Effects of Oral Exposure to Mining Waste on in Vivo Dopamine Release from Rat Striatum

Rodríguez, Verónica; Dufour, L; Carrizales, Leticia; Díaz‐Barriga, Fernando; Jiménez‐Capdeville, María E.

doi:10.2307/3434181

Cited by 14 publications

(19 citation statements)

References 6 publications

(6 reference statements)

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“…However, data presented herein delineate a health risk potential associated with effects of the parent chemical. Accidental exposures through spills or unintended uses of MMT-amended gasoline provides a routine human exposure route, which, noting both the demonstrated effects of manganese on dopaminergic neurochemical systems (Olanow et al, 1996;Rodruigez et al, 1998) and long blood plasma half-life of MMT (Zheng et al, 2000), may potentially play a role in environmentally mediated, geriatric onset PD. Recent epidemiological and case-control studies support the role of environmental exposure to metals and other organic toxicants such as pesticides in idiopathic PD (Gorrel et al, 1999;Tanner et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress and Mitochondrial-Mediated Apoptosis in Dopaminergic Cells Exposed to Methylcyclopentadienyl Manganese Tricarbonyl

Kitazawa

Wagner²,

Kirby

et al. 2002

The Journal of Pharmacology and Experimental Therapeutics

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Methylcyclopentadienyl manganese tricarbonyl (MMT), an organic manganese-containing gasoline additive, was investigated to determine whether MMT potentially causes dopaminergic neurotoxic effects. MMT is acutely cytotoxic and dopamine-producing cells (PC-12) seemed to be more susceptible to cytotoxic effects than nondopaminergic cells (striatal ␥-aminobutyric acidergic and cerebellar granule cells). MMT also potently depleted dopamine apparently by cytoplasmic vesicular release to the cytosol, a neurochemical change resembling other dopaminergic neurotoxicants. Generation of reactive oxygen species (ROS), an early effect in toxicantinduced apoptosis, occurred within 15 min of MMT exposure. MMT caused a loss of mitochondrial transmembrane potential (⌬⌿m), a likely source of ROS generation. The ROS signal further activated caspase-3, an important effector caspase, which could be inhibited by antioxidants (Trolox or N-acetyl cysteine). Predepletion of dopamine by using ␣-methyl-p-tyrosine (tyrosine hydroxylase inhibitor) treatment partially prevented caspase-3 activation, denoting a significant dopamine and/or dopamine by-product contribution to initiation of apoptosis. Genomic DNA fragmentation, a terminal hallmark of apoptosis, was induced concentration dependently by MMT but completely prevented by pretreatment with Trolox, deprenyl (monoamine oxidase-B inhibitor), and ␣-methyl-p-tyrosine. A final set of critical experiments was performed to verify the pharmacological studies using a stable Bcl-2-overexpressing PC-12 cell line. Bcl-2-overexpressing cells were significantly refractory to MMT-induced ROS generation, caspase-3 activation, and loss of ⌬⌿m and were completely resistant to MMTinduced DNA fragmentation. Taken together, the results presented herein demonstrate that oxidative stress plays an important role in mitochondrial-mediated apoptotic cell death in cultured dopamine-producing cells after exposure to MMT.

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Section: Discussionmentioning

confidence: 99%

Oxidative Stress and Mitochondrial-Mediated Apoptosis in Dopaminergic Cells Exposed to Methylcyclopentadienyl Manganese Tricarbonyl

Kitazawa

Wagner²,

Kirby

et al. 2002

The Journal of Pharmacology and Experimental Therapeutics

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“…Moreover, lead, cadmium, arsenic and manganese have all been demonstrated to inhibit depolarization-evoked neurotransmitter release. This effect has even been shown to be synergistic when these metals are administered as a mixture (43). By either inhibiting signal transmission or producing spontaneous depolarization in the absence of environmental stimuli, the effect of toxic metals may be to add noise to the neuronal signaling processes which determine synaptic pruning and synaptogenesis.…”

Section: Early Life Programming Of Neurodevelopmentmentioning

confidence: 99%

The Challenge Posed to Children's Health by Mixtures of Toxic Waste: The Tar Creek Superfund Site as a Case-Study

Shine²,

Wright

2007

Pediatric Clinics of North America

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“…The two chemicals that have been examined in this way are lead and manganese. The rationale for examining these metals is provided by studies in rodents indicating that, compared to animals exposed to one metal at a time, combined exposure to arsenic, lead, and manganese resulted in lower brain levels of monoamines [53] and reduced dopamine response to stimulation [54], greater brain levels of delta-amino levulinic acid [55], greater white matter damage [56], reduction in glial fibrillary acid protein expression and increased apoptosis of astrocytes [57]. In three epidemiological studies, all conducted in Mexico, no evidence supporting a significant interaction between arsenic and lead was found [29,36,41].…”

Section: Co-exposuresmentioning

confidence: 99%

Inorganic Arsenic Exposure and Children’s Neurodevelopment: A Review of the Evidence

Bellinger

2013

Toxics

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Experimental studies suggest a myriad of mechanisms by which inorganic arsenic can interfere with central nervous system development, and, indeed, epidemiological studies published in the last dozen years suggest that exposure to arsenic impairs children's cognitive development. Most of the studies have been conducted in developing countries (e.g., Bangladesh, India, Mexico), where exposure to arsenic is thought to be considerably higher than it is in developed countries. This review summarizes the results of these studies, focusing in particular on issues pertinent to risk assessment, including the existence of critical windows of vulnerability, characteristics of the dose-effect relationships (e.g., the lowest adverse effect level, the functional form), the most sensitive neurodevelopmental endpoints, and potential effect modifiers such as host characteristics (e.g., methylation efficiency, sex) and co-exposures to other neurotoxicants (e.g., lead, manganese). At present, the epidemiological data do not permit firm conclusions to be drawn regarding these issues. Several factors that complicate an effort to compare the results of studies are identified, including use of a variety of indices of external and internal exposure, and inconsistency in the measurement of important potential confounders for neurodevelopmental outcomes.

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Effects of Oral Exposure to Mining Waste on in Vivo Dopamine Release from Rat Striatum

Cited by 14 publications

References 6 publications

Oxidative Stress and Mitochondrial-Mediated Apoptosis in Dopaminergic Cells Exposed to Methylcyclopentadienyl Manganese Tricarbonyl

Oxidative Stress and Mitochondrial-Mediated Apoptosis in Dopaminergic Cells Exposed to Methylcyclopentadienyl Manganese Tricarbonyl

The Challenge Posed to Children's Health by Mixtures of Toxic Waste: The Tar Creek Superfund Site as a Case-Study

Inorganic Arsenic Exposure and Children’s Neurodevelopment: A Review of the Evidence

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