Sodium channels and GABAA receptor-channel complex as targets of environmental toxicants.


:Voltage-activated sodium channels and GABAA receptor-chloride channel complex are among the most important target sites of various environmental neurotoxicants. Pyrethroids keep the sodium channels open for prolonged periods of time leading to hyperexcitation of the entire nervous system. In rat cerebellar Purkinje neurons and dorsal root ganglion neurons, only about 1% of sodium channel population needed to be modified by the pyrethroid tetramethrin to increase the depolarizing after-potential to the level of the threshold membrane potential for generation of repetitive after-discharges. This concept of toxicity amplification is applicable to other chemicals that go through a threshold phenomenon to exert their effects. The potency of pyrethroids on neuronal sodium channels increased with lowering the temperature with a Q10 value of 0.2. The selective pyrethroid toxicity between mammals and insects can be quantitatively explained on the basis of the differences in 5 factors, i.e. the intrinsic sodium channel sensitivity, the sodium channel modification due to temperature difference, the reversibility of sodium channel, the detoxication of pyrethroids, and body size. These 5 factors are multiplied to approximately 2000 which is in the same order of magnitude as that of the difference in LD50. Dieldrin had a dual action on the GABAA receptor-chloride channel complex of rat dorsal root ganglion neurons. The initial transient potentiation of GABA-induced currents after application of dieldrin was followed by a suppression. Dieldrin-induced potentiation of current was observed only when the gamma 2 subunit was present in embryonic kidney cells (HEK-293) transfected with GABA receptor subunits. Dieldrin-induced suppression was observed in the presence and absence of the gamma 2 subunit. The dieldrin suppression of GABA-induced currents is deemed directly responsible for hyperactive symptoms of poisoning in animals.


Toxicol Lett


Toxicology letters


Narahashi T,Carter DB,Frey J,Ginsburg K,Hamilton BJ,Nagata K,Roy ML,Song JH,Tatebayashi H




Has Abstract


1995-12-01 00:00:00












  • Acid hydrolases in brain, spinal cord and sciatic nerves of acrylamide-intoxicated rats.

    abstract::Activity of beta-glucuronidase and cathepsin-D were studied in brain, spinal cord and sciatic nerves of rats at 24 h or 10 days after daily i.p. administration of 50 mg/kg acrylamide. The activities of beta-glucuronidase and cathepsin-D in brain, spinal cord and sciatic nerves remained unaffected on single exposure bu...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Srivastava SP,Srivastava SP,Seth PK

    更新日期:1984-08-01 00:00:00

  • Generally recognized as safe (GRAS): history and description.

    abstract::Generally recognized as safe (GRAS), a system for review and approval of ingredients for addition to food, was conceived at a time when the need for a less doctrinaire review of food ingredients was critical. The GRAS approval process for a food ingredient relies on the judgment of "...experts qualified by scientific ...

    journal_title:Toxicology letters

    pub_type: 历史文章,杂志文章,评审


    authors: Burdock GA,Carabin IG

    更新日期:2004-04-15 00:00:00

  • Fluoride as a pro-inflammatory factor and inhibitor of ATP bioavailability in differentiated human THP1 monocytic cells.

    abstract::Chronic exposure of humans to fluorine compounds in the air, water and food may be atherogenic via the activation of oxidative stress and increased ROS production. The most important factor that promotes the formation of ROS seems to be the oxidoreduction of electron carriers in the critical points of the respiratory ...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Gutowska I,Baranowska-Bosiacka I,Baśkiewicz M,Milo B,Siennicka A,Marchlewicz M,Wiszniewska B,Machaliński B,Stachowska E

    更新日期:2010-07-01 00:00:00

  • Valproate-induced developmental neurotoxicity is affected by maternal conditions including shipping stress and environmental change during early pregnancy.

    abstract::Prenatal stress is known to affect the development of the brain, and exaggerate the developmental toxicity of chemicals. Many studies of developmental neurotoxicity (DNT) use pregnant rodents mated at the supplier, which consequently suffer from the stress of shipping and of environmental changes. Here, we demonstrate...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Ogawa T,Kuwagata M,Hori Y,Shioda S

    更新日期:2007-11-01 00:00:00

  • N-nitrososdimethylamine is activated in microsomes from hepatocytes to reactive metabolites which damage DNA of non-parenchymal cells in rat liver.

    abstract::The liver carcinogen N-nitrosodimethylamine (NDMA) has to be metabolically activated by specific cytochromes before it can react with cellular macromolecules (e.g. proteins or DNA). Although hepatocytes are believed to be responsible for this activation, the liver tumours originate mainly from non-parenchymal cells (N...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Frei E,Kuchenmeister F,Gliniorz R,Breuer A,Schmezer P

