The Effect of Diet and Drugs on Hepatic Microsomal Aminopyrine N-demcthylase Activity in Vitro and Susceptibility to Carbon Tetrachloride in Sheep

Sheep liver microsomal enzymes can N-demethylate aminopyrine to 4-amino-antipyrine. This enzyme activity is unaffected by freezing and thawing. Samples of liver collected from sheep from different flocks had different mean levels of the enzyme activity. Treatment with DDT and phenobarbitone causes a 3- to 9-fold increase in susceptibility of the animals to carbon tetrachloride and a similar increase in liver microsomal enzyme activity. Beetling a diet high in protein for 3 weeks causes a 3- to 4-fold increase in susceptibility to carbon tetrachloride but no change in aminopyrine N-demcthylase activity in vitro. Dosing susceptible sheep with carbon tetrachloride temporarily depresses microsomal enzyme activity. Loss of hepatic microsomal detoxicating activity due to liver injury may thus be a factor in mortalities in the field.