Silver nanoparticles induce liver inflammation through ferroptosis in zebrafish
Yuansi Zheng1, Jie Song2, Qiuhui Qian2
1College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China; Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, 310022, China.
Chemosphere
|June 30, 2024
Summary
Silver nanoparticles (AgNPs) induce liver injury by triggering ferroptosis, a cell death pathway. This study identifies key genes and pathways involved, revealing AgNPs
Area of Science:
- Biomedical research
- Nanotoxicology
- Molecular biology
Background:
- Silver nanoparticles (AgNPs) are widely used nanomaterials with known links to liver injury.
- The exact mechanisms of AgNP-induced hepatotoxicity remain unclear.
- Ferroptosis, a regulated cell death pathway, is increasingly recognized for its role in various pathologies.
Purpose of the Study:
- To elucidate the mechanisms of AgNP-induced liver injury.
- To investigate the role of ferroptosis in AgNP hepatotoxicity.
- To identify key molecular players and pathways involved in AgNP-induced liver dysfunction.
Main Methods:
- Bioinformatic analysis of GEO datasets (GSE139560, GSE111407, GSE183158) for gene expression and pathway analysis.
- Gene Set Enrichment Analysis (GSEA) to identify activated pathways.
- miRNA-mRNA interaction network analysis.
- Experimental validation using an adult zebrafish model exposed to AgNPs.
Main Results:
- Three key ferroptosis-associated genes (Arrdc3, Txnip, Egfr) were identified in AgNP-exposed murine liver tissues.
- AgNP exposure significantly altered glucose metabolism and insulin signaling pathways, linked to ferroptosis genes.
- Ferroptosis-associated pathways (MAPK, PPAR) were activated by AgNPs.
- miRNA-mRNA network analysis revealed upstream regulators of ferroptosis genes.
- Zebrafish experiments showed increased Fe2+ and MDA, and mitochondrial damage, confirming ferroptosis induction by AgNPs.
- AgNPs impair liver glucose metabolism and insulin sensitivity, leading to dysfunction.
Conclusions:
- Ferroptosis is a primary mechanism underlying AgNP-induced hepatotoxicity.
- AgNPs disrupt liver glucose metabolism and insulin signaling via ferroptosis.
- Understanding these mechanisms is crucial for mitigating AgNP-related health risks.
