Abstract
Manganese (Mn) is an essential trace element maintained at an optimal level in human body. Mn plays the important activator of enzymes in metabolism for protein digestion and utilization. The major exposure source of Mn is from the occupational environment, including welders and miners are the occupational exposure population. Manganese nitrate (Mn(NO3)2), a Mn compound, is the major material in alloy and battery. There are evidence have demonstrated that Mn is a potential risk factor in neurological disorders. Up to now, the evidence for Mn(NO3)2-induced cytotoxicity and genotoxicity and its related mechanism in macrophages is not supportive. At the present study, we first found that Mn(NO3)2 induced cytotoxicity in RAW 264.7 cells in a concentration- and time-dependent manners. Genotoxicty, including microcucleus (MN) formation and DNA damage, was induced by Mn(NO3)2 in a concentration-dependent manner via alkaline single cell gel electrophoresis (COMET) and cytokinesis-block MN assays. In addition, apoptosis and related signal molecular mechanism, including caspases (-3, -8, and -9) activation and mitochondria disruption, were induced by Mn(NO3)2. ROS generation play an important role in apoptosis. Here, we also found intracellular ROS generation induced by Mn(NO3)2. More, N-acetyl-cysteine (NAC), a ROS scavenger, decreased the effects of cytotoxicity and genotoxicity induced by Mn(NO3)2.In conclusion, we had demonstrated that Mn(NO3)2-induced cytotoxicity and genotoxicity on RAW 264.7cells were mediated by caspase-3,-8,and -9 activation.
