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Sample records for chlorpyrifos developmental neurotoxicity

  1. DOES THYROID DISRUPTION CONTRIBUTE TO THE DEVELOPMENTAL NEUROTOXICITY OF CHLORPYRIFOS?

    OpenAIRE

    Slotkin, Theodore A.; Cooper, Ellen M.; Stapleton, Heather M.; Seidler, Frederic J

    2013-01-01

    Although organophosphate pesticides are not usually characterized as “endocrine disruptors,” recent work points to potential, long-term reductions of circulating thyroid hormones after developmental exposures to chlorpyrifos that are devoid of observable toxicity. We administered chlorpyrifos to developing rats on gestational days 17–20 or postnatal days 1–4, regimens that produce distinctly different, sex-selective effects on neurobehavioral performance. The prenatal regimen produced a small...

  2. Developmental neurotoxic effects of two pesticides : behavior and biomolecular studies on chlorpyrifos and carbaryl

    OpenAIRE

    Lee, Iwa; Eriksson, Per; Fredriksson, Anders; Buratovic, Sonja; Viberg, Henrik

    2015-01-01

    In recent times, an increased occurrence of neurodevelopmental disorders, such as neurodevelopmental delays and cognitive abnormalities has been recognized. Exposure to pesticides has been suspected to be a possible cause of these disorders, as these compounds target the nervous system of pests. Due to the similarities of brain development and composition, these pesticides may also be neurotoxic to humans. We studied two different pesticides, chlorpyrifos and carbaryl, which specifically inhi...

  3. Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos

    International Nuclear Information System (INIS)

    Nicotine and chlorpyrifos are developmental neurotoxicants that, despite their differences in structure and mechanism of action, share many aspects for damage to the developing brain. Both are thought to generate oxidative radicals; in the current study, we evaluated their ability to produce lipid peroxidation in two in vitro models of neural cell development (PC12 and SH-SY5Y cells) and for nicotine, with treatment of adolescent rats in vivo. Nicotine and chlorpyrifos, in concentrations relevant to human exposures, elicited an increase in thiobarbituric-acid-reactive species (TBARS) in undifferentiated cells, an effect that was prevented by addition of the antioxidant, Vitamin E. Initiating differentiation with nerve growth factor, which enhances nicotinic acetylcholine receptor expression, increased the TBARS response to nicotine but not chlorpyrifos, suggesting that the two agents act by different originating mechanisms to converge on the endpoint of oxidative damage. Furthermore, nicotine protected the cells from oxidative damage evoked by chlorpyrifos and similarly blocked the antimitotic effect of chlorpyrifos. Treatment of adolescent rats with nicotine elicited increases in TBARS in multiple brain regions when given in doses that simulate plasma nicotine concentrations found in smokers or at one-tenth the dose. Our results indicate that nicotine and chlorpyrifos elicit oxidative damage to developing neural cells both in vitro and in vivo, a mechanism that explains some of the neurodevelopmental endpoints that are common to the two agents. The balance between neuroprotectant and neurotoxicant actions of nicotine may be particularly important in situations where exposure to tobacco smoke is combined with other prooxidant insults

  4. Developmental neurotoxicity of organophosphorous pesticides: fetal and neonatal exposure to chlorpyrifos alters sex-specific behaviors at adulthood in mice.

    Science.gov (United States)

    Ricceri, Laura; Venerosi, Aldina; Capone, Francesca; Cometa, Maria Francesca; Lorenzini, Paola; Fortuna, Stefano; Calamandrei, Gemma

    2006-09-01

    Developmental exposure to the organophosphorous insecticide chlorpyrifos (CPF) induces long-term effects on brain and behavior in laboratory rodents. We evaluated in adult mice the behavioral effects of either fetal and/or neonatal CPF exposure at doses not inhibiting fetal and neonatal brain cholinesterase. CPF (3 or 6 mg/kg) was given by oral treatment to pregnant females on gestational days 15-18 and offspring were treated sc (1 or 3 mg/kg) on postnatal days (PNDs) 11-14. Serum and brain acetylcholinesterase (AChE) activity was evaluated at birth and 24 h from termination of postnatal treatments. On PND 70, male mice were assessed for spontaneous motor activity in an open-field test and in a socioagonistic encounter with an unfamiliar conspecific. Virgin females underwent a maternal induction test following presentation of foster pups. Both sexes were subjected to a plus-maze test to evaluate exploration and anxiety levels. Gestational and postnatal CPF exposure (higher doses) affected motor activity in the open field and enhanced synergically agonistic behavior. Postnatal CPF exposure increased maternal responsiveness toward pups in females. Mice of both sexes exposed to postnatal CPF showed reduced anxiety response in the plus-maze, an effect greater in females. Altogether, developmental exposure to CPF at doses that do not cause brain AChE inhibition induces long-term alterations in sex-specific behavior patterns of the mouse species. Late neonatal exposure on PNDs 11-14 was the most effective in causing behavioral changes. These findings support the hypothesis that developmental CPF may represent a risk factor for increased vulnerability to neurodevelopmental disorders in humans. PMID:16760416

  5. Prenatal Dexamethasone Augments the Sex-Selective Developmental Neurotoxicity of Chlorpyrifos: Implications for Vulnerability after Pharmacotherapy for Preterm Labor

    OpenAIRE

    Slotkin, Theodore A.; Card, Jennifer; Infante, Alice; Seidler, Frederic J

    2013-01-01

    Glucocorticoids are routinely given in preterm labor and are also elevated by maternal stress; organophosphate exposures are virtually ubiquitous, so coexposures to these two agents are pervasive. We administered dexamethasone to pregnant rats on gestational days 17–19 at a standard therapeutic dose (0.2 mg/kg); offspring were then given chlorpyrifos on postnatal days 1–4, at a dose (1 mg/kg) that produces barely-detectable (

  6. Developmental cholinotoxicants: nicotine and chlorpyrifos.

    OpenAIRE

    Slotkin, T A

    1999-01-01

    The stimulation of cholinergic receptors in target cells during a critical developmental period provides signals that influence cell replication and differentiation. Accordingly, environmental agents that promote cholinergic activity evoke neurodevelopmental damage because of the inappropriate timing or intensity of stimulation. Nicotine evokes mitotic arrest in brain cells possessing high concentrations of nicotinic cholinergic receptors. In addition, the cholinergic overstimulation programs...

  7. Acute Toxicity and Neurotoxicity of Chlorpyrifos in Black Tiger Shrimp, Penaeus monodon

    OpenAIRE

    Tassanee Eamkamon; Sirawut Klinbunga; Kumthorn Thirakhupt; Piamsak Menasveta; Narongsak Puanglarp

    2012-01-01

    Acute toxicity and neurotoxicity of chlorpyrifos were determined in black tiger shrimp, P. monodon. LC50 values after 24 to 96 h of exposure were between 149.55 and 59.16 nmol/L. To determine the neurotoxicity of chlorpyrifos, the inhibition of acetylcholinesterase was monitored in the gill of the shrimps exposed to lethal (0.019, 0.194, and 1.942 µmol/L) and sub-lethal (0.019, 0.194, and 1.942 nmol/L) concentrations of chlorpyrifos. In lethal dose exposure, the AChE activities observed in sh...

  8. Anesthetic-Induced Developmental Neurotoxicity

    Institute of Scientific and Technical Information of China (English)

    Jia-RenLiu; Qian Liu; Jing Li; Sulpicio G. Soriano

    2011-01-01

    1 IntroductionMillions of newborn and infants receive anesthetic,sedative and analgesic drugs for surgery and painful procedures on a daily basis.Recent laboratory reports clearly demonstrate that anesthetic and sedative drugs induced both neuroapoptosis and neurocognitive deficits in laboratory models.This issue is of paramount interest to pediatric anesthesiologists and intensivists because it questions the safety of anesthetics used for fetal and neonatal anesthesia[1-2].In an attempt to summarize the rapidly expanding laboratorybased literature on anesthetic-induced developmental neurotoxicity (AIDN),this review will examine published reports on the characterization,mechanisms and alleviation of this phenomenon.

  9. Involvement of glial cells in the neurotoxicity of parathion and chlorpyrifos

    International Nuclear Information System (INIS)

    An in vitro model, the aggregating brain cell culture of fetal rat telencephalon, has been used to investigate the influence of glial cells on the neurotoxicity of two organophosphorus pesticides (OPs), chlorpyrifos and parathion. Mixed-cell aggregate cultures were treated continuously for 10 days between DIV 5 and 15. Parathion induced astrogliosis at concentration at which MAP-2 immunostaining, found here to be more sensitive than neuron-specific enzyme activities, was not affected. In contrast, chlorpyrifos induced a comparatively weak gliotic reaction, and only at concentrations at which neurons were already affected. After similar treatments, increased neurotoxicity of parathion and chlorpyrifos was found in aggregate cultures deprived of glial cells. These results suggest that glial cells provide neuroprotection against OPs toxicity. To address the question of the difference in toxicity between parathion and chlorpyrifos, the toxic effects of their leaving groups, p-nitrophenol and trichloropyridinol, were studied in mixed-cell aggregates. General cytotoxicity was more pronounced for trichloropyridinol and both compounds had similar toxic effects on neuron-specific enzyme activities. In contrast, trichloropyridinol induced a much stronger decrease in glutamine synthetase activity, the enzymatic marker of astrocytes. Trichloropyridinol may exert a toxic effect on astrocytes, compromising their neuroprotective function, thus exacerbating the neurotoxicity of chlorpyrifos. This is in line with the suggestion that glial cells may contribute to OPs neurotoxicity, and with the view that OPs may exert their neurotoxic effects through different mechanisms

  10. EVALUATION OF POTENTIAL DEVELOPMENTAL NEUROTOXICITY OF ORGANOTINS.

    Science.gov (United States)

    Organotins, including monomethyltin (MMT), dimethyltin (DMT), and dibutyltin (DBT), are widely used as heat stabilizers in PVC and CPVC piping, which results in their presence in drinking water supplies. Concern for developmental neurotoxic effects were raised by published findi...

  11. Biomarkers of adult and developmental neurotoxicity

    International Nuclear Information System (INIS)

    Neurotoxicity may be defined as any adverse effect on the structure or function of the central and/or peripheral nervous system by a biological, chemical, or physical agent. A multidisciplinary approach is necessary to assess adult and developmental neurotoxicity due to the complex and diverse functions of the nervous system. The overall strategy for understanding developmental neurotoxicity is based on two assumptions: (1) significant differences in the adult versus the developing nervous system susceptibility to neurotoxicity exist and they are often developmental stage dependent; (2) a multidisciplinary approach using neurobiological, including gene expression assays, neurophysiological, neuropathological, and behavioral function is necessary for a precise assessment of neurotoxicity. Application of genomic approaches to developmental studies must use the same criteria for evaluating microarray studies as those in adults including consideration of reproducibility, statistical analysis, homogenous cell populations, and confirmation with non-array methods. A study using amphetamine to induce neurotoxicity supports the following: (1) gene expression data can help define neurotoxic mechanism(s) (2) gene expression changes can be useful biomarkers of effect, and (3) the site-selective nature of gene expression in the nervous system may mandate assessment of selective cell populations

  12. Comparative Developmental Neurotoxicity of Organophosphates In Vivo: Transcriptional Responses of Pathways for Brain Cell Development, Cell Signaling, Cytotoxicity and Neurotransmitter Systems

    OpenAIRE

    Slotkin, Theodore A.; Seidler, Frederic J

    2007-01-01

    Organophosphates affect mammalian brain development through a variety of mechanisms beyond their shared property of cholinesterase inhibition. We used microarrays to characterize similarities and differences in transcriptional responses to chlorpyrifos and diazinon, assessing defined gene groupings for the pathways known to be associated with the mechanisms and/or outcomes of chlorpyrifos-induced developmental neurotoxicity. We exposed neonatal rats to daily doses of chlorpyrifos (1 mg/kg) or...

  13. Acute Toxicity and Neurotoxicity of Chlorpyrifos in Black Tiger Shrimp, Penaeus monodon

    Directory of Open Access Journals (Sweden)

    Tassanee Eamkamon

    2012-01-01

    Full Text Available Acute toxicity and neurotoxicity of chlorpyrifos were determined in black tiger shrimp, P. monodon. LC50 values after 24 to 96 h of exposure were between 149.55 and 59.16 nmol/L. To determine the neurotoxicity of chlorpyrifos, the inhibition of acetylcholinesterase was monitored in the gill of the shrimps exposed to lethal (0.019, 0.194, and 1.942 µmol/L and sub-lethal (0.019, 0.194, and 1.942 nmol/L concentrations of chlorpyrifos. In lethal dose exposure, the AChE activities observed in shrimp exposed to 0.194, and 1.942 µmol/L of chlorpyrifos were significantly lower (1.7 and 3.3 times than that of control shrimp after 30 min of exposure (p<0.05. In sub-lethal exposure tests, the AChE activity of shrimp was significantly lower (1.9 times than that of control shrimp after exposure to 1.942 nmol/L of chlorpyrifos for 72 h (p<0.05. The sensitive reduction of AChE activity at the sub-lethal concentration, which was 30 times lower than 96 h LC50 value found in this study, indicates the potential use as a biomarker of chlorpyrifos exposure.

  14. Zebrafish provide a sensitive model of persisting neurobehavioral effects of developmental chlorpyrifos exposure: Comparison with nicotine and pilocarpine effects and relationship to dopamine deficits

    OpenAIRE

    Eddins, Donnie; Cerutti, Daniel; Williams, Paul; Linney, Elwood; Levin, Edward D.

    2009-01-01

    Chlorpyrifos (CPF) an organophosphate pesticide causes persisting behavioral dysfunction in rat models when exposure is during early development. In earlier work zebrafish were used as a complementary model to study mechanisms of CPF-induced neurotoxicity induced during early development. We found that developmental (first five days after fertilization) chlorpyrifos exposure significantly impaired learning in zebrafish. However, this testing was time and labor intensive. In the current study ...

  15. Comparative Developmental Neurotoxicity of Organophosphate Insecticides: Effects on Brain Development Are Separable from Systemic Toxicity

    OpenAIRE

    Slotkin, Theodore A.; Levin, Edward D.; Seidler, Frederic J

    2006-01-01

    A comparative approach to the differences between systemic toxicity and developmental neurotoxicity of organophosphates is critical to determine the degree to which multiple mechanisms of toxicity carry across different members of this class of insecticides. We contrasted neuritic outgrowth and cholinergic synaptic development in neonatal rats given different organophosphates (chlorpyrifos, diazinon, parathion) at doses spanning the threshold for impaired growth and viability. Animals were tr...

  16. Nanoimages show disruption of tubulin polymerization by chlorpyrifos oxon: Implications for neurotoxicity

    International Nuclear Information System (INIS)

    Organophosphorus agents cause cognitive deficits and depression in some people. We hypothesize that the mechanism by which organophosphorus agents cause these disorders is by modification of proteins in the brain. One such protein could be tubulin. Tubulin polymerizes to make the microtubules that transport cell components to nerve axons. The goal of the present work was to measure the effect of the organophosphorus agent chlorpyrifos oxon on tubulin polymerization. An additional goal was to identify the amino acids covalently modified by chlorpyrifos oxon in microtubule polymers and to compare them to the amino acids modified in unpolymerized tubulin dimers. Purified bovine tubulin (0.1 mM) was treated with 0.005-0.1 mM chlorpyrifos oxon for 30 min at room temperature and then polymerized by addition of 1 mM GTP to generate microtubules. Microtubules were visualized by atomic force microscopy. Chlorpyrifos oxon-modified residues were identified by tandem ion trap electrospray ionization and matrix-assisted laser desorption/ionization mass spectrometry of tryptic peptides. Nanoimaging showed that low concentrations (0.005 and 0.01 mM) of chlorpyrifos oxon yielded short, thin microtubules. A concentration of 0.025 mM stimulated polymerization, while high concentrations (0.05 and 0.1 mM) caused aggregation. Of the 17 tyrosines covalently modified by chlorpyrifos oxon in unpolymerized tubulin dimers, only 2 tyrosines were labeled in polymerized microtubules. The two labeled tyrosines in polymerized tubulin were Tyr 103 in EDAANNY*R of alpha tubulin, and Tyr 281 in GSQQY*R of beta tubulin. In conclusion, chlorpyrifos oxon binding to tubulin disrupts tubulin polymerization. These results may lead to an understanding of the neurotoxicity of organophosphorus agents.

  17. Meeting Report: Alternatives for Developmental Neurotoxicity Testing

    OpenAIRE

    Lein, Pamela; Locke, Paul; Goldberg, Alan

    2007-01-01

    Developmental neurotoxicity testing (DNT) is perceived by many stakeholders to be an area in critical need of alternatives to current animal testing protocols and guidelines. To address this need, the Johns Hopkins Center for Alternatives to Animal Testing (CAAT), the U.S. Environmental Protection Agency, and the National Toxicology Program are collaborating in a program called TestSmart DNT, the goals of which are to: (a) develop alternative methodologies for identifying and prioritizing che...

  18. Developmental neurotoxicity of propylthiouracil in rats

    DEFF Research Database (Denmark)

    Petersen, Marta Axelstad; Hansen, Pernille Reimer; Christiansen, Sofie;

    2007-01-01

    early in pregnancy may cause adverse effects on the offspring. This has led to increased concern about thyroid hormone disrupting chemicals (TDCs) in our environment. We have studied how developmental exposure to the known antithyroid agent propylthiouracil (PTU) affects the development of rat pups. The...... overall aim was to provide detailed knowledge on the relationship between effects on thyroid hormone levels and long-lasting developmental neurotoxicity effects. Groups of 16–18 pregnant rats (HanTac:WH) were dosed with PTU (0, 0.8, 1.6 or 2.4 mg/(kg day)) from gestation day 7 to postnatal day (PND) 16...

  19. The Sea Urchin Embryo, an Invertebrate Model for Mammalian Developmental Neurotoxicity, Reveals Multiple Neurotransmitter Mechanisms for Effects of Chlorpyrifos: Therapeutic Interventions and a Comparison with the Monoamine Depleter, Reserpine

    OpenAIRE

    Buznikov, Gennady A; Nikitina, Lyudmila A.; Rakić, Ljubiša M.; Miloševi, Ivan; Bezuglov, Vladimir V.; Lauder, Jean M.; Slotkin, Theodore A.

    2007-01-01

    Lower organisms show promise for the screening of neurotoxicants that might target mammalian brain development. Sea urchins use neurotransmitters as embryonic growth regulatory signals, so that adverse effects on neural substrates for mammalian brain development can be studied in this simple organism. We compared the effects of the organophosphate insecticide, chlorpyrifos in sea urchin embryos with those of the monoamine depleter, reserpine, so as to investigate multiple neurotransmitter mec...

  20. Developmental Exposure of Rats to Chlorpyrifos Elicits Sex-Selective Hyperlipidemia and Hyperinsulinemia in Adulthood

    OpenAIRE

    Slotkin, Theodore A.; Kathleen K Brown; Seidler, Frederic J

    2005-01-01

    Developmental exposure to chlorpyrifos alters cell signaling both in the brain and in peripheral tissues, affecting the responses to a variety of neurotransmitters and hormones. We administered 1 mg/kg/day chlorpyrifos to rats on postnatal days 1–4, a regimen below the threshold for systemic toxicity. When tested in adulthood, chlorpyrifos-exposed animals displayed elevations in plasma cholesterol and triglycerides, without underlying alterations in nonesterified free fatty acids and glycerol...

  1. Mental retardation and developmental disabilities influenced by environmental neurotoxic insults.

    OpenAIRE

    Schroeder, S R

    2000-01-01

    This paper sets a framework for the discussion of neurotoxicity as a potentially major contributor to the etiology of many types of mental retardation and developmental disabilities. In the past the literatures on developmental neurotoxicology and on mental retardation have evolved independently, yet we know that the developing brain is a target for neurotoxicity in the developing central nervous system through many stages of pregnancy as well as during infancy and early childhood. Our defini...

  2. Current techniques for assessing developmental neurotoxicity of pesticides

    Institute of Scientific and Technical Information of China (English)

    Yu GAO; Ying TIAN; Xiaoming SHEN

    2008-01-01

    Organophosphates (OPs) and Pyrethroids (PRY) have been widely used in agriculture and in the home as broad spectrum insecticides, but may produce considerable risk to human health, especially to children. Children are more susceptible to environmental exposure, and concern about the neurotoxic effects of pesticide exposure on children is increasing. There is a need for better understanding of the potential developmental neu-rotoxicity of pesticides. Techniques for assessing devel-opmental neurotoxicity of pesticides will continue to be developed, rendering a need for flexibility of testing para-digms. Current techniques used in evaluating the devel-opmental neurotoxicity of OPs and PRY are presented in this review. These include: (1) In vitro techniques (PC12 cells, C6 cells and other cell models); (2) Non-mammalian models (sea urchins, zebrafish and other non-mammalian models); and (3) In vivo mammalian models (morpho-logical techniques, neurobehavioral assessments and biomarkers).

  3. Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Tingting; Zhao, Ling; Liu, Mengyu; Xie, Fei; Ma, Xuemei, E-mail: xmma@bjut.edu.cn; Zhao, Pengxiang; Liu, Yunqi; Li, Jiala; Wang, Minglian; Yang, Zhaona; Zhang, Yutong

    2014-10-01

    Chronic exposure to low-levels of organophosphate (OP) compounds, such as chlorpyrifos (CPF), induces oxidative stress and could be related to neurological disorders. Hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals. We explore whether intake of hydrogen-rich water (HRW) can protect Wistar rats from CPF-induced neurotoxicity. Rats were gavaged daily with 6.75 mg/kg body weight (1/20 LD{sub 50}) of CPF and given HRW by oral intake. Nissl staining and electron microscopy results indicated that HRW intake had protective effects on the CPF-induced damage of hippocampal neurons and neuronal mitochondria. Immunostaining results showed that the increased glial fibrillary acidic protein (GFAP) expression in astrocytes induced by CPF exposure can be ameliorated by HRW intake. Moreover, HRW intake also attenuated CPF-induced oxidative stress as evidenced by enhanced level of MDA, accompanied by an increase in GSH level and SOD and CAT activity. Acetylcholinesterase (AChE) activity tests showed significant decrease in brain AChE activity after CPF exposure, and this effect can be ameliorated by HRW intake. An in vitro study demonstrated that AChE activity was more intense in HRW than in normal water with or without chlorpyrifos-oxon (CPO), the metabolically-activated form of CPF. These observations suggest that HRW intake can protect rats from CPF-induced neurotoxicity, and the protective effects of hydrogen may be mediated by regulating the oxidant and antioxidant status of rats. Furthermore, this work defines a novel mechanism of biological activity of hydrogen by directly increasing the AChE activity. - Highlights: • Hydrogen molecules protect rats from CPF-induced damage of hippocampal neurons. • The increased GFAP expression induced by CPF can also be ameliorated by hydrogen. • Hydrogen molecules attenuated the increase in CPF-induced oxidative stress. • Hydrogen molecules attenuated AChE inhibition in vivo

  4. Potential developmental neurotoxicity of pesticides used in Europe.

    OpenAIRE

    Grandjean Philippe; Andersen Helle; Bjørling-Poulsen Marina

    2008-01-01

    Abstract Pesticides used in agriculture are designed to protect crops against unwanted species, such as weeds, insects, and fungus. Many compounds target the nervous system of insect pests. Because of the similarity in brain biochemistry, such pesticides may also be neurotoxic to humans. Concerns have been raised that the developing brain may be particularly vulnerable to adverse effects of neurotoxic pesticides. Current requirements for safety testing do not include developmental neurotoxici...

