Acute exposure to maneb alters some behavioral functions in the mouse

Morato, Gina Struffaldi; Lemos, Tadeu; Takahashi, Reinaldo Ν.

doi:10.1016/0892-0362(89)90018-4

Cited by 55 publications

(30 citation statements)

References 22 publications

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“…The risk of PD or PD-like pathology in animal models associated with exposure to pesticides has been reported in multiple studies (i.e., Morato et al, 1989;Takahashi et al, 1989;Fredriksson et al, 1993;Alam and Schmidt, 2002;McCormack et al, 2002;Gao et al, 2003). With respect to ATR, several studies indicate that both in vivo (Rodriguez et al, 2005;Coban and Filipov, 2007) and in vitro (Das et al, 2000;Das et al, 2003;Filipov et al, 2007) exposure to this herbicide causes dopaminergic neurotoxicity manifested with decreased DA.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, case control studies suggest that the risk of PD is increased when the duration of exposure to pesticides exceeds a particular threshold (Seidler et al, 1996;Gorell et al, 1998). Specific pesticides that have been associated with PD-like symptomology (i.e., dopaminergic toxicity) are paraquat (Fredriksson et al, 1993;McCormack et al, 2002), maneb (Morato et al, 1989;Takahashi et al, 1989), and rotenone (Alam and Schmidt, 2002;Gao et al, 2003). In the case of paraquat and maneb, greater dopaminergic toxicity was observed in animals exposed to both of these pesticides (Thiruchelvam et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Alteration of dopamine uptake into rat striatal vesicles and synaptosomes caused by an in vitro exposure to atrazine and some of its metabolites

Hossain

Filipov

2008

Toxicology

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Studies have shown that both in vivo and in vitro exposure to the herbicide atrazine (ATR) results in dopaminergic neurotoxicity manifested by decreased striatal dopamine (DA) levels. However, the mechanism behind this reduction is largely unknown. A decrease in striatal DA could be due to ATR exposure affecting vesicular and/or synaptosomal uptake resulting in disrupted vesicular storage and/ or cellular uptake of DA. Hence, we investigated the effects of in vitro ATR exposure on DA uptake into isolated rat striatal synaptosomes and synaptic vesicles. In addition to ATR, effects of its major mammalian metabolites, didealkyl atrazine (DACT), desethyl atrazine (DE) and desiopropyl atrazine (DIP) were investigated. ATR (1-250 μM) inhibited DA uptake into synaptic vesicles in a dose dependent manner. Of the three ATR metabolites tested, DACT did not affect vesicular DA uptake. DE and DIP, on the other hand, significantly decreased vesicular DA uptake with the effect of 100 μM DE/DIP being similar to the effect of the same concentration of ATR. Kinetic analysis of vesicular DA uptake indicated that ATR significantly decreased the V max while the K m value was not affected. Contrary to the inhibitory effects on vesicular DA uptake, synaptosomal DA uptake was marginally (6-13%) increased by ATR and DE, but not by DACT and DIP, at concentrations of ≤100 μM. As a result, ATR, DIP and DE increased the synaptosomal/vesicular (DAT/VMAT-2) uptake ratio. Collectively, results from this study suggest that ATR and two of its metabolites, DIP and DE, but not its major mammalian metabolite, DACT, decrease striatal DA levels, at least in part, by increasing cytosolic DA, which is prone to oxidative breakdown.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alteration of dopamine uptake into rat striatal vesicles and synaptosomes caused by an in vitro exposure to atrazine and some of its metabolites

Hossain

Filipov

2008

Toxicology

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“…The adverse effects of MZ in humans and other living organisms have not been widely studied and there are few studies to evaluate the neurotoxic action of MZ in experimental models (Soleo et al, 1996;Vaccari et al, 1999;Domico et al, 2006a). However, other dithiocarbamate fungicides, including maneb (MB), have been implicated in selective dopaminergic neurotoxicity and mitochondrial dysfunction in rodents and humans, resulting in motor deficits, and ultimately, parkinsonism (Morato et al, 1989;Meco et al, 1994;Soleo et al, 1996;Zhang et al, 2003).…”

Section: Introductionmentioning

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

122

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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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“…Additionally, in experimental mouse models, maneb administration causes motor deficit (69) and potentiates the effects of MPTP (101).…”

Section: Mitochondria Both Mppmentioning

confidence: 99%

Toxin Models of Mitochondrial Dysfunction in Parkinson's Disease

Martinez

Greenamyre

2012

Antioxidants & Redox Signaling

228

155

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Significance: Parkinson's disease (PD) is a neurodegenerative disorder characterized, in part, by the progressive and selective loss of dopaminergic neuron cell bodies within the substantia nigra pars compacta (SNpc) and the associated deficiency of the neurotransmitter dopamine (DA) in the striatum, which gives rise to the typical motor symptoms of PD. The mechanisms that contribute to the induction and progressive cell death of dopaminergic neurons in PD are multi-faceted and remain incompletely understood. Data from epidemiological studies in humans and molecular studies in genetic, as well as toxin-induced animal models of parkinsonism, indicate that mitochondrial dysfunction occurs early in the pathogenesis of both familial and idiopathic PD. In this review, we provide an overview of toxin models of mitochondrial dysfunction in experimental Parkinson's disease and discuss mitochondrial mechanisms of neurotoxicity. Recent Advances: A new toxin model using the mitochondrial toxin trichloroethylene was recently described and novel methods, such as intranasal exposure to toxins, have been explored. Additionally, recent research conducted in toxin models of parkinsonism provides an emerging emphasis on extranigral aspects of PD pathology. Critical Issues: Unfortunately, none of the existing animal models of experimental PD completely mimics the etiology, progression, and pathology of human PD. Future Directions: Continued efforts to optimize established animal models of parkinsonism, as well as the development and characterization of new animal models are essential, as there still remains a disconnect in terms of translating mechanistic observations in animal models of experimental PD into bona fide diseasemodifying therapeutics for human PD patients. Antioxid. Redox Signal. 16, 920-934.

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Acute exposure to maneb alters some behavioral functions in the mouse

Cited by 55 publications

References 22 publications

Alteration of dopamine uptake into rat striatal vesicles and synaptosomes caused by an in vitro exposure to atrazine and some of its metabolites

Alteration of dopamine uptake into rat striatal vesicles and synaptosomes caused by an in vitro exposure to atrazine and some of its metabolites

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

Toxin Models of Mitochondrial Dysfunction in Parkinson's Disease

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