Document Detail

Food restriction and stimulation of monooxygenation of p-nitroanisole in perfused rat liver.
MedLine Citation:
PMID:  8053926     Owner:  NLM     Status:  MEDLINE    
This study assessed the effect of food restriction on the metabolism of model monooxygenase substrates in the perfused rat liver. Female Sprague-Dawley rats has access ad lib. to a Purina 5001 nonpurified diet (control) or were given 65% of the intake of controls for 3 weeks. Livers were perfused with oxygenated Krebs-Henseleit buffer using a non-recirculating system, and the rates of monooxygenation of p-nitroanisole and 7-ethoxycoumarin were measured. The results indicate that food restriction stimulated p-nitroanisole O-demethylation from 2.9 +/- 0.2 to 4.6 +/- 0.5 mumol/( when saturating concentrations of p-nitroanisole were infused. Concomitantly, the ratio of beta-hydroxybutyrate to acetoacetate (B/A) and the rates of ketogenesis (B + A) were increased significantly by food restriction. Further, p-nitroanisole (200 mumol/L) increased hepatic malate concentration nearly 3-fold in liver extracts from food-restricted rats. However, infusion of either a low concentration of p-nitroanisole (50 mumol/L) or 7-ethoxycoumarin (200 mumol/L) did not alter these parameters. On the other hand, food restriction did not alter rates of monooxygenation in isolated microsomes supplemented with excess NADPH. Taken together, these data support the hypothesis that high concentrations of p-nitroanisole increased monooxygenation in food-restricted rats by stimulating fatty acid oxidation, which elevates the mitochondrial NADH/NAD+ ratio. This, in turn, increases the availability of reducing equivalents in the form of NADPH by a malate-pyruvate exchange system, leading to increased drug metabolism.
W Qu; F C Kauffman; R G Thurman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  48     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  1994 Jul 
Date Detail:
Created Date:  1994-09-06     Completed Date:  1994-09-06     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  311-7     Citation Subset:  IM    
Department of Pharmacology, University of North Carolina at Chapel Hill, 27599-7365.
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MeSH Terms
7-Alkoxycoumarin O-Dealkylase / metabolism
Anisoles / pharmacology
Enzyme Activation / drug effects
Fatty Acids / metabolism
Ketone Bodies / analysis
Liver / enzymology*
Nitroanisole O-Demethylase / metabolism*
Rats, Sprague-Dawley
Grant Support
Reg. No./Substance:
0/Anisoles; 0/Fatty Acids; 0/Ketone Bodies; 100-17-4/4-nitroanisole; 53-59-8/NADP; EC 1.-/Nitroanisole O-Demethylase; EC 1.14.13.-/7-Alkoxycoumarin O-Dealkylase

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