Induction of liver and kidney CYP1A1/1A2 by caffeine in rat

Biochem Pharmacol. 1996 Dec 24;52(12):1915-9. doi: 10.1016/s0006-2952(96)00522-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cytochrome P-450 CYP1A1 / biosynthesis*
  • Cytochrome P-450 CYP1A2 / biosynthesis*
  • Enzyme Induction / drug effects
  • Gene Expression Regulation, Enzymologic / drug effects
  • Kidney / enzymology
  • Male
  • Microsomes, Liver / enzymology
  • RNA, Messenger / genetics
  • Rats
  • Rats, Wistar


  • RNA, Messenger
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP1A2