Systems assessment of statins hazard: Integrating in silico prediction, developmental toxicity profile and transcriptomics in zebrafish.
Ecotoxicol Environ Saf
; 243: 113981, 2022 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-36029576
ABSTRACT
Statins are prescribed widely as lipid-lowering agents. However, statins are associated with an increased harmful risk on public health and the ecosystem. Little is known about statins' toxicity on biological development and the underlying molecular mechanisms. We exposed zebrafish embryos to a series of statins to evaluate their development toxicity. Statins-induced embryonic developmental defects in a concentration-dependent manner. 72 h LC50 values for lovastatin, simvastatin, fluvastatin, atorvastatin, rosuvastatin, and pravastatin were 0.01 µM, 0.04 µM, 1.93 µM, 37.28 µM, 79.29 µM, and 2170 µM, respectively. Moreover, the expression of genes involved in heart contraction, calcium ion binding, transcription factors, nucleus, and G protein-coupled receptor signaling pathway was altered by statins. The early growth response gene (egr4) and transcription factor genes (fosab and fosb) were screened as potential toxicity targets due to their significant upregulation based on protein-protein interaction (PPI) and drug-gene interaction network analysis. Finally, the ecotoxicity profile of statins was predicted by in silico method, and statins were high or moderate risk to aquatic organisms. We provide a systems toxicology strategy to explore the toxicity of statins and illustrate the potential mechanisms of action.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Hidroximetilglutaril-CoA Redutases
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article