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Maneb and paraquat-mediated neurotoxicity: involvement of peroxiredoxin/thioredoxin system.
Toxicol Sci. 2011 Jun; 121(2):368-75.TS

Abstract

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.

Authors+Show Affiliations

Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Emory University, Atlanta, Georgia 30322, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21402726

Citation

Roede, James R., et al. "Maneb and Paraquat-mediated Neurotoxicity: Involvement of Peroxiredoxin/thioredoxin System." Toxicological Sciences : an Official Journal of the Society of Toxicology, vol. 121, no. 2, 2011, pp. 368-75.
Roede JR, Hansen JM, Go YM, et al. Maneb and paraquat-mediated neurotoxicity: involvement of peroxiredoxin/thioredoxin system. Toxicol Sci. 2011;121(2):368-75.
Roede, J. R., Hansen, J. M., Go, Y. M., & Jones, D. P. (2011). Maneb and paraquat-mediated neurotoxicity: involvement of peroxiredoxin/thioredoxin system. Toxicological Sciences : an Official Journal of the Society of Toxicology, 121(2), 368-75. https://doi.org/10.1093/toxsci/kfr058
Roede JR, et al. Maneb and Paraquat-mediated Neurotoxicity: Involvement of Peroxiredoxin/thioredoxin System. Toxicol Sci. 2011;121(2):368-75. PubMed PMID: 21402726.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Maneb and paraquat-mediated neurotoxicity: involvement of peroxiredoxin/thioredoxin system. AU - Roede,James R, AU - Hansen,Jason M, AU - Go,Young-Mi, AU - Jones,Dean P, Y1 - 2011/03/14/ PY - 2011/3/16/entrez PY - 2011/3/16/pubmed PY - 2011/9/20/medline SP - 368 EP - 75 JF - Toxicological sciences : an official journal of the Society of Toxicology JO - Toxicol Sci VL - 121 IS - 2 N2 - 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. SN - 1096-0929 UR - https://www.unboundmedicine.com/medline/citation/21402726/Maneb_and_paraquat_mediated_neurotoxicity:_involvement_of_peroxiredoxin/thioredoxin_system_ L2 - https://academic.oup.com/toxsci/article-lookup/doi/10.1093/toxsci/kfr058 DB - PRIME DP - Unbound Medicine ER -