Skip to main content

Advertisement

SpringerLink
Log in

Increased Reactive Oxygen Species Production in the Brain After Repeated Low-Dose Pesticide Paraquat Exposure in Rats. A Comparison with Peripheral Tissues

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

The pesticide paraquat (PQ) was found to be a suitable xenobiotic to model Parkinson’s disease. The reactive oxygen species (ROS) production was suggested to be the main cause of PQ toxicity but very few evidences were found for its generation in the brain in vivo after ip administration. We compared the effects of PQ-induced ROS generation between the brain structures and the peripheral tissues using two different hydroxyl radical generation markers. Repeated but not single ip PQ administration increased the levels of ROS in the striatal homogenates but, when measured in the extracellular microdialysis filtrate, no change was observed. The increased dopamine release was detected in the striatum after the fourth PQ administration and its basal levels were decreased. A single treatment with the pesticide did not influence ROS production in the lungs or kidneys but repeated intoxication decreased its levels. These results suggest that repeated, systemic administration of a low dose of PQ triggers intracellular ROS formation in the brain and can cause slowly progressing degenerative processes, without the toxic effects in the peripheral tissues.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

2,3-DHBA:

2,3-Dihydroxybenzoic acid

2,5-DHBA:

2,5-Dihydroxybenzoic acid

3,4-DHBA:

3,4-Dihydroxybenzoic acid

4-HBA:

4-Hydroxybenzoic acid

BBB:

Blood brain barrier DA dopamine

FC:

Frontal cortex

HNE:

4-Hydroxy-2-trans-nonenal

PD:

Parkinson’s disease

PQ:

Paraquat

ROS:

Reactive oxygen species

SAL:

Salicylic acid

SN:

Substantia nigra

STR:

Striatum

References

  1. Costello S, Cockburn M, Bronstein J et al (2009) Parkinson’s disease and residential exposure to maneb and paraquat from agricultural applications in the central valley of California. Am J Epidemiol 8:919–926

    Article  Google Scholar 

  2. Di Monte DA, Lavasani M, Manning-Bog AB (2002) Environmental factors in Parkinson’s disease. Neurotoxicology 4–5:487–502

    Article  Google Scholar 

  3. Hertzman C, Wiens M, Bowering D et al (1990) Parkinson’s disease: a case–control study of occupational and environmental risk factors. Am J Ind Med 3:349–355

    Article  Google Scholar 

  4. Liou HH, Tsai MC, Chen CJ et al (1997) Environmental risk factors and Parkinson’s disease: a case-control study in Taiwan. Neurology 6:1583–1588

    Google Scholar 

  5. Semchuk KM, Love EJ, Lee RG (1992) Parkinson’s disease and exposure to agricultural work and pesticide chemicals. Neurology 7:1328–1335

    Google Scholar 

  6. Ossowska K, Wardas J, Smialowska M et al (2005) A slowly developing dysfunction of dopaminergic nigrostriatal neurons induced by long-term paraquat administration in rats: an animal model of preclinical stages of Parkinson’s disease? Eur J Neurosci 6:1294–1304

    Article  Google Scholar 

  7. Ossowska K, Smialowska M, Kuter K et al (2006) Degeneration of dopaminergic mesocortical neurons and activation of compensatory processes induced by a long-term paraquat administration in rats: implications for Parkinson’s disease. Neuroscience 4:2155–2165

    Article  Google Scholar 

  8. Kuter K, Smialowska M, Wieronska J et al (2007) Toxic influence of subchronic paraquat administration on dopaminergic neurons in rats. Brain Res 1155:196–207

    Article  CAS  PubMed  Google Scholar 

  9. Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 6:889–909

    Article  Google Scholar 

  10. Casetta I, Govoni V, Granieri E (2005) Oxidative stress, antioxidants and neurodegenerative diseases. Curr Pharm Des 16:2033–2052

    Article  Google Scholar 

  11. Halliwell B (2006) Oxidative stress and neurodegeneration: where are we now? J Neurochem 6:1634–1658

    Article  Google Scholar 

  12. Dinis-Oliveira RJ, Duarte JA, Sanchez-Navarro A et al (2008) Paraquat poisonings: mechanisms of lung toxicity, clinical features, and treatment. Crit Rev Toxicol 1:13–71

    Article  Google Scholar 

  13. Shimada H, Hirai K, Simamura E et al (2009) Paraquat toxicity induced by voltage-dependent anion channel 1 acts as an NADH-dependent oxidoreductase. J Biol Chem 42:28642–28649

    Article  Google Scholar 

  14. Bus JS, Gibson JE (1984) Paraquat: model for oxidant-initiated toxicity. EnvironHealth Perspect 55:37–46

    Article  CAS  Google Scholar 

  15. Clejan L, Cederbaum AI (1989) Synergistic interactions between NADPH-cytochrome P-450 reductase, paraquat, and iron in the generation of active oxygen radicals. Biochem Pharmacol 11:1779–1786

