Hepatic Glutathione Content and Aryl Hydrocarbon Hydroxylase Activity of Acetaminophen-Treated Mice as a Function of Age

Abstract

Glutathione (GSH) plays an important role in cells as an anti-oxidant, and participates in the detoxification of drugs and foreign chemicals. The effect of age on hepatic glutathione (GSH) levels and aryl hydrocarbon hydroxylase (AHH) activity and the ability of these mice to respond to the acute administration of acetaminophen (AAP) has been studied. Female Swiss Webster mice at ages 3, 9, and 18 mo were treated i.p. with 500 mg/kg AAP, and hepatic GSH content and AHH activity were determined at 0, 0.5, 2, 4, 6, 8, 10, 12, and 24 hrs. The hepatic GSH levels and the AHH activity in 18 mo old mice were 43% and 36% lower, respectively, as compared to the 3 mo old animals. Maximum AAP-induced depletion of GSH occurred 2–4 hrs after treatment. Only in 18 mo animals did GSH fail to return to or exceed control levels 24 hr after AAP administration. Maximum decrease in hepatic AHH activity occurred in all age groups at 10 hr post-AAP administration, and had not returned to control values 24 hr after treatment. The results support the hypothesis that a decrease in GSH and mixed function oxidases may contribute to changes associated with aging as well as to the increased susceptibility to disease and drugs which occur with advanced age.