The effects of 2,2-diethylallylacetamide on hepatic cytochromes in rats and in vitro.

The application of 0.15 and 0.3% of diethylallylacetamide (DA) in the drinking water to rats during 10 days increased the relative liver weight, the yield of hepatic microsomes, and cytochromes P-450 and b5. Single s.c. doses of 400 mg DA per kg reduced cytochrome P-450 concentrations in the hepatic endoplasmic reticulum of rats. This effect was considerably more pronounced in rats pretreated with phenobarbital. The activity of 5-aminolaevulinic acid synthesis in liver mitochondria, and total liver porphyrins increased. In incubations of metabolizing hepatic microsomes from rabbits pretreated with phenobarbital 75% of 0.1 mM DA was degraded after 1 h. The aerobic incubation of 0.1 mM DA with rabbit hepatic microsomes in the presence of NADPH produced 50% destruction of cytochrome P-450 within 1 h. Addition of EDTA revealed that a part of this destruction cannot be explained by accelerated lipid peroxidation.