<i>In vitro</i>dopaminergic neurotoxicity of pesticides: a link with neurodegeneration?

Heusinkveld, Harm J.; Berg, Martin van den; Westerink, Remco H.S.

doi:10.1080/01652176.2014.980934

Cited by 14 publications

(3 citation statements)

References 111 publications

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“…xenobiotic exposure activates dopamine D-like receptors that are involved in the modulation of ATPase activities in animals. This was corroborated by the works of Neve, Seamans, and Trantham-Davidson, H. (2004) and Heusinkveld, Van der Berg, and Westerink (2014) which showed that pesticides and xenobiotics activate the dopamine D 1 receptors that are linked to the feedback mechanism that regulate the voltage-gated calcium ion channel via the protein kinase A (PKA)-and protein kinase C (PKC)-mediated protein phosphorylations that stimulate Ca + -ATPase activity unlike the effect of stimulating dopamine D 2 receptors that results in less phosphorylation with inhibitory effect on the voltage-gated calcium channel with attendant decrease in dopaminergic neurotransmission. Pesticide exposure stimulates the activity of adenyl cyclases resulting in higher production of cAMP that promotes phosphorylation of the sensitive sites on the C-terminal of calcium channels thereby increasing the likelihood of opening the calcium channels and stimulating the activity of Ca 2+ -ATPase activity (Varadi, Mori, Mikala, & Schwrtz, 1995).…”

Section: Discussionsupporting

confidence: 64%

Tissue-specific changes in Ca2+-ATPase and Na+/K+-ATPase activities in freshwater African catfish Clarias gariepinus juvenile exposed to oxadiazon

Oluah

Mgbenka

Nwani

et al. 2020

JoBAZ

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Background: This study investigated the effect of sublethal concentrations (0.0, 0.3, 0.6, and 1.2 mg•L-1) of herbicide oxadiazon (ODZ) on the activities of Ca 2+-ATPase and Na + /K +-ATPase in juvenile Clarias gariepinus. Methods: One hundred eighty juveniles of Clarias gariepinus (mean weight 58.88 ± 1.24 g and mean length 22.34 ± 1.52 cm) were randomly divided into four groups and exposed to sublethal concentrations (0.00, 0.3, 0.6, and 1.2 mg•L-1 ODZ) for 21 days in a static renewal bioassay system in which the herbicide and water were replaced completely every day. The changes in Ca 2+-and Na + /K +-ATPase activities in the gill, kidney, liver, and heart of the fish were assayed on days 1, 7, 14, and 21. Result: The result showed significant alteration in the activity of these membrane-bound enzymes. There was duration and concentration-dependent significant (p < 0.05) increase in Ca 2+-ATPase activity in the treatment groups when compared with the control. The Na + /K +-ATPase activity was significantly (p < 0.05) inhibited in all the tissues when compared with control. The observed alterations in the activities of both Ca 2+-ATPase and Na + /K +-ATPase in this study may be indication of impaired ionic transport and imbalance in the fish which may trigger other biochemical, physiological, and even neurological consequences that may compromise several body functions. Conclusion: The alteration of the ATPase activities in C. gariepinus by ODZ is likely to affect the ATP usage and energy metabolism in the fish serious repercussions on Ca 2+ homeostasis, Na + /K + sodium pump, and Ca 2+ /Na + exchanger The results suggested that assay of the enzymes could be used as a biomarker of water pollution.

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Section: Discussionsupporting

confidence: 64%

Tissue-specific changes in Ca2+-ATPase and Na+/K+-ATPase activities in freshwater African catfish Clarias gariepinus juvenile exposed to oxadiazon

Oluah

Mgbenka

Nwani

et al. 2020

JoBAZ

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“…Since tebufenpyrad and pyridaben have a terrestrial field dissipation half-life of about 50 and 11 days, respectively (TOXNET and NLM - CASRN: 119168-77-3 and CASRN: 96489-71-3), persistent exposure in closed environments such as a greenhouse setting likely poses a risk to humans. Several screening methodologies using cell model systems have been explored recently for rapid identification of adverse effects of environmental pesticide contaminations (Heusinkveld et al, 2014, Meijer et al, 2014). …”

