Hepatotoxic evaluation of toosendanin via biomarker quantification and pathway mapping of large-scale chemical proteomics.
Food Chem Toxicol
; 153: 112257, 2021 Jul.
Article
em En
| MEDLINE
| ID: mdl-34000341
ABSTRACT
Drug-induced liver injury (DILI) is a major side effect, sometimes can't be exactly evaluated by current approaches partly as the covalent modification of drug or its reactive metabolites (RMs) with proteins is a possible reason. In this study, we developed a rapid, sensitive, and specific analytical method to assess the hepatotoxicity induced by drug covalently modified proteins based on the quantification of the modified amino acids using toosendanin (TSN), a hepatotoxic chemical, as an example. TSN RM-protein adducts both in rat liver and blood showed good correlation with the severity of hepatotoxicity. Thus, TSN RM-protein adducts in serum can potentially serve as minimally invasive biomarkers of hepatotoxicity. Meanwhile, large-scale chemical proteomics analysis showed that at least 84 proteins were modified by TSN RMs in rat liver, and the bioinformatics analysis revealed that TSN might induce hepatotoxicity through multi-target protein-protein interaction especially involved in energy metabolism. These findings suggest that our approach may serve as a valuable tool to evaluate DILI and investigate the possible mechanism, especially for complex compounds.
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Base de dados:
MEDLINE
Medicinas Tradicionais:
Medicinas_tradicionales_de_asia
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Medicina_china
Assunto principal:
Medicamentos de Ervas Chinesas
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Proteínas Sanguíneas
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Doença Hepática Induzida por Substâncias e Drogas
Idioma:
En
Revista:
Food Chem Toxicol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China