  5. Zebrafish as a systems toxicology model for developmental neurotoxicity testing.

    Science.gov (United States)

    Nishimura, Yuhei; Murakami, Soichiro; Ashikawa, Yoshifumi; Sasagawa, Shota; Umemoto, Noriko; Shimada, Yasuhito; Tanaka, Toshio

    2015-02-01

    The developing brain is extremely sensitive to many chemicals. Exposure to neurotoxicants during development has been implicated in various neuropsychiatric and neurological disorders, including autism spectrum disorder, attention deficit hyperactive disorder, schizophrenia, Parkinson's disease, and Alzheimer's disease. Although rodents have been widely used for developmental neurotoxicity testing, experiments using large numbers of rodents are time-consuming, expensive, and raise ethical concerns. Using alternative non-mammalian animal models may relieve some of these pressures by allowing testing of large numbers of subjects while reducing expenses and minimizing the use of mammalian subjects. In this review, we discuss some of the advantages of using zebrafish in developmental neurotoxicity testing, focusing on central nervous system development, neurobehavior, toxicokinetics, and toxicodynamics in this species. We also describe some important examples of developmental neurotoxicity testing using zebrafish combined with gene expression profiling, neuroimaging, or neurobehavioral assessment. Zebrafish may be a systems toxicology model that has the potential to reveal the pathways of developmental neurotoxicity and to provide a sound basis for human risk assessments. PMID:25109898

  6. Critical Duration of Exposure for Developmental Chlorpyrifos-Induced Neurobehavioral Toxicity

    OpenAIRE

    Sledge, Damiyon; Yen, Jerry; Morton, Terrell; Dishaw, Laura; Petro, Ann; Donerly, Susan; Linney, Elwood; Levin, Edward D.

    2011-01-01

    Developmental exposure of rats to the pesticide chlorpyrifos (CPF) causes persistent neurobehavioral impairment. In a parallel series of studies with zebrafish, we have also found persisting behavioral dysfunction after developmental CPF exposure. We have developed a battery of measures of zebrafish behavior, which are reliable and sensitive to toxicant-induced damage. This study determined the critical duration of developmental CPF exposure for causing persisting neurobehavioral effects. Tes...

  7. A critical review of neonicotinoid insecticides for developmental neurotoxicity

    OpenAIRE

    Sheets, Larry P.; Li, Abby A.; Minnema, Daniel J.; Collier, Richard H.; Creek, Moire R.; Peffer, Richard C.

    2015-01-01

    Abstract A comprehensive review of published and previously unpublished studies was performed to evaluate the neonicotinoid insecticides for evidence of developmental neurotoxicity (DNT). These insecticides have favorable safety profiles, due to their preferential affinity for nicotinic receptor (nAChR) subtypes in insects, poor penetration of the mammalian blood–brain barrier, and low application rates. Nevertheless, examination of this issue is warranted, due to their insecticidal mode of a...

  8. Long-Term Effects on Hypothalamic Neuropeptides after Developmental Exposure to Chlorpyrifos in Mice

    OpenAIRE

    Tait, Sabrina; Ricceri, Laura; Venerosi, Aldina; Maranghi, Francesca; Mantovani, Alberto; Calamandrei, Gemma

    2008-01-01

    Background Increasing evidence from animal and human studies indicates that chlorpyrifos (CPF), similar to other organophosphorus insecticides still widely used, is a developmental neurotoxicant. Developmental exposure to CPF in rodents induces sex-dimorphic behavioral changes at adulthood, including social and agonistic responses, which suggests that CPF may interfere with maturation of neuroendocrine mechanisms. Objectives We assessed the hypothesis that CPF affects the levels of neurohypop...

  9. A mechanistic view of polybrominated diphenyl ether (PBDE) developmental neurotoxicity.

    Science.gov (United States)

    Costa, Lucio G; de Laat, Rian; Tagliaferri, Sara; Pellacani, Claudia

    2014-10-15

    Polybrominated diphenyl ethers (PBDEs), extensively used in the past few decades as flame retardants in a variety of consumer products, have become world-wide persistent environmental pollutants. Levels in North America are usually higher than those in Europe and Asia, and body burden is 3-to-9-fold higher in infants and toddlers than in adults. The latter has raised concern for potential developmental toxicity and neurotoxicity of PBDEs. Experimental studies in animals and epidemiological observations in humans suggest that PBDEs may be developmental neurotoxicants. Pre- and/or post-natal exposure to PBDEs may cause long-lasting behavioral abnormalities, particularly in the domains of motor activity and cognition. The mechanisms underlying the developmental neurotoxic effects of PBDEs are not known, though several hypotheses have been put forward. One general mode of action relates to the ability of PBDEs to impair thyroid hormone homeostasis, thus indirectly affecting the developing brain. An alternative or additional mode of action involves a direct effect of PBDEs on nervous system cells; PBDEs can cause oxidative stress-related damage (DNA damage, mitochondrial dysfunction, apoptosis), and interfere with signal transduction (particularly calcium signaling), and with neurotransmitter systems. Important issues such as bioavailability and metabolism of PBDEs, extrapolation of results to low level of exposures, and the potential effects of interactions among PBDE congeners and between PBDEs and other contaminants also need to be taken into account. PMID:24270005

  10. Microcystin-LR exposure induces developmental neurotoxicity in zebrafish embryo.

    Science.gov (United States)

    Wu, Qin; Yan, Wei; Liu, Chunsheng; Li, Li; Yu, Liqin; Zhao, Sujuan; Li, Guangyu

    2016-06-01

    Microcystin-LR (MCLR) is a commonly acting potent hepatotoxin and has been pointed out of potentially causing developmental neurotoxicity, but the exact mechanism is little known. In this study, zebrafish embryos were exposed to 0, 0.8, 1.6 or 3.2 mg/L MCLR for 120 h. MCLR exposure through submersion caused serious hatching delay and body length decrease. The content of MCLR in zebrafish larvae was analyzed and the results demonstrated that MCLR can accumulate in zebrafish larvae. The locomotor speed of zebrafish larvae was decreased. Furthermore, the dopamine and acetylcholine (ACh) content were detected to be significantly decreased in MCLR exposure groups. And the acetylcholinesterase (AChE) activity was significantly increased after exposure to 1.6 and 3.2 mg/L MCLR. The transcription pattern of manf, chrnα7 and ache gene was consistent with the change of the dopamine content, ACh content and AChE activity. Gene expression involved in the development of neurons was also measured. ɑ1-tubulin and shha gene expression were down-regulated, whereas mbp and gap43 gene expression were observed to be significantly up-regulated upon exposure to MCLR. The above results indicated that MCLR-induced developmental toxicity might attribute to the disorder of cholinergic system, dopaminergic signaling, and the development of neurons. PMID:27038211

  11. International STakeholder NETwork (ISTNET): Creating a Developmental Neurotoxicity Testing (DNT) Roadmap for Regulatory Purposes

    Science.gov (United States)

    A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a m...

  12. Assessment of the developmental neurotoxicity of compounds by measuring locomotor activity in zebrafish embryos and larvae

    OpenAIRE

    Selderslaghs, Ingrid W. T.; Hooyberghs, Jef; Blust, Ronny; Witters, Hilda E.

    2013-01-01

    The developmental neurotoxic potential of the majority of environmental chemicals and drugs is currently undetermined. Specific in vivo studies provide useful data for hazard assessment but are not amenable to screen thousands of untested compounds. In this study, methods which use zebrafish embryos, eleutheroembryos and larvae as model organisms, were proposed as alternatives for developmental neurotoxicity (DNT) testing. The evaluation of spontaneous tail coilings in zebrafish embryos aged ...

  13. Methylmercury and brain development: imprecision and underestimation of developmental neurotoxicity in humans

    DEFF Research Database (Denmark)

    Grandjean, Philippe; Herz, Katherine T

    2011-01-01

    Methylmercury is now recognized as an important developmental neurotoxicant, though this insight developed slowly over many decades. Developmental neurotoxicity was first reported in a Swedish case report in 1952, and from a serious outbreak in Minamata, Japan, a few years later. Whereas the infa...

  14. Developmental exposure of zebrafish larvae to organophosphate flame retardants causes neurotoxicity.

    Science.gov (United States)

    Sun, Liwei; Xu, Wenbin; Peng, Tao; Chen, Haigang; Ren, Lin; Tan, Hana; Xiao, Dan; Qian, Haifeng; Fu, Zhengwei

    2016-01-01

    With the gradual ban on brominated flame retardants (FRs), the application of organophosphate flame retardants (OPFRs) has increased remarkably. Considering the structural similarity between OPFRs and organophosphate pesticides, hypotheses that OPFRs may interfere with neurodevelopment as organophosphate pesticides are reasonable. In this study, the neurotoxicity of three OPFRs, including tri-n-butyl phosphate (TNBP), tris (2-butoxyethyl) phosphate (TBOEP) and tris (2-chloroethyl) phosphate (TCEP), was evaluated in zebrafish larvae and then compared with the neurotoxicity of organophosphate pesticide chlorpyrifos (CPF). The results showed that similar to CPF, exposure to OPFRs for 5days resulted in significant changes in locomotor behavior, either in free swimming or in photomotor response. However, given the transcriptional changes that occur in nervous system genes in response to OPFRs and CPF, as well as the altered enzyme activity of AChE and its mRNA level, the underlying mechanisms for neurotoxicity among these organophosphate chemicals might be varied. In summary, the results confirm the potential neurodevelopmental toxicity of OPFRs and underscore the importance of identifying the mechanistic targets of the OPFRs with specific moieties. Furthermore, as the neurobehavioral responses are well conserved among vertebrates and the exposure of children to OPFRs is significant, a thorough assessment of the risk of OPFRs exposure during early development should be highly emphasized in future studies. PMID:27018022

  15. Advancing the Science of Developmental Neurotoxicity (DNT) Testing for Better Safety Evaluation

    DEFF Research Database (Denmark)

    Bal-Price, Anna; Coecke, Sandra; Costa, Lucio;

    2012-01-01

    Bal-Price AK, Coecke S, Costa L, Crofton KM, Fritsche E, Goldberg A, Grandjean P, Lein PJ, Li A, Lucchini R, Mundy WR, Padilla S, Persico A, Seiler AEM, Kreysa J. Conference Report: Advancing the Science of Developmental Neurotoxicity (DNT) Testing for Better Safety Evaluation. Altex 2012: 29: 202-15....

  16. Recommendations for Developing Alternative Test Methods for Screening and Prioritization of Chemicals for Developmental Neurotoxicity

    Science.gov (United States)

    Developmental neurotoxicity testing (DNT) is perceived by many stakeholders to be an area in critical need of alternative methods to current animal testing protocols and gUidelines. An immediate goal is to develop test methods that are capable of screening large numbers of chemic...

  17. Developmental exposure to chlorpyrifos alters reactivity to environmental and social cues in adolescent mice.

    Science.gov (United States)

    Ricceri, Laura; Markina, Nadja; Valanzano, Angela; Fortuna, Stefano; Cometa, Maria Francesca; Meneguz, Annarita; Calamandrei, Gemma

    2003-09-15

    Neonatal mice were treated daily on postnatal days (pnds) 1 through 4 or 11 through 14 with the organophosphate pesticide chlorpyrifos (CPF), at doses (1 or 3 mg/kg) that do not evoke systemic toxicity. Brain acetylcholinesterase (AChE) activity was evaluated within 24 h from termination of treatments. Pups treated on pnds 1-4 underwent ultrasonic vocalization tests (pnds 5, 8, and 11) and a homing test (orientation to home nest material, pnd 10). Pups in both treatment schedules were then assessed for locomotor activity (pnd 25), novelty-seeking response (pnd 35), social interactions with an unfamiliar conspecific (pnd 45), and passive avoidance learning (pnd 60). AChE activity was reduced by 25% after CPF 1-4 but not after CPF 11-14 treatment. CPF selectively affected only the G(4) (tetramer) molecular isoform of AChE. Behavioral analysis showed that early CPF treatment failed to affect neonatal behaviors. Locomotor activity on pnd 25 was increased in 11-14 CPF-treated mice at both doses, and CPF-treated animals in both treatment schedules were more active when exposed to environmental novelty in the novelty-seeking test. All CPF-treated mice displayed more agonistic responses, and such effect was more marked in male mice exposed to the low CPF dose on pnds 11-14. Passive avoidance learning was not affected by CPF. These data indicate that developmental exposure to CPF induces long-term behavioral alterations in the mouse species and support the involvement of neural systems in addition to the cholinergic system in the delayed behavioral toxicity of CPF. PMID:13678652

  18. Developmental exposure to chlorpyrifos alters reactivity to environmental and social cues in adolescent mice

    International Nuclear Information System (INIS)

    Neonatal mice were treated daily on postnatal days (pnds) 1 through 4 or 11 through 14 with the organophosphate pesticide chlorpyrifos (CPF), at doses (1 or 3 mg/kg) that do not evoke systemic toxicity. Brain acetylcholinesterase (AChE) activity was evaluated within 24 h from termination of treatments. Pups treated on pnds 1-4 underwent ultrasonic vocalization tests (pnds 5, 8, and 11) and a homing test (orientation to home nest material, pnd 10). Pups in both treatment schedules were then assessed for locomotor activity (pnd 25), novelty-seeking response (pnd 35), social interactions with an unfamiliar conspecific (pnd 45), and passive avoidance learning (pnd 60). AChE activity was reduced by 25% after CPF 1-4 but not after CPF 11-14 treatment. CPF selectively affected only the G4 (tetramer) molecular isoform of AChE. Behavioral analysis showed that early CPF treatment failed to affect neonatal behaviors. Locomotor activity on pnd 25 was increased in 11-14 CPF-treated mice at both doses, and CPF-treated animals in both treatment schedules were more active when exposed to environmental novelty in the novelty-seeking test. All CPF-treated mice displayed more agonistic responses, and such effect was more marked in male mice exposed to the low CPF dose on pnds 11-14. Passive avoidance learning was not affected by CPF. These data indicate that developmental exposure to CPF induces long-term behavioral alterations in the mouse species and support the involvement of neural systems in addition to the cholinergic system in the delayed behavioral toxicity of CPF

  19. Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach

    OpenAIRE

    Krug, Anne K.; Kolde, Raivo; Gaspar, John A.; Rempel, Eugen; Balmer, Nina V.; Meganathan, Kesavan; Vojnits, Kinga; Baquié, Mathurin; Waldmann, Tanja; Ensenat-Waser, Roberto; Jagtap, Smita, 1978-; Evans, Richard M.; Julien, Stephanie; Peterson, Hedi; Zagoura, Dimitra

    2012-01-01

    Developmental neurotoxicity (DNT) and many forms of reproductive toxicity (RT) often manifest themselves in functional deficits that are not necessarily based on cell death, but rather on minor changes relating to cell differentiation or communication. The fields of DNT/RT would greatly benefit from in vitro tests that allow the identification of toxicant-induced changes of the cellular proteostasis, or of its underlying transcriptome network. Therefore, the ‘human embryonic stem cell (hESC)-...

  20. Developmental neurotoxicity : challenges in the 21st century and in vitro opportunities

    OpenAIRE

    Smirnova, Lena; Hogberg, Helena T.; Leist, Marcel; Hartung, Thomas

    2014-01-01

    In recent years neurodevelopmental problems in children have increased at a rate that suggests lifestyle factors and chemical exposures as likely contributors. When environmental chemicals contribute to neurodevelopmental disorders developmental neurotoxicity (DNT) becomes an enormous concern. But how can it be tackled? Current animal test-based guidelines are prohibitively expensive, at $1.4 million per substance, while their predictivity for human health effects may be limited, and mechanis...

  1. Zebrafish as potential model for developmental neurotoxicity testing: a mini review.

    Science.gov (United States)

    de Esch, Celine; Slieker, Roderick; Wolterbeek, André; Woutersen, Ruud; de Groot, Didima

    2012-01-01

    The zebrafish is a powerful toxicity model; biochemical assays can be combined with observations at a structural and functional level within one individual. This mini review summarises the potency of zebrafish as a model for developmental neurotoxicity screening, and its possibilities to investigate working mechanisms of toxicants. The use of zebrafish in toxicity research can ultimately lead to the refinement or reduction of animal use. PMID:22971930

  2. Human Neurospheres as Three-Dimensional Cellular Systems for Developmental Neurotoxicity Testing

    OpenAIRE

    Moors, Michaela; Rockel, Thomas Dino; Abel, Josef; Cline, Jason E.; Gassmann, Kathrin; Schreiber, Timm; Schuwald, Janette; Weinmann, Nicole; Fritsche, Ellen

    2009-01-01

    Background Developmental neurotoxicity (DNT) of environmental chemicals is a serious threat to human health. Current DNT testing guidelines propose investigations in rodents, which require large numbers of animals. With regard to the “3 Rs” (reduction, replacement, and refinement) of animal testing and the European regulation of chemicals [Registration, Evaluation, and Authorisation of Chemicals (REACH)], alternative testing strategies are needed in order to refine and reduce animal experimen...

  3. Developmental origins of adult diseases and neurotoxicity: Epidemiological and experimental studies

    DEFF Research Database (Denmark)

    Fox, Donald A; Grandjean, Philippe; de Groot, Didima;

    2012-01-01

    To date, only a small number of commercial chemicals have been tested and documented as developmental neurotoxicants. Moreover, an increasing number of epidemiological, clinical and experimental studies suggest an association between toxicant or drug exposure during the perinatal period and the......, motivation and short-term memory in aged Rhesus monkeys following acute 24 h exposure to ketamine during early development. Overall, these presentations addressed fundamental issues in the emerging areas of lifetime neurotoxicity testing, differential vulnerable periods of exposure, nonmonotonic dose...

  4. The developmental neurotoxicity of polybrominated diphenyl ethers: Effect of DE-71 on dopamine in zebrafish larvae.

    Science.gov (United States)

    Wang, Xianfeng; Yang, Lihua; Wu, Yuanyuan; Huang, Changjiang; Wang, Qiangwei; Han, Jian; Guo, Yongyong; Shi, Xiongjie; Zhou, Bingsheng

    2015-05-01

    The potential neurotoxicity of polybrominated diphenyl ethers (PBDEs) is still a great concern. In the present study, the authors investigated whether exposure to PBDEs could affect the neurotransmitter system and cause developmental neurotoxicity in zebrafish. Zebrafish embryos (2 h postfertilization) were exposed to different concentrations of the PBDE mixture DE-71 (0-100 μg/L). The larvae were harvested at 120 h postfertilization, and the impact on dopaminergic signaling was investigated. The results revealed significant reductions in content of whole-body dopamine and its metabolite, dihydroxyphenylacetic acid, in DE-71-exposed larvae. The transcription of genes involved in the development of dopaminergic neurons (e.g., manf, bdnf, and nr4a2b) was significantly downregulated upon exposure to DE-71. Also, DE-71 resulted in a significant decrease of tyrosine hydroxylase and dopamine transporter protein levels in dopaminergic neurons. The expression level of tyrosine hydroxylase in forebrain neurons was assessed by whole-mount immunofluorescence, and the results further demonstrated that the tyrosine hydroxylase protein expression level was reduced in dopaminergic neurons. In addition to these molecular changes, the authors observed reduced locomotor activity in DE-71-exposed larvae. Taken together, the results of the present study demonstrate that acute exposure to PBDEs can affect dopaminergic signaling by disrupting the synthesis and transportation of dopamine in zebrafish, thereby disrupting normal neurodevelopment. In accord with its experimental findings, the present study extends knowledge of the mechanisms governing PBDE-induced developmental neurotoxicity. PMID:25651517

  5. Diphenyl ditelluride induces neurotoxicity and impairment of developmental behavioral in rat pups

    International Nuclear Information System (INIS)

    The purpose of the present study was to investigate if acute exposure to diphenyl ditelluride (PhTe)2 causes impairment of developmental behavioral performance in rat pups. Rat pups received a single subcutaneous injection of (PhTe)2 (0.1 mg kg-1, 3 mL kg-1) or vehicle (3 mL kg-1) at 14th postnatal day. After exposure to (PhTe)2, the general parameters of neurotoxicity, behavioral tasks, cerebral myelin content, histological analysis and acetylcholinesterase (AChE) activity were performed during seven days. The appearance of classic signs of toxicity, behavioral alterations and the reduction in myelin content were dependent on the time after (PhTe)2 exposure to pups. Neuronal damage, reduction of myelin content, and the increase in AChE activity occurred mainly at 4th and 5th day after (PhTe)2 exposure, indicating that the critical period of neurotoxicity is coincident with the major behavioral alterations. In conclusion, exposure to (PhTe)2 induced neurotoxicity and impairment of developmental behavioral in rat pups. (author)

  6. Assessment of learning, memory, and attention in developmental neurotoxicity regulatory studies: synthesis, commentary, and recommendations.

    Science.gov (United States)

    Vorhees, Charles V; Makris, Susan L

    2015-01-01

    Cognitive tests of learning and memory (L&M) have been required by U.S. Environmental Protection Agency (EPA) developmental neurotoxicity test (DNT) guidelines for more than two decades. To evaluate the utility of these guidelines, the EPA reviewed 69 pesticide DNT studies. This review found that the DNT provided or could provide the point-of-departure for risk assessment by showing the Lowest Observable Adverse Effect Level (LOAEL) in 28 of these studies in relation to other reported end points. Among the behavioral tests, locomotor activity and auditory/acoustic startle provided the most LOAELs, and tests of cognitive function and the Functional Observational Battery (FOB) the fewest. Two issues arose from the review: (1) what is the relative utility of cognitive tests versus tests of unconditioned behavior, and (2) how might cognitive tests be improved? The EPA sponsored a symposium to address this. Bushnell reviewed studies in which both screening (locomotor activity, FOB, reflex ontogeny, etc.) and complex tests (those requiring training) were used within the same study; he found relatively little evidence that complex tests provided a LOAEL lower than screening tests (with exceptions). Levin reviewed reasons for including cognitive tests in regulatory studies and methods and evidence for the radial arm maze and its place in developmental neurotoxicity assessments. Driscoll and Strupp reviewed the value of serial reaction time operant methods for assessing executive function in developmental neurotoxicity studies. Vorhees and Williams reviewed the value of allocentric (spatial) and egocentric cognitive tests and presented methods for using the Morris water maze for spatial and the Cincinnati water maze for egocentric cognitive assessment. They also reviewed the possible use of water radial mazes. The relatively lower impact of cognitive tests in previous DNT studies in the face of the frequency of human complaints of chemical-induced cognitive dysfunction

  7. Induced pluripotent stem cell-derived neuron as a human model for testing environmentally induced developmental neurotoxicity

    Science.gov (United States)

    Induced pluripotent stem cell-derived neurons as a human model for testing environmentally induced developmental neurotoxicity Ingrid L. Druwe1, Timothy J. Shafer2, Kathleen Wallace2, Pablo Valdivia3 ,and William R. Mundy2. 1University of North Carolina, Curriculum in Toxicology...

  8. Markers of murine embryonic and neural stem cells, neurons and astrocytes: reference points for developmental neurotoxicity testing

    Science.gov (United States)

    Developmental neurotoxicity (DNT) is a significant concern for environmental chemicals, as well as for food and drug constituents. The sensitivity of animal-based DNT models is unclear, and they are expensive and time consuming. Murine embryonic stem cells (mESC) recapitulate sev...

