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Effect of zinc and paraquat co-exposure on neurodegeneration: Modulation of oxidative stress and expression of metallothioneins, toxicant responsive and transporter genes in rats.
Free Radic Res. 2010 Aug; 44(8):950-65.FR

Abstract

Oxidative stress is implicated in Parkinson's disease (PD). Metallothioneins (MT), cytochrome P450 IIE1 (CYP2E1) and glutathione S-transferases alpha4-4 (GSTA4-4) are involved in oxidative stress-mediated damage. Altered dopamine transporter (DAT) and vesicular monoamine transporter-2 (VMAT-2) are also documented in PD. The present study was undertaken to investigate the effect of Zn and PQ co-exposure on neurodegeneration in rats. A significant reduction was observed in spontaneous locomotor activity (SLA), striatal dopamine (DA) levels, tyrosine hydroxylase (TH) immunoreactivity, glutathione reductase (GR) and catalase activity along with increased lipid peroxidation (LPO) and glutathione peroxidase (GPx) activity after Zn and/or PQ exposure. Zn and/or PQ exposure increased gene expression of DAT, CYP2E1, GSTA4-4, MT-I and MT-II, but reduced the expression of VMAT-2. Protein expression analysis of TH, VMAT-2 and DAT showed results similar to those obtained with gene expression study. Zn and PQ co-exposure caused a more pronounced effect than that of individual exposure. The results obtained in this study suggest that, similar to PQ, Zn induced neurodegeneration via alterations in oxidative stress and expression of the above-mentioned genes. However, the effect of Zn+PQ was only slightly higher than that of alone, indicating that probably Zn and PQ follow some different molecular events leading to neurodegeneration.

Authors+Show Affiliations

Indian Institute of Toxicology Research, Lucknow 226 001, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20553223

Citation

Kumar, Ashutosh, et al. "Effect of Zinc and Paraquat Co-exposure On Neurodegeneration: Modulation of Oxidative Stress and Expression of Metallothioneins, Toxicant Responsive and Transporter Genes in Rats." Free Radical Research, vol. 44, no. 8, 2010, pp. 950-65.
Kumar A, Ahmad I, Shukla S, et al. Effect of zinc and paraquat co-exposure on neurodegeneration: Modulation of oxidative stress and expression of metallothioneins, toxicant responsive and transporter genes in rats. Free Radic Res. 2010;44(8):950-65.
Kumar, A., Ahmad, I., Shukla, S., Singh, B. K., Patel, D. K., Pandey, H. P., & Singh, C. (2010). Effect of zinc and paraquat co-exposure on neurodegeneration: Modulation of oxidative stress and expression of metallothioneins, toxicant responsive and transporter genes in rats. Free Radical Research, 44(8), 950-65. https://doi.org/10.3109/10715762.2010.492832
Kumar A, et al. Effect of Zinc and Paraquat Co-exposure On Neurodegeneration: Modulation of Oxidative Stress and Expression of Metallothioneins, Toxicant Responsive and Transporter Genes in Rats. Free Radic Res. 2010;44(8):950-65. PubMed PMID: 20553223.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of zinc and paraquat co-exposure on neurodegeneration: Modulation of oxidative stress and expression of metallothioneins, toxicant responsive and transporter genes in rats. AU - Kumar,Ashutosh, AU - Ahmad,Israr, AU - Shukla,Smriti, AU - Singh,Brajesh Kumar, AU - Patel,Devendra Kumar, AU - Pandey,Haushila Prasad, AU - Singh,Chetna, PY - 2010/6/18/entrez PY - 2010/6/18/pubmed PY - 2011/2/15/medline SP - 950 EP - 65 JF - Free radical research JO - Free Radic Res VL - 44 IS - 8 N2 - Oxidative stress is implicated in Parkinson's disease (PD). Metallothioneins (MT), cytochrome P450 IIE1 (CYP2E1) and glutathione S-transferases alpha4-4 (GSTA4-4) are involved in oxidative stress-mediated damage. Altered dopamine transporter (DAT) and vesicular monoamine transporter-2 (VMAT-2) are also documented in PD. The present study was undertaken to investigate the effect of Zn and PQ co-exposure on neurodegeneration in rats. A significant reduction was observed in spontaneous locomotor activity (SLA), striatal dopamine (DA) levels, tyrosine hydroxylase (TH) immunoreactivity, glutathione reductase (GR) and catalase activity along with increased lipid peroxidation (LPO) and glutathione peroxidase (GPx) activity after Zn and/or PQ exposure. Zn and/or PQ exposure increased gene expression of DAT, CYP2E1, GSTA4-4, MT-I and MT-II, but reduced the expression of VMAT-2. Protein expression analysis of TH, VMAT-2 and DAT showed results similar to those obtained with gene expression study. Zn and PQ co-exposure caused a more pronounced effect than that of individual exposure. The results obtained in this study suggest that, similar to PQ, Zn induced neurodegeneration via alterations in oxidative stress and expression of the above-mentioned genes. However, the effect of Zn+PQ was only slightly higher than that of alone, indicating that probably Zn and PQ follow some different molecular events leading to neurodegeneration. SN - 1029-2470 UR - https://www.unboundmedicine.com/medline/citation/20553223/Effect_of_zinc_and_paraquat_co_exposure_on_neurodegeneration:_Modulation_of_oxidative_stress_and_expression_of_metallothioneins_toxicant_responsive_and_transporter_genes_in_rats_ L2 - https://www.tandfonline.com/doi/full/10.3109/10715762.2010.492832 DB - PRIME DP - Unbound Medicine ER -