title: Oxidative stress in zinc-induced dopaminergic neurodegeneration: implications of superoxide dismutase and heme oxygenase-1.
abstract: The study was undertaken to investigate the effect of zinc (Zn) on glutathione S-transferase (GST) and superoxide dismutases (SOD) activities and on the expressions of cytosolic Cu, Zn-SOD (SOD1), mitochondrial Mn-SOD (SOD2), γ-glutamyl cysteine synthetase (γ-GCS) and heme oxygenase-1 (HO-1) in the nigrostriatal tissue of rats. Additionally, Zn-induced alterations in the neurobehavioral parameters, lipid peroxidation (LPO), striatal dopamine and its metabolites and tyrosine hydroxylase (TH) protein expression were measured to assess their correlations with the oxidative stress. Zn exposure reduced the locomotor activity, rotarod performance, striatal dopamine and its metabolites and TH protein expression. LPO, total SOD, SOD1 and SOD2 activities were increased while GST and catalase were reduced in a dose and time dependent manner. Expressions of SOD1 and HO-1 were increased while no change was observed in SOD2 and γ-GCS expressions. The results obtained suggest that Zn-induced augmentation of total SOD, SOD1, SOD2 and HO-1 was associated with increased oxidative stress and neurodegenerative indexes indicating the involvement of both cytosolic and mitochondrial machinery in Zn-induced oxidative stress leading to dopaminergic neurodegeneration.
authors.affiliation: Indian Institute of Toxicology Research (IITR), Lucknow- 226 001, UP, India.
authors.forename: Brajesh Kumar
authors.initials: BK
authors.lastname: Singh
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Kumar
authors.forename: Israr
authors.initials: I
authors.lastname: Ahmad
authors.forename: Vinod
authors.initials: V
authors.lastname: Kumar
authors.forename: Devendra Kumar
authors.initials: DK
authors.lastname: Patel
authors.forename: Swatantra Kumar
authors.initials: SK
authors.lastname: Jain
authors.forename: Chetna
authors.initials: C
authors.lastname: Singh
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000201:enzymology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism*; D019287:Zinc Sulfate / Q000494:pharmacology*
chemical_list: D019287:Zinc Sulfate; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D005721:Glutamate-Cysteine Ligase; D004298:Dopamine