachloride (CCl 4)-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 p O 2, attaining a maximum between 1–10 mmHg (0.1–1.3 kPa). Under these conditions, at the hypoxic end of the physiological p O 2 in liver, CCl 4 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 p O 2. These data clearly demonstrate the critical role of low steady-state p O 2 in CCl 4-induced lipid peroxidation and support lipid peroxidation as a key factor in CCl 4 hepatotoxicity.