Catalysis of catechol oxidation by metal-dithiocarbamate complexes in pesticides

Dithiocarbamate -based pesticides have been implicated in Parkinson’s disease through epidemiological links to increased risk of PD, clinical reports of parkinsonism following occupational exposure to the DTC-based pesticide maneb, and experimental studies showing dopaminergic neurodegeneration with combined exposure of rats to maneb and paraquat

Vanessa A Fitsanakis; Venkataraman Amarnath; Joshua T Moore; Kathleen S Montine; Jing Zhang; Thomas J Montine

2002

Scholarcy highlights

  • Dithiocarbamate-based pesticides have been implicated in Parkinson’s disease through epidemiological links to increased risk of PD, clinical reports of parkinsonism following occupational exposure to the DTC-based pesticide maneb, and experimental studies showing dopaminergic neurodegeneration with combined exposure of rats to maneb and paraquat
  • We hypothesize that the manganese-ethylene-bis-dithiocarbamate complex in maneb may produce oxidative stress by catalyzing catechol oxidation. We tested this hypothesis by performing a structure-function analysis of metal-EBDC and metal-diethyldithiocarbamate complexes of Mn2+, Zn2+, and Cu2+ to catalyze oxidation of N-acetyldopamine and 3,4-dihydroxyphenylacetic acid in the presence and absence of N-acetylcysteine, a model of glutathione
  • Both Mn-DTCs retained the capacity of the parent ion to catalyze one-electron oxidation of NA-DA, but lost the ability to catalyze DP oxidation
  • Similar results were obtained with MnEBDC and dopamine or norepinephrine; zinc-ethylene-bis-dithiocarbamate was less efficient at catalyzing oxidation of these catechols
  • Our results point to the potential for manganese- and zinc-containing EBDC pesticides to promote oxidative stress in catecholaminergic regions of the brain

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