    Article  Google Scholar 

  16. DeGray JA, Rao DN, Mason RP (1991) Reduction of paraquat and related bipyridylium compounds to free radical metabolites by rat hepatocytes. Arch Biochem Biophys 1:145–152

    Article  Google Scholar 

  17. Fukushima T, Tawara T, Isobe A et al (1995) Radical formation site of cerebral complex I and Parkinson’s disease. J Neurosci Res 3:385–390

    Article  Google Scholar 

  18. Schmuck G, Rohrdanz E, Tran-Thi QH et al (2002) Oxidative stress in rat cortical neurons and astrocytes induced by paraquat in vitro. Neurotox Res 1:1–13

    Article  Google Scholar 

  19. Shimada H, Hirai K, Simamura E et al (1998) Mitochondrial NADH-quinone oxidoreductase of the outer membrane is responsible for paraquat cytotoxicity in rat livers. Arch Biochem Biophys 1:75–81

    Article  Google Scholar 

  20. Tampo Y, Tsukamoto M, Yonaha M (1999) Superoxide production from paraquat evoked by exogenous NADPH in pulmonary endothelial cells. Free Radic Biol Med 5–6:588–595

    Article  Google Scholar 

  21. Tomita M, Okuyama T (1994) Effect of paraquat on the malondialdehyde level in rat liver microsomes (in vitro). Arch Toxicol 3:187–192

    Article  Google Scholar 

  22. Wong RC, Stevens JB (1985) Paraquat toxicity in vitro. I. Pulmonary alveolar macrophages. J Toxicol Environ Health 3–4:417–429

    Article  Google Scholar 

  23. Yang W, Tiffany-Castiglioni E (2005) The bipyridyl herbicide paraquat produces oxidative stress-mediated toxicity in human neuroblastoma SH-SY5Y cells: relevance to the dopaminergic pathogenesis. J Toxicol Environ Health A 22:1939–1961

    Article  Google Scholar 

  24. Hara S, Endo T, Kuriiwa F et al (1991) Mechanism of paraquat-stimulated lipid peroxidation in mouse brain and pulmonary microsomes. J Pharm Pharmacol 10:731–733

    Google Scholar 

  25. Yumino K, Kawakami I, Tamura M et al (2002) Paraquat- and diquat-induced oxygen radical generation and lipid peroxidation in rat brain microsomes. J Biochem 4:565–570

    Google Scholar 

  26. Kim PM, Wells PG (1996) Phenytoin-initiated hydroxyl radical formation: characterization by enhanced salicylate hydroxylation. Mol Pharmacol 1:172–181

    Google Scholar 

  27. McCormack AL, Atienza JG, Johnston LC et al (2005) Role of oxidative stress in paraquat-induced dopaminergic cell degeneration. J Neurochem 4:1030–1037

    Article  Google Scholar 

  28. Prasad K, Winnik B, Thiruchelvam MJ et al (2007) Prolonged toxicokinetics and toxicodynamics of paraquat in mouse brain. Environ Health Perspect 10:1448–1453

    Google Scholar 

  29. Thiruchelvam M, Prokopenko O, Cory-Slechta DA et al (2005) Overexpression of superoxide dismutase or glutathione peroxidase protects against the paraquat + maneb-induced Parkinson disease phenotype. J Biol Chem 23:22530–22539

    Article  Google Scholar 

  30. Bartlett RM, Holden JE, Nickles RJ et al (2009) Paraquat is excluded by the blood brain barrier in rhesus macaque: an in vivo pet study. Brain Res 1259:74–79

    Article  CAS  PubMed  Google Scholar 

  31. Prasad K, Tarasewicz E, Mathew J et al (2009) Toxicokinetics and toxicodynamics of paraquat accumulation in mouse brain. Exp Neurol 2:358–367

    Article  Google Scholar 

  32. Ossowska K, Wardas J, Kuter K et al (2005) Influence of paraquat on dopaminergic transporter in the rat brain. Pharmacol Rep 3:330–335

    Google Scholar 

  33. Giovanni A, Liang LP, Hastings TG et al (1995) Estimating hydroxyl radical content in rat brain using systemic and intraventricular salicylate: impact of methamphetamine. J Neurochem 4:1819–1825

    Google Scholar 

  34. Golembiowska K, Dziubina A, Kowalska M et al (2008) Paradoxical effects of adenosine receptor ligands on hydroxyl radical generation by l-DOPA in the rat striatum. Pharmacol Rep 3:319–330

    Google Scholar 

  35. Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press, New York

    Google Scholar 

  36. Ingelman-Sundberg M, Kaur H, Terelius Y et al (1991) Hydroxylation of salicylate by microsomal fractions and cytochrome P-450. Lack of production of 2, 3-dihydroxybenzoate unless hydroxyl radical formation is permitted. Biochem J 276:753–757

