In Vivo Effects of Deltamethrin on Dopamine Neurochemistry and the Role of Augmented Neurotransmitter Release

Kirby, Michael; Castagnoli, Kay; Bloomquist, Jeffrey R.

doi:10.1006/pest.1999.2440

Cited by 51 publications

(37 citation statements)

References 28 publications

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“…Control mice were injected intraperitoneally with vehicle (methoxytriglycol; n = 12) and treated mice were injected with deltamethrin (3 mg/kg; n = 6) or permethrin (0.8 mg/ kg; n = 6) three times over a 2-week period (Days 1, 8, and 15) as described previously (Kirby et al, 1999;Miller et al, 1999b;Gillette and Bloomquist, 2003). One day following the last treatment, striatal tissue was dissected out and prepared for assay as described below.…”

Section: Animals and Treatmentsmentioning

confidence: 99%

“…Briefly, crude synaptosomes were prepared from fresh striatal tissue and incubated in assay buffer (4 mM Tris, 6.25 HEPES, 120 mM NaCl, 5 mM KCl, 1.2 mM CaCl 2 , 1.2 mM MgSO 4 , 0.6 mM ascorbic acid, 5.5 mM glucose, 10 μM pargyline; pH 7.4) containing a saturating concentration of dopamine (1 μM final concentration) and a tracer amount of 3 Hdopamine (20 nM). A single saturating concentration of dopamine was chosen to assess effects of pyrethroids on the V max of DAT, since previous studies using the same dosing paradigm have demonstrated no significant effect on K m (Kirby et al, 1999;Karen et al, 2001). Uptake was allowed to proceed for 3 min at 37 °C, and then terminated by the addition of ice-cold buffer and rapid vacuum filtration over GF/B filter paper using a Brandel harvester.…”

Section: Synaptosomal Dopamine Uptake 3 H-win 35428 Binding and Wementioning

confidence: 99%

“…In addition to heptachlor, exposure of mice to the pyrethroid pesticides deltamethrin and permethrin has been demonstrated to increase DAT-mediated dopamine uptake (Kirby et al, 1999;Karen et al, 2001;Gillette and Bloomquist, 2003). Pesticides in the pyrethroid class are widely used in household and agricultural applications and are popular because of their low mammalian toxicity.…”

mentioning

confidence: 99%

“…Acute toxicity of pyrethroids is primarily mediated through interaction with sodium channels, leading to prolonged depolarization and hyperexcitation of the nervous system (Narahashi, 1982;Tabarean and Narahashi, 2001). Pyrethroids have also been shown to be potent releasers of neurotransmitters, including dopamine (Eells and Dubocovich, 1988;Kirby et al, 1999). However, the mechanism by which pyrethroids are capable of increasing DAT-mediated dopamine uptake is not clear.…”

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confidence: 99%

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Pyrethroid pesticide-induced alterations in dopamine transporter function

Elwan

Richardson

Guillot

et al. 2006

Toxicology and Applied Pharmacology

103

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Parkinson's disease (PD) is a progressive neurodegenerative disease affecting the nigrostriatal dopaminergic pathway. Several epidemiological studies have demonstrated an association between pesticide exposure and the incidence of PD. Studies from our laboratory and others have demonstrated that certain pesticides increase levels of the dopamine transporter (DAT), an integral component of dopaminergic neurotransmission and a gateway for dopaminergic neurotoxins. Here, we report that repeated exposure (3 injections over 2 weeks) of mice to two commonly used pyrethroid pesticides, deltamethrin (3 mg/kg) and permethrin (0.8 mg/kg), increases DATmediated dopamine uptake by 31 and 28%, respectively. Using cells stably expressing DAT, we determined that exposure (10 min) to deltamethrin and permethrin (1 nM-100 μM) had no effect on DAT-mediated dopamine uptake. Extending exposures to both pesticides for 30 min (10 μM) or 24 h (1, 5, and 10 μM) resulted in significant decrease in dopamine uptake. This reduction was not the result of competitive inhibition, loss of DAT protein, or cytotoxicity. However, there was an increase in DNA fragmentation, an index of apoptosis, in cells exhibiting reduced uptake at 30 min and 24 h. These data suggest that up-regulation of DAT by in vivo pyrethroid exposure is an indirect effect and that longer-term exposure of cells results in apoptosis. Since DAT can greatly affect the vulnerability of dopamine neurons to neurotoxicants, up-regulation of DAT by deltamethrin and permethrin may increase the susceptibility of dopamine neurons to toxic insult, which may provide insight into the association between pesticide exposure and PD. KeywordsDeltamethrin; Permethrin; Pyrethroid; Dopamine transporter; Parkinson's disease Parkinson's disease (PD) is a disabling neurodegenerative disorder characterized by the loss of nigrostriatal dopamine neurons and the formation of intraneuronal inclusions termed Lewy bodies (Olanow and Tatton, 1999). Although the exact etiology of PD is unknown, both genetic and environmental factors are thought to contribute to the pathogenesis of PD. While there are rare instances of genetically-linked PD, data from a recent comprehensive

