The effects of heavy metal ions, phthalates and ochratoxin A on oxidation of carcinogenic aristolochic acid I causing Balkan endemic nephropathy
Jazyk angličtina Země Švédsko Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
14329
Cancer Research UK - United Kingdom
PubMed
26757129
PII: NEL360915A01
Knihovny.cz E-zdroje
- MeSH
- arsen farmakologie MeSH
- balkánská nefropatie * MeSH
- ionty MeSH
- jaterní mikrozomy metabolismus MeSH
- kadmium farmakologie MeSH
- karcinogeny metabolismus MeSH
- krysa rodu Rattus MeSH
- kyseliny aristolochové metabolismus MeSH
- kyseliny ftalové farmakologie MeSH
- ochratoxiny farmakologie MeSH
- olovo farmakologie MeSH
- oxidace-redukce účinky léků MeSH
- selen farmakologie MeSH
- těžké kovy farmakologie MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- aristolochic acid I MeSH Prohlížeč
- arsen MeSH
- ionty MeSH
- kadmium MeSH
- karcinogeny MeSH
- kyseliny aristolochové MeSH
- kyseliny ftalové MeSH
- ochratoxin A MeSH Prohlížeč
- ochratoxiny MeSH
- olovo MeSH
- selen MeSH
- těžké kovy MeSH
OBJECTIVES: Balkan endemic nephropathy (BEN) is a chronic progressive fibrosis associated with upper urothelial carcinoma (UUC). Aetiology of BEN is still not fully explained. Although carcinogenic aristolochic acid I (AAI) was proven as the major cause of BEN/UUC, this nephropathy is considered to be multifactorial. Hence, we investigated whether other factors considered as potential causes of BEN [a mycotoxin ochratoxin A (OTA), Cd, Pb, Se and As ions and organic compounds (i.e. phthalates) released from lignite deposits in BEN areas] can influence detoxication of AAI, whose concentrations are crucial for BEN development. METHODS: Oxidation of AAI to 8-hydroxyaristolochic acid I (AAIa) in the presence of Cd, Pb, Se, As ions, dibutylphthalate (DBP), butylbenzylphthalate (BBP), bis(2-ethylhexyl)phthalate (DEHP) and OTA by rat liver microsomes was determined by HPLC. RESULTS: Only OTA, cadmium and selenium ions, and BBP inhibited AAI oxidation by rat liver microsomes. These compounds also inhibited activities of CYP1A1 and/or CYP2C6/11 catalysing AAI demethylation in rat livers. Therefore, these CYP inhibitions can be responsible for a decrease in AAIa formation. When the combined effects of these compounds were investigated, the most efficient inhibition was caused by OTA combined with BBP and selenium ions. CONCLUSION: The results show low effects of BBP, cadmium and selenium ions, and/or their combinations on AAI detoxication. No effects were produced by the other metal ions (Pb, As) and phthalates DBP and DEHP. This finding suggests that they do not influence AAI-mediated BEN development. In contrast, OTA might influence this process, by inhibition of AAI detoxication.
Department of Biochemistry Faculty of Science Charles University Prague Czech Republic
Division of Molecular Toxicology German Cancer Research Center Heidelberg Germany
Balkan endemic nephropathy: an update on its aetiology
