Objectives: Manganese chloride (MnCl(2)) is one of heavy metals for causing neurogenerative dysfunction like Manganism. The purpose of this study was to determine the acute toxicity of MnCl(2) using different times and various concentrations including whether manganese toxicity may involve in two intrinsic pathways, endoplasmic reticulum (ER) stress and mitochondria dysfunction and lead to neuronal apoptosis mediated by organelle disorders in neuroblastoma cell line SK-N-MC.
Methods: In the acute toxicity test, five concentrations (200, 400, 600, 800, 1,000 uM) of MnCl(2) with 3, 6, 12, 24, 48 hours exposure were selected to analyze cell viability. In addition, to better understand their toxicity, acute toxicity was examined with 1,000 uM MnCl(2) for 24 hours exposure via reactive oxygen species (ROS), mitochondria membrane potential, western blotting and mitochondrial complex activities.
Results: Our results showed that both increments of dose and time prompt the increments in the number of dead cells. Cells treated by 1,000 µM MnCl(2) activated 265% (±8.1) caspase-3 compared to control cell. MnCl(2) induced intracellular ROS produced 168% (±2.3%) compared to that of the control cells and MnCl(2) induced neurotoxicity significantly dissipated 48.9% of mitochondria membrane potential compared to the control cells.
Conclusions: This study indicated that MnCl(2) induced apoptosis via ER stress and mitochondria dysfunction. In addition, MnCl(2) affected only complex I except complex II, III or IV activities.
Keywords: Apoptosis; Endoplasmic reticulum stress; Manganese chloride (MnCl2); Mitochondria dysfunction.