Section: Discussionmentioning

confidence: 99%

Alterations in mitochondrial dynamics induced by tebufenpyrad and pyridaben in a dopaminergic neuronal cell culture model

et al. 2016

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Tebufenpyrad and pyridaben are two agro-chemically important acaricides that function like the known mitochondrial toxicant rotenone. Although these two compounds have been commonly used to kill populations of mites and ticks in commercial greenhouses, their neurotoxic profiles remain largely unknown. Therefore, we investigated the effects of these two pesticides on mitochondrial structure and function in an in vitro cell culture model using the Seahorse bioanalyzer and confocal fluorescence imaging. The effects were compared with rotenone. Exposing rat dopaminergic neuronal cells (N27 cells) to tebufenpyrad and pyridaben for 3 h induced dose-dependent cell death with an EC50 of 3.98 μM and 3.77 μM, respectively. Also, tebufenpyrad and pyridaben (3 μM) exposure induced reactive oxygen species (ROS) generation and m-aconitase damage, suggesting that the pesticide toxicity is associated with oxidative damage. Morphometric image analysis with the MitoTracker red fluorescent probe indicated that tebufenpyrad and pyridaben, as well as rotenone, caused abnormalities in mitochondrial morphology, including reduced mitochondrial length and circularity. Functional bioenergetic experiments using the Seahorse XF96 analyzer revealed that tebufenpyrad and pyridaben very rapidly suppressed the basal mitochondrial oxygen consumption rate similar to that of rotenone. Further analysis of bioenergetic curves also revealed dose-dependent decreases in ATP-linked respiration and respiratory capacity. The luminescence-based ATP measurement further confirmed that pesticide-induced mitochondrial inhibition of respiration is accompanied by the loss of cellular ATP. Collectively, our results suggest that exposure to the pesticides tebufenpyrad and pyridaben induces neurotoxicity by rapidly initiating mitochondrial dysfunction and oxidative damage in dopaminergic neuronal cells. Our findings also reveal that monitoring the kinetics of mitochondrial respiration with Seahorse could be used as an early neurotoxicological high-throughput index for assessing the risk that pesticides pose to the dopaminergic neuronal system.

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“…One such compound, rotenone, is used to model PD in rodents; its mechanism of action involves the production of toxic reactive oxygen species (ROS) (Xiong et al 2012). While not necessarily the only mechanism involved in the toxic effect of pesticides, this process is likely to be a component of the pathogenic mechanism of PD associated with many such environmental toxins (Heusinkveld et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Agricultural work and reduced circulating uric acid are both associated with initial hospital admission for Parkinson’s disease

et al. 2019

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Monoamine oxidase type B inhibitors act in Parkinson's disease (PD) via potentiation of dopamine, but may also have neuroprotective effects by reducing oxidative damage. Oxidative damage is also a feature of environmental toxins, including pesticides, that are an established risk factor for PD. Another risk factor is low circulating uric acid (UA), which may relate to UA being the major endogenous antioxidant in the human body. We have undertaken a study of 192 initial admissions for PD in a general hospital neurology department in a partly rural region of Southern China to determine if there is an increased rate of PD in agricultural workers who have a high risk of exposure to pesticides, and how it may relate to deficits in UA. We found a disproportionately high number of agricultural workers admitted with PD (66.7% vs. 54.3% of all neurology admissions) and that PD subjects have a substantial reduction in UA. This is further reduced in agricultural workers and thus may contribute to the increased vulnerability of this group to PD.

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In vitrodopaminergic neurotoxicity of pesticides: a link with neurodegeneration?

Cited by 14 publications

References 111 publications

Tissue-specific changes in Ca2+-ATPase and Na+/K+-ATPase activities in freshwater African catfish Clarias gariepinus juvenile exposed to oxadiazon

Tissue-specific changes in Ca2+-ATPase and Na+/K+-ATPase activities in freshwater African catfish Clarias gariepinus juvenile exposed to oxadiazon

Alterations in mitochondrial dynamics induced by tebufenpyrad and pyridaben in a dopaminergic neuronal cell culture model

Agricultural work and reduced circulating uric acid are both associated with initial hospital admission for Parkinson’s disease

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