Selenium and zinc protect against heavy metal mixture-induced, olfactory bulb and hippocampal damage by augmenting antioxidant capacity and activation of Nrf2-Hmox-1 signaling in male rats

Heavy metals and metalloids have been implicated in neurodenerative diseases. Present study has evaluated the potential protective effects of Se and Zn on heavy metals and metalloids mixture-induced (Cd, Pb, Hg and As) toxicity in the hippocampus and olfactory bulb in male rats.Five groups of Wistar rats were randomly divided in to: controls, toxic metals mixture (TMM) exposed rats (PbCl2, 20 mg·kg-1; CdCl2, 1.61 mg·kg-1; HgCl2, 0.40 mg·kg-1 and NaAsO3, 10 mg·kg-1)), TMM + Zn, TMM + Se and TMM-+Zn + Se groups and were orally treated for 60 days.We found that in hippocampus and olfactory bulb, TMM generated increased lipid peroxidation and diminished antioxidant capacity. These adverse effects induced by TMM were alleviated by Zn and Se co-treatment; moreover, essential trace elements (Zn and Se) decreased activity of acetylcholinesterase, reduced Cd, Pb, Hg and As bioaccumulation in hippocampus and olfactory bulb and decreased levels of TNF-α in the hippocampus. TMM treated rats had lower levels of Hmox-1 (hippocampus), higher levels of Nrf2 (olfactory bulb and hippocampus) and NF-kB (olfactory bulb). TMM treated rats showed significantly highest time in locating the escape hole. Histopathological examination revealed hypertrophied granule cells in OB of TMM exposed rats.Zn and Se supplementation can reverse quaternary mixture-induced (Cd, Pb, Hg and As) toxicity in hippocampus and OB in male albino rats.