Abstract:
Metal neurotoxicity is a primary cause of neurological illnesses throughout the world. Over 2.5 billion people worldwide obtain their drinking water from groundwater resources. Excessive presence of heavy metals like arsenic (As) in ground water can be detrimental to human health. Over 40% of people in Pakistan suffer from water contaminated with arsenic. As neurotoxicity disrupts synaptic plasticity, memory, and learning and causes oxidative stress. The primary focus of the research was to evaluate the effects of metformin on learning and memory and antioxidant potential. Three groups, each with 10 male rats were given sodium arsenite (20 mg/kg) in drinking water and metformin (75 mg/kg) in feed for 28 day. Behavioral tests Y-maze and Morris Water Maze (MWM) tests were conducted to investigate the effects of As and metformin treatments on learning and memory. The antioxidant enzyme activity was also measured by biochemical analysis using superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Histological assessment was conducted using Hematoxylin and Eosin stain in the cerebral cortex and hippocampus of the brain. The results demonstrated that in comparison to the As-treated group, the group that received As+metformin showed improvement (p< 0.05) in the spatial memory. Additionally, As+ metformin treated group exhibited a significant improvement (p<0.05) in both spatial and hippocampal dependent learning and memory in MWM. When compared with the As+metformin treated group, the As-treated group exhibited lower levels of enzymes SOD, GPx, and CAT. The result of our study highlights that there is a substantial decrease in the cell count in As-treated group when compared with control group and treatment group showed recovered cell count but not showed significant results(p>0.05). Additionally, molecular docking revealed that the metformin had higher binding affinities with the eight targeted genes. Numerous biological pathways such as nitrogen metabolism, drug metabolism were found to have enriched predicted targets.
In conclusion, these findings suggested a potential effect of antidiabetic drug on aberrant learning and oxidative stress which provides basis for future drug repurposing for better therapeutic interventions for As neurotoxicity..