  9. Non-invasive fluorescent imaging of gliosis in transgenic mice for profiling developmental neurotoxicity

    International Nuclear Information System (INIS)

    Gliosis is a universal response of Brain to almost all types of neural insults, including neurotoxicity, neurodegeneration, viral infection, and stroke. A hallmark of gliotic reaction is the up-regulation of the astrocytic biomarker GFAP (glial fibrillary acidic protein), which often precedes the anatomically apparent damages in Brain. In this study, neonatal transgenic mice at postnatal day (PD) 4 expressing GFP (green fluorescent protein) under the control of a widely used 2.2-kb human GFAP promoter in Brain are treated with two model neurotoxicants, 1-methyl-4(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH3-MPTP), and kainic acid (KA), respectively, to induce gliosis. Here we show that the neurotoxicant-induced acute gliosis can be non-invasively imaged and quantified in Brain of conscious (un-anesthetized) mice in real-time, at 0, 2, 4, 6, and 8 h post-toxicant dosing. Therefore the current methodology could be a useful tool for studying the developmental aspects of neuropathies and neurotoxicity

  10. The DNT-EST: A predictive embryonic stem cell-based assay for developmental neurotoxicity testing in vitro

    International Nuclear Information System (INIS)

    As the developing brain is exquisitely vulnerable to chemical disturbances, testing for developmental neurotoxicity of a substance is an important aspect of characterizing its tissue specific toxicity. Mouse embryonic stem cells (mESCs) can be differentiated toward a neural phenotype, and this can be used as a model for early brain development. We developed a new in vitro assay using mESCs to predict adverse effects of chemicals and other compounds on neural development – the so-called DNT-EST. After treatment of differentiating stem cells for 48 h or 72 h, at two key developmental stages endpoint for neural differentiation, viability, and proliferation were assessed. As a reference, we similarly treated undifferentiated stem cells 2 days after plating for 48 h or 72 h in parallel to the differentiating stem cells. Here, we show that chemical testing of a training set comprising nine substances (six substances of known developmental toxicity and three without specific developmental neurotoxicity) enabled a mathematical prediction model to be formulated that provided 100% predictivity and accuracy for the given substances, including in leave-one-out cross-validation. The described test method can be performed within two weeks, including data analysis, and provides a prediction of the developmental neurotoxicity potency of a substance

  11. Global methylmercury exposure from seafood consumption and risk of developmental neurotoxicity: a systematic review

    Directory of Open Access Journals (Sweden)

    Mary C Sheehan

    2014-04-01

    Full Text Available Objective To examine biomarkers of methylmercury (MeHg intake in women and infants from seafood-consuming populations globally and characterize the comparative risk of fetal developmental neurotoxicity. Methods A search was conducted of the published literature reporting total mercury (Hg in hair and blood in women and infants. These biomarkers are validated proxy measures of MeHg, a neurotoxin found primarily in seafood. Average and high-end biomarkers were extracted, stratified by seafood consumption context, and pooled by category. Medians for average and high-end pooled distributions were compared with the reference level established by a joint expert committee of the Food and Agriculture Organization (FAO and the World Health Organization (WHO. Findings Selection criteria were met by 164 studies of women and infants from 43 countries. Pooled average biomarkers suggest an intake of MeHg several times over the FAO/WHO reference in fish-consuming riparians living near small-scale gold mining and well over the reference in consumers of marine mammals in Arctic regions. In coastal regions of south-eastern Asia, the western Pacific and the Mediterranean, average biomarkers approach the reference. Although the two former groups have a higher risk of neurotoxicity than the latter, coastal regions are home to the largest number at risk. High-end biomarkers across all categories indicate MeHg intake is in excess of the reference value. Conclusion There is a need for policies to reduce Hg exposure among women and infants and for surveillance in high-risk populations, the majority of which live in low-and middle-income countries.

  12. Co-exposure to an ortho-substituted PCB (PCB 153) and methylmercury enhances developmental neurotoxic effects

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, C.; Fredriksson, A.; Eriksson, P. [Dept. Environment. Toxicol., Uppsala Univ. (Sweden)

    2004-09-15

    In our environment there are innumerable hazardous contaminants. Many of these compounds are the well-known persistent organic pollutants (POPs) like PCB and DDT. Another persistent agent in our environment is methylmercury (MeHg). These agents are known to be neurotoxic in laboratory animals and humans. Fetuses and neonates are known to be high-risk groups for exposure to these agents. A naturally occurring circumstance is the exposure to a combination of different persistent compounds. The knowledge of interaction between different toxic agents during development is sparse. In several studies we have shown that low-dose exposure of environmental toxic agents such as PCBs, DDT, BFRs (brominated flame retardants) as well as well-known neurotoxic agents such as nicotine, organophosphorous compounds and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), during the ''BGS'', in neonatal mice can lead to disruption of the adult brain function, and to an increased susceptibility to toxic agents as adults. Our studies concerning developmental neurotoxic effects after neonatal exposure to single PCB congeners have shown that some orthosubstituted PCBs (such as PCB 28, PCB 52, PCB 153) and some co-planar PCBs (such as PCB 77, PCB 126, PCB 169) cause derangement of adult behaviour that can worsen with age. Furthermore, the cholinergic receptors in the brain were also found to be affected8. Just recently we have seen that neonatal co-exposure to an ortho-substituted PCB, 2,2',5,5'-tetrachlorobiphenyl (PCB 52), together with a brominated flame retardant, 2,2',4,4',5-pentabromodiphenylether (PBDE 99), can enhance developmental neurotoxic effects when the exposure occurs during a critical stage of neonatal brain development. The present study was carried out in order to see whether PCB and MeHg could interact to cause enhanced developmental neurotoxic effects on spontaneous behaviour and habituation capability when given to neonatal mice.

  13. Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: Impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yi; Wei, Wei; Wang, Yuan; Dong, Jing; Song, Binbin; Min, Hui [Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang (China); Teng, Weiping, E-mail: twpendocrine@yahoo.com.cn [Liaoning Provincial Key Laboratory of Endocrine Diseases, the First Hospital of China Medical University, Shenyang (China); Chen, Jie, E-mail: chenjie@mail.cmu.edu.cn [Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang (China)

    2013-09-01

    Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism on long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway – a pathway closely associated with synaptic plasticity and learning and memory – was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and

  14. Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: Impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway

    International Nuclear Information System (INIS)

    Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism on long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway – a pathway closely associated with synaptic plasticity and learning and memory – was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and

  15. Food for Thought …: Developmental Neurotoxicity – Challenges in the 21st Century and In Vitro Opportunities

    OpenAIRE

    Smirnova, Lena; Hogberg, Helena T.; Leist, Marcel; Hartung, Thomas

    2014-01-01

    In recent years neurodevelopmental problems in children have increased at a rate that suggests lifestyle factors and chemical exposures as likely contributors. When environmental chemicals contribute to neurodevelopmental disorders developmental neurotoxicity (DNT) becomes an enormous concern. But how can it be tackled? Current animal test-based guidelines are prohibitively expensive, at $1.4 million per substance, while their predictivity for human health effects may be limited, and mechanis...

  16. Workgroup Report: Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity into International Hazard and Risk Assessment Strategies

    OpenAIRE

    Coecke S.; Goldberg A.M.; Allen S; Buzanska L.; Calamandrei G.; Crofton K.; Hareng L.; Hartung T.; Knaut H.; Honegger P.; Jacobs M.; Lein P.; Li A.; Mundy W.; Owen D.

    2007-01-01

    This is the report of the first workshop on Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity (DNT) Testing into International Hazard and Risk Assessment Strategies, held in Ispra, Italy, on 19-21 April 2005. The workshop was hosted by the European Centre for the Validation of Alternative Methods (ECVAM) and jointly organized by ECVAM, the European Chemical Industry Council, and the Johns Hopkins University Center for Alternatives to Animal Testing. The primary aim of...

  17. Effect of Different Administration Paradigms on Cholinesterase Inhibition following Repeated Chlorpyrifos Exposure in Late Preweanling Rats

    OpenAIRE

    Carr, Russell L.; Nail, Carole A.

    2008-01-01

    Chlorpyrifos (CPS) is widely used in agricultural settings and residue analysis has suggested that children in agricultural communities are at risk of exposure. This has resulted in a large amount of literature investigating the potential for CPS-induced developmental neurotoxic effects. Two developmental routes of administration of CPS are orally in corn oil at a rate of 0.5 ml/kg and subcutaneously in dimethyl sulfoxide (DMSO) at a rate of 1.0 ml/kg. For comparison between these methods, ra...

  18. Recommended Methods for Brain Processing and Quantitative Analysis in Rodent Developmental Neurotoxicity Studies.

    Science.gov (United States)

    Garman, Robert H; Li, Abby A; Kaufmann, Wolfgang; Auer, Roland N; Bolon, Brad

    2016-01-01

    Neuropathology methods in rodent developmental neurotoxicity (DNT) studies have evolved with experience and changing regulatory guidance. This article emphasizes principles and methods to promote more standardized DNT neuropathology evaluation, particularly procurement of highly homologous brain sections and collection of the most reproducible morphometric measurements. To minimize bias, brains from all animals at all dose levels should be processed from brain weighing through paraffin embedding at one time using a counterbalanced design. Morphometric measurements should be anchored by distinct neuroanatomic landmarks that can be identified reliably on the faced block or in unstained sections and which address the region-specific circuitry of the measured area. Common test article-related qualitative changes in the developing brain include abnormal cell numbers (yielding altered regional size), displaced cells (ectopia and heterotopia), and/or aberrant differentiation (indicated by defective myelination or synaptogenesis), but rarely glial or inflammatory reactions. Inclusion of digital images in the DNT pathology raw data provides confidence that the quantitative analysis was done on anatomically matched (i.e., highly homologous) sections. Interpreting DNT neuropathology data and their presumptive correlation with neurobehavioral data requires an integrative weight-of-evidence approach including consideration of maternal toxicity, body weight, brain weight, and the pattern of findings across brain regions, doses, sexes, and ages. PMID:26296631

  19. From Drug-Induced Developmental Neuroapoptosis to Pediatric Anesthetic Neurotoxicity-Where Are We Now?

    Science.gov (United States)

    Creeley, Catherine E

    2016-01-01

    The fetal and neonatal periods are critical and sensitive periods for neurodevelopment, and involve rapid brain growth in addition to natural programmed cell death (i.e., apoptosis) and synaptic pruning. Apoptosis is an important process for neurodevelopment, preventing redundant, faulty, or unused neurons from cluttering the developing brain. However, animal studies have shown massive neuronal cell death by apoptosis can also be caused by exposure to several classes of drugs, namely gamma-aminobutyric acid (GABA) agonists and N-methyl-d-aspartate (NMDA) antagonists that are commonly used in pediatric anesthesia. This form of neurotoxic insult could cause a major disruption in brain development with the potential to permanently shape behavior and cognitive ability. Evidence does suggest that psychoactive drugs alter neurodevelopment and synaptic plasticity in the animal brain, which, in the human brain, may translate to permanent neurodevelopmental changes associated with long-term intellectual disability. This paper reviews the seminal animal research on drug-induced developmental apoptosis and the subsequent clinical studies that have been conducted thus far. In humans, there is growing evidence that suggests anesthetics have the potential to harm the developing brain, but the long-term outcome is not definitive and causality has not been determined. The consensus is that there is more work to be done using both animal models and human clinical studies. PMID:27537919

  20. Developmental neurotoxicity of ethanol (EtOH): Interaction with muscarinic receptor (MR) stimulated phosphoinositide metabolism

    International Nuclear Information System (INIS)

    We have previously reported that administration of EtOH (4g/kg/day) to rats from postnatal day 4 to day 10 causes microencephaly and decreases MR-stimulated inositol metabolism on days 7 and 10. An identical exposure to EtOH of adult rats, which resulted in similar blood EtOH concentrations, did not have any effect on the same system. To test whether a differential sensitivity of the phosphoinostitide (PI) system coupled to MR during development could account for these findings, we have investigated the in vitro effects of EtOH on carbachol (CB)-stimulated PI metabolism in rat brain slices. EtOH (500 mM) caused a 30% decrease of maximal accumulation of [3H] inositol phosphates (InsPs) induced by CB and a two fold increase in its EC50 in 7 day-old rats, but had no effect on adults. The effect of EtOH on MR-stimulated PI metabolism in 7 day-old rats was dependent on the time of preincubation of the slices with EtOH. After 90 min preincubation, the effect of EtOH was significant at a concentration as low as 50 mM, which is obtained after in vivo administration of EtOH. The inhibitory effect of EtOH was brain region- and age- dependent, with its maximal effect occurring on days 7-10. These results confirm that the PI system coupled to MR could represent a relevant target for the developmental neurotoxicity of EtOH

  1. Differentiating human NT2/D1 neurospheres as a versatile in vitro 3D model system for developmental neurotoxicity testing

    International Nuclear Information System (INIS)

    Developmental neurotoxicity is a major issue in human health and may have lasting neurological implications. In this preliminary study we exposed differentiating Ntera2/clone D1 (NT2/D1) cell neurospheres to known human teratogens classed as non-embryotoxic (acrylamide), weakly embryotoxic (lithium, valproic acid) and strongly embryotoxic (hydroxyurea) as listed by European Centre for the Validation of Alternative Methods (ECVAM) and examined endpoints of cell viability and neuronal protein marker expression specific to the central nervous system, to identify developmental neurotoxins. Following induction of neuronal differentiation, valproic acid had the most significant effect on neurogenesis, in terms of reduced viability and decreased neuronal markers. Lithium had least effect on viability and did not significantly alter the expression of neuronal markers. Hydroxyurea significantly reduced cell viability but did not affect neuronal protein marker expression. Acrylamide reduced neurosphere viability but did not affect neuronal protein marker expression. Overall, this NT2/D1-based neurosphere model of neurogenesis, may provide the basis for a model of developmental neurotoxicity in vitro

  2. Assessment of attention and inhibitory control in rodent developmental neurotoxicity studies.

    Science.gov (United States)

    Driscoll, Lori L; Strupp, Barbara J

    2015-01-01

    In designing screens to assess potential neurotoxicants, the paramount goal is that the selected assessment tools detect dysfunction if it exists. This goal is particularly challenging in the case of cognitive assessments. Cognition is not a unitary phenomenon, and indeed there is growing evidence that different aspects of cognitive functioning are subserved by distinct neural systems. As a result, if a particular neurotoxicant selectively damages certain neural systems but not others, it can impair some cognitive, sensory, or affective functions, but leave many others intact. Accordingly, studies with human subjects use batteries of cognitive tests, cognizant of the fact that no one test is capable of detecting all forms of cognitive dysfunction. In contrast, assessment of cognitive functioning in non-human animal developmental neurotoxicity (DNT) studies typically consists of a single, presumably representative, "learning and memory" task that is expected to detect all potential effects on cognitive functioning. Streamlining the cognitive assessment in these studies saves time and money, but these shortcuts can have serious consequences if the aspect of cognitive functioning that is impaired is not tapped by the single selected task. In particular, executive functioning - a constellation of cognitive functions which enables the organism to focus on multiple streams of information simultaneously, and revise plans as necessary - is poorly assessed in most animal DNT studies. The failure to adequately assess these functions - which include attention, working memory, inhibitory control, and planning - is particularly worrisome in light of evidence that the neural systems that subserve these functions may be uniquely vulnerable to early developmental insults. We illustrate the importance of tapping these areas of functioning in DNT studies by describing the pattern of effects produced by early developmental Pb exposure. Rats exposed to lead (Pb) early in development

  3. 3-Nitropropionic acid neurotoxicity in hippocampal slice cultures: developmental and regional vulnerability and dependency on glucose

    DEFF Research Database (Denmark)

    Noer, Helle; Kristensen, Bjarne W; Noraberg, Jens;

    2002-01-01

    : CA1 > CA3 > fascia dentata. In low glucose much lower concentrations of 3-NP (25 microM) triggered neurotoxicity. One-week-old cultures were less susceptible to 3-NP toxicity than 3-week-old cultures, but the dentate granule cells were relatively more affected in the immature cultures. We found no...

  4. Developmental exposure to terbutaline and chlorpyrifos: pharmacotherapy of preterm labor and an environmental neurotoxicant converge on serotonergic systems in neonatal rat brain regions

    International Nuclear Information System (INIS)

    Developmental exposure to unrelated neurotoxicants can nevertheless produce similar neurobehavioral outcomes. We examined the effects of developmental exposure to terbutaline, a tocolytic β2-adrenoceptor agonist used to arrest preterm labor, and chlorpyrifos (CPF), a widely used organophosphate pesticide, on serotonin (5HT) systems. Treatments were chosen to parallel periods typical of human developmental exposures, terbutaline (10 mg/kg) on postnatal days (PN) 2-5 and CPF (5 mg/kg) on PN11-14, with assessments conducted on PN45, comparing each agent alone as well as sequential administration of both. Although neither treatment affected growth or viability, each elicited similar alterations in factors that are critical to the function of the 5HT synapse: 5HT1A receptors, 5HT2 receptors, and the presynaptic 5HT transporter (5HTT). Either agent elicited global increases in 5HT receptors and the 5HTT in brain regions possessing 5HT cell bodies (midbrain, brainstem) as well as in the hippocampus, which contains 5HT projections. For both terbutaline and CPF, males were affected more than females, although there were some regional disparities in the sex selectivity between the two agents. Both altered 5HT receptor-mediated cell signaling, suppressing stimulatory effects on adenylyl cyclase and enhancing inhibitory effects. When animals were exposed sequentially to both agents, the outcomes were no more than additive and, for many effects, less than additive, suggesting convergence of the two agents on a common set of developmental mechanisms. Our results indicate that 5HT systems represent a target for otherwise unrelated neuroteratogens

  5. Developmental exposure to terbutaline alters cell signaling in mature rat brain regions and augments the effects of subsequent neonatal exposure to the organophosphorus insecticide chlorpyrifos

    International Nuclear Information System (INIS)

    Exposure to apparently unrelated neurotoxicants can nevertheless converge on common neurodevelopmental events. We examined the long-term effects of developmental exposure of rats to terbutaline, a β-adrenoceptor agonist used to arrest preterm labor, and the organophosphorus insecticide chlorpyrifos (CPF) separately and together. Treatments mimicked the appropriate neurodevelopmental stages for human exposures: terbutaline on postnatal days (PN) 2-5 and CPF on PN11-14, with assessments conducted on PN45. Although neither treatment affected growth or viability, each elicited alterations in CNS cell signaling mediated by adenylyl cyclase (AC), a transduction pathway shared by numerous neuronal and hormonal signals. Terbutaline altered signaling in the brainstem and cerebellum, with gender differences particularly notable in the cerebellum (enhanced AC in males, suppressed in females). By itself, CPF exposure elicited deficits in AC signaling in the midbrain, brainstem, and striatum. However, sequential exposure to terbutaline followed by CPF produced larger alterations and involved a wider spectrum of brain regions than were obtained with either agent alone. In the cerebral cortex, adverse effects of the combined treatment intensified between PN45 and PN60, suggesting that exposures alter the long-term program for development of synaptic communication, leading to alterations in AC signaling that emerge even after adolescence. These findings indicate that terbutaline, like CPF, is a developmental neurotoxicant, and reinforce the idea that its use in preterm labor may create a subpopulation that is sensitized to long-term CNS effects of organophosphorus insecticides

  6. BRAIN AND BLOOD TIN LEVELS IN A DEVELOPMENTAL NEUROTOXICITY STUDY OF DIBUTYLTIN.

    Science.gov (United States)

    Dibutyltin (DBT), a widely used plastic stabilizer, is detected in the environment and human tissues. While teratological and developmental effects are known, we could find no published report of DBT effects on the developing nervous system. As part of a developmental neurotoxi...

  7. Generation and Characterization of Neurogeninl-GFP Transgenic Medaka for High Throughput Developmental Neurotoxicity Screening

    Science.gov (United States)

    Fish models such as zebrafish and medaka are increasingly used as alternatives to rodents in developmental and toxicological studies. These developmental and toxicological studies can be facilitated by the use of transgenic reporters that permit the real-time, noninvasive observa...

  8. Generation and characterization of neurogenin1-GFP transgenic medaka with potential for rapid developmental neurotoxicity screening

    Energy Technology Data Exchange (ETDEWEB)

    Fan Chunyang [Integrated Systems Toxicology and Toxicity Assessment Divisions, National Health and Environmental Effects Research Laboratory, US EPA, Research Triangle Park, NC 27711 (United States); Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 (United States); Simmons, Steven O. [Integrated Systems Toxicology and Toxicity Assessment Divisions, National Health and Environmental Effects Research Laboratory, US EPA, Research Triangle Park, NC 27711 (United States); Law, Sheran H.W. [Environmental Sciences and Policy Division, Nicholas School of the Environment and Earth Sciences, Duke University, Durham, NC 27708 (United States); Jensen, Karl; Cowden, John [Integrated Systems Toxicology and Toxicity Assessment Divisions, National Health and Environmental Effects Research Laboratory, US EPA, Research Triangle Park, NC 27711 (United States); Hinton, David [Environmental Sciences and Policy Division, Nicholas School of the Environment and Earth Sciences, Duke University, Durham, NC 27708 (United States); Padilla, Stephanie [Integrated Systems Toxicology and Toxicity Assessment Divisions, National Health and Environmental Effects Research Laboratory, US EPA, Research Triangle Park, NC 27711 (United States); Ramabhadran, Ram, E-mail: Ram.Ramabhadran@gmail.com [Integrated Systems Toxicology and Toxicity Assessment Divisions, National Health and Environmental Effects Research Laboratory, US EPA, Research Triangle Park, NC 27711 (United States)

    2011-09-15

    Fish models such as zebrafish and medaka are increasingly used as alternatives to rodents in developmental and toxicological studies. These developmental and toxicological studies can be facilitated by the use of transgenic reporters that permit the real-time, noninvasive observation of the fish. Here we report the construction and characterization of transgenic medaka lines expressing green fluorescent protein (GFP) under the control of the zebrafish neurogenin 1 (ngn1) gene promoter. Neurogenin (ngn1) is a helix-loop-helix transcription factor expressed in proliferating neuronal progenitor cells early in neuronal differentiation and plays a crucial role in directing neurogenesis. GFP expression was detected from 24 h post-fertilization until hatching, in a spatial pattern consistent with the previously reported zebrafish ngn1 expression. Temporal expression of the transgene parallels the expression profile of the endogenous medaka ngn1 transcript. Further, we demonstrate that embryos from the transgenic line permit the non-destructive, real-time screening of ngn1 promoter-directed GFP expression in a 96-well format, enabling higher throughput studies of developmental neurotoxicants. This strain has been deposited with and maintained by the National BioResource Project and is available on request ( (http://www.shigen.nig.ac.jp/medaka/strainDetailAction.do?quickSearch=true and strainId=5660)).

  9. Generation and characterization of neurogenin1-GFP transgenic medaka with potential for rapid developmental neurotoxicity screening

    International Nuclear Information System (INIS)

    Fish models such as zebrafish and medaka are increasingly used as alternatives to rodents in developmental and toxicological studies. These developmental and toxicological studies can be facilitated by the use of transgenic reporters that permit the real-time, noninvasive observation of the fish. Here we report the construction and characterization of transgenic medaka lines expressing green fluorescent protein (GFP) under the control of the zebrafish neurogenin 1 (ngn1) gene promoter. Neurogenin (ngn1) is a helix-loop-helix transcription factor expressed in proliferating neuronal progenitor cells early in neuronal differentiation and plays a crucial role in directing neurogenesis. GFP expression was detected from 24 h post-fertilization until hatching, in a spatial pattern consistent with the previously reported zebrafish ngn1 expression. Temporal expression of the transgene parallels the expression profile of the endogenous medaka ngn1 transcript. Further, we demonstrate that embryos from the transgenic line permit the non-destructive, real-time screening of ngn1 promoter-directed GFP expression in a 96-well format, enabling higher throughput studies of developmental neurotoxicants. This strain has been deposited with and maintained by the National BioResource Project and is available on request ( (http://www.shigen.nig.ac.jp/medaka/strainDetailAction.do?quickSearch=true and strainId=5660)).

  10. THE MUSCARINIC ANTAGONIST SCOPOLAMINE ATTENUATES CHLORPYRIFOS INDUCED HYPOTHERMIA IN THE DEVELOPING RAT.

    Science.gov (United States)

    Chlorpyrifos (CHP), an anticholinesterase organophosphate (OP) pesticide, induces acute hypothermia in adult and developing rats. Previously we demonstrated that thermoregulation in preweanling pups is markedly more sensitive to the neurotoxic effects of CHP than in adults. The c...

  11. An Overview on Human Umbilical Cord Blood Stem Cell-Based Alternative In Vitro Models for Developmental Neurotoxicity Assessment.

