title: Induction of liver and kidney CYP1A1/1A2 by caffeine in rat.
abstract: Caffeine metabolism by hepatic microsomal P450 enzymes is well documented in experimental animals and humans. However, its induction effect on P450 enzymes has not been thoroughly studied. In a preliminary experiment, the time-dependent incubation of 1 mM caffeine with rat hepatocyte culture resulted in an increase of its own metabolic rate. The dose-dependent expression of rat hepatic and renal cytochromes (CYP) 1A1/1A2 was then investigated after per os administration of caffeine. P450 expression was monitored by using specific enzymatic activities and Northern blot analysis. Caffeine caused a dose-dependent elevation of hepatic CYP1A1/1A2 activities in microsomal preparations, which ranged from 1.7- to 6-fold for ethoxyresorufin O-deethylase and 3- to 8.9-fold for methoxy-resorufin O-demethylase according to the dose regimen of 50 and 150 mg caffeine/kg/day for 3 days, respectively. Northern blot analysis demonstrated that caffeine treatment increased liver CYP1A1 and CYP1A2 mRNA levels over the dose regimen of 50-150 mg caffeine/kg/day for 3 days, respectively. The result of this study demonstrates that caffeine increases its own metabolism in a dose-dependent manner and induces CYP1A1/1A2 expression through either transcriptional activation or mRNA stabilization.
authors.affiliation: Laboratoires de Biochimie-Nutrition EA-948, Faculté de Medecine, Brest, France.
authors.forename: T
authors.initials: T
authors.lastname: Goasduff
authors.forename: Y
authors.initials: Y
authors.lastname: Dréano
authors.forename: B
authors.initials: B
authors.lastname: Guillois
authors.forename: J F
authors.initials: JF
authors.lastname: Ménez
authors.forename: F
authors.initials: F
authors.lastname: Berthou
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007668:Kidney / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
chemical_list: D012333:RNA, Messenger; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2