Are zebrafish larvae suitable for assessing the hepatotoxicity potential of drug candidates?
J Appl Toxicol
; 35(9): 1017-29, 2015 Sep.
Article
em En
| MEDLINE
| ID: mdl-25663337
ABSTRACT
Drug-induced liver injury (DILI) is poorly predicted by single-cell-based assays, probably because of the lack of physiological interactions with other cells within the liver. An intact whole liver system such as one present in zebrafish larvae could provide added value in a screening strategy for DILI; however, the possible occurrence of other organ toxicities and the immature larval stage of the zebrafish might complicate accurate and fast analysis. We investigated whether expression analysis of liver-specific fatty acid binding protein 10a (lfabp10a) was an appropriate endpoint for assessing hepatotoxic effects in zebrafish larvae. It was found that expression analysis of lfabp10a was a valid marker, as after treatment with hepatotoxicants, dose-response curves could be obtained and statistically significant abnormal lfabp10 expression levels correlated with hepatocellular histopathological changes in the liver. However, toxicity in other vital organs such as the heart could impact liver outgrowth and thus had to be assessed concurrently. Whether zebrafish larvae were suitable for assessing human relevant drug-induced hepatotoxicity was assessed with hepatotoxicants and non-hepatotoxicants that have been marketed for human use and classified according to their mechanism of toxicity. The zebrafish larva showed promising predictivity towards a number of mechanisms and was capable of distinguishing between hepatotoxic and non-hepatotoxic chemical analogues, thus implying its applicability as a potential screening model for DILI.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peixe-Zebra
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Preparações Farmacêuticas
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Testes de Toxicidade
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Alternativas ao Uso de Animais
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Doença Hepática Induzida por Substâncias e Drogas
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Fígado
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
J Appl Toxicol
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Bélgica