Potential cytotoxicity of silver nanoparticles: Stimulation of autophagy and mitochondrial dysfunction in cardiac...

Area of Science:

• Nanomaterial toxicology
• Cardiovascular research
• Cellular toxicology

Background:

• Silver nanoparticles (AgNPs) are increasingly used, necessitating an understanding of their biological impact.
• Cardiac cells, specifically H9c2 cardiomyoblasts, are crucial models for studying heart toxicity.
• Investigating the mechanisms of AgNP-induced cardiac cell damage is vital for risk assessment.

Purpose of the Study:

• To elucidate the cytotoxicity of AgNPs in H9c2 rat cardiomyoblasts.
• To identify the toxicological mechanisms underlying AgNP-induced cardiac cell injury.
• To evaluate the role of reactive oxygen species (ROS) and autophagy in AgNP toxicity.

Main Methods:

• Exposure of H9c2 cells to varying concentrations of AgNPs.
• Assessment of cell viability, cell cycle, and apoptosis.
• Measurement of reactive oxygen species (ROS) generation and mitochondrial function (ATP levels).
• Analysis of autophagy markers (Atg5, Beclin1, LC3BII) and the effect of N-acetyl-L-cysteine (NAC).

Main Results:

• AgNP exposure decreased H9c2 cell viability in a dose-dependent manner, inducing cell cycle arrest and apoptosis.
• AgNPs caused increased ROS production, mitochondrial dysfunction (reduced ATP), and elevated AMPK1α expression.
• AgNPs triggered ROS-mediated autophagy, evidenced by increased levels of autophagy markers (Atg5, Beclin1, LC3BII).
• NAC treatment inhibited autophagy and significantly attenuated AgNP-induced cytotoxicity.

Conclusions:

• AgNPs exhibit significant cytotoxicity towards H9c2 cardiac cells.
• The toxicity is mediated through ROS generation, mitochondrial dysfunction, and autophagy induction.
• NAC can ameliorate AgNP-induced cardiac toxicity, highlighting the role of oxidative stress and autophagy.
• These findings underscore the potential health risks associated with AgNP exposure to cardiac cells.