The digitoxin metabolism in isolated hepatocytes from young and old male Wistar rats

The metabolism of digitoxin (Dt3) in isolated hepatocyte preparations was studied in young (3-mth-old) male and female rats, young castrated (3-mth-old) male rats and old (22- to 28-mth-old) male rats. When hepatocytes were incubated with [3H]Dt3, the predominant metabolite of Dt3 was digitoxigenin-bis-digitoxoside (Dt2) which was 70-90% of the total metabolites in the three male rat groups. Only in the young female rat group was the proportion of Dt2 (40%) slightly exceeded by that of digoxigenin-bis-digitoxoside (Dg2) (50%). A kinetic analysis for Dt3 degradation velocity obtained from studies using different Dt3 concentrations in old male rats yielded a Vmax of only 21% of the young value. In young castrated males, the Vmax also decreased to 13% of the young non-castrated males, which is approaching the young female value. The changes were primarily due to the decline of Dt2 formation velocity in these groups. Apparent Km values also decreased with both castration and aging. The plasma testosterone levels which were much higher in young male rats than in female rats became significantly lower in young castrated rats as well as in old male rats. The results suggest that apparent decreases in Vmax and Km values observed in old male rats for Dt3 metabolic degradation may be at least partly through the steroidal hormone control, presumably, the decline of androgenic induction during aging.