THE INFLUENCE OF DIETARY RESTRICTION ON THE METABOLISM OF THEOPHYLLINE AND ANTIPYRINE IN THE AGING FEMALE BN BIRIJ RAT/

The influence of ageing and dietary restriction (DR) on the in vivo ac tivities of different P450 enzymes was studied longitudinally in femal e BN/BiRij rats. For this purpose, antipyrine (AP) and theophylline (T H) were used as substrates. The metabolic clearances of AP (Cl-m AP) a nd TH (Cl-m TH) were used as indicators for P450 enzyme activities in vivo. Therefore, we also included the assessment of the clearances of formation of three AP metabolites, i.e., 3-hydroxymethylantipyrine (Cl --->HMA) 4-hydroxyantipyrine (Cl-->(OHA) and norantipyrine (Cl--->NORA ). Ninety, 50 and 10% survival times were prolonged significantly in D R rats. In control animals, the contribution to the metabolism of AP i n the formation of HMA, OHA and NORA, expressed as percentage of the d ose, decreased with ageing, indicating that other pathways compensate for this decrease. Only a significant decrease in the metabolism to OH A was observed in DR animals. Cl--->HMA, Cl--->OHA and Cl--->NORA show ed an age-related decrease in the control rats, whereas in the DR rats an age-related decrease was observed for Cl--->HMA and Cl--->OHA. The results of the present study suggest that the decrease in the activit ies of the P450 enzymes involved in the formation of HMA, OHA and NORA have a later onset in the DR rats. In conclusion, DR not only has a s trong positive influence on the health and life span of the rats, but also results in a delayed onset of the decrease in activity of certain P450 enzymes.