DOSTÁLEK, Miroslav, Jana PISTOVČÁKOVÁ, Jan JUŘICA, Josef TOMANDL, Igor LINHART, Alexandra ŠULCOVÁ and Eva HADAŠOVÁ. Effect of St John's wort (Hypericum perforatum) on cytochrome P-450 activity in perfused rat liver. Life Sciences. Amsterdam, The Netherlands,: Elsevier, 2005, vol. 78, No 3, p. 239-244, 5 pp. ISSN 0024-3205.
Other formats:   BibTeX LaTeX RIS
Basic information
Original name Effect of St John's wort (Hypericum perforatum) on cytochrome P-450 activity in perfused rat liver
Name in Czech Vliv tťezalky tečkované na aktivitu CYP450 na modelu izolovaných perfundovaných jater potkanů
Authors DOSTÁLEK, Miroslav (203 Czech Republic, belonging to the institution), Jana PISTOVČÁKOVÁ (703 Slovakia, belonging to the institution), Jan JUŘICA (203 Czech Republic, belonging to the institution), Josef TOMANDL (203 Czech Republic, belonging to the institution), Igor LINHART (203 Czech Republic), Alexandra ŠULCOVÁ (203 Czech Republic, belonging to the institution) and Eva HADAŠOVÁ (203 Czech Republic, guarantor, belonging to the institution).
Edition Life Sciences, Amsterdam, The Netherlands, Elsevier, 2005, 0024-3205.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 30104 Pharmacology and pharmacy
Country of publisher Czech Republic
Confidentiality degree is not subject to a state or trade secret
Impact factor Impact factor: 2.512
RIV identification code RIV/00216224:14110/05:00014108
Organization unit Faculty of Medicine
UT WoS 000233330000003
Keywords in English St John's wort; cytochrome P450; perfused rat liver; drug interaction
Tags cytochrome P450, drug interaction, perfused rat liver, St John's wort
Tags International impact, Reviewed
Changed by Changed by: doc. RNDr. Josef Tomandl, Ph.D., učo 47. Changed: 6/6/2012 08:37.
Abstract
St. John's wort (Hypericum perforatum) is a popular over-the-counter dietary supplement and a herbal antidepressant that has been implicated in drug interactions with substrates of several cytochrome P-450 (CYP) isozymes. The effects of the St. John's wort extract (100 mg/kg, i.p., once daily for 10 days) on metabolic activity of CYP450 were assessed in the system of isolated perfused rat liver. The substrates used in this study were tolbutamide (CYP2C6), dextromethorphan (CYP2D2) and midazolam (CYP3A2). Validated HPLC method was used to quantify all compounds of interest. St. John's wort administration affected CYP activity, causing a significant decline in AUC of dextromethorphan [F(4,31) = 1511, p < 0.001; PLSD, p < 0.001] and AUC of midazolam [F(3,25) = 221, p < 0.001; PLSD, p = 0.035] and a significant increase in AUC of tolbutamide [F(3,26) = 200, p < 0.001; PLSD, p < 0.001]. St. John's wort administration resulted in a significant induction of CYP2D2 and CYP3A2, and in a significant inhibition of CYP2C6 metabolic activities.
Abstract (in Czech)
Cílem experimentu bylo, na modelu izolovaných perfundovaných jater potkanů popsat vliv standardizovaného extraktu třezalky tečkované (LI160) na metabolickou aktivitu nejvýznamnějších izoforem cytochromu P450. K experimentu byli použiti samci potkanů Wistar, extrakt LI160 byl podáván v dávce 100 mg/kg/den, i.p. po dobu 10 dnů. Jako markery metabolické aktivity CYP2C6/11, CYP2D1/2 a CYP3A1/2 byly zvoleny tolbutamid, dextrometorfan a midazolam. Pro přesné definovaní změny metabolické aktivity izoforem CYP450 byly použity komparační inhibitory a induktory. Byl popsán statisticky významný inhibiční vliv extraktu LI160 na metabolickou aktivitu CYP2C6/11 (p<0.001) a statisticky významný indukční vliv na metabolickou aktivitu CYP2D1/2 (p<0.001) a CYP3A1/2 (p<0.01). Prokázali jsme dosud nepopsaný signifikantní vliv LI160 na metabolickou aktivitu vybraných izoforem cytochromu P450 (indukce CYP2D1/2 a inhibice CYP2C6/11 a CYP3A1/2), což má v klinické užití tohoto léčiva nesmírný význam pro predikci interakcí s jinými léčivy či složkami diety metabolizovanými stejným způsobem.
Links
MSM 141100001, plan (intention)Name: Plasticita řídících systémů centrálního nervového systému a možnosti jejího ovlivnění
PrintDisplayed: 20/5/2024 12:05