Exploring the protective role of metformin and dehydrozingerone in sodium fluoride-induced neurotoxicity: evidence from prenatal rat models

This study is aimed at evaluating the neurotoxic effects of chronic exposure of sodium fluoride (NaF) in developmental stages in rat using prenatal models. NaF (100 ppm, orally) dosing via drinking water was given to pregnant rats in disease group. In the treatment groups, Metformin & Dehydrozingerone (DHZ) (200 mg/kg) were administered orally along with NaF, and the dosing was continued throughout the gestation and lactation periods to the pups until the end of experiment. Behavioural studies like Novel Object Recognition Test (NORT), Open Field & Actophotometer test and biochemical estimations like Acetylcholinesterase (AchE), Glutathione (GSH), Malondialdehyde (MDA) were conducted on animals followed by histopathological image analysis. It was observed that NaF exposure significantly decreased learning, memory and locomotor ability (at p < 0.05, p ≤ 0.01) in rat pups and was also able to induce anxiety like behavior. Levels of AchE (p ≤ 0.001) and MDA (p ≤ 0.01, p ≤ 0.001) was found to be significantly elevated and GSH levels were significantly decreased (p ≤ 0.01, p ≤ 0.001) in hippocampus and frontal cortex in the disease group. Histopathological image analysis showed presence of degenerated neurons in hippocampus of disease group. From this study, it was observed that treatment with Metformin and DHZ, was able to significantly ameliorate the cognitive impairments, improve the condition of oxidative stress and decrease neuronal degeneration in NaF fed rat pups. These results established the protective role of Metformin and DHZ in NaF induced neurodevelopmental toxicity with particular emphasis on their antioxidant properties.