Evaluation of cytotoxicity, apoptosis, and genotoxicity induced by indium chloride in macrophages through mitochondrial dysfunction and reactive oxygen species generation

Abstract

Due to rapid advances in the era of electronic technologies, indium has played the important material for the production of liquid crystal display screens in the semiconductor and optoelectronic industries. The present study focuses on evaluating the toxic effects and related mechanisms of indium chloride (InCl₃) on RAW264.7 macrophages. Cytotoxicity was induced by InCl₃ in a concentration- and time-dependent manner. InCl₃ had the ability to induce macrophage death through apoptosis rather than through necrosis. According to the cytokinesis-block micronucleus assay and alkaline single-cell gel electrophoresis assay, InCl₃ induced DNA damage, also called genotoxicity, in a concentration-dependent manner. Cysteine-dependent aspartate-directed protease (caspase)-3, -8, and -9 were activated by InCl₃ in a concentration-dependent manner. Mitochondria dysfunction and cytochrome c release from the mitochondria were induced by InCl₃ in a concentration-dependent manner. Downregulation of BCL2 and upregulation of BAD were induced by InCl₃ in a concentration-dependent manner. More, we proposed that InCl₃ treatment generated reactive oxygen species (ROS) in a concentration-dependent manner. In conclusion, the current study revealed that InCl₃ induced macrophage cytotoxicity, apoptosis, and genotoxicity via a mitochondria-dependent apoptotic pathway and ROS generation.

Keywords: Apoptosis; Genotoxicity; InCl(3); Macrophages; Mitochondrial dysfunction; ROS generation.