Catalysis of catechol oxidation by metal-dithiocarbamate complexes in pesticides.
Dithiocarbamate (DTC)-based pesticides have been implicated in Parkinson's disease (PD) 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 (MnEBDC) 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 (DEDC) complexes of Mn2+, Zn2+, and Cu2+ to catalyze oxidation of N-acetyldopamine (NA-DA) and 3,4-dihydroxyphenylacetic acid (DP) in the presence and absence of N-acetylcysteine (NAC), 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. Strikingly, while Zn2+ did not catalyze catechol oxidation, both Zn-DTCs catalyzed one-electron oxidation of NA-DA but not DP. While Cu2+ catalyzed oxidation of both catechols, Cu-DTCs were inert. Similar results were obtained with MnEBDC and dopamine or norepinephrine; however, 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.
Fitsanakis
Vanessa A
VA
Departments of Pathology and Pharmacology and Centers for Molecular Toxicology and Molecular Neurosciences, Vanderbilt University Medical Center, Nashville, TN, USA. tmontine@u.washington.edu
Amarnath
Venkataraman
V
Moore
Joshua T
JT
Montine
Kathleen S
KS
Zhang
Jing
J
Montine
Thomas J
TJ
D002219:Carbamates / Q000737:chemistry*; D002384:Catalysis; D002396:Catechols / Q000737:chemistry*; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D010575:Pesticides / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000032:analysis / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D002219:Carbamates; D002396:Catechols; D016877:Oxidants; D010575:Pesticides; D017382:Reactive Oxygen Species; C034221:catechol; D010100:Oxygen