The generation of ROS and lipid peroxidation has been considered to play an important role in the pathogenesis of chronic fluoride toxicity. In the present study, we observed that fluoride activated BV-2 microglia cell line by observing OX-42 expression in immunocytochemistry. Intracellular superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), reactive oxygen species (ROS), superoxide anions ( ), nitric oxide synthase (NOS), nitrotyrosine (NT) and nitric oxide (NO), NOS in cell medium were determined for oxidative stress assessment. Our study found that NaF of concentration from 5 to 20？mg/L can stimuli BV-2 cells to change into activated microglia displaying upregulated OX-42 expression. SOD activities significantly decreased in fluoride-treated BV-2 cells as compared with control, and MDA concentrations and contents of ROS and increased in NaF-treated cells. Activities of NOS in cells and medium significantly increased with fluoride concentrations in a dose-dependent manner. NT concentrations also increased significantly in 10 and 50？mg/L NaF-treated cells compared with the control cells. Our present study demonstrated that toxic effects of fluoride on the central nervous system possibly partly ascribed to activiting of microglia, which enhanced oxidative stress induced by ROS and reactive nitrogen species. 1. Introduction Fluoride is an ubiquitous element in the environment and has a remarkable prophylactic effect at low concentrations by inhibiting dental caries, while at higher concentrations it causes dental and skeletal fluorosis [1]. Endemic fluorosis is prevalent in many parts of the world and causes damage not only to hard tissues of teeth and skeleton, but also to soft tissues, such as brain, liver, kidney, and spinal cord [2]. Epidemiological investigations reveal that intelligence quotient (IQ) of children living in endemic fluorosis areas is lower than that of children living in low fluoride areas [3–7]. It has been demonstrated that high concentrations of fluoride can decrease learning ability and memory in some animal experiments [8, 9] and result in dysfunctions of the central nervous system (CNS) [10, 11]. As the cases of many chronic degenerative diseases, the increase of reactive oxygen species (ROS) and lipid peroxidation (LPO) has been considered to play an important role in the pathogenesis of chronic fluoride toxicity [12–14]. Fluoride administration significantly increases brain LPO level compared with control group in rat, while reduced glutathione (GSH) content and superoxide dismutase (SOD), glutathione
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