    CAS  PubMed  Google Scholar 

  37. Chen ZH, Yoshida Y, Saito Y et al (2005) Adaptation to hydrogen peroxide enhances PC12 cell tolerance against oxidative damage. Neurosci Lett 3:256–259

    Article  Google Scholar 

  38. Yoo HY, Chang MS, Rho HM (1999) The activation of the rat copper/zinc superoxide dismutase gene by hydrogen peroxide through the hydrogen peroxide-responsive element and by paraquat and heat shock through the same heat shock element. J Biol Chem 34:23887–23892

    Article  Google Scholar 

  39. Zhou LZ, Johnson AP, Rando TA (2001) NF kappa B and AP-1 mediate transcriptional responses to oxidative stress in skeletal muscle cells. Free Radic Biol Med 11:1405–1416

    Article  Google Scholar 

  40. Shimizu K, Matsubara K, Ohtaki K et al (2003) Paraquat induces long-lasting dopamine overflow through the excitotoxic pathway in the striatum of freely moving rats. Brain Res 2:243–252

    Article  Google Scholar 

  41. Liu D, Yang J, Li L et al (1995) Paraquat—a superoxide generator—kills neurons in the rat spinal cord. Free Radic Biol Med 5:861–867

    Article  Google Scholar 

  42. Dinis-Oliveira RJ, de Pinho PG, Ferreira AC et al (2008) Reactivity of paraquat with sodium salicylate: formation of stable complexes. Toxicology 2–3:130–139

    Article  Google Scholar 

  43. Lagrange P, Romero IA, Minn A et al (1999) Transendothelial permeability changes induced by free radicals in an in vitro model of the blood-brain barrier. Free Radic Biol Med 5–6:667–672

    Article  Google Scholar 

  44. Hong H, Lu Y, Ji ZN et al (2006) Up-regulation of P-glycoprotein expression by glutathione depletion-induced oxidative stress in rat brain microvessel endothelial cells. J Neurochem 5:1465–1473

    Article  Google Scholar 

  45. Kortekaas R, Leenders KL, van Oostrom JC et al (2005) Blood-brain barrier dysfunction in parkinsonian midbrain in vivo. Ann Neurol 2:176–179

    Article  Google Scholar 

  46. Smith LL, Wyatt I (1981) The accumulation of putrescine into slices of rat lung and brain and its relationship to the accumulation of paraquat. Biochem Pharmacol 10:1053–1058

    Article  Google Scholar 

  47. Dey MS, Breeze RG, Hayton WL et al (1990) Paraquat pharmacokinetics using a subcutaneous toxic low dose in the rat. Fundam Appl Toxicol 1:208–216

    Article  Google Scholar 

  48. Saito K (1986) Effects of paraquat on macromolecule synthesis in cultured pneumocytes. Tohoku J Exp Med 3:303–312

    Article  Google Scholar 

  49. Podprasart V, Satayavivad J, Riengrojpitak S et al (2007) No direct hepatotoxic potential following a multiple-low dose paraquat exposure in rat as related to its bioaccumulation. Toxicol Lett 3:193–202

    Article  Google Scholar 

  50. Franco AA, Odom RS, Rando TA (1999) Regulation of antioxidant enzyme gene expression in response to oxidative stress and during differentiation of mouse skeletal muscle. Free Radic Biol Med 9–10:1122–1132

    Article  Google Scholar 

Download references

Acknowledgments

This study was supported by the statutory funds of Department of Neuropsychopharmacology, Polish Academy of Sciences in Krakow. We thank Ms M. Zapała, Ms U. Mikołajun and also W. Kolasiewicz for excellent technical assistance.

Conflict of Interests

The authors declare no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Neuropsychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna St., 31-343, Krakow, Poland

    Katarzyna Kuter & Krystyna Ossowska

  2. Department of Pharmacology, Medical University of Silesian, 19 Jordana St., 41-808, Zabrze, Poland

    Przemysław Nowak

  3. Department of Pharmacology, Polish Academy of Sciences, 12 Smętna St., 31-343, Krakow, Poland

    Krystyna Gołembiowska

Authors
  1. Katarzyna Kuter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Przemysław Nowak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Krystyna Gołembiowska
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Krystyna Ossowska
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Katarzyna Kuter.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kuter, K., Nowak, P., Gołembiowska, K. et al. Increased Reactive Oxygen Species Production in the Brain After Repeated Low-Dose Pesticide Paraquat Exposure in Rats. A Comparison with Peripheral Tissues. Neurochem Res 35, 1121–1130 (2010). https://doi.org/10.1007/s11064-010-0163-x

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-010-0163-x

Keywords

Search

Navigation