The perinatal development of epoxide-metabolizing enzyme activities in liver and extrahepatic organs of guinea pig and rabbit

Abstract

We have measured the activities of epoxide hydrase in microsomes and glutathione S-epoxidetransferase and glutathione S-aryltransferase in cytosol fractions of liver, lungs, kidneys, and small intestine from fetal and neonatal guinea pigs and rabbits. The rates at which adult values of these enzyme activities are reached in extrahepatic tissues differ from the rates of maturation of the hepatic enzyme activities for both species. In addition, the two pathways of epoxide metabolism studied here developed with age at different rates in any one organ. However, both cytosol glutathione S-transferases showed very similar developmental profiles in any one organ. It was especially interesting that the activities of both glutathione S-transferases were within the adult range in pulmonary cytosol fraction of guinea pig and rabbit before birth. Intestinal microsomes did not have adult values for epoxide hydrase activity until several weeks after birth. A feature common to both epoxide-metabolizing activities in hepatic and extrahepatic organs was a drop in mean specific activity, sometimes not statistically significant, around the time of birth. This decrease appeared to be due to dilution of the active enzyme with other protein, inasmuch as the total organ activity, in general, showed no such decline. We found that the pattern of development of hepatic microsomal epoxide hydrase activity was similar to developmental patterns published by others for hepatic microsomal mixed-function oxidases, and also that development of hepatic cytosol glutathione S-transferase was similar to hepatic development of glutathione S-transferase towards other substrates described in the literature.