High fat diet deteriorates the memory impairment induced by arsenic in mice: a sub chronic in vivo study

Both arsenic (As) and obesity are associated with brain disorders. However, long term studies to evaluate their concomitant adverse effects on the brain functions are lacking. Present study was conducted to evaluate the long term co-exposure of As and high fat diet (HFD) on memory and brain mitochondrial function in mice. Male mice were randomly divided into 7 groups fed with HFD or ordinary diet (OD) and instantaneously exposed to As (25 or 50 ppm) in drinking water for, 4, 8, 12, 16 or 20 weeks. Step-down passive avoidance method was used for memory assessment and post exposure various parameters including mitochondrial damage, level of reactive oxygen species (ROS), malondialdeid (MDA) and glutathione (GSH) were determined. Results indicated that the retention latency decreased in As (25 and 50 ppm) and HFD received mice after 12 and 16 weeks respectively. Same results were observed at significantly shorter duration (8th week) when As was administered along with HFD as compared to control group. In the HFD alone fed mice increased the mitochondrial membrane damage, levels of ROS and MDA were observed while GSH contents decreased significantly. Concomitant administration of HFD and As amplified those mentioned toxic effects (p<0.001). In conclusion, our findings demonstrated that the simultaneous HFD and As impaired memory at least three times more than exposing each one alone. These toxic effects could be due to the mitochondria originated oxidative stress along with the depleted antioxidant capacity of the brain of mice.