title: The effect of St John's wort (hypericum perforatum) on cytochrome p450 1a2 activity in perfused rat liver.
abstract: OBJECTIVE
  We previously reported the effect of St John's wort (Hypericum perforatum) standardised extract LI 160 on the activities of cytochrome P450 2C6, 2D2 and 3As (Dostalek et al., Life Sciences 2005;78(3):239-44). In this study, we aimed to assess the effect of St John's wort on the activity of cytochrome P450 1A2.
  
  
  METHODS
  The isolated perfused rat liver model was used in our experiments with phenacetin as a marker substrate for cytochrome P450 1A2. Male Wistar rats were treated with St John's wort extract (100 mg/kg, once daily for 10 days); comparative inhibitor (alpha-naphthoflavone, 100 mg/kg) or comparative inducer (omeprazole, 30 mg/kg).
  
  
  RESULTS
  The rate of formation of acetaminophen was significantly inhibited by the use of St John's wort (P<0.001). In addition, St John's wort extract inhibited cytochrome P450 1A2 activity significantly more than the control inhibitor (P<0.001).
  
  
  CONCLUSIONS
  St John's wort significantly inhibited cytochrome P450 1A2 enzyme activity. It remains to be determined whether the co-administration of St John's wort extract and other medications or substrates for cytochrome P450 1A2 could result in significant drug interactions.
authors.affiliation: Department of Biochemistry, Masaryk University Brno, Czech Republic.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Dostalek
authors.forename: Jana
authors.initials: J
authors.lastname: Pistovcakova
authors.forename: Jan
authors.initials: J
authors.lastname: Jurica
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sulcova
authors.forename: Josef
authors.initials: J
authors.lastname: Tomandl
mesh_terms: D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020902:Hypericum; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology*; D008297:Male; D009853:Omeprazole / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001571:Benzoflavones; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D004791:Enzyme Inhibitors; D010936:Plant Extracts; C011512:alpha-naphthoflavone; D019388:Cytochrome P-450 CYP1A2; D009853:Omeprazole