Food restriction prevents the loss of isosafrole inducible cytochrome P-450 mRNA and enzyme levels in aging rats.
The influence of food restriction (FR) on the drug-inducible capacity of liver microsomal cytochrome P-450s IA1, IA2 and IIB1 and IIB2 was studied in 20-month-old male Fischer-344 rats. ELISA and Western Blotting revealed that the induction of the cytochrome P-450-IA1/IA2 and P-450-IIB1/IIB2 enzymes was considerably higher in the liver microsomes of FR rats than in their ad libitum (AL) fed counterparts. In order to determine whether the higher P-450 enzyme levels in FR rats were a reflection of an increased synthesis rate or a stabilization of these enzymes, hybridization studies were performed with a cDNA probe for P-450-IIB1/IIB2. These studies show markedly higher levels of P-450-IIB1/IIB2 mRNAs in the livers of FR rats as compared to AL animals. These results suggest that it is possible to prevent the age-dependent loss of drug-induced cytochrome P-450s by 40% dietary restriction which suggest FR may improve the drug-metabolizing capacity during aging.
Horbach
G J
GJ
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7874.
Venkatraman
J T
JT
Fernandes
G
G
D000375:Aging / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D004149:Dioxoles / Q000494:pharmacology*; D004790:Enzyme Induction; D004797:Enzyme-Linked Immunosorbent Assay; D005508:Food Deprivation; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011916:Rats, Inbred F344; D012451:Safrole / Q000494:pharmacology*
D004149:Dioxoles; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D012451:Safrole; C015959:isosafrole