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Section: Animals and Treatmentsmentioning

confidence: 99%

Section: Synaptosomal Dopamine Uptake 3 H-win 35428 Binding and Wementioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Pyrethroid pesticide-induced alterations in dopamine transporter function

Elwan

Richardson

Guillot

et al. 2006

Toxicology and Applied Pharmacology

103

View full text Add to dashboard Cite

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“…Thirty-two rats were randomized into three experimental groups and one control group (n=8 for each group). Permethrin was given orally, three times in the experimental groups, on days 1, 7 and 14, respectively; group I rats (n=8), 75 mg kg -1 permethrin (1/20 of the LD 50 value); group II rats (n=8) 150 mg kg -1 permethrin (1/10 of the LD 50 value, group II) and group III rats (n=8) 300 mg kg -1 (1/5 of the LD 50 value, group III) (28)(29)(30). Corn oil (vehicle/one millilitre per animal) was orally administered to the control group (n=8) on the same days.…”

Section: Animals and Treatmentsmentioning

confidence: 99%

Biological Significance of the Overexpression of HSP70 and Alpha B-Crystallin in Rat Substantia Nigra Exposed to Different Doses of Permethrin

Güvenç

Kabak

Atmaca

et al. 2013

Archives of Industrial Hygiene and Toxicology

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The aim of this study was to investigate the possible role of the Heat Shock Protein 70 (HSP70) and Alpha B-crystallin (αBC) in the substantia nigra of rats exposed to permethrin at different doses on the apoptotic cell status. The orogastric gavage method was used to administer the different doses of permethrin (75 mg kg -1 in Group I, 150 mg kg -1 in group II, 300 mg kg -1 in group III) to the rats. Using the Western blot test, all the permethrin-treated groups showed a dose-dependent increase in the expression of HSP70 and αBC when compared to the control group. TUNEL positive apoptotic cells were not detected in the dopaminergic neurons of the substantia nigra after treatment with permethrin; however, upon immunofl uorescent staining, intense positive reactions for HSP70 and αBC were observed in all of the treated groups. No immunopositive cells were detected in the tissue sections of the control group. These results suggest that the different administered doses of permethrin did not cause apoptotic cell death in the substantia nigra dopaminergic neurons; however, they did induce an increase in HSP70 and αBC expression. Thus, it appears that HSP70 and αBC could play a neuroprotective role in permethrin-induced neurotoxicity.

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Deltamethrin induces mitochondrial membrane permeability and altered expression of cytochrome C in rat brain

Chen

Huang

Liu

et al. 2007

J of Applied Toxicology

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Deltamethrin is a type II synthetic pyrethroid insecticide and is used extensively. Numerous studies have demonstrated that deltamethrin can cause severe central nervous system symptoms. The mechanism of neuro-toxicity caused by deltamethrin is still poorly understood. This study investigated the effect of deltamethrin on the mitochondria-mediated apoptosis pathway in rat brain. The cortex and hippocampus mitochondrial membrane potential, permeability transition, expression of cytochrome c and activity of cytochrome c oxidase was assayed at 5, 24, 48 and 72 h following deltamethrin treatment. The study observed that the membrane potential, change of absorbance at 540 nm (A(540)), intensities of cytochrome c in mitochondria and activity of cytochrome c oxidase in the cortex and hippocampus of treated groups were significantly lower than those of the control group. The results of the study demonstrated that deltamethrin induced a decreased mitochondrial membrane potential and increased permeability, and reduced the expression of cytochrome c, thus depressing the activity of cytochrome c oxidase significantly. It indicates that deltamethrin may have an effect on mitochondria-mediated apoptosis of nerve cells in the rat brain.

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In Vivo Effects of Deltamethrin on Dopamine Neurochemistry and the Role of Augmented Neurotransmitter Release

Cited by 51 publications

References 28 publications

Pyrethroid pesticide-induced alterations in dopamine transporter function

Pyrethroid pesticide-induced alterations in dopamine transporter function

Biological Significance of the Overexpression of HSP70 and Alpha B-Crystallin in Rat Substantia Nigra Exposed to Different Doses of Permethrin

Deltamethrin induces mitochondrial membrane permeability and altered expression of cytochrome C in rat brain

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