    Science.gov (United States)

    Singh, Abhishek Kumar; Kashyap, Mahendra Pratap

    2016-07-01

    The developing brain is found highly vulnerable towards the exposure of different environmental chemicals/drugs, even at concentrations, those are generally considered safe in mature brain. The brain development is a very complex phenomenon which involves several processes running in parallel such as cell proliferation, migration, differentiation, maturation and synaptogenesis. If any step of these cellular processes hampered due to exposure of any xenobiotic/drug, there is almost no chance of recovery which could finally result in a life-long disability. Therefore, the developmental neurotoxicity (DNT) assessment of newly discovered drugs/molecules is a very serious concern among the neurologists. Animal-based DNT models have their own limitations such as ethical concerns and lower sensitivity with less predictive values in humans. Furthermore, non-availability of human foetal brain tissues/cells makes job more difficult to understand about mechanisms involve in DNT in human beings. Although, the use of cell culture have been proven as a powerful tool for DNT assessment, but many in vitro models are currently utilizing genetically unstable cell lines. The interpretation of data generated using such terminally differentiated cells is hard to extrapolate with in vivo situations. However, human umbilical cord blood stem cells (hUCBSCs) have been proposed as an excellent tool for alternative DNT testing because neuronal development from undifferentiated state could exactly mimic the original pattern of neuronal development in foetus when hUCBSCs differentiated into neuronal cells. Additionally, less ethical concern, easy availability and high plasticity make them an attractive source for establishing in vitro model of DNT assessment. In this review, we are focusing towards recent advancements on hUCBSCs-based in vitro model to understand DNTs. PMID:26041658

  12. TARGETING OF NEUROTROPHIC FACTORS, THEIR RECEPTORS, AND SIGNALING PATHWAYS IN THE DEVELOPMENTAL NEUROTOXICITY OF ORGANOPHOSPHATES IN VIVO AND IN VITRO

    OpenAIRE

    Slotkin, Theodore A.; Seidler, Frederic J; Fumagalli, Fabio

    2008-01-01

    Neurotrophic factors control neural cell differentiation and assembly of neural circuits. We previously showed that organophosphate pesticides differentially regulate members of the fibroblast growth factor (fgf) gene family. We administered chlorpyrifos and diazinon to neonatal rats on postnatal days 1–4 at doses devoid of systemic toxicity or growth impairment, and spanning the threshold for barely-detectable cholinesterase inhibition. We evaluated the impact on gene families for different ...

  13. Neonatal chlorpyrifos exposure induces loss of dopaminergic neurons in young adult rats

    International Nuclear Information System (INIS)

    Increasing epidemiological and toxicological evidence suggests that pesticides and other environmental exposures may be associated with the development of Parkinson’s disease (PD). Chlorpyrifos (CPF) is a widely used organophosphorous pesticide with developmental neurotoxicity. Its neurotoxicity, notably on the monoamine system, suggests that exposure of CPF may induce dopaminergic neuronal injury. We investigated whether neonatal exposure to CPF contributes to initiation and progression of dopaminergic neurotoxicity and explored the possible underlying mechanisms. The newborn rats were administrated 5 mg/kg CPF subcutaneously from postnatal day (PND) 11 to PND 14 daily. The effect of CPF on dopaminergic neurons, microglia, astrocyte, nuclear factor-κB (NF-κB) p. 65 and p. 38 mitogen-activated protein kinase (MAPK) signaling pathways was analyzed in the substantia nigra of rats at 12 h, 24 h, 72 h, 16 d and 46 d after exposure. CPF-treated rats exhibited significant reduction of dopaminergic neurons at 16 d and 46 d after exposure, and a significant increase in the expression of microglia and astrocytes in the substantia nigra after CPF exposure. Intense activation of NF-κB p. 65 and p. 38 MAPK inflammatory signaling pathways was observed. Our findings indicate that neonatal exposure to CPF may induce long-term dopaminergic neuronal damage in the substantia nigra mediated by the activation of inflammatory response via NF-κB p. 65 and p. 38 MAPK pathways in the nigrostriatal system

  14. Developmental neurotoxicity of chlorpyrifos at subthreshold dose of overt systemic toxicity%亚中毒阈剂量毒死蜱的神经发育毒性

    Institute of Scientific and Technical Information of China (English)

    邓礼; 赵玲玲

    2006-01-01

    毒死蟀(chlorpyrifos,CPF),又名乐斯本或氯吡硫磷,是一种高效广谱、中等毒性的有机磷酸酯类农药。随着人们环保意识逐渐加强,剧毒农药的逐步淘汰及禁用,其现已成为其他国家使用最普遍的农药之一,也将成为我国广泛应用的农药之一。近来研究发现CPF特别是亚中毒阈剂量CPF对中枢神经系统发育具有毒性作用,本文就亚中毒阈剂量毒死蟀的神经发育毒性作一简要综述。

  15. Bioconcentration and transfer of the organophorous flame retardant 1,3-dichloro-2-propyl phosphate causes thyroid endocrine disruption and developmental neurotoxicity in zebrafish larvae.

    Science.gov (United States)

    Wang, Qiangwei; Lai, Nelson Lok-Shun; Wang, Xianfeng; Guo, Yongyong; Lam, Paul Kwan-Sing; Lam, James Chung-Wah; Zhou, Bingsheng

    2015-04-21

    Organophosphate flame retardants are emerging environmental contaminants, although knowledge of their health risks is limited. Here, thyroid hormone homeostasis and neuronal development was studied in the progeny of adult zebrafish exposed to tris(1,3-dichloro-2-propyl) phosphate (TDCPP). Adult zebrafish were exposed to TDCPP (0, 4, 20, and 100 μg/L) for 3 months. Increased generation of reactive oxygen species and reduced survival rates was observed in exposed F1 larvae. We also observed a significant decrease in plasma thyroxine and 3,5,3'-triiodothyronine levels in F0 females and F1 eggs/larvae. The mRNA and protein expression of factors associated with neuronal development (e.g., α1-tubulin, myelin basic protein, and synapsin IIa) were significantly downregulated in exposed F1 larvae, as was the level of the neurotransmitters dopamine, serotonin, gamma amino butyric acid, and histamine. Larval locomotion was significantly decreased in exposed fish, but there was no effect on acetylcholinesterase activity. Bioconcentration of TDCPP was observed in F0 fish. TDCPP was also detected in F1 eggs following parental exposure, indicating maternal transfer of this compound. This study uniquely shows that TDCPP can be transferred to the offspring of exposed adults, causing thyroid endocrine disruption and developmental neurotoxicity. PMID:25826601

  16. Developmental Neurotoxic Effects of Percutaneous Drug Delivery: Behavior and Neurochemical Studies in C57BL/6 Mice.

    Science.gov (United States)

    Wu, Huali; Feng, Junyi; Lv, Wenting; Huang, Qiaoling; Fu, Mengsi; Cai, Minxuan; He, Qiangqiang; Shang, Jing

    2016-01-01

    Dermatosis often as a chronic disease requires effective long-term treatment; a comprehensive evaluation of mental health of dermatology drug does not receive enough attention. An interaction between dermatology and psychiatry has been increasingly described. Substantial evidence has accumulated that psychological stress can be associated with pigmentation, endocrine and immune systems in skin to create the optimal responses against pathogens and other physicochemical stressors to maintain or restore internal homeostasis. Additionally, given the common ectodermal origin shared by the brain and skin, we are interested in assessing how disruption of skin systems (pigmentary, endocrine and immune systems) may play a key role in brain functions. Thus, we selected three drugs (hydroquinone, isotretinoin, tacrolimus) with percutaneous excessive delivery to respectively intervene in these systems and then evaluate the potential neurotoxic effects. Firstly, C57BL/6 mice were administrated a dermal dose of hydroquinone cream, isotretinoin gel or tacrolimus ointment (2%, 0.05%, 0.1%, respectively, 5 times of the clinical dose). Behavioral testing was performed and levels of proteins were measured in the hippocampus. It was found that mice treated with isotretinoin or tacrolimus, presented a lower activity in open-field test and obvious depressive-like behavior in tail suspension test. Besides, they damaged cytoarchitecture, reduced the level of 5-HT-5-HT1A/1B system and increased the expression of apoptosis-related proteins in the hippocampus. To enable sensitive monitoring the dose-response characteristics of the consecutive neurobehavioral disorders, mice received gradient concentrations of hydroquinone (2%, 4%, 6%). Subsequently, hydroquinone induced behavioral disorders and hippocampal dysfunction in a dose-dependent response. When doses were high as 6% which was 3 times higher than 2% dose, then 100% of mice exhibited depressive-like behavior. Certainly, 6% hydroquinone

  17. Developmental neurotoxicity of Propylthiouracil (PTU) in rats: Relationship between transient hypothyroxinemia during development and long-lasting behavioural and functional changes

    International Nuclear Information System (INIS)

    Markedly lowered thyroid hormone levels during development may influence a child's behaviour, intellect, and auditory function. Recent studies, indicating that even small changes in the mother's thyroid hormone status early in pregnancy may cause adverse effects on her child, have lead to increased concern for thyroid hormone disrupting chemicals in the environment. The overall aim of the study was therefore to provide a detailed knowledge on the relationship between thyroid hormone levels during development and long-lasting effects on behaviour and hearing. Groups of 16-17 pregnant rats (HanTac:WH) were dosed with PTU (0, 0.8, 1.6 or 2.4 mg/kg/day) from gestation day (GD) 7 to postnatal day (PND) 17, and the physiological and behavioural development of rat offspring was assessed. Both dams and pups in the higher dose groups had markedly decreased thyroxine (T4) levels during the dosing period, and the weight and histology of the thyroid glands were severely affected. PTU exposure caused motor activity levels to decrease on PND 14, and to increase on PND 23 and in adulthood. In the adult offspring, learning and memory was impaired in the two highest dose groups when tested in the radial arm maze, and auditory function was impaired in the highest dose group. Generally, the results showed that PTU-induced hypothyroxinemia influenced the developing rat brain, and that all effects on behaviour and loss of hearing in the adult offspring were significantly correlated to reductions in T4 during development. This supports the hypothesis that decreased T4 may be a relevant predictor for long-lasting developmental neurotoxicity

  18. Progress in alternatives for developmental neurotoxicity testing on animals%神经发育毒性动物实验替代方法研究进展

    Institute of Scientific and Technical Information of China (English)

    张楠楠; 梁锦锋; 宋淑亮; 吉爱国

    2012-01-01

    Industrial chemical exposure during early embryonic development can cause fetal brain damage, such as neurodevelopmental disorders and sub-clinical brain dysfunction. Although the safety evaluation of chemicals based on animal toxicity tests is relatively reliable, many of these tests are expensive in terms of scientific resources and time and do not fit in with the current trend of reduced use of laboratory animals. As a result, alternatives for developmental neurotoxicity(DNT) testing attract more attention. The paper reviews establishment and improvement of alternatives, including sensitivity, low consumption and adaptability to high throughput screening, advantages, and current applications of cell-based models and non-mammalian models and finally the challenges existing. The alternatives will not completely replace a paradigm that involves in vivo testing in mammals, but they will be of great value in prioritizing chemicals and in identifying mechanisms of DNT.%胚胎早期暴露于某些工业化学物中,即使是很小剂量,也可导致胚胎脑损伤,引起神经发育性疾病和亚临床脑功能不良.虽然化学物基于动物毒性实验的安全性评价是较可靠的,但这种方法耗时长、成本高,而且不符合目前减少实验动物使用的趋势,因此神经发育毒性(DNT)实验的替代模型逐步引起重视.为建立和完善快速、经济又可高通量筛选受试物的替代方法,本文分别介绍了体外细胞模型和非哺乳动物模型的优势、现阶段应用以及所面临的挑战.这些替代法虽不能完全取代包括哺乳动物在内的体内实验,但它们在区分化合物和识别DNT机制方面将发挥巨大的作用.

  19. Toxicogenomic profiling in maternal and fetal rodent brains following gestational exposure to chlorpyrifos

    International Nuclear Information System (INIS)

    Considering the wide variety of effects that have been reported to occur in the developmental neurotoxicity of chlorpyrifos (CP) and the lack of consensus on their dependence of brain acetylcholinesterase (AChE) activity inhibition, we applied microarray technology to explore dose-dependent alterations in transcriptional response in the fetal and maternal C57BL/6 mouse brain after daily gestational exposure (days 6 to 17) to CP (2, 4, 10, 12 or 15 mg/kg, sc). We identified significantly altered genes across doses and assessed for overrepresentation of Gene Ontology (GO) biological processes and KEGG pathways. We further clustered genes based on their expression profiles across doses and repeated the GO/pathways analysis for each cluster. The dose-effect relationship of CP on gene expression, both at the gene and pathway levels was non-monotonic and not necessarily related to brain AChE inhibition. The largest impact was observed in the 10 mg/kg dose group which was also the LOAEL for brain AChE inhibition. In the maternal brain, lower doses (4 mg/kg) influenced GO categories and pathways such as cell adhesion, behavior, lipid metabolism, long-term potentiation, nervous system development, neurogenesis, synaptic transmission. In the fetal brain, lower doses (2 and/or 4 mg/kg) significantly altered cell division, translation, transmission of nerve impulse, chromatin modification, long-term potentiation. In addition, some genes involved in nervous system development and signaling were shown to be specifically influenced by these lower CP doses. Our approach was sensitive and reflected the diversity of responses known to be disrupted by CP and highlighted possible additional consequences of CP neurotoxicity, such as disturbance of the ubiquitin proteasome system.

  20. Chlorpyrifos exerts opposing effects on axonal and dendritic growth in primary neuronal cultures

    International Nuclear Information System (INIS)

    Evidence that children are widely exposed to organophosphorus pesticides (OPs) and that OPs cause developmental neurotoxicity in animal models raises significant concerns about the risks these compounds pose to the developing human nervous system. Critical to assessing this risk is identifying specific neurodevelopmental events targeted by OPs. Observations that OPs alter brain morphometry in developing rodents and inhibit neurite outgrowth in neural cell lines suggest that OPs perturb neuronal morphogenesis. However, an important question yet to be answered is whether the dysmorphogenic effect of OPs reflects perturbation of axonal or dendritic growth. We addressed this question by quantifying axonal and dendritic growth in primary cultures of embryonic rat sympathetic neurons derived from superior cervical ganglia (SCG) following in vitro exposure to chlorpyrifos (CPF) or its metabolites CPF-oxon (CPFO) and trichloropyridinol (TCP). Axon outgrowth was significantly inhibited by CPF or CPFO, but not TCP, at concentrations ≥0.001 μM or 0.001 nM, respectively. In contrast, all three compounds enhanced BMP-induced dendritic growth. Acetylcholinesterase was inhibited only by the highest concentrations of CPF (≥1 μM) and CPFO (≥1 nM); TCP had no effect on this parameter. In summary, these compounds perturb neuronal morphogenesis via opposing effects on axonal and dendritic growth, and both effects are independent of acetylcholinesterase inhibition. These findings have important implications for current risk assessment practices of using acetylcholinesterase inhibition as a biomarker of OP neurotoxicity and suggest that OPs may disrupt normal patterns of neuronal connectivity in the developing nervous system

  1. Chlorpyrifos induces oxidative stress in oligodendrocyte progenitor cells

    International Nuclear Information System (INIS)

    There are increasing concerns regarding the relative safety of chlorpyrifos (CPF) to various facets of the environment. Although published works suggest that CPF is relatively safe in adult animals, recent evidence indicates that juveniles, both animals and humans, may be more sensitive to CPF toxicity than adults. In young animals, CPF is neurotoxic and mechanistically interferes with cellular replication and cellular differentiation, which culminates in the alteration of synaptic neurotransmission in neurons. However, the effects of CPF on glial cells are not fully elucidated. Here we report that chlorpyrifos is toxic to oligodendrocyte progenitors. In addition, CPF produced dose-dependent increases in 2',7'-dichlorodihydrofluorescein diacetate (H2DCF-DA) and dihydroethidium (DHE) fluorescence intensities relative to the vehicle control. Moreover, CPF toxicity is associated with nuclear condensation and elevation of caspase 3/7 activity and Heme oxygenase-1 mRNA expression. Pan-caspase inhibitor QVDOPh and cholinergic receptor antagonists' atropine and mecamylamine failed to protect oligodendrocyte progenitors from CPF-induced injury. Finally, glutathione (GSH) depletion enhanced CPF-induced toxicity whereas nitric oxide synthetase inhibitor L-NAME partially protected progenitors and the non-specific antioxidant vitamin E (alpha-tocopherol) completely spared cells from injury. Collectively, this data suggests that CPF induced toxicity is independent of cholinergic stimulation and is most likely caused by the induction of oxidative stress.

  2. Developmental Neurotoxicity of 3,3',4,4'-Tetrachloroazobenzene with Thyroxine Deficit: Sensitivity of Glia and Dentate Granule Neurons in the Absence of Behavioral Changes

    Directory of Open Access Journals (Sweden)

    G. Jean Harry

    2014-09-01

    Full Text Available Thyroid hormones (TH regulate biological processes implicated in neurodevelopmental disorders and can be altered with environmental exposures. Developmental exposure to the dioxin-like compound, 3,3',4,4'-tetrachloroazobenzene (TCAB, induced a dose response deficit in serum T4 levels with no change in 3,5,3'-triiodothyronine or thyroid stimulating hormone. Female Sprague-Dawley rats were orally gavaged (corn oil, 0.1, 1.0, or 10 mg TCAB/kg/day two weeks prior to cohabitation until post-partum day 3 and male offspring from post-natal day (PND 4–21. At PND21, the high dose showed a deficit in body weight gain. Conventional neuropathology detected no neuronal death, myelin disruption, or gliosis. Astrocytes displayed thinner and less complex processes at 1.0 and 10 mg/kg/day. At 10 mg/kg/day, microglia showed less complex processes, unbiased stereology detected fewer hippocampal CA1 pyramidal neurons and dentate granule neurons (GC and Golgi staining of the cerebellum showed diminished Purkinje cell dendritic arbor. At PND150, normal maturation of GC number and Purkinje cell branching area was not observed in the 1.0 mg/kg/day dose group with a diminished number and branching suggestive of effects initiated during developmental exposure. No effects were observed on post-weaning behavioral assessments in control, 0.1 and 1.0 mg/kg/day dose groups. The demonstrated sensitivity of hippocampal neurons and glial cells to TCAB and T4 deficit raises support for considering additional anatomical features of brain development in future DNT evaluations.

  3. Cyanobacterial xenobiotics as evaluated by a Caenorhabditis elegans neurotoxicity screening test.

    Science.gov (United States)

    Ju, Jingjuan; Saul, Nadine; Kochan, Cindy; Putschew, Anke; Pu, Yuepu; Yin, Lihong; Steinberg, Christian E W

    2014-05-01

    In fresh waters cyanobacterial blooms can produce a variety of toxins, such as microcystin variants (MCs) and anatoxin-a (ANA). ANA is a well-known neurotoxin, whereas MCs are hepatotoxic and, to a lesser degree, also neurotoxic. Neurotoxicity applies especially to invertebrates lacking livers. Current standardized neurotoxicity screening methods use rats or mice. However, in order to minimize vertebrate animal experiments as well as experimental time and effort, many investigators have proposed the nematode Caenorhabditis elegans as an appropriate invertebrate model. Therefore, four known neurotoxic compounds (positive compounds: chlorpyrifos, abamectin, atropine, and acrylamide) were chosen to verify the expected impacts on autonomic (locomotion, feeding, defecation) and sensory (thermal, chemical, and mechanical sensory perception) functions in C. elegans. This study is another step towards successfully establishing C. elegans as an alternative neurotoxicity model. By using this protocol, anatoxin-a adversely affected locomotive behavior and pharyngeal pumping frequency and, most strongly, chemotactic and thermotactic behavior, whereas MC-LR impacted locomotion, pumping, and mechanical behavior, but not chemical sensory behavior. Environmental samples can also be screened in this simple and fast way for neurotoxic characteristics. The filtrate of a Microcystis aeruginosa culture, known for its hepatotoxicity, also displayed mild neurotoxicity (modulated short-term thermotaxis). These results show the suitability of this assay for environmental cyanotoxin-containing samples. PMID:24776722

  4. Cyanobacterial Xenobiotics as Evaluated by a Caenorhabditis elegans Neurotoxicity Screening Test

    Directory of Open Access Journals (Sweden)

    Jingjuan Ju

    2014-04-01

    Full Text Available In fresh waters cyanobacterial blooms can produce a variety of toxins, such as microcystin variants (MCs and anatoxin-a (ANA. ANA is a well-known neurotoxin, whereas MCs are hepatotoxic and, to a lesser degree, also neurotoxic. Neurotoxicity applies especially to invertebrates lacking livers. Current standardized neurotoxicity screening methods use rats or mice. However, in order to minimize vertebrate animal experiments as well as experimental time and effort, many investigators have proposed the nematode Caenorhabditis elegans as an appropriate invertebrate model. Therefore, four known neurotoxic compounds (positive compounds: chlorpyrifos, abamectin, atropine, and acrylamide were chosen to verify the expected impacts on autonomic (locomotion, feeding, defecation and sensory (thermal, chemical, and mechanical sensory perception functions in C. elegans. This study is another step towards successfully establishing C. elegans as an alternative neurotoxicity model. By using this protocol, anatoxin-a adversely affected locomotive behavior and pharyngeal pumping frequency and, most strongly, chemotactic and thermotactic behavior, whereas MC-LR impacted locomotion, pumping, and mechanical behavior, but not chemical sensory behavior. Environmental samples can also be screened in this simple and fast way for neurotoxic characteristics. The filtrate of a Microcystis aeruginosa culture, known for its hepatotoxicity, also displayed mild neurotoxicity (modulated short-term thermotaxis. These results show the suitability of this assay for environmental cyanotoxin-containing samples.

  5. Fingerprinting of neurotoxic compounds using a mouse embryonic stem cell dual luminescence reporter assay

    OpenAIRE

    Colaianna, Marilena; Ilmjarv, Sten; Peterson, Hedi; Kern, Ilse; Sgroi, Stéphanie; Baquie, Mathurin; Pallocca, Giorgia; Bosgra, Sieto; Sachinidis, Agapios; Hengstler, Jan G.; Leist, Marcel; Krause, Karl-Heinz

    2016-01-01

    Identification of neurotoxic drugs and environmental chemicals is an important challenge. However, only few tools to address this topic are available. The aim of this study was to develop a neurotoxicity/developmental neurotoxicity (DNT) test system, using the pluripotent mouse embryonic stem cell line CGR8 (ESCs). The test system uses ESCs at two differentiation stages: undifferentiated ESCs and ESC-derived neurons. Under each condition, concentration-response curves were obtained for three ...

