Caffeine increases its own metabolism through cytochrome P4501A induction in rats.
Caffeine is one of the most widely used - and maybe abused - xenobiotic compounds in the world. If numerous pharmacological properties of caffeine have been reported, the effects of caffeine treatment on the hepatic drug-metabolizing enzyme system have been scarcely studied. Pretreatment of rats for 3 days with 150 mg/kg/day of caffeine dramatically increased P4501A and P4502B dependent catalytic activities determined in vitro. Furthermore, N-demethylations and C-8 oxidation of caffeine were increased by about 2 fold by caffeine treatment. Immunoblot analysis demonstrated that the liver contents of P4501A2 and P4502B1/2B2, known to be involved in these monooxygenase activities, increased also by about 2 fold. Cytochrome P4503A1 and 2E1 were not modified. Taken together, there data suggest that caffeine increases its own metabolism through P4501A induction.
Berthou
F
F
Laboratoire de Biochimie-Nutrition, Faculté de Médecine, Brest, France.
Goasduff
T
T
Dréano
Y
Y
Ménez
J F
JF
D000818:Animals; D002110:Caffeine / Q000378:metabolism / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D015151:Immunoblotting; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D002110:Caffeine; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases