| Human cytochromes P450 1A1 and 1A2 participate in detoxication of carcinogenic aristolochic acid. | |
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MedLine Citation:
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PMID: 18987598 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Jana Sistkova; Jiri Hudecek; Petr Hodek; Eva Frei; Heinz H Schmeiser; Marie Stiborova |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Neuro endocrinology letters Volume: 29 ISSN: 0172-780X ISO Abbreviation: Neuro Endocrinol. Lett. Publication Date: 2008 Oct |
Date Detail:
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Created Date: 2008-11-25 Completed Date: 2009-02-19 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8008373 Medline TA: Neuro Endocrinol Lett Country: Sweden |
Other Details:
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Languages: eng Pagination: 733-7 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Faculty of Science, Charles University, Prague, Czech Republic. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aristolochic Acids / pharmacokinetics* Carcinogens / pharmacokinetics* Chromatography, High Pressure Liquid Cytochrome P-450 CYP1A1 / isolation & purification, metabolism* Cytochrome P-450 CYP1A2 / isolation & purification, metabolism* Humans Metabolic Detoxication, Drug Mice Mice, Inbred C57BL Microsomes, Liver / enzymology Rats |
| Chemical | |
Reg. No./Substance:
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0/Aristolochic Acids; 0/Carcinogens; 313-67-7/aristolochic acid I; EC 1.14.14.1/Cytochrome P-450 CYP1A1; EC 1.14.14.1/Cytochrome P-450 CYP1A2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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