Effect of zinc and paraquat co-exposure on neurodegeneration: Modulation of oxidative stress and expression of metallothioneins, toxicant responsive and transporter genes in rats.
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.
Kumar
Ashutosh
A
Indian Institute of Toxicology Research, Lucknow 226 001, India.
Ahmad
Israr
I
Shukla
Smriti
S
Singh
Brajesh Kumar
BK
Patel
Devendra Kumar
DK
Pandey
Haushila Prasad
HP
Singh
Chetna
C
D000818:Animals; D015153:Blotting, Western; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis / Q000235:genetics; D050483:Dopamine Plasma Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis* / Q000235:genetics; D009043:Motor Activity / Q000187:drug effects; D009410:Nerve Degeneration / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010269:Paraquat / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D050493:Vesicular Monoamine Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D015032:Zinc / Q000737:chemistry / Q000494:pharmacology*
D050483:Dopamine Plasma Membrane Transport Proteins; C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins; D008668:Metallothionein; D019392:Cytochrome P-450 CYP2E1; D005982:Glutathione Transferase; C412602:glutathione S-transferase Mu 2; D015032:Zinc; D010269:Paraquat