Essential Trace Elements Prevent the Impairment in the Retention Memory, Cerebral Cortex, and Cerebellum Damage in Male Rats Exposed to Quaternary Metal Mixture by Up-regulation, of Heme Oxygynase-1 and Down-regulation of Nuclear Factor Erythroid 2-related Factor 2-NOs Signaling Pathways

Abstract

In the present study, we examined adverse effects of metals and metalloids in the Cerebral cortex (CC) and Cerebellum (CE). Group 1 comprised from the controls while other four groups of male Wistar rats were treated with following pattern: Group II (Heavy Metal Mixture HMM only: PbCl2, 20 mg·kg−1; CdCl2, 1.61 mg·kg−1; HgCl2, 0.40 mg·kg−1, and NaAsO3,10 mg·kg−1), Groups III (HMM + ZnCl2); Group IV (HMM + Na2SeO3) and Group V (HMM + ZnCl2 + Na2SeO3) for 60 days per os. HMM promoted oxidative stress in the CC and CE of treated rats compared to controls; moreover, exposure to HMM led to increased activity of the AChE and pro-inflammatory cytokines; also, HMM promoted accumulation of caspase 3 and other transcriptional factors such as Nrf2 and decreased levels of Hmox-1. Essential metals reduced increased bioaccumulation of Pb, Cd, As and Hg in CC and CE caused by HMM exposure. Also, all mentioned adverse effects were diminished by essential metals treatment (Se and Zn). HMM exposed rats had considerably less escape dormancy than controls. Histopathological analysis revealed moderate cell loss at the intermediate (Purkinje cell) and granular layer.Zinc and selenium supplementations could reverse adverse effects of heavy metals at various cellular levels in neurons.