Human cytochromes P450 1A1 and 1A2 participate in detoxication of carcinogenic aristolochic acid
Jazyk angličtina Země Švédsko Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
18987598
PII: NEL290508A20
Knihovny.cz E-zdroje
- MeSH
- cytochrom P-450 CYP1A1 izolace a purifikace metabolismus MeSH
- cytochrom P-450 CYP1A2 izolace a purifikace metabolismus MeSH
- jaterní mikrozomy enzymologie MeSH
- karcinogeny farmakokinetika MeSH
- krysa rodu Rattus MeSH
- kyseliny aristolochové farmakokinetika MeSH
- lidé MeSH
- metabolická inaktivace MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- aristolochic acid I MeSH Prohlížeč
- cytochrom P-450 CYP1A1 MeSH
- cytochrom P-450 CYP1A2 MeSH
- karcinogeny MeSH
- kyseliny aristolochové MeSH
OBJECTIVES: A carcinogenic and nephrotoxic plant alkaloid, aristolochic acid (AA), causes the development of aristolochic acid nephropathy, which is characterized by chronic renal failure, tubulointerstitial fibrosis and urothelial cancer. AA may also cause a similar type of kidney fibrosis with malignant transformation of the urothelium, the Balkan endemic nephropathy. The aim of the study was to resolve which cytochromes P450 (CYP) detoxicate the major component of AA, aristolochic acid I (AAI), to its O-demethylated metabolite, aristolochic acid Ia (AAIa). METHODS: High performance liquid chromatography (HPLC) was employed for separation and characterization of AAI metabolites generated by CYPs. RESULTS: Human, rat and mouse hepatic CYPs oxidize AAI into its detoxication metabolite AAIa. Most of the detoxication of AAI in human hepatic microsomes is mediated by CYP1A2 and 1A1, while other CYPs play a minor role. CONCLUSIONS: The data are the first report on identification of human CYP enzymes detoxicating AAI.
Balkan endemic nephropathy: an update on its aetiology
