Effects of methotrexate and phenobarbital on the hepatic microsomal drug-metabolizing enzymes in normal rat

The effect of methotrexate on the NADPH-dependent hepatic microsomal drug-metabolizing enzymes of the normal rat has been investigated. Pre-treatment of the animals with methotrexate for 3 successive days resulted in significant increases in the activities of biphenyl hydroxylase and ethylmorphine N-demethylase. The activity of these enzymes obtained from liver microsome preparations was also increased by methotrexate in vitro. The body weight, liver weight and the amount of both protein and DNA in each liver were significantly depressed by methotrexate treatment. All values, except the body weight, were increased to the control levels by additional treatment of the animals with phenobarbital. A likely explanation for the increase of enzyme activity by methotrexate has been discussed.