Nerve membrane Na+ channels as targets of insecticides

Narahashi, Toshio

doi:10.1016/0165-6147(92)90075-h

Cited by 198 publications

(24 citation statements)

References 29 publications

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“…Based on previous studies, CPF is a highly toxic insecticide with neurotoxicity properties via inhibition of acetyl cholinesterase in acute intoxication in mammals . In addition, CPF chronic toxicity mode is related to inhibition of sodium and calcium channels, Calmodulin‐Calcium system, which mediated in inflammation, apoptosis, short‐term and long‐term memory, and the immune response, GABA receptors, disruption of membrane integrity and lipid level of cell membrane …”

Section: Discussionmentioning

confidence: 99%

Protective effects of Ziziphora tenuior extract against chlorpyrifos induced liver and lung toxicity in rat: Mechanistic approaches in subchronic study

Yazdinezhad

Abbasian

Hosseini

et al. 2017

Environmental Toxicology

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Chlorpyrifos (CPF) is one of the most widely used organophosphorus, which has spurred renewed interest. This study was conducted to investigate the protective effect of ziziphora tenuior extract against CPF-induced liver and lung toxicity. This study conducted 8-week rat sub-chronic toxicity study and then the effect of ziziphora tenuior extract in 3 different doses (40, 80, 160 mg/kg) was determined. We administrated maximum tolerated dose of CPF (6.75 mg/kg) by gavage for 8 weeks (5 times in week) to male rats. Rats were sacrificed 24 h after last dose and the biochemical analysis, which confirms involvement of oxidative stress in the pathogenesis of CPF toxicity in liver including increased in lipid peroxidation, protein carbonyl content, and ROS formation, glutathione depletion, decreased of antioxidant effect via frap oxidation and cytochrome c expulsion. In addition, pathological lesions confirm the dysfunction of the organs (liver and lung). In addition, using of ziziphora extract as an antioxidant is resulted in amelioration of oxidative stress marker in liver and lung damage. In conclusion, the current study revealed that CPF toxicity is related to oxidative stress and induction of cell death signaling and cotreatment with ziziphora extract is recommended in the routine therapy for the protection against CPF induced liver and lung tissue damage.

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Section: Discussionmentioning

confidence: 99%

Protective effects of Ziziphora tenuior extract against chlorpyrifos induced liver and lung toxicity in rat: Mechanistic approaches in subchronic study

Yazdinezhad

Abbasian

Hosseini

et al. 2017

Environmental Toxicology

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“…Pyrethroids enhance sodium channel activity by shifting activation to more negative membrane potentials and by inhibiting channel inactivation; type II compounds typically produce longer lasting delays in channel inactivation than do type I compounds (Narahashi 1996). VGSCs are responsible for the rapid influx of sodium that underlies the rising phase of the action potential in most electrically excitable cells, including neurons, and the difference in actions of type I and type II pyrethroids on VGSC kinetics is hypothesized to contribute significantly to the T and CS syndromes (Narahashi 1992). …”

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confidence: 99%

Additivity of Pyrethroid Actions on Sodium Influx in Cerebrocortical Neurons in Primary Culture

Cao

Shafer

Crofton

et al. 2011

Environ Health Perspect

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Background: Pyrethroid insecticides bind to voltage-gated sodium channels and modify their gating kinetics, thereby disrupting neuronal function. Although previous work has tested the additivity of pyrethroids in vivo, this has not been assessed directly at the primary molecular target using a functional measure.Objectives: We investigated the potency and efficacy of 11 structurally diverse food-use pyrethroids to evoke sodium (Na+) influx in neurons and tested the hypothesis of dose additivity for a mixture of these same 11 compounds.Methods: We determined pyrethroid-induced increases in Na+ influx in primary cultures of cerebrocortical neurons using the Na+-sensitive dye sodium-binding benzofuran isophthalate (SBFI). Concentration-dependent responses for 11 pyrethroids were determined, and the response to dilutions of a mixture of all 11 compounds at an equimolar mixing ratio was assessed. Additivity was tested assuming a dose-additive model.Results: Seven pyrethroids produced concentration-dependent, tetrodotoxin-sensitive Na+ influx. The rank order of potency was deltamethrin > S-bioallethrin > β-cyfluthrin > λ-cyhalothrin > esfenvalerate > tefluthrin > fenpropathrin. Cypermethrin and bifenthrin produced modest increases in Na+ influx, whereas permethrin and resmethrin were inactive. When all 11 pyrethroids were present at an equimolar mixing ratio, their actions on Na+ influx were consistent with a dose-additive model.Conclusions: These data provide in vitro relative potency and efficacy measurements for 7 pyrethroid compounds in intact mammalian neurons. Despite differences in individual compound potencies, we found the action of a mixture of all 11 pyrethroids to be additive when we used an appropriate statistical model. These results are consistent with a previous report of the additivity of pyrethroids in vivo.

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“…Pyrethroids are grouped into two categories, Type I and Type II, based on their distinct poisoning symptoms, effects on nerve preparations, and chemical structures (Narahashi, 1986). The mode of action of DDT and pyrethroids has been extensively reviewed by T. Narahashi (Narahashi, 1986, 1988, 1992, 1996; Narahashi et al, 1992) and other investigators (Bloomquist, 1996; Bloomquist and Soderlund, 1988; Soderlund, 2010, 2012). Historically, studies on the mode of action of DDT and pyrethroids were conducted using vertebrate and invertebrate nerve preparations.…”

Section: Introductionmentioning

confidence: 99%

Elucidation of pyrethroid and DDT receptor sites in the voltage-gated sodium channel

Zhorov

Dong

2017

NeuroToxicology

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DDT and pyrethroid insecticides were among the earliest neurotoxins identified to act on voltage-gated sodium channels. In the 1960s, equipped with, at the time, new voltage-clamp techniques, Professor Narahashi and associates provided the initial evidence that DDT and allethrin (the first commercial pyrethroid insecticide) caused prolonged flow of sodium currents in lobster and squid giant axons. Over the next several decades, continued efforts by Prof. Narahashi’s group as well as other laboratories led to a comprehensive understanding of the mechanism of action of DDT and pyrethroids on sodium channels. Fast forward to the 1990s, genetic, pharmacological and toxicological data all further confirmed voltage-gated sodium channels as the primary targets of DDT and pyrethroid insecticides. Modifications of the gating kinetics of sodium channels by these insecticides result in repetitive firing and/or membrane depolarization in the nervous system. This mini-review focuses on studies from Prof. Narahashi’s pioneer work and more recent mutational and computational modeling analyses which collectively elucidated the elusive pyrethroid receptor sites as well as the molecular basis of differential sensitivities of insect and mammalian sodium channels to pyrethroids.

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Nerve membrane Na+ channels as targets of insecticides

Cited by 198 publications

References 29 publications

Protective effects of Ziziphora tenuior extract against chlorpyrifos induced liver and lung toxicity in rat: Mechanistic approaches in subchronic study

Protective effects of Ziziphora tenuior extract against chlorpyrifos induced liver and lung toxicity in rat: Mechanistic approaches in subchronic study

Additivity of Pyrethroid Actions on Sodium Influx in Cerebrocortical Neurons in Primary Culture

Elucidation of pyrethroid and DDT receptor sites in the voltage-gated sodium channel

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