Aluminum, lead and manganese mixture exacerbates oxidative stress, neuroinflammation, and apoptosis via downregulation of Nrf-2/HO-1/BDNF signaling pathway in rats.

Heavy metals have been reported to induce neurotoxicity associated with neurodegenerative disorders. However, there is a dearth of information on Al, Pb, and Mn mixture exposure on cerebral cortex functions. This study is aimed at evaluating the effects of Al, Pb, and Mn mixture on the cerebral cortex functions. Rats were exposed to Pb 20 mg/kg, Al 35mg/kg and Mn 0.564mg/kg body weight singly or in combination for 90 days. Our results showed that Al, Pb and Mn singly or in combination exposure significantly (p ≤ 0.05) decreased antioxidant enzymes activities, glutathione level and increased oxidative stress and neuroinflammation biomarkers in the cerebral cortex of the exposed rats. Moreover, induction of inflammation maker i.e., COX-2 was associated with increases in apoptotic induction. Furthermore, Al, Pb and Mn singling or in combination exposure significantly (p ≤ 0.05) increased Nrf-2 and decreased BDNF and HO-1 induction as well as increased amyloid precursor proteins and decreased occludin level. Taken together, our result indicates that Al, Pb, and Mn mixture exacerbates oxidative stress, neuroinflammation, and apoptosis via downregulation of Nrf2/HO-1/BDNF signaling pathway.