Aims. 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.

Department of Biochemistry Faculty of Medicine Masaryk University Brno

Department of Biomedical and Pharmaceutical Sciences University of Rhode Island Kingston

Department of Pharmacology Faculty of Medicine Masaryk University Brno

Masaryk University Central European Institute of Technology c o Masaryk University Brno

Obsahuje 1 tabulku

Literatura

000      

00000naa a2200000 a 4500

001      

bmc12000419

003      

CZ-PrNML

005      

20120215151727.0

007      

ta

008      

120113s2011 xr d f 000 0eng||

009      

AR

040    __

$a ABA008 $d ABA008 $e AACR2 $b cze

041    0_

$a eng

044    __

$a xr

100    1_

$a Dostálek, Miroslav $7 xx0030377 $u Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno; Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston

245    14

$a The effect of st John's wort (hypericum perforatum) on cytochrome p450 1a2 activity in perfused rat liver / $c Miroslav Dostalek, Jana Pistovcakova, Jan Jurica, Alexandra Sulcova, Josef Tomandl

500    __

$a Obsahuje 1 tabulku

504    __

$a Literatura $b 23

520    9_

$a Aims. 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.

650    02

$a zvířata $7 D000818

650    02

$a antidepresiva $x farmakologie $7 D000928

650    02

$a plocha pod křivkou $7 D019540

650    02

$a systém (enzymů) cytochromů P-450 $x antagonisté a inhibitory $x biosyntéza $x metabolismus $7 D003577

650    02

$a dextromethorfan $x farmakokinetika $7 D003915

650    02

$a interakce bylin a léků $7 D041743

650    02

$a třezalka $7 D020902

650    02

$a injekce intraperitoneální $7 D007274

650    02

$a játra $x enzymologie $x účinky léků $7 D008099

650    02

$a mužské pohlaví $7 D008297

650    02

$a midazolam $x farmakokinetika $7 D008874

650    02

$a perfuze $7 D010477

650    02

$a rostlinné extrakty $x farmakologie $7 D010936

650    02

$a krysa rodu Rattus $7 D051381

650    02

$a potkani Wistar $7 D017208

650    02

$a tolbutamid $x farmakokinetika $7 D014044

650    _2

$a financování organizované $7 D005381

650    _2

$a játra $x enzymologie $x metabolismus $x účinky léků $7 D008099

650    _2

$a paracetamol $x farmakokinetika $x metabolismus $7 D000082

650    _2

$a fenacetin $x farmakokinetika $x metabolismus $7 D010615

650    _2

$a financování organizované $7 D005381

655    _2

$a techniky in vitro $7 D066298

700    1_

$a Pistovčáková, Jana, $d 1972- $7 mzk2004217471 $u Masaryk University, Central European Institute of Technology (CEITEC), c/o Masaryk University, Brno

700    1_

$a Juřica, Jan $7 xx0085543 $u Masaryk University, Central European Institute of Technology (CEITEC), c/o Masaryk University, Brno

700    1_

$a Šulcová, Alexandra, $d 1945- $7 jn20000402920 $u Masaryk University, Central European Institute of Technology (CEITEC), c/o Masaryk University, Brno

700    1_

$a Tomandl, Josef, $d 1964- $7 mzk2003175507 $u Department of Biochemistry, Faculty of Medicine, Masaryk University, Brno

773    0_

$t Biomedical papers $x 1213-8118 $g Roč. 155, č. 3 (2011), s. 253-258 $w MED00012606

910    __

$a ABA008 $b A 1502 $c 958 $y 2

990    __

$a 20120112154833 $b ABA008

991    __

$a 20120215151707 $b ABA008

999    __

$a ok $b bmc $g 893105 $s 757100

BAS    __

$a 3

BMC    __

$a 2011 $b 155 $c 3 $d 253-258 $i 1213-8118 $m Biomedical papers of the Medical Faculty of the University Palacký, Olomouc Czech Republic $n Biomed. Pap. Fac. Med. Palacký Univ. Olomouc Czech Repub. (Print) $x MED00012606

LZP    __

$a 2012-03/dkme