  6. Organophosphorus insecticides chlorpyrifos and diazinon and oxidative stress in neuronal cells in a genetic model of glutathione deficiency

    International Nuclear Information System (INIS)

    Over the past several years evidence has been accumulating from in vivo animal studies, observations in humans, and in vitro studies, that organophosphorus (OP) insecticides may induce oxidative stress. Such effects may contribute to some of the toxic manifestations of OPs, particularly upon chronic or developmental exposures. The aim of this study was to investigate the role of oxidative stress in the neurotoxicity of two commonly used OPs, chlorpyrifos (CPF) and diazinon (DZ), their oxygen analogs (CPO and DZO), and their 'inactive' metabolites (TCP and IMP), in neuronal cells from a genetic model of glutathione deficiency. Cerebellar granule neurons from wild type mice (Gclm +/+) and mice lacking the modifier subunit of glutamate cysteine ligase (Gclm -/-), the first and limiting step in the synthesis of glutathione (GSH), were utilized. The latter display very low levels of GSH and are more susceptible to the toxicity of agents that increase oxidative stress. CPO and DZO were the most cytotoxic compounds, followed by CPF and DZ, while TCP and IMP displayed lower toxicity. Toxicity was significantly higher (10- to 25-fold) in neurons from Gclm (-/-) mice, and was antagonized by various antioxidants. Depletion of GSH from Gclm (+/+) neurons significantly increased their sensitivity to OP toxicity. OPs increased intracellular levels of reactive oxygen species and lipid peroxidation and in both cases the effects were greater in neurons from Gclm (-/-) mice. OPs did not alter intracellular levels of GSH, but significantly increased those of oxidized glutathione (GSSG). Cytotoxicity was not antagonized by cholinergic antagonists, but was decreased by the calcium chelator BAPTA-AM. These studies indicate that cytotoxicity of OPs involves generation of reactive oxygen species and is modulated by intracellular GSH, and suggest that it may involve disturbances in intracellular homeostasis of calcium

  7. Prenatal chlorpyrifos exposure alters motor behavior and ultrasonic vocalization in cd-1 mouse pups

    OpenAIRE

    Calamandrei Gemma; Scattoni Maria; Ricceri Laura; Venerosi Aldina

    2009-01-01

    Abstract Background Chlorpyrifos (CPF) is a non-persistent organophosphate (OP) largely used as pesticide. Studies from animal models indicate that CPF is a developmental neurotoxicant able to target immature central nervous system at dose levels well below the threshold of systemic toxicity. So far, few data are available on the potential short- and long-term adverse effects in children deriving from low-level exposures during prenatal life and infancy. Methods Late gestational exposure [ges...

  8. DEVELOPMENTAL NEUROTOXICITY OF INHALED METHANOL IN RATS

    Science.gov (United States)

    Dr. Weiss and his colleagues conducted a controlled series of experiments in which they exposed pregnant rats and their newborn offspring to 4,500 parts per million (ppm) methanol by inhalation, and then submitted them to tests of behavioral function. Exposure to 4,500...

  9. Developmental Neurotoxicity Testing Using In vitro Approaches

    OpenAIRE

    Högberg, Helena

    2009-01-01

    There is a great concern about children’s health as the developing brain in foetuses and children is much more vulnerable to injury caused by different classes of chemicals than the adult brain. This vulnerability is partly due to the fact that the adult brain is well protected against chemicals by the blood brain barrier (BBB) and children have increased absorption rates and diminished ability to detoxify many exogenous compounds, in comparison to that of adults. Moreover, the development of...

  10. Chlorpyrifos, chlorpyrifos-oxon, and diisopropylfluorophosphate inhibit kinesin-dependent microtubule motility

    International Nuclear Information System (INIS)

    Diisopropylfluorophosphate, originally developed as a chemical warfare agent, is structurally similar to nerve agents, and chlorpyrifos has extensive worldwide use as an agricultural pesticide. While inhibition of cholinesterases underlies the acute toxicity of these organophosphates, we previously reported impaired axonal transport in the sciatic nerves from rats treated chronically with subthreshold doses of chlorpyrifos. Those data indicate that chlorpyrifos (and/or its active metabolite, chlorpyrifos-oxon) might directly affect the function of kinesin and/or microtubules-the principal proteins that mediate anterograde axonal transport. The current report describes in vitro assays to assess the concentration-dependent effects of chlorpyrifos (0-10 μM), chlorpyrifos-oxon (0-10 μM), and diisopropylfluorophosphate (0-0.59 nM) on kinesin-dependent microtubule motility. Preincubating bovine brain microtubules with the organophosphates did not alter kinesin-mediated microtubule motility. In contrast, preincubation of bovine brain kinesin with diisopropylfluorophosphate, chlorpyrifos, or chlorpyrifos-oxon produced a concentration-dependent increase in the number of locomoting microtubules that detached from the kinesin-coated glass cover slip. Our data suggest that the organophosphates-chlorpyrifos-oxon, chlorpyrifos, and diisopropylfluorophosphate-directly affect kinesin, thereby disrupting kinesin-dependent transport on microtubules. Kinesin-dependent movement of vesicles, organelles, and other cellular components along microtubules is fundamental to the organization of all eukaryotic cells, especially in neurons where organelles and proteins synthesized in the cell body must move down long axons to pre-synaptic sites in nerve terminals. We postulate that disruption of kinesin-dependent intracellular transport could account for some of the long-term effects of organophosphates on the peripheral and central nervous system

  11. Dose-related gene expression changes in forebrain following acute, low-level chlorpyrifos exposure in neonatal rats

    International Nuclear Information System (INIS)

    Chlorpyrifos (CPF) is a widely used organophosphorus insecticide (OP) and putative developmental neurotoxicant in humans. The acute toxicity of CPF is elicited by acetylcholinesterase (AChE) inhibition. We characterized dose-related (0.1, 0.5, 1 and 2 mg/kg) gene expression profiles and changes in cell signaling pathways 24 h following acute CPF exposure in 7-day-old rats. Microarray experiments indicated that approximately 9% of the 44,000 genes were differentially expressed following either one of the four CPF dosages studied (546, 505, 522, and 3,066 genes with 0.1, 0.5, 1.0 and 2.0 mg/kg CPF). Genes were grouped according to dose-related expression patterns using K-means clustering while gene networks and canonical pathways were evaluated using Ingenuity Pathway Analysis (registered) . Twenty clusters were identified and differential expression of selected genes was verified by RT-PCR. The four largest clusters (each containing from 276 to 905 genes) constituted over 50% of all differentially expressed genes and exhibited up-regulation following exposure to the highest dosage (2 mg/kg CPF). The total number of gene networks affected by CPF also rose sharply with the highest dosage of CPF (18, 16, 18 and 50 with 0.1, 0.5, 1 and 2 mg/kg CPF). Forebrain cholinesterase (ChE) activity was significantly reduced (26%) only in the highest dosage group. Based on magnitude of dose-related changes in differentially expressed genes, relative numbers of gene clusters and signaling networks affected, and forebrain ChE inhibition only at 2 mg/kg CPF, we focused subsequent analyses on this treatment group. Six canonical pathways were identified that were significantly affected by 2 mg/kg CPF (MAPK, oxidative stress, NFΚB, mitochondrial dysfunction, arylhydrocarbon receptor and adrenergic receptor signaling). Evaluation of different cellular functions of the differentially expressed genes suggested changes related to olfactory receptors, cell adhesion/migration, synapse

  12. Is the PentaBDE replacement, tris (1,3-dichloro-2-propyl) phosphate (TDCPP), a developmental neurotoxicant? Studies in PC12 cells

    Energy Technology Data Exchange (ETDEWEB)

    Dishaw, Laura V. [Nicholas School of the Environment, Duke University, Durham, NC 27708 (United States); Powers, Christina M. [Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710 (United States); Ryde, Ian T.; Roberts, Simon C. [Nicholas School of the Environment, Duke University, Durham, NC 27708 (United States); Seidler, Frederic J.; Slotkin, Theodore A. [Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710 (United States); Stapleton, Heather M., E-mail: heather.stapleton@duke.edu [Nicholas School of the Environment, Duke University, Durham, NC 27708 (United States)

    2011-11-15

    Organophosphate flame retardants (OPFRs) are used as replacements for the commercial PentaBDE mixture that was phased out in 2004. OPFRs are ubiquitous in the environment and detected at high concentrations in residential dust, suggesting widespread human exposure. OPFRs are structurally similar to neurotoxic organophosphate pesticides, raising concerns about exposure and toxicity to humans. This study evaluated the neurotoxicity of tris (1,3-dichloro-2-propyl) phosphate (TDCPP) compared to the organophosphate pesticide, chlorpyrifos (CPF), a known developmental neurotoxicant. We also tested the neurotoxicity of three structurally similar OPFRs, tris (2-chloroethyl) phosphate (TCEP), tris (1-chloropropyl) phosphate (TCPP), and tris (2,3-dibromopropyl) phosphate (TDBPP), and 2,2 Prime ,4,4 Prime -tetrabromodiphenyl ether (BDE-47), a major component of PentaBDE. Using undifferentiated and differentiating PC12 cells, changes in DNA synthesis, oxidative stress, differentiation into dopaminergic or cholinergic neurophenotypes, cell number, cell growth and neurite growth were assessed. TDCPP displayed concentration-dependent neurotoxicity, often with effects equivalent to or greater than equimolar concentrations of CPF. TDCPP inhibited DNA synthesis, and all OPFRs decreased cell number and altered neurodifferentiation. Although TDCPP elevated oxidative stress, there was no adverse effect on cell viability or growth. TDCPP and TDBPP promoted differentiation into both neuronal phenotypes, while TCEP and TCPP promoted only the cholinergic phenotype. BDE-47 had no effect on cell number, cell growth or neurite growth. Our results demonstrate that different OPFRs show divergent effects on neurodifferentiation, suggesting the participation of multiple mechanisms of toxicity. Additionally, these data suggest that OPFRs may affect neurodevelopment with similar or greater potency compared to known and suspected neurotoxicants.

  13. GSK3β in Ethanol Neurotoxicity

    Science.gov (United States)

    2016-01-01

    Alcohol consumption during pregnancy is a significant public health problem and may result in a wide range of adverse outcomes for the child. The developing central nervous system (CNS) is particularly susceptible to ethanol toxicity. Children with fetal alcohol spectrum disorders (FASD) have a variety of cognitive, behavioral, and neurological impairments. FASD currently represents the leading cause of mental retardation in North America ahead of Down syndrome and cerebral palsy. Ethanol exposure during development causes multiple abnormalities in the brain such as permanent loss of neurons, ectopic neurons, and alterations in synaptogenesis and myelinogenesis. These alcohol-induced structural alterations in the developing brain underlie many of the behavioral deficits observed in FASD. The cellular and molecular mechanisms of ethanol neurotoxicity, however, remain unclear. Ethanol elicits cellular stresses, including oxidative stress and endoplasmic reticulum stress. Glycogen synthase kinase 3β (GSK3β), a multifunctional serine/ threonine kinase, responds to various cellular stresses. GSK3β is particularly abundant in the developing CNS, and regulates diverse developmental events in the immature brain, such as neurogenesis and neuronal differentiation, migration, and survival. Available evidence indicates that the activity of GSK3β in the CNS is affected by ethanol. GSK3β inhibition provides protection against ethanol neurotoxicity, whereas high GSK3β activity/expression sensitizes neuronal cells to ethanol-induced damages. It appears that GSK3β is a converging signaling point that mediates some of ethanol’s neurotoxic effects. PMID:19507062

  14. Chlorpyrifos and chlorpyrifos-oxon inhibit axonal growth by interfering with the morphogenic activity of acetylcholinesterase

    International Nuclear Information System (INIS)

    A primary role of acetylcholinesterase (AChE) is regulation of cholinergic neurotransmission by hydrolysis of synaptic acetylcholine. In the developing nervous system, however, AChE also functions as a morphogenic factor to promote axonal growth. This raises the question of whether organophosphorus pesticides (OPs) that are known to selectively bind to and inactivate the enzymatic function of AChE also interfere with its morphogenic function to perturb axonogenesis. To test this hypothesis, we exposed primary cultures of sensory neurons derived from embryonic rat dorsal root ganglia (DRG) to chlorpyrifos (CPF) or its oxon metabolite (CPFO). Both OPs significantly decreased axonal length at concentrations that had no effect on cell viability, protein synthesis or the enzymatic activity of AChE. Comparative analyses of the effects of CPF and CPFO on axonal growth in DRG neurons cultured from AChE nullizygous (AChE-/-) versus wild type (AChE+/+) mice indicated that while these OPs inhibited axonal growth in AChE+/+ DRG neurons, they had no effect on axonal growth in AChE-/- DRG neurons. However, transfection of AChE-/- DRG neurons with cDNA encoding full-length AChE restored the wild type response to the axon inhibitory effects of OPs. These data indicate that inhibition of axonal growth by OPs requires AChE, but the mechanism involves inhibition of the morphogenic rather than enzymatic activity of AChE. These findings suggest a novel mechanism for explaining not only the functional deficits observed in children and animals following developmental exposure to OPs, but also the increased vulnerability of the developing nervous system to OPs

  15. Effect of In Vivo Nicotine Exposure on Chlorpyrifos Pharmacokinetics and Pharmacodynamics in Rats

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sookwang; Poet, Torka S.; Smith, Jordan N.; Busby-Hjerpe, Andrea L.; Timchalk, Charles

    2010-03-30

    Routine use of tobacco products may modify physiological and metabolic functions, including drug metabolizing enzymes, which may impact the pharmacokinetics of environmental contaminants. Chlorpyrifos is an organophosphorus (OP) insecticide that is bioactivated to chlorpyrifos-oxon, and manifests its neurotoxicity by inhibiting acetylcholinesterase (AChE). The objective of this study was to evaluate the impact of repeated nicotine exposure on the pharmacokinetics of chlorpyrifos (CPF) and its major metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) in blood and urine and also to determine the impact on cholinesterase (ChE) activity in plasma and brain. Animals were exposed to 7-daily doses of either 1 mg nicotine/kg or saline (sc), and to either a single oral dose of 35 mg CPF/kg or a repeated dose of 5 mg CPF/kg/day for 7 days. Groups of rats were then sacrificed at multiple time-points after receiving the last dose of CPF. Repeated nicotine and CPF exposures resulted in enhanced metabolism of CPF to TCPy, as evidenced by increases in the measured TCPy concentration and AUC in blood. However, there was no significant difference in the amount of TCPy (free or total) excreted in the urine. The extent of brain acetylcholinesterase (AChE) inhibition was reduced due to nicotine co-exposure consistent with an increase in CYP450-mediated dearylation (detoxification) versus desulfuration. It was of interest to note that the impact of nicotine co-exposure was experimentally observed only after repeated CPF doses. Physiologically based pharmacokinetic model simulations of CPF-oxon concentrations in blood and brain were predicted to be lower in nicotine treated groups, which were simulated by increasing the dearylation Vmax based upon previously conducted in vitro metabolism studies. These results were consistent with the experimental data. The current study demonstrated that repeated nicotine exposure could alter CPF metabolism in vivo, further modulating brain AChE inhibition.

  16. DOSE-RELATED GENE EXPRESSION CHANGES IN FOREBRAIN FOLLOWING ACUTE, LOW-LEVEL CHLORPYRIFOS EXPOSURE IN NEONATAL RATS

    OpenAIRE

    Ray, Anamika; Liu, Jing; Ayoubi, Patricia; Pope, Carey

    2010-01-01

    Chlorpyrifos (CPF) is a widely used organophosphorus insecticide (OP) and putative developmental neurotoxicant in humans. The acute toxicity of CPF is elicited by acetylcholinesterase (AChE) inhibition. We characterized dose-related (0.1, 0.5, 1 and 2 mg/kg) gene expression profiles and changes in cell signaling pathways 24 hr following acute CPF exposure in seven day-old rats. Microarray experiments indicated that approximately 9% of the 44,000 genes were differentially expressed following e...

  17. Chlorpyrifos chronic toxicity in broilers and effect of vitamin C

    OpenAIRE

    A.M. Kammon; Singh, J; Banga, H. S.; Sodhi, S.; Brar, R. S.; Nagra, N.S.

    2011-01-01

    An experiment was conducted to study chlorpyrifos chronic toxicity in broilers and the protective effect of vitamin C. Oral administration of 0.8 mg/kg body weight (bw) (1/50 LD50) chlorpyrifos (Radar®), produced mild diarrhea and gross lesions comprised of paleness, flaccid consistency and slightly enlargement of liver. Histopathologically, chlorpyrifos produced degenerative changes in various organs. Oral administration of 100 mg/kg bw vitamin C partially ameliorated the degenerative change...

  18. Human exposure and risk from indoor use of chlorpyrifos.

    OpenAIRE

    Gibson, J.E.; Peterson, R K; Shurdut, B A

    1998-01-01

    The toxicity, exposure, and risk from chlorpyrifos are briefly discussed in juxtaposition with two recent articles in Environmental Health Perspectives concerning potential exposures to children. In studies conducted according to EPA guidelines, chlorpyrifos has been shown not to be mutagenic, carcinogenic, or teratogenic, nor does it adversely affect reproduction. Chlorpyrifos toxicity does not occur in the absence of significant cholinesterase inhibition. If exposures are less than those th...

  19. Role of desensitization and subunit expression for kainate receptor-mediated neurotoxicity in murine neocortical cultures

    DEFF Research Database (Denmark)

    Jensen, J B; Schousboe, A; Pickering, D S;

    1999-01-01

    The neurotoxic actions of kainate and domoate were studied in cultured murine neocortical neurons at various days in culture and found to be developmentally regulated involving three components of neurotoxicity: (1) toxicity via indirect activation of N-methyl-D-aspartate (NMDA) receptors, (2) to...... produced by kainate receptors in mature cultures. Examining the subunit expression of the kainate receptor subunits GluR6/7 and KA2 did, however, not reveal any major change during development of the cultures....

  20. Degradation of chlorpyrifos in Turkish soil

    International Nuclear Information System (INIS)

    Surface (0-5 cm) and subsurface (40-60 cm) soils were collected from a field not treated with pesticide and 100 g triplicate samples of the soils were weighed in glass biometer incubation flasks. Other than the control samples, each soil was uniformly treated with 14C-chlorpyrifos to yield a soil concentration of 2 μg/g of chlorpyrifos and 7.4 x 104 Bq (2 μCi) of radioactivity and incubated for 97 days at 25 deg. C. The KOH traps were sampled for the evolved 14CO2. Soil samples were taken periodically, and the solvent was extracted and subjected to supercritical methanol extraction. The extracts were analysed by thin layer chromatography. The total 14C and the unextractable soil bound 14C residues were determined by combustion in a biological oxidizer. From the surface and subsurface soils, up to 40.6 and 42.6%, respectively, of the applied radiocarbon evolved as 14CO2 during the 97 day incubation period. The chlorpyrifos half-lives in the surface and subsurface soils were calculated as 7.2 and 4.3 days, respectively. The major products of degradation, in order of decreasing concentration, were 14CO2, chlorpyrifos, soil bound 14C residues and TCP, regardless of soil depth, and the percentages found were 28.9, 13.1, 11.7 and 3.8 of the applied 14C for the surface soils and 22.1, 12.4, 11.4 and 4.8 of the applied 14C for the subsurface soils, respectively. (author). 5 refs, 3 figs, 1 tab

  1. Chlorpyrifos toxicity in fish: A Review

    OpenAIRE

    Nobonita Deb; Suchismita Das

    2013-01-01

    Chlorpyrifos (CPF) is a broad spectrum organophosphate insecticide (OP) which is commercially used for more than a decade to control insect pest. It is the second largest selling OP and found to be more toxic to fish than organochlorine compounds. CPF passes via air drift or surface runoff into natural waters, where it is accumulated in different organisms living in water, especially in fish, thus making it vulnerable to several prominent effects. CPF is known to inhibit acetylcholinesterase,...

  2. Autophagy is a protective response to ethanol neurotoxicity

    OpenAIRE

    Chen, Gang; Ke, Zunji; Xu, Mei; Liao, Mingjun; Wang, Xin; Qi, Yuanlin; Zhang,Tao; Frank, Jacqueline A.; Bower, Kimberly A.; Shi, Xianglin; Luo, Jia

    2012-01-01

    Ethanol is a neuroteratogen and neurodegeneration is the most devastating consequence of developmental exposure to ethanol. The mechanisms underlying ethanol-induced neurodegeneration are complex. Ethanol exposure produces reactive oxygen species (ROS) which cause oxidative stress in the brain. We hypothesized that ethanol would activate autophagy to alleviate oxidative stress and neurotoxicity. Our results indicated that ethanol increased the level of the autophagic marker Map1lc3-II (LC3-II...

  3. Hypoxic Preconditioning Alleviates Ethanol Neurotoxicity: the Involvement of Autophagy

    OpenAIRE

    Wang, Haiping; Bower, Kimberly A.; Frank, Jacqueline A.; Xu, Mei; Luo, Jia

    2013-01-01

    Ethanol is a neuroteratogen and neurodegeneration is the most devastating consequence of developmental exposure to ethanol. A sublethal preconditioning has been proposed as a neuroprotective strategy against several central nervous system (CNS) neurodegenerative diseases. We have recently demonstrated that autophagy is a protective response to alleviate ethanol toxicity. A modest hypoxic preconditioning (1% oxygen) did not cause neurotoxicity but induced autophagy (Tzeng et al., 2010). We the...

  4. Chemotherapy-Related Neurotoxicity.

    Science.gov (United States)

    Taillibert, Sophie; Le Rhun, Emilie; Chamberlain, Marc C

    2016-09-01

    Chemotherapy may have detrimental effects on either the central or peripheral nervous system. Central nervous system neurotoxicity resulting from chemotherapy manifests as a wide range of clinical syndromes including acute, subacute, and chronic encephalopathies, posterior reversible encephalopathy, acute cerebellar dysfunction, chronic cognitive impairment, myelopathy, meningitis, and neurovascular syndromes. These clinical entities vary by causative agent, degree of severity, evolution, and timing of occurrence. In the peripheral nervous system, chemotherapy-induced peripheral neuropathy (CIPN) and myopathy are the two main complications of chemotherapy. CIPN is the most common complication, and the majority manifest as a dose-dependent length-dependent sensory axonopathy. In severe cases of CIPN, the dose of chemotherapy is reduced, the administration delayed, or the treatment discontinued. Few treatments are available for CIPN and based on meta-analysis, duloxetine is the preferred symptomatic treatment. Myopathy due to corticosteroid use is the most frequent cause of muscle disorders in patients with cancer. PMID:27443648

  5. Reversible Lithium Neurotoxicity: Review of the Literature

    OpenAIRE

    Netto, Ivan; Phutane, Vivek H

    2012-01-01

    Objective: Lithium neurotoxicity may be reversible or irreversible. Reversible lithium neurotoxicity has been defined as cases of lithium neurotoxicity in which patients recovered without any permanent neurologic sequelae, even after 2 months of an episode of lithium toxicity. Cases of reversible lithium neurotoxicity differ in clinical presentation from those of irreversible lithium neurotoxicity and have important implications in clinical practice. This review aims to study the clinical pre...

  6. 40 CFR 180.342 - Chlorpyrifos; tolerances for residues.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Chlorpyrifos; tolerances for residues...) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.342 Chlorpyrifos; tolerances for residues. (a) General. (1) Tolerances are established...

  7. Irradiation degradation of chlorpyrifos in water solution and asparagus

    International Nuclear Information System (INIS)

    In order to seek an effective technique to degrade chlorpyrifos residue, chlorpyrifos water solution and asparagus containing chlorpyrifos as testing materials were irradiated by 60Co γ-rays and their degradation rate were determined and compared. The results show the degradation rate in water-solution increases with irradiation dose in the range of 0 and 12 kGy, and it reached 95.5% at 4 kGy. The degradation rate of chlorpyrifos in asparagus is low and comes to the maximum of 30.0% when the dose is 8 kGy. Further study indicates that vitamin C, violaquercitrin and total sugar inhibit the irradiation degradation of chlorpyrifos in asparagus. (authors)

  8. The In Vivo Quantitation of Diazinon, Chlorpyrifos and their Major Metabolites in Rat Blood for the Refinement of a Physiologically-based Pharmacokinetic/pharmacodynamic Models.

