Abstract
Excessive exposure to the sources of fluoride in drinking water, oral care products, and food is a widespread problem. Fluoride is associated with impairment in child intelligence development. It causes DNA damage, oxidative stress, and mitochondrial dysfunction, mainly due to the production of reactive oxygen species (ROS). It has been postulated that the use of antioxidants such as astaxanthin, may alleviate fluoride's adverse effects. This study assessed the effects of fluoride on cellular ROS content and rat's learning and memory ability and investigated the protective potency of astaxanthin with emphasis on the role of glutamate using the Morris Water Maze test, glutamate concentration determination, and western blot techniques. The fluoride treatment of cells results in an increment of cellular ROS, whereas astaxanthin inhibits lipid peroxidation. Fluoride significantly decreases the cellular glutamate uptake and glutamate transporter, protein level, possibly due to the disruption of mitochondrial energy metabolism and defect of the transporter recycle, respectively. The in-vivo study indicated that the treatment of rats with fluoride led to a loss of learning, while astaxanthin improved memory dysfunction. Measurement of ROS and glutamate levels of rat brain hippocampus showed that fluoride increased the ROS but decreased the glutamate. On the other hand, the utilization of astaxanthin decreased the brain ROS content and increased the glutamate level. It seems that fluoride disrupts the normal function of neurons via increment of ROS production and decrement of glutamate level, whereas astaxanthin has neuroprotective potency due to the ROS scavenging ability.