    更新日期:2001-09-15 00:00:00

  • Protection against carbon tetrachloride hepatotoxicity by oleanolic acid is not mediated through metallothionein.

    abstract::Oleanolic acid is a triterpenoid compound that has been shown to protect against liver injury produced by some hepatotoxicants. This study was designed to characterize the protective effects of oleanolic acid on carbon tetrachloride-induced hepatotoxicity, and the role of metallothionein in the protection. Oleanolic a...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Liu Y,Hartley DP,Liu J

    更新日期:1998-03-31 00:00:00

  • Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde.

    abstract::Crotonaldehyde is an environment pollutant and lipid peroxidation product. Crotonaldehyde produces adverse effects to humans and serves as a risk factor for human pulmonary diseases. Like acrolein and 4-hydroxynonenal, crotonaldehyde seems likely to alter many cell signaling cascades, including inflammatory responses....

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Liu XY,Yang ZH,Pan XJ,Zhu MX,Xie JP

    更新日期:2010-08-16 00:00:00

  • Downregulation of metabotropic glutamate receptor 5 inhibits hepatoma development in a neurotoxin rotenone-induced Parkinson's disease model.

    abstract::Clinical epidemiological studies have shown that there is a link between Parkinson's disease (PD) and cancer, but how PD regulates cancer development remains unknown. In our study, the effect of metabotropic glutamate receptor 5 (mGlu5) on hepatoma was explored in a rotenone-induced PD model both in vitro and in vivo....

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Bai XX,Gu L,Yang HM,Xi SS,Xia N,Zhang S,Zhang H

    更新日期:2018-05-15 00:00:00

  • Lactulose attenuates METH-induced neurotoxicity by alleviating the impaired autophagy, stabilizing the perturbed antioxidant system and suppressing apoptosis in rat striatum.

    abstract::Methamphetamine (METH) is a widely abused psychostimulant. Lactulose is a non-absorbable sugar, which effectively decreases METH-induced neurotoxicity in rat. However, the exact mechanisms need further investigation. In this study, 5-week-old male Sprague Dawley rats received METH (15 mg/kg, 8 intraperitoneal injectio...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Xie XL,He JT,Wang ZT,Xiao HQ,Zhou WT,Du SH,Xue Y,Wang Q

    更新日期:2018-06-01 00:00:00

  • In vivo and in vitro effect of chelating agents on drug metabolizing enzymes of the rat.

    abstract::Rats given calcium disodium ethylenediaminetetraacetic acid (CaNa2EDTA), diethylenetriaminepentaacetic acid (DTPA), dimercaprol, p-aminosalicylic acid (PAS), or d-penicillamine (penicillamine) i.p. for 7 successive days showed a significant decrease in the activity of hepatic microsomal benzphetamine N-demethylase. Th...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Dalvi RR,McGowan C,Ademoyero A

    更新日期:1980-06-01 00:00:00

  • LLU-alpha, an endogenous metabolite of gamma-tocopherol, is more effective against metal nephrotoxicity in rats than gamma-tocopherol.

    abstract::Antioxidants of the vitamin E family have protective effects against metal toxicity. We examined the protective effect of racemic LLU-alpha [2,7,8-trimethyl-2-(carboxyethyl)-6-hydroxychroman] a metabolite of gamma-tocopherol, in comparison to the effect of alpha- and gamma-tocopherol in rats treated with sodium dichro...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Appenroth D,Karge E,Kiessling G,Wechter WJ,Winnefeld K,Fleck C

    更新日期:2001-07-06 00:00:00

  • Clinical relevance of ethanol coingestion in patients with GHB/GBL intoxication.

    abstract:OBJECTIVE:Ethanol intake can increase the sedative effects of gamma-hydroxybutyrate/gamma-butyrolactone (GHB/GBL), although the real clinical impact is unknown. We studied the clinical impact of the co-ingestion of ethanol in patients presenting to the Emergency Department (ED) with acute toxicity related to GHB/GBL us...

    journal_title:Toxicology letters

    pub_type: 杂志文章,多中心研究


    authors: Galicia M,Dargan PI,Dines AM,Yates C,Heyerdahl F,Hovda KE,Giraudon I,Euro-DEN Plus Research Group.,Wood DM,Miró Ò,Euro-DEN Plus Research Group.