    Energy Technology Data Exchange (ETDEWEB)

    Busby, Andrea L.; Kousba, Ahmed A.; Timchalk, Chuck

    2004-12-01

    Chlorpyrifos (CPF) and diazinon (DZN) are inhibitors of acetylcholinesterase due to the effects of their active oxon metabolites. The inhibition of acetylcholinesterase results in a buildup of acetylcholine within the nerve synapses leading to a variety of neurotoxic effects (Mileson et al., 1998). These effects are most clearly seen following acute high dose exposures but they can also be observed in lower dose chronic cases as well. Chlorpyrifos is the active ingredient in commonly used organophosphorous (OP) insecticides like DURSBAN and LORSBAN (Timchalk et. al, 2002). Chlorpyrifos and diazinon are used to eliminate pests in agricultural applications like cotton and fruit crops. Every year globally there are approximately 3 million cases of organophosphate poisoning reported resulting in 200,000 deaths (Haywood et al., 2000). The public is exposed to these chemicals on a regular basis at chronic low levels from food and water contamination, dermal contact and inhalation. The United States National Health and Nutrition Examination Survey indicated that of approximately 3,600 persons from all 64 NHANES III locations, 70% tested positive for TCP in urine, suggesting exposure to chlorpyrifos (NHANES III, 1994). The chemical structures of chlorpyrifos, diazinon, and their major metabolites trichlorpyridinol (TCP), and isopropyl-methyl-hydroxypyrimidine (IMHP) are shown in Figure 1. The parent compounds, CPF and DZN, are metabolized to their potent inhibiting oxon forms via a desulfuration reaction initiated by cytochrome P450 (CYP)(Poet et al., 2003; Amitai et al., 1998). Competing with the formation of oxon is the detoxification metabolism of CPF to TCP and DZN to IMHP via a dearylation reaction utilizing the same enzymes. A-esterase (PON1) and other B-esterases also contribute to the production of TCP and IMHP through the metabolism of CPF-oxon and DZN-oxon, respectively (Poet et al., 2003; Ma et al., 1994). The ratio between the toxification

  9. Modifying Effects of Vitamin E on Chlorpyrifos Toxicity in Atlantic Salmon

    OpenAIRE

    Olsvik, Pål A; Berntssen, Marc H. G.; Liv Søfteland

    2015-01-01

    The aim of this study was to elucidate how vitamin E (alpha tocopherol) may ameliorate the toxicity of the pesticide chlorpyrifos in Atlantic salmon. Freshly isolated hepatocytes were exposed to vitamin E, chlorpyrifos or a combination of vitamin E and chlorpyrifos (all 100 μM). Transcriptomics (RNA-seq) and metabolomics were used to screen for effects of vitamin E and chlorpyrifos. By introducing vitamin E, the number of upregulated transcripts induced by chlorpyrifos exposure was reduced fr...

  10. Chlorpyrifos toxicity in fish: A Review

    Directory of Open Access Journals (Sweden)

    Nobonita Deb

    2013-04-01

    Full Text Available Chlorpyrifos (CPF is a broad spectrum organophosphate insecticide (OP which is commercially used for more than a decade to control insect pest. It is the second largest selling OP and found to be more toxic to fish than organochlorine compounds. CPF passes via air drift or surface runoff into natural waters, where it is accumulated in different organisms living in water, especially in fish, thus making it vulnerable to several prominent effects. CPF is known to inhibit acetylcholinesterase, cause behavioural, neurological, oxidative, histopathological, endocrine and other effects at low doses. The present study reviews the various effects of CPF in fish

  11. Neurotoxic Shellfish Poisoning

    Directory of Open Access Journals (Sweden)

    Roberta Hammond

    2008-07-01

    Full Text Available Neurotoxic shellfish poisoning (NSP is caused by consumption of molluscan shellfish contaminated with brevetoxins primarily produced by the dinoflagellate, Karenia brevis. Blooms of K. brevis, called Florida red tide, occur frequently along the Gulf of Mexico. Many shellfish beds in the US (and other nations are routinely monitored for presence of K. brevis and other brevetoxin-producing organisms. As a result, few NSP cases are reported annually from the US. However, infrequent larger outbreaks do occur. Cases are usually associated with recreationally-harvested shellfish collected during or post red tide blooms. Brevetoxins are neurotoxins which activate voltage-sensitive sodium channels causing sodium influx and nerve membrane depolarization. No fatalities have been reported, but hospitalizations occur. NSP involves a cluster of gastrointestinal and neurological symptoms: nausea and vomiting, paresthesias of the mouth, lips and tongue as well as distal paresthesias, ataxia, slurred speech and dizziness. Neurological symptoms can progress to partial paralysis; respiratory distress has been recorded. Recent research has implicated new species of harmful algal bloom organisms which produce brevetoxins, identified additional marine species which accumulate brevetoxins, and has provided additional information on the toxicity and analysis of brevetoxins. A review of the known epidemiology and recommendations for improved NSP prevention are presented.

  12. Phthalates and neurotoxic effects on hippocampal network plasticity.

    Science.gov (United States)

    Holahan, Matthew R; Smith, Catherine A

    2015-05-01

    Phthalates are synthetically derived chemicals used as plasticizers in a variety of common household products. They are not chemically bound to plastic polymers and over time, easily migrate out of these products and into the environment. Experimental investigations evaluating the biological impact of phthalate exposure on developing organisms are critical given that estimates of phthalate exposure are considerably higher in infants and children compared to adults. Extensive growth and re-organization of neurocircuitry occurs during development leaving the brain highly susceptible to environmental insults. This review summarizes the effects of phthalate exposure on brain structure and function with particular emphasis on developmental aspects of hippocampal structural and functional plasticity. In general, it appears that widespread disruptions in hippocampal functional and structural plasticity occur following developmental (pre-, peri- and post-natal) exposure to phthalates. Whether these changes occur as a direct neurotoxic effect of phthalates or an indirect effect through disruption of endogenous endocrine functions is not fully understood. Comprehensive investigations that simultaneously assess the neurodevelopmental, neurotoxic, neuroendocrine and behavioral correlates of phthalate exposure are needed to provide an opportunity to thoroughly evaluate the neurotoxic potential of phthalates throughout the lifespan. PMID:25749100

  13. Protein tyrosine adduct in humans self-poisoned by chlorpyrifos

    International Nuclear Information System (INIS)

    Studies of human cases of self-inflicted poisoning suggest that chlorpyrifos oxon reacts not only with acetylcholinesterase and butyrylcholinesterase but also with other blood proteins. A favored candidate is albumin because in vitro and animal studies have identified tyrosine 411 of albumin as a site covalently modified by organophosphorus poisons. Our goal was to test this proposal in humans by determining whether plasma from humans poisoned by chlorpyrifos has adducts on tyrosine. Plasma samples from 5 self-poisoned humans were drawn at various time intervals after ingestion of chlorpyrifos for a total of 34 samples. All 34 samples were analyzed for plasma levels of chlorpyrifos and chlorpyrifos oxon (CPO) as a function of time post-ingestion. Eleven samples were analyzed for the presence of diethoxyphosphorylated tyrosine by mass spectrometry. Six samples yielded diethoxyphosphorylated tyrosine in pronase digests. Blood collected as late as 5 days after chlorpyrifos ingestion was positive for CPO-tyrosine, consistent with the 20-day half-life of albumin. High plasma CPO levels did not predict detectable levels of CPO-tyrosine. CPO-tyrosine was identified in pralidoxime treated patients as well as in patients not treated with pralidoxime, indicating that pralidoxime does not reverse CPO binding to tyrosine in humans. Plasma butyrylcholinesterase was a more sensitive biomarker of exposure than adducts on tyrosine. In conclusion, chlorpyrifos oxon makes a stable covalent adduct on the tyrosine residue of blood proteins in humans who ingested chlorpyrifos. - Highlights: • Chlorpyrifos-poisoned patients have adducts on protein tyrosine. • Diethoxyphosphate-tyrosine does not lose an alkyl group. • Proteins in addition to AChE and BChE are modified by organophosphates

  14. Protein tyrosine adduct in humans self-poisoned by chlorpyrifos

    Energy Technology Data Exchange (ETDEWEB)

    Li, Bin, E-mail: binli@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States); Eyer, Peter, E-mail: peter.eyer@lrz.uni-muenchen.de [Walther-Straub-Institut Für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München, 80336 München (Germany); Eddleston, Michael, E-mail: M.Eddleston@ed.ac.uk [Clinical Pharmacology Unit, University of Edinburgh, Edinburgh (United Kingdom); Jiang, Wei, E-mail: wjiang@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States); Schopfer, Lawrence M., E-mail: lmschopf@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States); Lockridge, Oksana, E-mail: olockrid@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States)

    2013-06-15

    Studies of human cases of self-inflicted poisoning suggest that chlorpyrifos oxon reacts not only with acetylcholinesterase and butyrylcholinesterase but also with other blood proteins. A favored candidate is albumin because in vitro and animal studies have identified tyrosine 411 of albumin as a site covalently modified by organophosphorus poisons. Our goal was to test this proposal in humans by determining whether plasma from humans poisoned by chlorpyrifos has adducts on tyrosine. Plasma samples from 5 self-poisoned humans were drawn at various time intervals after ingestion of chlorpyrifos for a total of 34 samples. All 34 samples were analyzed for plasma levels of chlorpyrifos and chlorpyrifos oxon (CPO) as a function of time post-ingestion. Eleven samples were analyzed for the presence of diethoxyphosphorylated tyrosine by mass spectrometry. Six samples yielded diethoxyphosphorylated tyrosine in pronase digests. Blood collected as late as 5 days after chlorpyrifos ingestion was positive for CPO-tyrosine, consistent with the 20-day half-life of albumin. High plasma CPO levels did not predict detectable levels of CPO-tyrosine. CPO-tyrosine was identified in pralidoxime treated patients as well as in patients not treated with pralidoxime, indicating that pralidoxime does not reverse CPO binding to tyrosine in humans. Plasma butyrylcholinesterase was a more sensitive biomarker of exposure than adducts on tyrosine. In conclusion, chlorpyrifos oxon makes a stable covalent adduct on the tyrosine residue of blood proteins in humans who ingested chlorpyrifos. - Highlights: • Chlorpyrifos-poisoned patients have adducts on protein tyrosine. • Diethoxyphosphate-tyrosine does not lose an alkyl group. • Proteins in addition to AChE and BChE are modified by organophosphates.

  15. VARIATIONS IN THE NEUROTOXIC POTENCY OF TRIMETHYLTIN

    Science.gov (United States)

    Seven samples of trimethyltin obtained from three commercial sources were evaluated for neurotoxic potency in the rat. Hippocampus weight, histology and assays of the astrocyte protein, glial fibrillary acidic protein, were used as indices of neurotoxicity. A single administratio...

  16. Effects of Nicotine Exposure on In Vitro Metabolism of Chlorpyrifos in Male Sprague-Dawley Rats

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sookwang; Busby, Andrea L.; Timchalk, Charles; Poet, Torka S.

    2009-01-30

    Chlorpyrifos (CPF) is a common organophosphate (OP) insecticide which is metabolized by CYP450s to the neurotoxic metabolite, chlorpyrifos-oxon (CPF-oxon) and a non-toxic metabolite, 3,5,6-trichloro-2-pyridinol (TCP). The objective of this study was to quantify the effect of repeated in vivo nicotine exposures on CPF in vitro metabolism and marker substrate activities in rats. Male Sprague-Dawley rats were dosed subcutaneously with 1 mg nicotine/kg/, for up to 10 days. Animals showed signs of cholinergic crisis after the initial nicotine doses, but exhibited adaptation after a couple days of treatment. Rats were sacrificed on selected days 4 or 24 hr after the last nicotine-treatment. While CYP450 reduced CO spectra were not different across the treatments, the single nicotine dose group showed a 2-fold increase in CYP2E1 marker substrate (p-nitrophenol) activity 24 hr after a single nicotine treatment compared to saline controls. Conversely, repeated nicotine treatments resulted in decreased EROD marker substrate activity 4 hr after the 7th day of treatment. CPF-oxon Vmax and Km did not show significant changes across the different nicotine treatment groups. The Vmax describing the metabolism of CPF to TCP was increased on all groups (days 1, 7, and 10) 24 hr after nicotine treatment but were unchanged 4 hr after nicotine treatment. Results of this in vitro study suggest that repeated nicotine exposure (i.e., from smoking) may result in altered metabolism of CPF. Future in vivo experiments based on these results will be conducted to ascertain the impact of in vivo nicotine exposures on CPF metabolism in rats.

  17. Development of the Artificial Antigens for the Organophosphorus Insecticide chlorpyrifos

    Institute of Scientific and Technical Information of China (English)

    ZHU Guo-nian; WU Gang; WU Hui-ming

    2004-01-01

    This study reported that the hapten of the organophosphorus insecticide chlorpyrifos,O,Odiethyl-O-[3,5-dichloro-6-(2-carboxyethyl)thio-2-pyridyl]phosphorothioate(named AR) was synthesized by using technical grade chlorpyrifos reacted with 3-marcapropanoic acid in hot alkaline solution.The hapten was conjugated to bovine serum albumin (BSA) with the modified active ester method to form artificial immune antigen.The ratio of AR:BSA was 39:1.The artificial coating antigen for chlorpyrifos was synthesized by conjugating AR to ovalbumin (OVA) with the mixed-anhydride method,and the ratio was 13:1.The anti-chlorpyrifos polyclonal antibodies were obtained by using the artificial immune antigen (AR-BSA) to immune in the rabbits.

  18. Chlorpyrifos chronic toxicity in broilers and effect of vitamin C

    Directory of Open Access Journals (Sweden)

    A.M. Kammon

    2011-02-01

    Full Text Available An experiment was conducted to study chlorpyrifos chronic toxicity in broilers and the protective effect of vitamin C. Oral administration of 0.8 mg/kg body weight (bw (1/50 LD50 chlorpyrifos (Radar®, produced mild diarrhea and gross lesions comprised of paleness, flaccid consistency and slightly enlargement of liver. Histopathologically, chlorpyrifos produced degenerative changes in various organs. Oral administration of 100 mg/kg bw vitamin C partially ameliorated the degenerative changes in kidney and heart. There was insignificant alteration in biochemical and haematological profiles. It is concluded that supplementation of vitamin C reduced the severity of lesions induced by chronic chlorpyrifos toxicity in broilers.

  19. Assessment of Health Risk in Human Populations Due to Chlorpyrifos

    OpenAIRE

    Jeevani Marasinghe; Qiming Yu; Des Connell

    2014-01-01

    A wide ranging survey was carried out of the available data from ten different countries on human exposure to chlorpyrifos, in many different occupational and nonoccupational settings. Low levels of chlorpyrifos residues were found to be widely distributed in the global human population, but most of these do not constitute a public health risk, as evaluated using the U.S. Environmental Protection Agency (USEPA) Guidelines. For example, the general populations in USA, Germany and Italy had det...

  20. What is microglia neurotoxicity (Not)?

    DEFF Research Database (Denmark)

    Biber, Knut; Owens, Trevor; Boddeke, Erik

    2014-01-01

    and vulnerable organ like the brain should host numerous potential killers, we here review the concept of microglia neurotoxicity. On one hand it is discussed that most of our understanding about how microglia kill neurons is based on in vitro experiments or correlative staining studies that suffer...

  1. Mobility Studies of (14)C-Chlorpyrifos in Malaysian Oil Palm Soils.

    Science.gov (United States)

    Halimah, Muhamad; Ismail, B Sahid; Nashriyah, Mat; Maznah, Zainol

    2016-01-01

    The mobility of (14)C-chlorpyrifos using soil TLC was investigated in this study. It was found that chlorpyrifos was not mobile in clay, clay loam and peat soil. The mobility of (14)C-chlorpyrifos and non-labelled chlorpyrifos was also tested with silica gel TLC using three types of developing solvent hexane (100%), hexane:ethyl acetate (95:5, v/v); and hexane:ethyl acetate (98:2, v/v). The study showed that both the (14)C-labelled and non-labelled chlorpyrifos have the same Retardation Factor (Rf) for different developing solvent systems. From the soil column study on mobility of chlorpyrifos, it was observed that no chlorpyrifos residue was found below 5 cm depth in three types of soil at simulation rainfall of 20, 50 and 100 mm. Therefore, the soil column and TLC studies have shown similar findings in the mobility of chlorpyrifos. PMID:26546229

  2. Biodegradation of Chlorpyrifos by Pseudomonas Resinovarans Strain AST2.2 Isolated from Enriched Cultures.

    Directory of Open Access Journals (Sweden)

    Anish Sharma*,

    2016-04-01

    Full Text Available A bacterial strain AST2.2 with chlorpyrifos degrading ability was isolated by enrichment technique from apple orchard soil with previous history of chlorpyrifos use. Based on the morphological, biochemical tests and 16S rRNA sequence analysis, AST2.2 strain was identified as Pseudomonas resinovarans. The strain AST2.2 utilized chlorpyrifos as the sole source of carbon and energy. This strain exhibited growth upto 400mg/l concentration of chlorpyrifos and exhibited high extracellular organophosphorus hydrolase (OPH activity. Gas chromatography-flame ionization detector (GC-FID studies revealed that Pseudomonas resinovarans AST2.2 degraded 43.90 % of chlorpyrifos (400 mg/l within 96 hrs. Intermediates of chlorpyrifos degradation were identified using GC-MS. This strain have potential to degrade chlorpyrifos and thus can be used for bioremediation and ecological restoration of sites contaminated with chlorpyrifos.

  3. Complete genome sequence of a novel chlorpyrifos degrading bacterium, Cupriavidus nantongensis X1.

    Science.gov (United States)

    Fang, Lian-Cheng; Chen, Yi-Fei; Zhou, Yan-Long; Wang, Dao-Sheng; Sun, Le-Ni; Tang, Xin-Yun; Hua, Ri-Mao

    2016-06-10

    Cupriavidus nantongensis X1 is a chlorpyrifos degrading bacterium, which was isolated from sludge collected at the drain outlet of a chlorpyrifos manufacture plant. It is the first time to report the complete genome sequence of C. nantongensis species, which has been reported as a novel species of Cupriavidus genus. It could provide further pathway information in chlorpyrifos degradation. PMID:27063140

  4. Taxane-Induced Peripheral Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Roser Velasco

    2015-04-01

    Full Text Available Taxane-derived agents are chemotherapy drugs widely employed in cancer treatment. Among them, paclitaxel and docetaxel are most commonly administered, but newer formulations are being investigated. Taxane antineoplastic activity is mainly based on the ability of the drugs to promote microtubule assembly, leading to mitotic arrest and apoptosis in cancer cells. Peripheral neurotoxicity is the major non-hematological adverse effect of taxane, often manifested as painful neuropathy experienced during treatment, and it is sometimes irreversible. Unfortunately, taxane-induced neurotoxicity is an uncertainty prior to the initiation of treatment. The present review aims to dissect current knowledge on real incidence, underlying pathophysiology, clinical features and predisposing factors related with the development of taxane-induced neuropathy.

  5. Adsorption and desorption of chlorpyrifos to soils and sediments.

    Science.gov (United States)

    Gebremariam, Seyoum Yami; Beutel, Marc W; Yonge, David R; Flury, Markus; Harsh, James B

    2012-01-01

    Chlorpyrifos, one of the most widely used insecticides, has been detected in air, rain, marine sediments, surface waters, drinking water wells, and solid and liquid dietary samples collected from urban and rural areas. Its metabolite, TCP, has also been widely detected in urinary samples collected from people of various age groups. With a goal of elucidating the factors that control the environmental contamination, impact, persistence, and ecotoxicity of chlorpyrifos, we examine, in this review, the peer-reviewed literature relating to chlorpyrifos adsorption and desorption behavior in various solid-phase matrices. Adsorption tends to reduce chlorpyrifos mobility, but adsorption to erodible particulates, dissolved organic matter, or mobile inorganic colloids enhances its mobility. Adsorption to suspended sediments and particulates constitutes a major off-site migration route for chlorpyrifos to surface waters, wherein it poses a potential danger to aquatic organisms. Adsorption increases the persistence of chlorpyrifos in the environment by reducing its avail- ability to a wide range of dissipative and degradative forces, whereas the effect of adsorption on its ecotoxicity is dependent upon the route of exposure. Chlorpyrifos adsorbs to soils, aquatic sediments, organic matter, and clay minerals to differing degrees. Its adsorption strongly correlates with organic carbon con- tent of the soils and sediments. A comprehensive review of studies that relied on the batch equilibrium technique yields mean and median Kd values for chlorpyrifos of 271 and 116 L/kg for soils, and 385 and 403 L/kg for aquatic sediments. Chlorpyrifos adsorption coefficients spanned two orders of magnitude in soils. Normalizing the partition coefficient to organic content failed to substantially reduce variability to commonly acceptable level of variation. Mean and median values for chlorpyrifos partition coefficients normalized to organic carbon, K, were 8,163 and 7,227 L/kg for soils and 13

  6. Chlorpyrifos-induced toxicity in Duttaphrynus melanostictus (Schneider 1799) larvae.

    Science.gov (United States)

    Wijesinghe, M R; Bandara, M G D K; Ratnasooriya, W D; Lakraj, G P

    2011-05-01

    This study investigates the effects of continuous exposure to a widely used organophosphate pesticide, chlorpyrifos, on survival, growth, development, and activity of larvae of the Asian common toad, Duttaphrynus melanostictus Schneider 1799. Larvae were continuously exposed to six different concentrations (1-1,500 μg l(-1)) of commercial-grade chlorpyrifos for 14 days and monitored for 1 additional week. Chlorpyrifos at ≥1,000 μg l(-1) caused significantly high and dose-dependent mortality, and the weekly LC50(7 day-21 day) values ranged from 3,003 to 462 μg l(-1). Larvae surviving exposure to ≥500 μg l(-1) chlorpyrifos showed significant growth impairment, delays in metamorphosis, and decreased swimming activity. Tail abnormalities were the most common morphologic deformity at concentrations of 1,000 and 1,500 μg l(-1) chlorpyrifos. The findings of the present study highlight the need to recognize the potential risk that agrochemicals pose to amphibians inhabiting agricultural landscapes in Sri Lanka and other Asian countries. PMID:20669016

  7. Multiple mechanisms of PCB neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter, D.O.; Stoner, C.T.; Lawrence, D.A. [Univ. of New York, Albany, NY (United States)] [and others

    1996-12-31

    Polychlorinated biphenyls (PCBs) have been implicated in cancer, but many of the symptoms in humans exposed to PCBs are related to the nervous system and behavior. We demonstrated three different direct mechanisms whereby PCBs are neurotoxic in rats. By using flow cytometry, we demonstrated that the orthosubstituted PCB congener 2,4,4{prime}, but neither TCDD nor the coplanar PCB congener 3,4,5,3{prime},4{prime}, causes rapid death of cerebellar granule cells. The ortho-substituted congener 2,4,4{prime} reduced long-term potentiation, an indicator of cognitive potential, in hippocampal brain slices, but a similar effect was observed for the coplanar congener 3,4,3{prime},4{prime}, indicating that this effect may be caused by both ortho- and coplanar congeners by mechanisms presumably not mediated via the Ah receptor. It was previously shown that some ortho-substituted PCB congeners cause a reduction in levels of the neurotransmitter dopamine, and we present in vitro and in vivo evidence that this is due to reduction of synthesis of dopamine via inhibition of the enzyme tyrosine hydroxylase. Thus, PCBs have a variety of mechanisms of primary neurotoxicity, and neurotoxicity is a characteristic of ortho-substituted, non-dioxin-like congeners as well as some coplanar congeners. The relative contribution of each of these mechanisms to the loss of cognitive function in humans exposed to PCBs remains to be determined. 42 refs., 3 figs., 1 tab.

