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Author Notes:

To whom correspondence should be addressed at Emory University, 615 Michael Street, RM 205P, Atlanta, GA 30322. Fax: (404) 712-2974. E-mail: dpjones@emory.edu.


Research Funding:

National Institute of Environmental Health Sciences at the National Institutes of Health (RO1 ES009047 to D.P.J. and T32 ES012870 to J.R.R.); The Emory-Egleston Children’s Research Committee (to J.M.H.).


  • paraquat
  • maneb
  • thioredoxin
  • peroxiredoxin
  • Nrf2
  • Parkinson’s disease

Maneb and Paraquat-Mediated Neurotoxicity: Involvement of Peroxiredoxin/Thioredoxin System


Journal Title:

Toxicological Sciences


Volume 121, Number 2


, Pages 368-375

Type of Work:

Article | Post-print: After Peer Review


Epidemiological and in vivo studies have demonstrated that exposure to the pesticides paraquat (PQ) and maneb (MB) increase the risk of developing Parkinson’s disease (PD) and cause dopaminergic cell loss, respectively. PQ is a well-recognized cause of oxidative toxicity; therefore, the purpose of this study was to determine if MB potentiates oxidative stress caused by PQ, thus providing a mechanism for enhanced neurotoxicity by the combination. The results show that PQ alone at a moderately toxic dose (20–30% cell death in 24 h) caused increased reactive oxygen species (ROS) generation, oxidation of mitochondrial thioredoxin-2 and peroxiredoxin-3, lesser oxidation of cytoplasmic thioredoxin-1 and peroxiredoxin-1, and no oxidation of cellular GSH/GSSG. In contrast, MB alone at a similar toxic dose resulted in no ROS generation, no oxidation of thioredoxin and peroxiredoxin, and an increase in cellular GSH after 24 h. Together, MB increased GSH and inhibited ROS production and thioredoxin/peroxiredoxin oxidation observed with PQ alone, yet resulted in more extensive (> 50%) cell death. MB treatment resulted in increased abundance of nuclear Nrf2 and mRNA for phase II enzymes under the control of Nrf2, indicating activation of cell protective responses. The results show that MB potentiation of PQ neurotoxicity does not occur by enhancing oxidative stress and suggests that increased toxicity occurs by a combination of divergent mechanisms, perhaps involving alkylation by MB and oxidation by PQ.

Copyright information:

© The Author 2011. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com

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