Rat liver oxidative N-dealkylase and N-oxidase activities as a function of animal age

Abstract

The enzymic NADPH and oxygen-dependent oxidations of N, N-dimethylaniline (DMA), N-methylaniline, and N-methyl- n-octylamine were measured in microsomes isolated from liver homogenates obtained from normal male albino rats that varied in age from 3–24 weeks. Oxidative N-dealkylase activities were estimated by measuring the formation of formaldehyde; the N-oxidase activities were determined by measuring the formation of the tertiary amine oxide and the N-hydroxylamine derivatives of the secondary amines. The concentration of hepatic microsomal oxidative N-dealkylase enzymes was low in weanling rats, increased to a maximum in the young adults, and then remained relatively constant or decreased in the older animals. The DMA N-oxidase activity, however, was consistently highest in liver microsomes from the older animals. Microsomes from the youngest rats catalyzed N-oxidation of 30% of the total DMA oxidized, whereas 48% of the DMA oxidized was converted to the amine oxide by microsomes obtained from the oldest animals. In normal rats, there appears to be a direct correlation between hepatic N-oxidase activity and the age of the animal. Hepatic microsomes from all ages of animals catalyzed the Oxidative N-dealkylation and N-hydroxylation of both secondary amines tested. In general, the highest N-hydroxylase rates were observed with microsomes from the older animals.