Exploring the cytotoxicity mechanisms of copper ions and copper oxide nanoparticles in cells from the excretory system

Abstract

Copper oxide nanoparticles (CuO NPs) are widely applied in various products, including food, cosmetic, biomedical, and environmental goods. Despite their broad use, potential risks are still associated with these NPs, therefore, the aim of this study is to delve deeper into the cytotoxic effects of 85 nm CuO NPs on kidney MDCK and liver AML-12 cells, representing cell models from the excretory system. Our findings pointed out that the viability of both cell lines decreased in a concentration-dependent manner when exposed to CuO NPs. Additionally, CuO NPs induced the overproduction of reactive oxygen species (ROS) and caused depolarization of the mitochondrial membrane, thereby arresting the cell cycle at the G2/M phase in MDCK and AML-12 cells. Importantly, unlike others our study uncovered distinctive forms of cellular death induced by CuO NPs in these cell lines. MDCK cells exhibited a combination of apoptosis and autophagy while early apoptosis was predominant in AML-12 cells. Moreover, the role of Cu²⁺ ions and CuO NPs in exerting cytotoxic effects was investigated, revealing that MDCK cells were affected by both copper ions and NPs. In contrast, AML-12 cells experienced toxic effects solely from CuO NPs. These findings provide crucial insights into the different cell death mechanisms caused either by CuO NPs or Cu²⁺ ions in excretory system cells in vitro. Nevertheless, further research is needed to explore the underlying mechanisms at the in vivo level, ensuring the safe use of CuO NPs. The results suggest that specific concentrations of metal oxide NPs can impact the physiology of cells within the excretory system of various mammals, including humans, and pave the way for comparing the toxic effects between ions and nanoparticles for further nanotoxicological studies.

Keywords: AML-12 cells; Copper oxide nanoparticles; MDCK cells; Nanotoxicology.