Ferritinophagy was involved in long-term SiNPs exposure induced ferroptosis and liver fibrosis.

Nanotoxicology

Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, PR China.

Published: March 2023

SiNPs could induce liver fibrosis, but the mechanism was not completely clear. This study focused on exploring whether long-term SiNPs exposure at human-related exposure dosage could lead to ferritinophagy-mediated ferroptosis and liver fibrosis. , long-term SiNPs exposure induced liver fibrosis inrats accompanied by ferritinophagy and ferroptosis in hepatocytes. Interestingly, the progression of liver fibrosis was alleviated after exposure cessation and recovery, meanwhile ferritinophagy and ferroptosis were not further activated. , after long-term SiNPs exposure, the mitochondrial membrane ruptured, lipid peroxidation intensified, the level of redox active iron increased and the repair protein of lipid peroxidation were consumed in L-02 cells, demonstrating ferroptosis occurrence. Notably, knockdown inhibited ferritin degradation, alleviated the increase of intracellular ferrous iron level, reduced lipid peroxidation and the depletion of glutathione peroxidase 4 (GPX4). In conclusion, ferritinophagy mediated by NCOA4 was responsible for long-term SiNPs exposure induced hepatocytes ferroptosis and liver fibrosis, which provided a scientific basis for toxicological assessment of SiNPs and would be benefited for the safety design of SiNPs-based products.

Download full-text PDF

Source
http://dx.doi.org/10.1080/17435390.2023.2197055DOI Listing

Publication Analysis

Top Keywords

liver fibrosis
24
long-term sinps
20
sinps exposure
20
exposure induced
12
ferroptosis liver
12
lipid peroxidation
12
ferritinophagy ferroptosis
8
sinps
7
exposure
7
ferroptosis
6

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!