  8. The enigma of fetal alcohol neurotoxicity.

    Science.gov (United States)

    Olney, John W; Wozniak, David F; Farber, Nuri B; Jevtovic-Todorovic, Vesna; Bittigau, Petra; Ikonomidou, Chrysanthy

    2002-01-01

    The neurotoxic effects of ethanol on the human fetal brain (fetal alcohol syndrome, FAS) have been recognized for three decades, but the underlying mechanisms have remained elusive. Recently, we discovered that a single episode of ethanol intoxication lasting for several hours can trigger a massive wave of apoptotic neurodegeneration in the developing rat or mouse brain. The window of vulnerability coincides with the developmental period of synaptogenesis, also known as the brain growth-spurt period, which in rodents is a postnatal event, but in humans extends from the sixth month of gestation to several years after birth. We propose that the N-methyl-D-aspartate (NMDA) antagonist and gamma-aminobutyric (GABA)mimetic properties of ethanol are responsible for its apoptogenic action, in that we have found that other drugs that block NMDA glutamate receptors or mimic GABA at GABA(A) receptors also trigger apoptotic neurodegeneration in the developing brain. Our findings have clinical significance, not only because they can explain the reduced brain mass and neurobehavioral disturbances associated with the human FAS, but because many agents in the human environment, other than ethanol, have NMDA antagonist or GABAmimetic properties. Such agents include drugs that may be abused by pregnant mothers [phencyclidine (angel dust), ketamine (Special K), nitrous oxide (laughing gas), barbiturates, benzodiazepines], and many medicinals used in obstetric and pediatric neurology (anticonvulsants), and anesthesiology (all general anesthetics are either NMDA antagonists or GABAmimetics). PMID:12108574

  9. Trace elements as paradigms of developmental neurotoxicants

    DEFF Research Database (Denmark)

    Grandjean, Philippe; Herz, Katherine T

    2015-01-01

    Trace elements have contributed unique insights into developmental neurotoxicity and serve as paradigms for such adverse effects. Many trace elements are retained in the body for long periods and can be easily measured to assess exposure by inexpensive analytical methods that became available sev...

  10. Examining the joint toxicity of chlorpyrifos and atrazine in the aquatic species: Lepomis macrochirus, Pimephales promelas and Chironomus tentans

    Energy Technology Data Exchange (ETDEWEB)

    Tyler Mehler, W.; Schuler, Lance J. [Fisheries and Illinois Aquaculture Center and Department of Zoology, Southern Illinois University at Carbondale, Carbondale, IL 62901-6511 (United States); Lydy, Michael J. [Fisheries and Illinois Aquaculture Center and Department of Zoology, Southern Illinois University at Carbondale, Carbondale, IL 62901-6511 (United States)], E-mail: mlydy@siu.edu

    2008-03-15

    The joint toxicity of chlorpyrifos and atrazine was compared to that of chlorpyrifos alone to discern any greater than additive response using both acute toxicity testing and whole-body residue analysis. In addition, acetylcholinesterase (AChE) inhibition and biotransformation were investigated to evaluate the toxic mode of action of chlorpyrifos in the presence of atrazine. The joint toxicity of atrazine and chlorpyrifos exhibited no significant difference in Lepomis macrochirus compared to chlorpyrifos alone; while studies performed with Pimephales promelas and Chironomus tentans, did show significant differences. AChE activity and biotransformation showed no significant differences between the joint toxicity of atrazine and chlorpyrifos and that of chlorpyrifos alone. From the data collected, the combination of atrazine and chlorpyrifos pose little additional risk than that of chlorpyrifos alone to the tested fish species. - The joint toxicity between atrazine and chlorpyrifos caused greater than additive responses in invertebrates, but the interactions in vertebrates was less pronounced.

  11. Characterization of chlorpyrifos-induced apoptosis in placental cells

    International Nuclear Information System (INIS)

    The mechanism by which chlorpyrifos exerts its toxicity in fetal and perinatal animals has yet to be elucidated. Since the placenta is responsible for transport of nutrients and is a major supplier hormone to the fetus, exposure to xenobiotics that alter the function or viability of placenta cells could ostensibly alter the development of the fetus. In this study, JAR cells were used to determine if CPF and the metabolites 3,5,6-trichloro-2-pyridinol (TCP) and chlorpyrifos-oxon (CPO) are toxic to the placenta. Our results indicate that chlorpyrifos (CPF), and its metabolite chlorpyrifos-oxon (CPO) caused a dose-dependent reduction in cellular viability with CPF being more toxic than its metabolites. Chlorpyrifos-induced toxicity was characterized by the loss of mitochondrial potential, the appearance of nuclear condensation and fragmentation, down-regulation of Bcl-2 as well as up-regulation of TNFα and FAS mRNA. Pharmacological inhibition of FAS, nicotinic and TNF-α receptors did not attenuate CPF-induced toxicity. Atropine exhibited minimal ability to reverse toxicity. Furthermore, signal transduction inhibitors PD98059, SP600125, LY294002 and U0126 failed to attenuate toxicity; however, SB202190 (inhibitor of p38α and p38ss MAPK) sensitized cells to CPF-induced toxicity. Pan-caspase inhibitor Q-VD-OPh produced a slight but significant reversal of CPF-induced toxicity indicating that the major caspase pathways are not integral to CPF-induced toxicity. Taken collectively, these results suggest that chlorpyrifos induces apoptosis in placental cells through pathways not dependent on FAS/TNF signaling, activation of caspases or inhibition of cholinesterase. In addition, our data further indicates that activation of p38 MAPK is integral to the protection cells against CPF-induced injury

  12. Characterization of Chlorpyrifos Induced Apoptosis in Placental Cells

    OpenAIRE

    Saulsbury, Marilyn D.; Heyliger, Simone O.; Wang, Kaiyu; Round, Dorothy

    2007-01-01

    The mechanism by which chlorpyrifos exerts its toxicity in fetal and perinatal animals has yet to be elucidated. Since the placenta is responsible for transport of nutrients and is a major supplier hormones to the fetus, exposure to xenobiotics that alter the function or viability of placenta cells could ostensibly alter the development of the fetus. In this study, JAR cells were used to determine if CPF and the metabolites 3,5,6-trichloro-2-pyridinol (TCP) and chlorpyrifos-oxon (CPO) are tox...

  13. Modeling of neural differentiation by using embryonic stem cells to detect developmental toxicants

    OpenAIRE

    Zimmer, Bastian

    2011-01-01

    Developmental disabilities and congenital malformations associated with neural development are increasing problems in western countries. More and more evidence emerges from human epidemiological studies that environmental chemicals as well as drug and food constituents contribute to such an increase. Unfortunately, developmental neurotoxicity is currently the least examined form of developmental toxicity. Less then 200 compounds worldwide, mostly pesticides, have been tested in vivo according...

  14. Screening for Developmental Neurotoxicants using In Vitro "Brain on a Chip" Cultures

    Science.gov (United States)

    Currently there are thousands of chemicals in the environment that have not been screened for their potential to cause developmental neurotoxicity (DNT). The use of microelectrode array (MEA) technology allows for simultaneous extracellular measurement of action potential (spike)...

  15. Effect of in vivo nicotine exposure on chlorpyrifos pharmacokinetics and pharmacodynamics in rats

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Soo Kwang; Poet, Torka S.; Smith, Jordan N.; Busby-Hjerpe, Andrea L.; Timchalk, Charles

    2010-03-30

    Chlorpyrifos (CPF) is one of the most studied and widely used broad spectrum organophosphorus (OP) insecticides. The neurotoxicity of CPF results from inhibition of cholinesterase (ChE) by its metabolite, chlorpyrifos-oxon (CPF-oxon), which subsequently leads to cholinergic hyperstimulation. The routine consumption of alcoholic beverages and tobacco products will modify a number of metabolic and physiological processes which may impact the metabolism and pharmacokinetics of other xenobiotics including pesticides. The objective of this study was to evaluate the influence of repeated ethanol and nicotine co-exposure on in vivo CPF pharmacokinetics and pharmacodynamics. The major CPF metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) in blood and urine along with changes in plasma and brain AChE activities were measured in male Sprague-Dawley (S-D) rats. Animals were repeatedly treated with either saline or ethanol (1 g/kg/day, po) and nicotine (1 mg/kg/day, sc) in addition to CPF (1 or 5 mg/kg/day, po) for 7 days. Rats were sacrificed at times from 1 to 24 hr post-last dosing of CPF. There were apparent differences in blood TCPy pharmacokinetics following ethanol and nicotine pretreatments in both CPF dose groups, which showed higher TCPy peak concentrations and increased blood TCPy AUC in ethanol and nicotine groups over CPF-only (~1.8- and 3.8-fold at 1 and 5 mg CPF doses, respectively). Brain acetylcholinesterase (AChE) activities from both ethanol and nicotine-treated groups showed substantially less inhibition following repeated 5 mg CPF/kg dosing compared to CPF-only controls (96 ± 13 and 66 ± 7% of naïve at 4 hr post-last CPF dosing, respectively). Inhibition of brain AChE activities was minimal in both 1 mg CPF/kg/day dosing groups, but a similar trend indicating less inhibition following ethanol/nicotine pretreatment was apparent. No differences were observed in plasma ChE activities due to the combined alcohol and nicotine treatments. In vitro, CPF

  16. Autophagy regulates chlorpyrifos-induced apoptosis in SH-SY5Y cells

    International Nuclear Information System (INIS)

    Recent studies have shown that up-regulation of autophagy may be a tractable therapeutic intervention for clearing disease-causing proteins, including α-synuclein, ubiquitin, and other misfolded or aggregated proteins in pesticide-induced neurodegeneration. In a previous study, we reported that chlorpyrifos (CPF)-induced mitochondria-dependent apoptosis is mediated through reactive oxygen species in SH-SY5Y cells. In this study, we explored a novel pharmacotherapeutic approach to prevent CPF neurotoxicity involving the regulation of autophagy. We investigated the modulation of CPF-induced apoptosis according to autophagy regulation. We found that CPF induced apoptosis in SH-SY5Y cells, as demonstrated by the activation of caspase-3 and nuclear condensation. In addition, we observed that cells treated with CPF underwent autophagic cell death by monitoring the expression of LC3-II and p62. Pretreatment with the autophagy inducer rapamycin significantly enhanced the cell viability of CPF-exposed cells, and the enhancement of cell viability was partially due to alleviation of CPF-induced apoptosis via a decrease in levels of cleaved caspase-3. Specifically, rapamycin pretreatment decreased Bax and increased Bcl-2 expression in mitochondria. In addition, rapamycin significantly decreased cytochrome c release in from mitochondria into the cytosol. However, pretreatment of cells with the autophagy inhibitor, 3-methyladenine (3MA), remarkably increased CPF toxicity in these cells; this with correlated with increased expression of Bax and decreased expression of Bcl-2 in mitochondria. Our results suggest that CPF-induced cytotoxicity is modified by autophagy regulation and that rapamycin protects against CPF-induced apoptosis by enhancing autophagy. Pharmacologic induction of autophagy by rapamycin may be a useful treatment strategy in neurodegenerative disorders. - Highlights: ► Chlorpyrifos (CPF) is cytotoxic to SH-SY5Y cells ► CPF-induced cytotoxicity is mediated by

  17. Autophagy regulates chlorpyrifos-induced apoptosis in SH-SY5Y cells

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jae Hyeon [Department of Pharmacology, College of Medicine, Hanyang University (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of); Lee, Jeong Eun [Department of Pharmacology, College of Medicine, Hanyang University (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Shin, In Chul [Department of Pharmacology, College of Medicine, Hanyang University (Korea, Republic of); Koh, Hyun Chul, E-mail: hckoh@hanyang.ac.kr [Department of Pharmacology, College of Medicine, Hanyang University (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of)

    2013-04-01

    Recent studies have shown that up-regulation of autophagy may be a tractable therapeutic intervention for clearing disease-causing proteins, including α-synuclein, ubiquitin, and other misfolded or aggregated proteins in pesticide-induced neurodegeneration. In a previous study, we reported that chlorpyrifos (CPF)-induced mitochondria-dependent apoptosis is mediated through reactive oxygen species in SH-SY5Y cells. In this study, we explored a novel pharmacotherapeutic approach to prevent CPF neurotoxicity involving the regulation of autophagy. We investigated the modulation of CPF-induced apoptosis according to autophagy regulation. We found that CPF induced apoptosis in SH-SY5Y cells, as demonstrated by the activation of caspase-3 and nuclear condensation. In addition, we observed that cells treated with CPF underwent autophagic cell death by monitoring the expression of LC3-II and p62. Pretreatment with the autophagy inducer rapamycin significantly enhanced the cell viability of CPF-exposed cells, and the enhancement of cell viability was partially due to alleviation of CPF-induced apoptosis via a decrease in levels of cleaved caspase-3. Specifically, rapamycin pretreatment decreased Bax and increased Bcl-2 expression in mitochondria. In addition, rapamycin significantly decreased cytochrome c release in from mitochondria into the cytosol. However, pretreatment of cells with the autophagy inhibitor, 3-methyladenine (3MA), remarkably increased CPF toxicity in these cells; this with correlated with increased expression of Bax and decreased expression of Bcl-2 in mitochondria. Our results suggest that CPF-induced cytotoxicity is modified by autophagy regulation and that rapamycin protects against CPF-induced apoptosis by enhancing autophagy. Pharmacologic induction of autophagy by rapamycin may be a useful treatment strategy in neurodegenerative disorders. - Highlights: ► Chlorpyrifos (CPF) is cytotoxic to SH-SY5Y cells ► CPF-induced cytotoxicity is mediated by

  18. Pharmacokinetic and pharmacodynamic interaction for a binary mixture of chlorpyrifos and diazinon in the rat

    International Nuclear Information System (INIS)

    Chlorpyrifos (CPF) and diazinon (DZN) are two commonly used organophosphorus (OP) insecticides and a potential exists for concurrent exposures. The primary neurotoxic effects from OP pesticide exposures result from the inhibition of acetylcholinesterase (AChE). The pharmacokinetic and pharmacodynamic impact of acute binary exposures of rats to CPF and DZN was evaluated in this study. Rats were orally administered CPF, DZN, or a CPF/DZN mixture (0, 15, 30, or 60 mg/kg) and blood (plasma and RBC), and brain were collected at 0, 3, 6, 12, and 24 h postdosing, urine was also collected at 24 h. Chlorpyrifos, DZN, and their respective metabolites, 3,5,6-trichloro-2-pyridinol (TCP) and 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMHP), were quantified in blood and/or urine and cholinesterase (ChE) inhibition was measured in brain, RBC, and plasma. Coexposure to CPF/DZN at the low dose of 15/15 mg/kg did not alter the pharmacokinetics of CPF, DZN, or their metabolites in blood. A high binary dose of 60/60 mg/kg increased the C max and AUC and decreased the clearance for both parent compounds, likely due to competition between CPF and DZN for CYP450 metabolism. At lower doses, most likely to be encountered in occupational or environmental exposures, the pharmacokinetics were linear. A dose-dependent inhibition of ChE was noted in tissues for both the single and coexposures, and the extent of inhibition was plasma > RBC ≥ brain. The overall relative potency for ChE inhibition was CPF/DZN > CPF > DZN. A comparison of the ChE response at the low binary dose (15/15 mg/kg), where there were no apparent pharmacokinetic interactions, suggested that the overall ChE response was additive. These experiments represent important data concerning the potential pharmacokinetic and pharmacodynamic interactions for pesticide mixtures and will provide needed insight for assessing the potential cumulative risk associated with occupational or environmental exposures to these insecticides

  19. Developmental neurotoxicity after toluene inhalation exposure in rats

    DEFF Research Database (Denmark)

    Hass, Ulla; Lund, Søren Peter; Hougaard, Karin Sørig; Simonsen, Leif

    1999-01-01

    increased motor activity in the open field was registered in the exposed offspring. Impaired cognitive function was revealed in the exposed female offspring at the age of 3.5 months, i.e., they used more time to locate the hidden platform in the Morris water maze after platform relocation. The difference...

  20. 40 CFR 799.9630 - TSCA developmental neurotoxicity.

    Science.gov (United States)

    2010-07-01

    ... be removed, weighed, and immersion-fixed in an appropriate aldehyde fixative. The remaining animals... and semiquantitative analysis as well as simple morphometrics. (A) Fixation and processing of tissue... immersion fixed in an appropriate aldehyde fixative. The brains must be postfixed and processed according...

  1. 40 CFR 795.250 - Developmental neurotoxicity screen.

    Science.gov (United States)

    2010-07-01

    ... appropriate fixative for further examination. After dehydration, tissue specimens shall be cleared with xylene... nerve (mid-thigh and sciatic notch), sural nerve (at knee), and tibial nerve (at knee). Tissue samples... section. Tissue sections shall be prepared from the tissue blocks. The following general testing...

  2. Dissipation of 14C chlorpyrifos in the rhizosphere of rice

    International Nuclear Information System (INIS)

    The root exudates from the plants contribute to the biodegradation of insecticides. Although, different mechanisms have been proposed, there is no clear elucidation of any mechanism. This study investigates the dissipation of an organophosphorus insecticide, chlorpyrifos in the rhizospheric soil planted with rice plant. Two sets of experimental tanks were maintained with or without plants using soil spiked with 1 mg kg-1 and 10 mg kg-1 of chlorpyrifos. Experiment was conducted for 180 days till the rice plant starts bearing seeds. The 14C activity decreased rapidly in the rhizospheric soil as compare to the non-rhizospheric soil. The total culturable microflora were higher in the rhizospheric than the non-rhizospheric soil. The plant extract had given few counts indicating some negligible amount of chlorpyrifos uptake. The 14C activity in the water was disappeared after 30 days. It was observed that very low amount of residue persisted in soil. This studies revealed that the plants play an important role in the dissipation of the chlorpyrifos from the rice flooded rhizospheric soil. (author)

  3. Soil bacterial and fungal community successions under the stress of chlorpyrifos application and molecular characterization of chlorpyrifos-degrading isolates using ERIC-PCR.

    Science.gov (United States)

    Chen, Lie-zhong; Li, Yan-li; Yu, Yun-long

    2014-04-01

    Chlorpyrifos is a widely used insecticide in recent years, and it will produce adverse effects on soil when applied on crops or mixed with soil. In this study, nested polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE) were combined to explore the bacterial and fungal community successions in soil treated with 5 and 20 mg/kg of chlorpyrifos. Furthermore, isolates capable of efficiently decomposing chlorpyrifos were molecular-typed using enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR). Under the experimental conditions, degradation of chlorpyrifos in soil was interpreted with the first-order kinetics, and the half-lives of chlorpyrifos at 5 and 20 mg/kg doses were calculated to be 8.25 and 8.29 d, respectively. DGGE fingerprint and principal component analysis (PCA) indicated that the composition of the fungal community was obviously changed with the chlorpyrifos treatment, and that samples of chlorpyrifos treatment were significantly separated from those of the control from the beginning to the end. While for the bacterial community, chlorpyrifos-treated soil samples were apparently different in the first 30 d and recovered to a similar level of the control up until 60 d, and the distance in the PCA between the chlorpyrifos-treated samples and the control was getting shorter through time and was finally clustered into one group. Together, our results demonstrated that the application of chlorpyrifos could affect the fungal community structure in a quick and lasting way, while only affecting the bacterial community in a temporary way. Finally, nine typical ERIC types of chlorpyrifos-degrading isolates were screened. PMID:24711353

  4. Cholinesterase inhibition and alterations of hepatic metabolism by oral acute and repeated chlorpyrifos administration to mice.

    Science.gov (United States)

    Cometa, Maria Francesca; Buratti, Franca Maria; Fortuna, Stefano; Lorenzini, Paola; Volpe, Maria Teresa; Parisi, Laura; Testai, Emanuela; Meneguz, Annarita

    2007-05-01

    Chlorpyrifos (CPF) is a broad spectrum organophosphorus insecticide bioactivated in vivo to chlorpyrifos-oxon (CPFO), a very potent anticholinesterase. A great majority of available animal studies on CPF and CPFO toxicity are performed in rats. The use of mice in developmental neurobehavioural studies and the availability of transgenic mice warrant a better characterization of CPF-induced toxicity in this species. CD1 mice were exposed to a broad range of acute (12.5-100.0mg/kg) and subacute (1.56-25mg/kg/day from 5 to 30 days) CPF oral doses. Functional and biochemical parameters such as brain and serum cholinesterase (ChE) and liver xenobiotic metabolizing system, including the biotransformation of CPF itself, have been studied and the no observed effect levels (NOELs) identified. Mice seem to be more susceptible than rats at least to acute CPF treatment (oral LD(50) 4.5-fold lower). The species-related differences were not so evident after repeated exposures. In mice a good correlation was observed between brain ChE inhibition and classical cholinergic signs of toxicity. After CPF-repeated treatment, mice seemed to develop some tolerance to CPF-induced effects, which could not be attributed to an alteration of P450-mediated CPF hepatic metabolism. CPF-induced effects on hepatic microsomal carboxylesterase (CE) activity and reduced glutathione (GSH) levels observed at an early stage of treatment and then recovered after 30 days, suggest that the detoxifying mechanisms are actively involved in the protection of CPF-induced effects and possibly in the induction of tolerance in long term exposure. The mouse could be considered a suitable experimental model for future studies on the toxic action of organophosphorus pesticides focused on mechanisms, long term and age-related effects. PMID:17382447

  5. An Age-Dependent Physiologically-Based Pharmacokinetic/Pharmacodynamic Model for the Organophosphorus Insecticide Chlorpyrifos in the Preweanling Rat

    Energy Technology Data Exchange (ETDEWEB)

    Timchalk, Chuck; Kousba, Ahmed A.; Poet, Torka S.

    2007-08-01

    Juvenile rats are more susceptible than adults to the acute toxicity of organophosphorus insecticides like chlorpyrifos (CPF). Age- and dose-dependent differences in metabolism may be responsible. Of importance is CYP450 activation and detoxification of CPF to chlorpyrifos-oxon (CPF-oxon) and trichloropyridinol (TCP), as well as B-esterase (cholinesterase; ChE) and A-esterase (PON-1) detoxification of CPF-oxon to TCP. In the current study, a modified physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model incorporating age-dependent changes in CYP450, PON-1, and tissue ChE levels for rats was developed. In this model, age was used as a dependent function to estimate body weight which was then used to allometrically scale both metabolism and tissue ChE levels. Model simulations suggest that preweanling rats are particularly sensitive to CPF toxicity, with levels of CPF-oxon in blood and brain disproportionately increasing, relative to the response in adult rats. This age-dependent non-linear increase in CPF-oxon concentration may potentially result from the depletion of non-target B-esterases, and a lower PON-1 metabolic capacity in younger animals. These results indicate that the PBPK/PD model behaves consistently with the general understanding of CPF toxicity, pharmacokinetics and tissue ChE inhibition in neonatal and adult rats. Hence, this model represents an important starting point for developing a computational model to assess the neurotoxic potential of environmentally relevant organophosphate exposures in infants and children.

  6. Structural and metabolic responses of microbial community to sewage-borne chlorpyrifos in constructed wetlands.

    Science.gov (United States)

    Zhang, Dan; Wang, Chuan; Zhang, Liping; Xu, Dong; Liu, Biyun; Zhou, Qiaohong; Wu, Zhenbin

    2016-06-01

    Long-term use of chlorpyrifos poses a potential threat to the environment that cannot be ignored, yet little is known about the succession of substrate microbial communities in constructed wetlands (CWs) under chlorpyrifos stress. Six pilot-scale CW systems receiving artificial wastewater containing 1mg/L chlorpyrifos were established to investigate the effects of chlorpyrifos and wetland vegetation on the microbial metabolism pattern of carbon sources and community structure, using BIOLOG and denaturing gradient gel electrophoresis (DGGE) approaches. Based on our samples, BIOLOG showed that Shannon diversity (H') and richness (S) values distinctly increased after 30days when chlorpyrifos was added. At the same time, differences between the vegetated and the non-vegetated systems disappeared. DGGE profiles indicated that H' and S had no significant differences among four different treatments. The effect of chlorpyrifos on the microbial community was mainly reflected at the physiological level. Principal component analysis (PCA) of both BIOLOG and DGGE showed that added chlorpyrifos made a difference on test results. Meanwhile, there was no difference between the vegetation and no-vegetation treatments after addition of chlorpyrifos at the physiological level. Moreover, the vegetation had no significant effect on the microbial community at the genetic level. Comparisons were made between bacteria in this experiment and other known chlorpyrifos-degrading bacteria. The potential chlorpyrifos-degrading ability of bacteria in situ may be considerable. PMID:27266297

  7. Modifying effects of vitamin E on chlorpyrifos toxicity in atlantic salmon.

    Directory of Open Access Journals (Sweden)

    Pål A Olsvik

    Full Text Available The aim of this study was to elucidate how vitamin E (alpha tocopherol may ameliorate the toxicity of the pesticide chlorpyrifos in Atlantic salmon. Freshly isolated hepatocytes were exposed to vitamin E, chlorpyrifos or a combination of vitamin E and chlorpyrifos (all 100 μM. Transcriptomics (RNA-seq and metabolomics were used to screen for effects of vitamin E and chlorpyrifos. By introducing vitamin E, the number of upregulated transcripts induced by chlorpyrifos exposure was reduced from 941 to 626, while the number of downregulated transcripts was reduced from 901 to 742 compared to the control. Adding only vitamin E had no effect on the transcriptome. Jak-STAT signaling was the most significantly affected pathway by chlorpyrifos treatment according to the transcriptomics data. The metabolomics data showed that accumulation of multiple long chain fatty acids and dipeptides and amino acids in chlorpyrifos treated cells was partially alleviated by vitamin E treatment. Significant interaction effects between chlorpyrifos and vitamin E were seen for 15 metabolites, including 12 dipeptides. The antioxidant had relatively modest effects on chlorpyrifos-induced oxidative stress. By combining the two data sets, the study suggests that vitamin E supplementation prevents uptake and accumulation of fatty acids, and counteracts inhibited carbohydrate metabolism. Overall, this study shows that vitamin E only to a moderate degree modifies chlorpyrifos toxicity in Atlantic salmon liver cells.

