Comparison of the oxidation of carcinogenic aristolochic acid I and II by microsomal cytochromes P450 in vitro: experimental and theoretical approaches

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F17%3A10364679" target="_blank" >RIV/00216208:11310/17:10364679 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1007/s00706-017-2014-9" target="_blank" >http://dx.doi.org/10.1007/s00706-017-2014-9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00706-017-2014-9" target="_blank" >10.1007/s00706-017-2014-9</a>

Result language

angličtina

Original language name

Comparison of the oxidation of carcinogenic aristolochic acid I and II by microsomal cytochromes P450 in vitro: experimental and theoretical approaches

Original language description

The herbal drug aristolochic acid, a natural mixture of 8-methoxy-6-nitrophenanthro[3,4-d]-1,3-dioxole-5-carboxylic acid (AAI) and 6-nitrophenanthro[3,4-d]-1,3-dioxole-5-carboxylic acid (AAII), is derived from Aristolochia species and is the cause of two nephropathies. Ingestion of aristolochic acid is associated with the development of urothelial tumors linked with aristolochic acid nephropathy and is implicated in the development of Balkan endemic nephropathy-associated urothelial tumors. The O-demethylated metabolite of AAI, 8-hydroxyaristolochic acid (AAIa), is the detoxification product of AAI generated by its oxidative metabolism. Whereas the formation of AAIa from AAI by cytochrome P450 (CYP) enzymes has been found in vitro and in vivo, this metabolite has not been found from AAII as yet. Therefore, the present study has been designed to compare the amenability of AAI and AAII to oxidation; experimental and theoretical approaches were used for such a study. In the case of experimental approaches, the enzyme (CYP)-mediated formation of AAIa from both carcinogens was investigated using CYP enzymes present in subcellular microsomal fractions and recombinant CYP enzymes. We found that in contrast to AAI, AAII is oxidized only by several CYP enzymatic systems and their efficiency is much lower for oxidation of AAII than AAI. Using the theoretical approaches, such as flexible in silico docking methods and ab initio calculations, contribution to explanation of these differences was established. Indeed, the results found by both used approaches determined the reasons why AAI is better oxidized than AAII; the key factor causing the differences in AAI and AAII oxidation is their different amenability to chemical oxidation.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/GA17-12816S" target="_blank" >GA17-12816S: Construction of modified apoferritin nanocarriers bearing anticancer drugs and study of mechanisms enhancing their efficiency in anticancer therapy</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Monatshefte für Chemie - Chemical Monthly

ISSN

0026-9247

e-ISSN

—

Volume of the periodical

148

Issue of the periodical within the volume

11

Country of publishing house

AT - AUSTRIA

Number of pages

11

Pages from-to

1971-1981

UT code for WoS article

000413626000011

EID of the result in the Scopus database

2-s2.0-85026923427