Cirovic A

References (4)

Title : Ni and Al mixture amplifies cerebellar oxido-inflammatory responses, down regulates AChE and BDNF\/NGF levels in motor impairment in male albino rats - Anyachor_2023_J.Trace.Elem.Med.Biol_80_127318
Author(s) : Anyachor CP , Orish CN , Ezejiofor AN , Cirovic A , Ezealisiji KM , Patrick-Iwuanyanwu K , Thuppil V , Orisakwe OE
Ref : J Trace Elem Med Biol , 80 :127318 , 2023
Abstract : BACKGROUND: Aluminum and nickel are potent neurotoxicants to which humans are constantly exposed. Previous studies have demonstrated that these two metals can affect the motor system, but their effects on the cerebellum, a central nervous system region with the highest number of neurons, have remained largely unexplored. Therefore, we conducted a study to investigate the adverse effects of Al, Ni, and Al+Ni in vivo. METHODS: In our study, seven male Sprague Dawley rats per group were orally exposed to deionized water, 0.2 mg/kg of Ni, 1 mg/kg of Al, and 0.2 mg/kg of Ni + 1 mg/kg of Al (as a binary heavy metals mixture; HMM), respectively. RESULTS: Ni, Al, and HMM exposed rats accumulated higher levels of Al and Ni compared to controls, and HMM treated animals had higher levels of Ca and Fe in the cerebellum (p < 0.05). Malondialdehyde (MDA) levels were significantly (p < 0.05) higher in the HMM, Ni, and Al treated groups compared to the control group that received deionized water. Superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GPx) activities were significantly (p < 0.05) reduced in the HMM, Ni, and Al treated groups compared to the control group that received deionized water. Ni, Al, and HMM significantly (p < 0.05) shortened the length of time of the grip in comparison to the control. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) levels were significantly decreased in the nickel, Al, and heavy metal mixture groups compared with the control group. Moreover, there was a significant decrease in the activity of acetylcholinesterase (AChE) and a increase in cyclooxygenase-2 (COX-2) activity in the Ni, Al, and HMM treated groups compared to the control group. CONCLUSION: HMM exposed animals had significantly poorer performance in the Rotarod test (p < 0.05) than controls. Al and Ni induced impairment of cerebellar function at various levels.
ESTHER : Anyachor_2023_J.Trace.Elem.Med.Biol_80_127318
PubMedSearch : Anyachor_2023_J.Trace.Elem.Med.Biol_80_127318
PubMedID: 37864919

Title : 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 - Ikpeama_2023_Int.J.Neurosci__1
Author(s) : Ikpeama EU , Orish CN , Ezejiofor AN , Cirovic A , Nwaogazie IL , Orisakwe OE
Ref : International Journal of Neuroscience , :1 , 2023
Abstract : PURPOSE/AIM OF THE STUDY: 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. MATERIALS AND METHODS: Five groups of Wistar rats were randomly divided in to: controls, toxic metals mixture (TMM) exposed rats (PbCl(2), 20 mg.kg(-1); CdCl(2), 1.61 mg.kg(-1); HgCl(2), 0.40 mg.kg(-1) and NaAsO(3), 10 mg.kg(-1))), TMM + Zn, TMM + Se and TMM-+Zn + Se groups and were orally treated for 60 days. RESULTS: 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-alpha 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. CONCLUSION: Zn and Se supplementation can reverse quaternary mixture-induced (Cd, Pb, Hg and As) toxicity in hippocampus and OB in male albino rats.
ESTHER : Ikpeama_2023_Int.J.Neurosci__1
PubMedSearch : Ikpeama_2023_Int.J.Neurosci__1
PubMedID: 38108304

