Oxidative stress-related canonical pyroptosis pathway, as a target of liver toxicity triggered by zinc oxide nanoparticles.
J Hazard Mater
; 442: 130039, 2023 01 15.
Article
em En
| MEDLINE
| ID: mdl-36166902
ABSTRACT
Zinc oxide nanoparticles (ZnO NPs) have been widely used in the fields of daily necessities, clinical diagnosis, drug delivery and agricultural production. The improper use of ZnO NPs could pose a risk to ecological environment and public health. Liver has been known as a critical toxic target of ZnO NPs. However, the question whether ZnO NPs lead to hepatocyte death through pyroptosis has not been answered yet, and the effect of oxidative stress on ZnO NPs-induced pyroptosis remains a mystery. We revealed that ZnO NPs disrupted zinc homeostasis and induced oxidative stress impairment in rat liver. Meanwhile, ZnO NPs triggered the assembly of NLRP3-ASC-Caspase-1 inflammatory complex and pyroptosis in both rat liver and HepG2 cells, further causing the activation of GSDMD, promoting the leakage of inflammatory cytokines including IL-1ß and IL-18. Importantly, the inhibition of oxidative stress was found to provide protection against pyroptosis in hepatocyte exposed to ZnO NPs. We identified a novel mechanism of liver damage induced by ZnO NPs, demonstrating the activation of canonical Caspase-1-dependent pyroptosis pathway and clarifying the protection of antioxidation against pyroptosis damage. Our discovery provided a support for risk assessment of ZnO NPs and target exploration for clinical treatment related to pyroptosis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Óxido de Zinco
/
Nanopartículas
Limite:
Animals
Idioma:
En
Revista:
J Hazard Mater
Assunto da revista:
SAUDE AMBIENTAL
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS