Induction of oxidative stress and inflammatory cytokines by manganese chloride in cultured T98G cells, human brain glioblastoma cell line

Manganese, an essential trace nutrient in human beings, has been widely used in the steel industry to improve hardness, stiffness, and strength. With the increased applications of manganese compounds, discharge into the environment has rapidly increased and may exert adverse effects on human health. In this study, manganese toxicity was investigated using cultured T98G cells, which are derived from human glioblasts with the ability to differentiate into several different types of neuroglia. Cytotoxicity was shown in manganese-treated groups (100, 200, 400, and 800 μM of MnCl2), and cell viability was decreased to 58.8% of the control group at 2 days after treatment with 800 μM of MnCl2. When cells were treated with manganese for 24 h, ROS dose-dependently increased while antioxidant intracellular GSH decreased. With the generation of ROS, the increased activity of caspase-3 was shown, and was followed by chromatin condensation and breakage, which is an indication of the cellular apoptotic process. ROS also triggered pro-inflammatory responses in cultured T98G cells, which were demonstrated by the increased gene expression and protein levels of IL-6 and IL-8.