    更新日期:2019-10-10 00:00:00

  • The mutagenicity of butadiene towards Salmonella typhimurium.

    abstract::Gaseous butadiene (BUT) was mutagenic towards S. typhimurium strain TA 1530 when the incubation mixture was supplemented with a NADPH-fortified rat liver microsomal preparation; mutagenicity increased with the dose. A significant mutagenic effect was similarly observed when the petri dishes, containing the bacteria bu...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: de Meester C,Poncelet F,Roberfroid M,Mercier M

    更新日期:1980-08-01 00:00:00

  • Diesel exhaust particles in blood trigger systemic and pulmonary morphological alterations.

    abstract::Short-term exposure to elevated levels of particulate matter is associated with increased respiratory and cardiovascular mortality and morbidity. However, the mechanisms underlying these effects are still unclear. Recent studies have suggested that inhaled ultrafine particles are able to translocate into the bloodstre...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Nemmar A,Inuwa IM

    更新日期:2008-01-04 00:00:00

  • The effects of mono-2-ethylhexyl phathalate, adriamycin and N-ethyl-N-nitrosourea on stage-specific apoptosis and DNA synthesis in the mouse spermatogenesis.

    abstract::Tubule segments from defined stages of the mouse seminiferous epithelium were incubated for 4, 8 and 24 h in the presence of different concentrations of mono-2-ethylhexyl phthalate (MEHP), adriamycin, and N-ethyl-N-nitrosourea (ENU) to study the effects of these chemicals on germ cell apoptosis and DNA synthesis. Apop...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Suominen JS,Linderborg J,Nikula H,Hakovirta H,Parvinen M,Toppari J

    更新日期:2003-07-20 00:00:00

  • Effect of diet on colonic-programmed cell death: molecular mechanism of action.

    abstract::Colon cancer evolves from a progressive inhibition of apoptosis and is influenced strongly by diet. Among dietary factors, butyrate (derived from fermentable fibers) may have utility as a chemopreventive agent because of its ability to promote apoptosis. Because CD95 (APO-1/Fas) transduces signals resulting in apoptos...

    journal_title:Toxicology letters

    pub_type: 杂志文章,评审


    authors: Chapkin RS,Fan Y,Lupton JR

    更新日期:2000-03-15 00:00:00

  • Correlation of liver tumor morphology and weight to incidence of pulmonary metastases in the mouse.

    abstract::Benzidine dihydrochloride administered in water at 0, 30, 60, 120, 200 or 400 ppm to 1664 mice induced a total of 368 hepatocellular carcinomas, of which 34 or 9.2% metastasized to the lungs. Liver tumors which were larger and heavier were more prone to metastasize and all that metastasized contained areas of prominen...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Frith CH,Baetcke KP,Nelson CJ,Schieferstein G

    更新日期:1980-12-01 00:00:00

  • Tin decreases femoral calcium independently of calcium homeostasis in rats.

    abstract::Oral administration of stannous chloride (SnCl2) (1.0 mg Sn2$/kg body weight) to rats, twice daily for 28 days, caused a significant increase in the tin (Sn) content and a corresponding decrease of the calcium (Ca) content in the femoral epiphysis, but was without effect on serum Ca, intestinal Ca absorption, and urin...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Yamaguchi M,Sugii K,Okada S

    更新日期:1982-01-01 00:00:00

  • The application of in-situ hybridisation and immuno-cytochemistry to problem resolution in drug development.

    abstract::Localization of specific mRNA and protein molecules within cells and tissues can provide important information on the effects of a drug within a biological test system and help elucidate mechanisms of drug-induced toxicity and organ dysfunction. The most widely used techniques for measuring the cellular and tissue dis...

    journal_title:Toxicology letters

    pub_type: 杂志文章,评审


    authors: Kind CN

    更新日期:2000-03-15 00:00:00

  • The relationship between itai-itai disease among inhabitants of the Jinzu River basin and cadmium in rice.

    abstract::Women over 50 years of age in 32 cadmium(Cd)-polluted and 16 nonpolluted hamlets were studied. Itai-itai disease patients and proteinuria with glucosuria were used as indices of the effect of Cd on health. Unpolished rice samples were collected from 568 households in the same area and analyzed for Cd. The hamlet's ave...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Nogawa K,Yamada Y,Honda R,Ishizaki M,Tsuritani I,Kawano S,Kato T

    更新日期:1983-07-01 00:00:00

  • Monitoring internal exposure to metals and organic substances in workers at a hazardous waste incinerator after 3 years of operation.

    abstract::The potential adverse effects of hazardous waste incinerators (HWI) continue to be a subject of worry. The construction of the first and up till now only HWI in Spain finished in 1999. Twenty-six subjects employed at this HWI were divided into three groups: plant, laboratory and administration. Plasma analyses of HCB,...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Carmen Agramunt M,Domingo A,Domingo JL,Corbella J

    更新日期:2003-12-15 00:00:00

  • Additive pro-oxidative effects of methylmercury and ebselen in liver from suckling rat pups.

