Catalysis of catechol oxidation by metal-dithiocarbamate complexes in pesticides

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

doi:10.1016/s0891-5849(02)01169-3

Cited by 90 publications

(32 citation statements)

References 31 publications

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“…These data are consistent with findings from previous studies that evaluated other EBDCs and their role in oxidative stress and neuronal toxicity. Fitsanakis et al (2002) found that Mn-EBDCs catalyze a one electron transfer from dopamine or norepinephrine to molecular oxygen, resulting in ROS products like superoxide and semiquinone species. Barlow et al (2005) reported that MB, a Mn-EBDC very similar to MZ, at doses not affecting cell viability induced significant changes in the GSH antioxidant system in PC12 cells (catecholaminergic cell line) and in mesencephalic cells.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the oxidation of dopamine produces dopamine quinones, reactive species that can cause damage to lipids, proteins, and DNA (Hastings, 1995). Mn-EBDCs, like MB and MZ, can catalyze the oxidation of catechols (Fitsanakis et al, 2002). If DA becomes available to MZ or MB in the cytosol or extracellularly, the EBDC-catalyzed oxidation of catecholamines denotes another potential source of highly reactive free radicals and ROS.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Reactive oxygen species generation by the ethylene-bis-dithiocarbamate (EBDC) fungicide mancozeb and its contribution to neuronal toxicity in mesencephalic cells

Domico

Cooper

Bernard³

et al. 2007

NeuroToxicology

120

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Previous in vitro studies in our laboratory have shown that mancozeb (MZ) and maneb (MB), both widely used EBDC fungicides, are equipotent neurotoxicants that produce cell loss in mesencephalic dopaminergic and GABAergic cells after an acute 24 h exposure. Mitochondrial uncoupling and inhibition were associated with fungicide exposure. Inhibition of mitochondrial respiration is known to increase free radical production. Here the mechanism(s) of neuronal damage associated with MZ exposure was further explored by determining the role that reactive oxygen species (ROS) played in toxicity. Damage to mesencephalic dopamine and GABA cell populations were significantly attenuated when carried out in the presence of ascorbate or SOD indicative of a free radical mediated contribution to toxicity. ROS generation monitored by H 2 O 2 production using Amplex Red increased in a dose-dependent manner in response to MZ. Inhibition of intracellular catalase with aminotriazole had little effect on H 2 O 2 generation, whereas exogenously added catalase significantly reduced H 2 O 2 production demonstrating a large extracellular contribution to ROS generation. Conversely, cells preloaded with the ROS indicator dye DCF showed significant MZ-induced ROS production, demonstrating an increase in intracellular ROS. Both the organic backbone of MZ as well as its associated Mn ion, but not Zn ion were responsible and required for H 2 O 2 generation. The functionally diverse NADPH oxidase inhibitors, diphenylene iodonium chloride, apocynin, and 4-(2-aminoethyl)benzene-sulfonyl fluoride hydrochloride significantly attenuated H 2 O 2 production by MZ. In growth medium lacking cells, MZ produced little H 2 O 2 , but enhanced H 2 O 2 generation when added with xanthine plus xanthine oxidase whereas, in cultured cells, allopurinol partially attenuated H 2 O 2 production by MZ. Minocycline, an inhibitor of microglial activation, modestly reduced H 2 O 2 formation in mesencephalic cells. In contrast, neuronal enriched cultures or cultures treated with MAC-1-SAP to kill microglia, did not show an attenuation of ROS production. These findings demonstrate that Mn-containing EBDC fungicides such as MZ and MB can produce robust ROS generation that likely occurs via redox cycling with extracellular and intracellular oxidases. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeurotoxicology. Author manuscript; available in PMC 2008 November 1. The findings further show that microglia may contribute to but are not required for ROS production by MZ.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Reactive oxygen species generation by the ethylene-bis-dithiocarbamate (EBDC) fungicide mancozeb and its contribution to neuronal toxicity in mesencephalic cells

Domico

Cooper

Bernard³

et al. 2007

NeuroToxicology

120

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“…In vitro studies indicate that the dopaminergic neurotoxicity of maneb may be associated with its ability to inhibit the activity of complex III in the mitochondrial respiratory chain . Fitsanakis et al (2002) had earlier proposed that the dopaminergic neurotoxicity of maneb might be associated with its ability to facilitate catecholamine oxidation. Furthermore, besides being toxic to dopaminergic neurons by itself, repeated systemic administration of maneb and paraquat to mice induced a synergistic reduction in ST dopamine content, degeneration of SN dopaminergic neurons, and development of motor behavioral abnormalities (Thiruchelvam et al 2000a(Thiruchelvam et al , 2000b.…”

Section: Exposure To Pesticides and Development Of Pdmentioning

confidence: 99%

Parkinson's disease and exposure to infectious agents and pesticides and the occurrence of brain injuries: role of neuroinflammation.

Liu

Gao

Hong

2003

Environ Health Perspect

250

185

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Idiopathic Parkinson's disease (PD) is a devastating movement disorder characterized by selective degeneration of the nigrostriatal dopaminergic pathway. Neurodegeneration usually starts in the fifth decade of life and progresses over 5-10 years before reaching the fully symptomatic disease state. Despite decades of intense research, the etiology of sporadic PD and the mechanism underlying the selective neuronal loss remain unknown. However, the late onset and slow-progressing nature of the disease has prompted the consideration of environmental exposure to agrochemicals, including pesticides, as a risk factor. Moreover, increasing evidence suggests that early-life occurrence of inflammation in the brain, as a consequence of either brain injury or exposure to infectious agents, may play a role in the pathogenesis of PD. Most important, there may be a self-propelling cycle of inflammatory process involving brain immune cells (microglia and astrocytes) that drives the slow yet progressive neurodegenerative process. Deciphering the molecular and cellular mechanisms governing those intricate interactions would significantly advance our understanding of the etiology and pathogenesis of PD and aid the development of therapeutic strategies for the treatment of the disease.

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“…Stimulation of non selective cation channels by thiram, ziram, and maneb cause the influx of Ca ++ and Cu ++ into mitochondria increasing oxidative stress which induce apoptosis of PC12 cells and dopaminergic neuronal damage (Sook Han et al, 2003;Barlow et al, 2005). DTC metal complexes induce dopamine oxidation and produce intraneuronal oxidative stress leading to neuronal damage (Fitsanakis et al, 2002). Since DTC chelate heavy metals such as Cu, Zn, and Fe, leading to their intraneuronal accumulations, these metals have been implicated in promoting lipid peroxidation, oxidative stress, and enzyme inhibitions causing neurotoxic effects (Nobel et al, 1995;Valentine et al, 2009;Viquez et al, 2009;Viola-Rhenals et al, 2007).…”

Section: Neuropathic Effectsmentioning

confidence: 99%

Dithiocarbamate Toxicity - An Appraisal

Rath¹,

Rasaputra²,

Liyanage³

et al. 2011

Pesticides in the Modern World - Effects of Pesticides Exposure

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Catalysis of catechol oxidation by metal-dithiocarbamate complexes in pesticides

Cited by 90 publications

References 31 publications

Reactive oxygen species generation by the ethylene-bis-dithiocarbamate (EBDC) fungicide mancozeb and its contribution to neuronal toxicity in mesencephalic cells

Reactive oxygen species generation by the ethylene-bis-dithiocarbamate (EBDC) fungicide mancozeb and its contribution to neuronal toxicity in mesencephalic cells

Parkinson's disease and exposure to infectious agents and pesticides and the occurrence of brain injuries: role of neuroinflammation.

Dithiocarbamate Toxicity - An Appraisal

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