Autoxidative injury with loss of cytochrome P-450 following acute exposure of rats to fasting and ether anaesthesia

Abstract

1. Exposure of fasted rats (20 h) to ether anaesthesia for 4 min resulted in increased exhalation of alkanes, an indication of lipid peroxidation in vivo.

2. Liver and kidney of the fasted rats anaesthetized with ether showed immediate 4-fold increases in luminol-amplined chemiluminescence, reaching maxima 30 min later, indicating the production of reactive oxygen species.

3. Liver and kidney cytosols of the fasted anaesthetized rats similarly showed immediate 4-fold increases of thiobarbituric acid-reactive material (malondialdehyde and other lipid peroxidation breakdown products) which attained maxima 60 min later.

4. Total cytochromes P-450 of liver and kidney of rats were decreased to 25-30% of control values after 20 h fasting and 4 min of ether anaesthesia, but were restored to normal levels 2h later. Cytochrome P450 I (EROD activity) was decreased to 35-44% of control values by the ether anaesthesia and was restored to 80% of normal levels 2h later.

5. Diether ether is known to be metabolized by cytochrome P450 IIE1 which is induced by fasting and by diethyl ether, and is possibly involved in the observed radical production, lipid peroxidation, and loss of cytochromes P-450.