Multigenerational evaluation was made in rats on exposure to high fluoride (100 and 200 ppm) to assess neurotoxic potential of fluoride in discrete areas of the brain in terms of lipid peroxidation and the activity of antioxidant enzyme system. The rats were given fluoride through drinking water (100 and 200 ppm) and maintained subsequently for three generations. Fluoride treatment significantly increased the lipid peroxidation and decreased the activity of antioxidant enzymes viz, catalase, superoxide dismutase, glutathione peroxidase, glutathione S-transferase, and glutathione level in first-generation rats and these alterations were more pronounced in the subsequent second and third-generation rats in both the doses tested. Decreased feed and water consumption, litter size and organ (brain) somatic index, marginal drop in body growth rate and mortality were observed in all three generations. Decreased antioxidant enzyme activity and increased malondialdehyde levels found in the present study might be related to oxidative damage that occurs variably in discrete regions of the brain. Results of this study can be taken as an index of neurotoxicity in rats exposed to water fluoridation over several generations.
… Histological analysis of cerebral cortex, cerebellum and hippocampus of control and fluoride-treated rats are depicted in Figs. 1,2, and 3. The histopathological changes in both doses of fluoride groups were more or less the same but differed only in their degree of severity. The cerebral cortex of control rats showed normal morphology with intact neuron and cytoplasm (Fig. 1). Fluoride treatment resulted in necrosis, which is depicted by hyperchromasia and disintegrated cytoplasm. Cytoplasm showed edema depicted by vacuoles and also eosinophilia (red neurons) visible at many instances. Fluoride-treated second and third-generation rats showed similar but more severe necrotic signs… Fluoride treatment resulted in a decrease in the number of granular cells, and Purkinje cells showed eosinophilic character (red neurons). There was a presence of gap/space between the Purkinje cells and the granular layer in the fluoride-treated rats, and this alteration was very prominent especially in third-generation rats treated with 200 ppm fluoride. Fig. 3 shows normal morphology of the hippocampus of the control rats. Presence of degenerating neurons was observed in the fluoride-treated rats. The severity of the alterations was most pronounced in the third-generation fluoride-treated rats…