Title : Selenium and zinc alleviate quaternary metal mixture -induced neurotoxicity in rats by inhibiting oxidative damage and modulating the expressions of NF-kB and Nrf2\/Hmox-1 pathway - Dike_2023_IBRO.Neurosci.Rep_15_57
Author(s) : Dike C , Orish CN , Ezejiofor AN , Cirovic A , Babatunde B , Sikoki F , Orisakwe OE
Ref : IBRO Neurosci Rep , 15 :57 , 2023
Abstract : BACKGROUND: This study evaluated the potential protective effects of Zn and Se in the cerebellum and cerebral cortex, two fundamentally important brain regions, in albino rats that were exposed to heavy metals mixture (Al, Pb, Hg and Mn). METHODS: Animals were divided into five groups of seven animals per group with following patterns of exposure, controls group 1 were orally treated with deionized water for 60 days; group 2 was exposed to heavy metal mixture (HMM) with following concentrations (20 mg.kg(-1) of Pb body weight; 0.40 mg.kg(-1) of Hg; 0.56 mg.kg(-1) of Mn; and 35 mg.kg(-1); of Al), while groups 3,4 and 5 were exposed to HMM and orally co-treated with zinc chloride (ZnCl(2); 0.80 mg/kg), sodium selenite (Na(2)SeO(3);1.50 mg/kg) and zinc chloride plus sodium selenite (ZnCl(0.2) + Na(2)SeO(3)) respectively. RESULTS: Exposure to HMM depressed cellular antioxidant apparatus, induced generation of lipid peroxidation markers (Malondialdehyde and NO), downregulated expression of transcription factors (Nrf2, and NF-kB) and upregulated Caspase 3 levels. HMM potentiated acetylcholinesterase activity and induced moderate histopathological alterations. Nevertheless, Zn, Se and in particular Zn + Se had recovering effects on all mentioned hazardous effects produced by HMM exposure in the cerebral cortex and cerebellum. CONCLUSIONS: Selenium and zinc exert neuroprotection via Nrf2/NF-kB signaling pathways against quaternary heavy metal mixture-induced impairments in albino Sprague Dawley rats.
ESTHER : Dike_2023_IBRO.Neurosci.Rep_15_57
PubMedSearch : Dike_2023_IBRO.Neurosci.Rep_15_57
PubMedID: 37415728

Title : Nickel and aluminium mixture elicit memory impairment by activation of oxidative stress, COX-2, and diminution of AChE, BDNF and NGF levels in cerebral cortex and hippocampus of male albino rats - Anyachor_2023_Curr.Res.Toxicol_5_100129
Author(s) : Anyachor CP , Orish CN , Ezejiofor AN , Cirovic A , Ezealisiji KM , Orisakwe OE
Ref : Curr Res Toxicol , 5 :100129 , 2023
Abstract : This study evaluated nickel and aluminium-induced neurotoxicity, as a binary metal mixture. Twenty-eight male Sprague Dawley albino rats were weight-matched and divided into four groups. Group 1 (control) received deionized water. Group 2 and 3 received Aluminium (1 mg/kg) and Nickel (0.2 mg/kg) respectively, while Group 4 received Ni and Al mixture HMM three times a week orally for 90 days. Barnes maze tests was performed. Rats were sacrificed under pentobarbital anaesthesia, cerebral cortex and hippocampus were separated, and metal levels were measured using Atomic Absorption Spectroscopy (AAS). Malondialdehyde (MDA), catalase (CAT), glutathione content (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), Brain Derived Neurotrophic Factor (BDNF), Nerve growth factor NGF, cyclo-oxygenase COX-2 and Acetylcholinesterase (AChE) were assayed using ELISA kits. Ni/Al binary mixture exposed rats showed a shorter latency period (though not significant) of 3.21 +/- 1.40 s in comparison to 3.77 +/- 1.11 (Ni only) and 3.99 +/- 1.16(Al only). Ni/Al mixture gp had the lowest levels of Mg in both the hippocampus and frontal cortex when compared with the individual metals. In the hippocampus Al only exposed rats significantly showed p < 0.05 higher iron and Ca levels in comparison to Ni/Al mixture. Al alone significantly showed p < 0.05 lower levels of Fe but higher Ca than the Ni/Al mixture group. Exposure to Al only showed lower levels of BDNF in comparison to Ni/Al combination, whereas Ni/Al mixture gp had lower levels of NGF in comparison to the individual metals in the hippocampus. In the frontal cortex Ni only, group showed significantly lower BDNF in comparison to Ni/Al mixture whereas the mixture showed significantly lower NGF when compared with Al only group. There were higher levels of COX-2 in the Ni/Al mixture than individual metal treated rats in both hippocampus and frontal cortex. AChE levels in the Ni/Al mixture group was higher than Ni or Al only gps in the hippocampus whereas in the frontal cortex, Ni/Al exposed rats showed significantly lower AChE levels in comparison to Al only group. Ni, Al and Ni/Al mixture exhibited memory impairment by activation of oxidative stress, COX-2, and diminution of AChE, BDNF and NGF levels in cerebral cortex and hippocampus. The BDNF-COX-2 AChE signalling pathway may be involved in the neurotoxicity of Ni and Al.
ESTHER : Anyachor_2023_Curr.Res.Toxicol_5_100129
PubMedSearch : Anyachor_2023_Curr.Res.Toxicol_5_100129
PubMedID: 37841055