K. Groen et al., THE INFLUENCE OF DIETARY RESTRICTION ON THE METABOLISM OF THEOPHYLLINE AND ANTIPYRINE IN THE AGING FEMALE BN BIRIJ RAT/, The Journal of pharmacology and experimental therapeutics, 274(1), 1995, pp. 143-147
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.