Silver nanoparticles induce endoplasmatic reticulum stress response in zebrafish

Area of Science:

• Environmental toxicology
• Nanomaterial safety
• Cellular stress responses

Background:

• Increasing applications of silver nanoparticles (AgNPs) lead to greater human and environmental exposure.
• Potential toxicological implications of AgNPs are not fully understood.
• Zebrafish and human hepatoma cells serve as models to investigate AgNP toxicity.

Purpose of the Study:

• To investigate the effects of AgNPs on zebrafish (in vitro and in vivo) and human hepatoma cells (Huh7).
• To compare the toxicological responses of AgNPs in different cell types and organisms.
• To elucidate the mechanisms of AgNP-induced toxicity, focusing on endoplasmic reticulum (ER) stress and apoptosis.

Main Methods:

• Exposure of zebrafish liver cells (ZFL), Huh7 cells, and zebrafish embryos to AgNPs.
• Analysis of reactive oxygen species (ROS), ER stress markers (BiP, ATF-6, XBP-1), TNF-α, and apoptosis-related genes (p53, Bax, Noxa, p21).
• Assessment of hatching rates and morphological defects in zebrafish embryos.

Main Results:

• AgNPs were incorporated into ZFL, Huh7 cells, and zebrafish embryos.
• AgNPs induced ROS, ER stress, and TNF-α in ZFL cells, with distinct transcriptional profiles compared to Huh7 cells.
• In zebrafish embryos, AgNPs affected hatching and caused morphological defects at higher concentrations, alongside ER stress and apoptosis gene upregulation.

Conclusions:

• AgNPs induce endoplasmic reticulum (ER) stress in zebrafish liver cells and embryos, a finding demonstrated here for the first time.
• ER stress induction by AgNPs can trigger downstream apoptotic and inflammatory pathways.
• The study underscores the potential toxicological risks associated with AgNP exposure in aquatic organisms and provides insights into cellular mechanisms of toxicity.