Abstract

Prolonged oral administration of 5% PAS in the diet induces glycogen infiltration of the hepatic cell. Animals maintained on a 5% PAS diet also exhibited prolonged hexobarbital sleeping time, apparently due to a decreased ability of the organism to eliminate the barbiturate. In vitro microsomal metabolism of hexobarbital and aminopyrine was reduced in hepatic 9000 x g supernatant fractions prepared from animals maintained on the 5% PAS diet. Acute administration of PAS had no effect on hexobarbital sleeping time, and the addition in vitro of PAS to drug metabolizing enzyme systems was not inhibitory. The inhibitory actions of PAS on the microsomal enzymes from animals fed the drug for 2 weeks were not reversed by dialysis or washing of the microsomes. The defect in drug metabolizing activity in livers from PAS-treated animals was localized in the microsome. The possibility of a correlation between hepatic glycogen level, structure of the smooth-surfaced endoplasmic reticulum, and the activity of certain microsomal enzymes is discussed.