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

Azmat Ali Khan; Amer M Alanazi; Nawaf Alsaif; Mohammad Al-Anazi; Ahmed Y A Sayed; Mashooq Ahmad Bhat

doi:10.1016/j.sjbs.2021.03.021

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

Saudi J Biol Sci. 2021 May;28(5):2762-2771. doi: 10.1016/j.sjbs.2021.03.021. Epub 2021 Mar 17.

Authors

Azmat Ali Khan¹, Amer M Alanazi¹, Nawaf Alsaif¹, Mohammad Al-Anazi¹, Ahmed Y A Sayed¹, Mashooq Ahmad Bhat¹

Affiliation

¹ Pharmaceutical Biotechnology Laboratory, Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

Abstract

In the present study, we elucidated the potential cytotoxicity of AgNPs in H9c2 rat cardiomyoblasts and assessed the underlying toxicological manifestations responsible for their toxicity thereof. The results indicated that the exposure of AgNPs to H9c2 cardiac cells decreased cell viability in a dose-dependent manner and caused cell cycle arrest followed by induction of apoptosis. The AgNPs treated cardiac cells showed a generation of reactive oxygen species (ROS) and mitochondrial dysfunction where mitochondrial ATP was reduced and the expression of AMPK1α increased. AgNPs also induced ROS-mediated autophagy in H9c2 cells. There was a significant time-dependent increase in intracellular levels of Atg5, Beclin1, and LC3BII after exposure to AgNPs, signifying the autophagic response in H9c2 cells. More importantly, the addition of N-acetyl-L-cysteine (NAC) inhibited autophagy and significantly reduced the cytotoxicity of AgNPs in H9c2 cells. The study highlights the prospective toxicity of AgNPs on cardiac cells, collectively signifying a potential health risk.

Keywords: Autophagy; Cardiomyocytes; Mitochondrial dysfunction; Nanoparticles; ROS.