Protective Effect of Curcumin on Hippocampal and Behavior Changes in Rats Exposed to Fluoride During Pre- and Post-natal Period

Introduction: Curcumin, a yellow-pigment, found in the popular Indian spice turmeric (Curcuma longa), poses pharmaceutical applications due to its anti-inflammatory, antioxidant, and chemoprotective properties. Excessive fluoride causes fluorosis leading to neurodegeneration and associated behavioral deficits, particularly in children. This study aimed at investigating the neuroprotective ability of curcumin on sodium fluoride (NaF)-related alterations of acetylcholine, catecholamines, histological changes in hippocampus and behavior of rats exposed to NaF during pre- and post-natal period.  Methods: Pregnant albino Wistar rats were chosen and divided into four groups. The experimental period lasted 53 days (i.e. the gestational period of 23 days and post-gestational period of 30 days), at which the control group received normal tap water, the experimental group received NaF (20 ppm/kg bw) through drinking water, and the protective groups received curcumin (10 mg and 20mg/kg bw) by gavage and NaF (20 ppm/kg bw) through drinking water. Behavioral study (open field test) was done using postnatal pups aged 21 and 30 days. The brains of postnatal pups aged 1, 7, 14, 21, and 30 days were collected and used for biochemical analysis and those of pups aged 14, 21, and 30 days were used for histopathological analysis.  Results: NaF-exposed rats showed a significant (p<0.05) decrease in body weight, brain weight, and behavioral activities, which were significantly reversed with curcumin treatment. The levels of epinephrine significantly (p<0.05) increased, whereas norepinephrine, dopamine and acetylcholine levels declined in NaF-treated group compared with the control group, which were significantly (p<0.05) reversed after treatment by curcumin (10 mg/kg bw and 20 mg/kg bw) along with NaF. The histological alterations, including shrinkage of neurons and nissal substances were observed in the hippocampus of NaF-treated pups that the control pups, whereas co-treatment with curcumin and NaF showed ameliorative effects and controlled the histological alterations. Conclusion: The results showed the neuroprotective effect of curcumin on behavior, neurotransmitter levels, and histological changes in the hippocampus against NaF-induced neurotoxicity in developing rat pups.