Aristolactam I a metabolite of aristolochic acid I upon activation forms an adduct found in DNA of patients with Chinese herbs nephropathy
Jazyk angličtina Země Německo Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
10445409
DOI
10.1016/s0940-2993(99)80033-5
PII: S0940-2993(99)80033-5
Knihovny.cz E-zdroje
- MeSH
- adukty DNA analýza metabolismus MeSH
- dioxoly analýza metabolismus MeSH
- DNA metabolismus MeSH
- fenantreny metabolismus MeSH
- fibróza MeSH
- indoly analýza metabolismus MeSH
- křenová peroxidasa metabolismus MeSH
- krysa rodu Rattus MeSH
- kyseliny aristolochové * MeSH
- léky rostlinné čínské škodlivé účinky MeSH
- lidé MeSH
- nemoci ledvin chemicky indukované MeSH
- peroxid vodíku farmakologie MeSH
- potkani Sprague-Dawley MeSH
- systém (enzymů) cytochromů P-450 metabolismus MeSH
- ureter chemie MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adukty DNA MeSH
- aristolactam I MeSH Prohlížeč
- aristolochic acid I MeSH Prohlížeč
- dioxoly MeSH
- DNA MeSH
- fenantreny MeSH
- indoly MeSH
- křenová peroxidasa MeSH
- kyseliny aristolochové * MeSH
- léky rostlinné čínské MeSH
- peroxid vodíku MeSH
- systém (enzymů) cytochromů P-450 MeSH
Aristolochic acid (AA) a naturally occuring nephrotoxin and carcinogen is implicated in a unique type of renal fibrosis, designated Chinese herbs nephropathy (CHN). We identified AA-specific DNA adducts in kidneys and in a ureter obtained from CHN patients after renal transplantation. AA is a plant extract of aristolochia species containing AA I as the major component. Aristolactams are the principal detoxication metabolites of AA, which were detected in urine and faeces from animals and humans. They are activated by cytochrome P450 (P450) and peroxidase to form DNA adducts. Using the 32P-postlabelling assay we investigated the formation of DNA adducts by aristolactam I in these two activation systems. A combination of two independent chromatographic systems (ion-exchange chromatography TLC and reversed-phase HPLC) with reference compounds was used for the identification of adducts. Aristolactam I activated by peroxidase led to the formation of several adducts. Two major adducts were identical to adducts previously observed in vivo. 7-(deoxyguanosin-N2-yl)aristolactam I (dG-AAI) and 7-(deoxyadenosin-N6-yl)aristolactam I (dA-AAI) were formed in DNA during the peroxidase-mediated one-electron oxidation of aristolactam I. Aristolactam I activated by P450 led to one major adduct and four minor ones. Beside the principal AA-DNA adducts identified recently in the ureter of one patient with CHN, an additional minor adduct was detected, which was found to have indistinguishable chromatographic properties on TLC and HPLC from the major adduct formed from aristolactam I by P450 activation. Thus, this minor AA-adduct might be evolved from the AAI detoxication metabolite (aristolactam I) by P450 activation. These results indicate a potential carcinogenic effect of aristolactam I in humans.
Citace poskytuje Crossref.org
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