    abstract::Oxidative stress has been pointed as an important molecular mechanism for liver injury in methylmercury (MeHg) poisoning. Ebselen, a seleno-organic compound that possesses anti-oxidant properties, is a useful therapeutic agent used in clinical situations involving oxidative stress. Here, we examined the possible in vi...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Farina M,Soares FA,Zeni G,Souza DO,Rocha JB

    更新日期:2004-02-02 00:00:00

  • Preclinical detection of nephrotoxicity: description of the tests and appraisal of their health significance.

    abstract::The prevention of renal diseases induced by chemicals requires the use of tests with which adverse renal effects can be detected at a stage when removal from exposure to the offending agent(s) may lead to complete recovery or may at least prevent an accelerated decline in renal function. The screening tests used in cl...

    journal_title:Toxicology letters

    pub_type: 杂志文章,评审


    authors: Lauwerys R,Bernard A

    更新日期:1989-03-01 00:00:00

  • Cadmium effects on hypothalamic activity and pituitary hormone secretion in the male.

    abstract::Cadmium specifically modify amine metabolism at the central nervous system and pituitary hormone secretions. Thus, the physiological functions controlled by these hormones can be modulated by cadmium. This xenobiotic is associated with deleterious effects on the gonadal function and with changes in the secretory patte...

    journal_title:Toxicology letters

    pub_type: 杂志文章,评审


    authors: Lafuente A,Esquifino AI

    更新日期:1999-11-22 00:00:00

  • Developmental exposure to cuprizone reduces intermediate-stage progenitor cells and cholinergic signals in the hippocampal neurogenesis in rat offspring.

    abstract::The exposure to cuprizone (CPZ) leads to demyelination in the central nervous system in rodents. To examine the developmental effects of CPZ exposure on hippocampal neurogenesis, pregnant rats were treated with 0, 0.1 or 0.4% CPZ in the diet from gestational day 6 to day 21 after delivery. On postnatal day 21, male of...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Abe H,Tanaka T,Kimura M,Mizukami S,Imatanaka N,Akahori Y,Yoshida T,Shibutani M

    更新日期:2015-05-05 00:00:00

  • Skin absorption of aniline from aqueous solutions in man.

    abstract::The skin absorption of aniline, aniline with 3% water content, and 1 and 2% aqueous aniline solutions was investigated in man. The time of exposure was 30 or 60 min. The absorbed amount of aniline was calculated on the basis of rho-aminophenol excretion in 24-h urine. The rate of aniline absorption from aqueous soluti...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Baranowska-Dutkeiwicz B

    更新日期:1982-03-01 00:00:00

  • The enemy at the gates? DNA adducts as biomarkers of exposure to exogenous and endogenous genotoxic agents.

    abstract::Genomic DNA is under continuous assault by various chemical species produced by normal cellular metabolism. In addition, exposure to exogenous agents adds further insult. Modification of DNA by chemical carcinogens has long been recognized as an early event in carcinogenesis and many DNA adducts have been characterize...

    journal_title:Toxicology letters

    pub_type: 杂志文章,评审


    authors: Shuker DE

    更新日期:2002-08-05 00:00:00

  • alpha-Zearalanol attenuates oxLDL-induced ET-1 gene expression, ET-1 secretion and redox-sensitive intracellular signaling activation in human umbilical vein endothelial cells.

    abstract::alpha-Zearalanol (alpha-ZAL), a phytochemical with both antioxidant and estrogen-like properties, has been shown to retard progression of atherosclerosis and regulate cardiovascular function in part through suppression of endothelin-1 (ET-1) secretion. However, the precise nature behind alpha-ZAL-elicited inhibition o...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Xu H,Duan J,Dai S,Wu Y,Sun R,Ren J

    更新日期:2008-07-10 00:00:00

  • The effect of copper deficiency on adriamycin toxicity.

    abstract::The effect of copper (Cu) deficiency on antioxidant status of liver and heart and its effect on adriamycin toxicity was assessed. Weanling rats were fed Cu-adequate (+Cu) and Cu-deficient (-Cu) diets for 3 weeks and then injected intraperitoneally once with saline or adriamycin (8 mg/kg). All -Cu rats had increased he...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: Fischer J,Johnson MA,Tackett RL

    更新日期:1991-07-01 00:00:00

  • Chromosome damage induced by carboplatin (CBDCA).

    abstract::The chromosome damage induced by carboplatin (CBDCA) was evaluated in vitro. In human lymphocytes 5 micrograms/ml CBDCA produced a 7-fold increase in the frequency of sister chromatid exchanges (SCE) and a 3-fold increase in the number of cells with structural abnormalities compared with the control. Likewise, at this...

    journal_title:Toxicology letters

    pub_type: 杂志文章


    authors: González Cid M,Mudry M,Larripa I

    更新日期:1995-03-01 00:00:00