  8. Presynaptic Mechanisms of Lead Neurotoxicity: Effects on Vesicular Release, Vesicle Clustering and Mitochondria Number

    OpenAIRE

    Zhang, Xiao-Lei; Sara R Guariglia; McGlothan, Jennifer L.; Stansfield, Kirstie H.; Stanton, Patric K.; Guilarte, Tomás R.

    2015-01-01

    Childhood lead (Pb2+) intoxication is a global public health problem and accounts for 0.6% of the global burden of disease associated with intellectual disabilities. Despite the recognition that childhood Pb2+ intoxication contributes significantly to intellectual disabilities, there is a fundamental lack of knowledge on presynaptic mechanisms by which Pb2+ disrupts synaptic function. In this study, using a well-characterized rodent model of developmental Pb2+ neurotoxicity, we show that Pb2+...

  9. MR findings of cyclosporine neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Po Song; Ahn, Kook Jin; Ahn, Bo Young; Jung, Hae An; Kim, Hee Je; Lee, Jae Mun [The Catholic Univ. St Mary' s Hospital, Seoul (Korea, Republic of)

    1998-12-01

    To analyze the MR findings of cyclosporine-induced neurotoxicity in patients receiving high dose of cyclosporine and to suggest the possible pathogenetic mechanism. The cases of seven patients (2 males, 5 females;18-36 years old) who suffered seizures after receiving high-dose cyclosporine for bone marrow transplantation due to diseases such as aplastic anemia or leukemia were retrospectively reviewed. We evaluated the location and pattern of abnormal signal intensity seen on T2 weighted images, the presence of contrast enhancement, and the changes seen on follow-up MR performed at intervals of 12-30 days after initial MR in five of seven patients. We analyzed levels of blood cyclosporine and magnesium, and investigated the presence of hypertension at the sity of the seizure. Locations of the lesions were bilateral(n=3D5), unilateral(n=3D2), parietal(n=3D6), occipital(n=3D6), temporal(n=3D4), and in the frontal lobe(n=3D3). Frontal lesions showed high signal intensities in the borderline ischemic zone of the frontal lobe between the territory of the anterior and middle cerebral arteries. In six of the seven patients, cortical and subcortical areas including subcortical U-fibers were seen on T2-weighted images to be involved in the parietooccipital lobes. Only one of the seven showed high signal intensity in the left basal ganglia. All lesions showed high signal intensity on T2-weighted images, and iso to low signal intensity on T1-weighted. In five of seven patients there was no definite enhancement, but in the other two, enhancement was slight. In four of seven patients seizures occurred within high therapeutic ranges(250-450ng/ml), while others suffered such attacks at levels below the therapeutic range. After cyclospirine was administered at a reduced dosage or stopped, follow-up MR images showed the complete or near-total disappearance of the abnormal findings previously described. Only two patients had hypertension, and the others normotension. Five of the

  10. Immunosuppressant-Associated Neurotoxicity Responding to Olanzapine

    Directory of Open Access Journals (Sweden)

    James A. Bourgeois

    2014-01-01

    Full Text Available Immunosuppressants, particularly tacrolimus, can induce neurotoxicity in solid organ transplantation cases. A lower clinical threshold to switch from tacrolimus to another immunosuppressant agent has been a common approach to reverse this neurotoxicity. However, immunosuppressant switch may place the graft at risk, and, in some cases, continuation of the same treatment protocol may be necessary. We report a case of immunosuppressant-associated neurotoxicity with prominent neuropsychiatric manifestation and describe psychiatric intervention with olanzapine that led to clinical improvement while continuing tacrolimus maintenance.

  11. Genotoxicity of Chlorpyrifos and the Antimutagenic Role of Lettuce Leaves in Male Mice

    OpenAIRE

    Kamilia Badrakhan Abdelaziz; Aida Ibrahim El Makawy; Ali Zain El-Abidin Abd Elsalam; Ahmed Mohamed Darwish

    2010-01-01

    Chlorpyrifos [O O-diethyl-O-(3 5 6-trichloro-2-pyridyl)-phosphorothioate] is one of the most widelyused organophosphate insecticides. Previous studies proved that chlorpyrifos, at different doses,induced genotoxicity. In Egyptian foods, the residual levels of pesticides are often higher than thosefound in developed country ones. So the aim of this research was to evaluate the genotoxicity of theinsecticide chlorpyrifos at doses equal to its maximum residue limit (MRL) in the leafy vegetables,...

  12. Soil bacteria showing a potential of chlorpyrifos degradation and plant growth enhancement

    OpenAIRE

    Akbar, Shamsa; Sultan, Sikander

    2016-01-01

    Background Since 1960s, the organophosphate pesticide chlorpyrifos has been widely used for the purpose of pest control. However, given its persistence and toxicity towards life forms, the elimination of chlorpyrifos from contaminated sites has become an urgent issue. For this process bioremediation is the method of choice. Results Two bacterial strains, JCp4 and FCp1, exhibiting chlorpyrifos-degradation potential were isolated from pesticide contaminated agricultural fields. These isolates w...

  13. Mortality among Pesticide Applicators Exposed to Chlorpyrifos in the Agricultural Health Study

    OpenAIRE

    Lee, Won Jin; Alavanja, Michael C.R.; Hoppin, Jane A; Rusiecki, Jennifer A.; Kamel, Freya; Blair, Aaron; Sandler, Dale P.

    2007-01-01

    Background Chlorpyrifos is one of the most widely used organophosphate insecticides in the United States. Although the toxicity of chlorpyrifos has been extensively studied in animals, the epidemiologic data are limited. Objective To evaluate whether agricultural chlorpyrifos exposure was associated with mortality, we examined deaths among pesticide applicators in the Agricultural Health Study, a prospective study of licensed pesticide applicators in Iowa and North Carolina. Methods A total o...

  14. Vitamin C Attenuates Chronic Chlorpyrifos-induced Alteration of Neurobehavioral Parameters in Wistar Rats

    OpenAIRE

    Suleiman F. Ambali; Joseph O. Ayo

    2012-01-01

    Background: Oxidative stress is one of the molecular mechanisms in chlorpyrifos toxicity. The present study was designed to evaluate the attenuating effect of vitamin C on chlorpyrifos-induced alteration of neurobehavioral performance and the role of muscle acetylchloinesterase (AChE), glycogen and lipoperoxidation in the accomplishment of this task. Materials and Methods: Male rats were randomly assigned into 4 groups with the following regimens: soya oil (S/oil), vitamin C (VC), chlorpyrifo...

  15. Complete biodegradation of chlorpyrifos by engineered Pseudomonas putida cells expressing surface-immobilized laccases.

    Science.gov (United States)

    Liu, Jin; Tan, Luming; Wang, Jing; Wang, Zhiyong; Ni, Hong; Li, Lin

    2016-08-01

    The long-term abuse use of chlorpyrifos-like pesticides in agriculture and horticulture has resulted in significant soil or water contamination and a worldwide ecosystem threat. In this study, the ability of a solvent-tolerant bacterium, Pseudomonas putida MB285, with surface-displayed bacterial laccase, to biodegrade chlorpyrifos was investigated. The results of compositional analyses of the degraded products demonstrate that the engineered MB285 was capable of completely eliminating chlorpyrifos via direct biodegradation, as determined by high-performance liquid chromatography and gas chromatography-mass spectrometry assays. Two intermediate metabolites, namely 3,5,6-trichloro-2-pyridinol (TCP) and diethyl phosphate, were temporarily detectable, verifying the joint and stepwise degradation of chlorpyrifos by surface laccases and certain cellular enzymes, whereas the purified free laccase incompletely degraded chlorpyrifos into TCP. The degradation reaction can be conducted over a wide range of pH values (2-7) and temperatures (5-55 °C) without the need for Cu(2+). Bioassays using Caenorhabditis elegans as an indicator organism demonstrated that the medium was completely detoxified of chlorpyrifos by degradation. Moreover, the engineered cells exhibited a high capacity of repeated degradation and good performance in continuous degradation cycles, as well as a high capacity to degrade real effluents containing chlorpyrifos. Therefore, the developed system exhibited a high degradation capacity and performance and constitutes an improved approach to address chlorpyrifos contamination in chlorpyrifos-remediation practice. PMID:27231878

  16. Developmental Dyspraxia

    Science.gov (United States)

    ... Enhancing Diversity Find People About NINDS NINDS Developmental Dyspraxia Information Page Synonym(s): Dyspraxia Table of Contents (click ... being done? Clinical Trials Organizations What is Developmental Dyspraxia? Developmental dyspraxia is a disorder characterized by an ...

  17. Fate of chlorpyrifos in a model rice-fish ecosystem

    International Nuclear Information System (INIS)

    The persistence and distribution of chlorpyrifos in a model rice-fish ecosystem and its potential for use on rice-fish culture were evaluated. Chlorpyrifos applied at the rate of 0.5 kg AI/ha had a half-life of 3.7 days in paddy water with maximum residues of 0.009 mg/Lat 2 Days After Spraying (DAS). In paddy soil, a maximum residue of 1.2 mg/kg was found 1 DAS. Chlorpyrifos residues obtained by ordinary and exhaustive extraction had half-lives of 1.7 and 2.8 days, respectively. Bound residues started to accumulate at 19 DAS. Residues were found below 20 cm in the paddy soil at 6 DAS. Residues decline in the leaves, stems and roots followed pseudo-first order kinetics with half-lives of 0.9, 1.5 and 1.2 days, respectively. Residues were not detected in the grain at harvest. They did not bioaccumulate in fish and were not toxic to Oreochromis niloticus 6 DAS. (author). 13 refs, 2 figs, 5 tabs

  18. Toxicity of chlorpyrifos on some marine cyanobacteria species

    International Nuclear Information System (INIS)

    Pakistan is an agricultural country and a wide variety of pesticides are used on its cropland. Pesticides pose serious threats to the natural ecosystem. In the present study cyanobacteria (blue green algae) were used to assess the ecotoxicological effect of chlorpyrifos (organophosphate pesticide). Cyanobacteria are the base of the food web providing food resource to consumers in higher trophic level. Cyanobacteria were isolated and purified from water samples collected from Manora channel. Fast growing cultures of cyanobacteria were used to assess the toxicity of test pesticide . The Light and Dark method was used to determine the primary production of the organisms. The acute toxicity of chlorpyrifos was determined by calculating IC/sub 50/ of the test organisms. The IC/sub 50/ was found to be 0.074, 0.013, 0.08 and 0.3 ppm for Synechocystis aquatilis, Komvophoron minutum, Gloeocapsa crepidinum and Gloeocapsa sanguinea when exposed to chlorpyrifos pesticide . Laboratory experiments with cyanobacteria have demonstrated that organophosphate pesticides are potent inhibitors of photosynthesis. (author)

  19. Fate and effects of the insecticide chlorpyrifos in outdoor plankton-dominated microcosms in Thailand.

    NARCIS (Netherlands)

    Daam, M.A.; Crum, S.J.H.; Brink, van den P.J.; Nogueira, A.J.A.

    2008-01-01

    The fate and effects of the insecticide chlorpyrifos were studied in plankton-dominated, freshwater microcosms in Thailand. Disappearance rates of chlorpyrifos from the water column in the present study were similar to those in temperate regions. Insecticide accumulation in the sediment was relative

  20. Phytoremediation of chlorpyrifos in aqueous system by riverine macrophyte, Acorus calamus: toxicity and removal rate.

    Science.gov (United States)

    Wang, Qinghai; Li, Cui; Zheng, Ruilun; Que, Xiaoe

    2016-08-01

    The potential of Acorus calamus to remove chlorpyrifos from water was assessed under laboratory conditions. Toxic effects of the insecticide in A. calamus were evaluated using pulse-amplitude modulated chlorophyll fluorescence techniques as well. At exposure concentrations above 8 mg L(-1), A. calamus showed obvious phytotoxic symptom with significant reduction in quantum efficiency of PSII (ΦPSII) and photochemical quenching coefficient (qP) in 20-day test; the inhibition of maximal quantum efficiency of PSII (Fv/Fm) was accompanied by a significant rise in initial chlorophyll fluorescence (Fo) within 15-day exposures. Fv/Fm and Fo recover to the normal level after 20-day exposure. The reduced removal rate to chlorpyrifos was observed with increase of initial chlorpyrifos concentrations. At application levels of 1, 2, and 4 mg L(-1), the disappearance rate of chlorpyrifos in the hydroponic system with plants was significantly greater than that without plants during the 20-day test periods. Chlorpyrifos was taken up from medium and transferred to above ground tissues by the plant and significant amounts of chlorpyrifos accumulated in plant tissues. The result indicated that A. calamus can promote the disappearance of chlorpyrifos from water and may be used for phytoremediation of water contaminated with a relatively low concentration of chlorpyrifos insecticide (<4 mg L(-1)). PMID:27154841

  1. Binding and detoxification of chlorpyrifos by lactic acid bacteria on rice straw silage fermentation.

    Science.gov (United States)

    Wang, Yan-Su; Wu, Tian-Hao; Yang, Yao; Zhu, Cen-Ling; Ding, Cheng-Long; Dai, Chuan-Chao

    2016-01-01

    This investigation examined the reduction of pesticide residues on straw inoculated with lactic acid bacteria (LAB) during ensiling. Lactobacillus casei WYS3 was isolated from rice straw that contained pesticide residues. Non-sterilized rice straw, which was inoculated with L. casei WYS3, showed increased removal of chlorpyrifos after ensiling, compared with rice straw that was not inoculated with L. casei WYS3 or sterilized rice straw. In pure culture, these strains can bind chlorpyrifos as indicated by high-performance liquid chromatography analysis. Viable L. casei WYS3 was shown to bind 33.3-42% of exogenously added chlorpyrifos. These results are similar to those of acid-treated cells but less than those of heat-treated cells, which were found to bind 32.0% and 77.2% of the added chlorpyrifos respectively. Furthermore, gas chromatography-mass spectrometry analysis determined that L. casei WYS3 detoxified chlorpyrifos via P-O-C cleavage. Real-time polymerized chain reaction analysis determined that organophosphorus hydrolase gene expression tripled after the addition of chlorpyrifos to LAB cultures, compared with the control group (without chlorpyrifos). This paper highlights the potential use of LAB starter cultures for the detoxification and removal of chlorpyrifos residues in the environment. PMID:26852781

  2. Endocytic pathways mediating oligomeric Aβ42 neurotoxicity

    Directory of Open Access Journals (Sweden)

    Laxton Kevin

    2010-05-01

    Full Text Available Abstract Background One pathological hallmark of Alzheimer's disease (AD is amyloid plaques, composed primarily of amyloid-β peptide (Aβ. Over-production or diminished clearance of the 42 amino acid form of Aβ (Aβ42 in the brain leads to accumulation of soluble Aβ and plaque formation. Soluble oligomeric Aβ (oAβ has recently emerged to be as a likely proximal cause of AD. Results Here we demonstrate that endocytosis is critical in mediating oAβ42-induced neurotoxicity and intraneuronal accumulation of Aβ. Inhibition of clathrin function either with a pharmacological inhibitor, knock-down of clathrin heavy chain expression, or expression of the dominant-negative mutant of clathrin-assembly protein AP180 did not block oAβ42-induced neurotoxicity or intraneuronal accumulation of Aβ. However, inhibition of dynamin and RhoA by expression of dominant negative mutants reduced neurotoxicity and intraneuronal Aβ accumulation. Pharmacologic inhibition of the dynamin-mediated endocytic pathway by genistein also reduced neurotoxicity. Conclusions These data suggest that dynamin-mediated and RhoA-regulated endocytosis are integral steps for oligomeric Aβ42-induced neurotoxicity and intraneuronal Aβ accumulation.

  3. Environmental Behavior of Chlorpyrifos and Endosulfan in a Tropical Soil in Central Brazil.

    Science.gov (United States)

    Dores, Eliana F G C; Spadotto, Claudio A; Weber, Oscarlina L S; Dalla Villa, Ricardo; Vecchiato, Antonio B; Pinto, Alicio A

    2016-05-25

    The environmental behavior of chlorpyrifos and endosulfan in soil was studied in the central-western region of Brazil by means of a field experiment. Sorption was evaluated in laboratory batch experiments. Chlorpyrifos and endosulfan were applied to experimental plots on uncultivated soil and the following processes were studied: leaching, runoff, and dissipation in top soil. Field dissipation of chlorpyrifos and endosulfan was more rapid than reported in temperate climates. Despite the high Koc of the studied pesticides, the two endosulfan isomers and endosulfan sulfate as well as chlorpyrifos were detected in percolated water. In runoff water and sediment, both endosulfan isomers and endosulfan sulfate were detected throughout the period of study. Observed losses of endosulfan by leaching (below a depth of 50 cm) and runoff were 0.0013 and 1.04% of the applied amount, whereas chlorpyrifos losses were 0.003 and 0.032%, respectively. Leaching of these highly adsorbed pesticides was attributed to preferential flow. PMID:26635198

  4. Neurotoxic effects associated with antibiotic use: management considerations

    OpenAIRE

    Grill, Marie F; Maganti, Rama K.

    2011-01-01

    The clinical manifestations of antibiotic-induced neurotoxic effects, the underlying mechanisms and management strategies have been reviewed. PubMed and OVID searches (January 1960–June 2010) were conducted using search terms such as antibiotics, side effects, neurotoxicity and encephalopathy which yielded approximately 300 articles. All relevant case reports, case series, letters and retrospective reviews describing neurotoxic effects and those discussing mechanisms of neurotoxicity were inc...

  5. Review of Toxicology of Atrazine and Chlorpyrifos on Fish

    Institute of Scientific and Technical Information of China (English)

    WANG Xu; LI Jilong; XING Houjuan; XU Shiwen

    2011-01-01

    Atrazine (ATR) and chlorpyrifos (CPF) are widely used in agriculture, but have resulted in a series of toxicological and environmental problems. They were heavily used which have potential threat to fish and rodents. Several recent laboratory studies have shown ATR and CPF could lead to oxidative damage, immunocyte reduced and inhibit acetylcholinesterase (ACHE). In order to clarify the toxicity of ATR and CPF, this paper summarized the adverse effects of ATR and CPF on reproduction, nerve and immune systems in fish.

  6. Oxidative stress in MeHg-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Farina, Marcelo, E-mail: farina@ccb.ufsc.br [Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Florianopolis, SC (Brazil); Aschner, Michael [Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN (United States); Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN (United States); Rocha, Joao B.T., E-mail: jbtrocha@yahoo.com.br [Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil)

    2011-11-15

    Methylmercury (MeHg) is an environmental toxicant that leads to long-lasting neurological and developmental deficits in animals and humans. Although the molecular mechanisms mediating MeHg-induced neurotoxicity are not completely understood, several lines of evidence indicate that oxidative stress represents a critical event related to the neurotoxic effects elicited by this toxicant. The objective of this review is to summarize and discuss data from experimental and epidemiological studies that have been important in clarifying the molecular events which mediate MeHg-induced oxidative damage and, consequently, toxicity. Although unanswered questions remain, the electrophilic properties of MeHg and its ability to oxidize thiols have been reported to play decisive roles to the oxidative consequences observed after MeHg exposure. However, a close examination of the relationship between low levels of MeHg necessary to induce oxidative stress and the high amounts of sulfhydryl-containing antioxidants in mammalian cells (e.g., glutathione) have led to the hypothesis that nucleophilic groups with extremely high affinities for MeHg (e.g., selenols) might represent primary targets in MeHg-induced oxidative stress. Indeed, the inhibition of antioxidant selenoproteins during MeHg poisoning in experimental animals has corroborated this hypothesis. The levels of different reactive species (superoxide anion, hydrogen peroxide and nitric oxide) have been reported to be increased in MeHg-exposed systems, and the mechanisms concerning these increments seem to involve a complex sequence of cascading molecular events, such as mitochondrial dysfunction, excitotoxicity, intracellular calcium dyshomeostasis and decreased antioxidant capacity. This review also discusses potential therapeutic strategies to counteract MeHg-induced toxicity and oxidative stress, emphasizing the use of organic selenocompounds, which generally present higher affinity for MeHg when compared to the classically

  7. Cu(2+) and Fe(2+) mediated photodegradation studies of soil-incorporated chlorpyrifos.

    Science.gov (United States)

    Rafique, Nazia; Tariq, Saadia R; Ahad, Karam; Taj, Touqeer

    2016-03-01

    The influences of Cu(2+) and Fe(2+) on the photodegradation of soil-incorporated chlorpyrifos were investigated in the present study. The soil samples spiked with chlorpyrifos and selected metal ions were irradiated with UV light for different intervals of time and analyzed by HPLC. The unsterile and sterile control soil samples amended with pesticides and selected metals were incubated in the dark at 25 °C for the same time intervals. The results of the study evidenced that photodegradation of chlorpyrifos followed the first-order kinetics. The dissipation t0.5 of chlorpyrifos was found to decrease from 41 to 20 days under UV irradiation. The rate of chlorpyrifos photodegradation was increased in the presence of both metals, i.e., Cu(2+) and Fe(2+). Thus, initially observed t0.5 of 19.8 days was decreased to 4.39 days in the case of Cu(+2) and 19.25 days for Fe(+2). Copper was found to increase the rate of photodegradation by 4.5 orders of magnitude while the microbial degradation of chlorpyrifos was increased only twofold. The microbial degradation of chlorpyrifos was only negligibly affected by Fe(2+) amendment. The studied trace metals also affected the abiotic degradation of the pesticide in the order Cu(2+) > Fe(2+). PMID:26507736

  8. Degradation of chlorpyrifos in laboratory soil and its impact on soil microbial functional diversity

    Institute of Scientific and Technical Information of China (English)

    FANG Hua; YU Yunlong; CHU Xiaoqiang; WANG Xiuguo; YANG Xiaoe; YU Jingquan

    2009-01-01

    Degradation of chlorpyrifos at different concentrations in soil and its impact on soil microbial functional diversity were investigated under laboratory conditions. The degradation half-lives of chlorpyrifos at levels of 4, 8, and 12 mg/kg in soil were calculated to be 14.3, 16.7, and 18.0 d, respectively. The Biolog study showed that average well color development (AWCD) in soils was significantly (P < 0.05) inhibited by chlorpyrifos within the first two weeks and thereafter recovered to the similar level as the control. A similar variation in the diversity indices (Simpson index 1/D and McIntosh index U) in chlorpyrifos-treated soils was observed, no significant difference in the Shannon-Wiener index H' was found in these soils. With increasing chlorpyrifos concentration, the half-lives of chlorpyrifos were significantly (P ≤ 0.05) extended and its inhibitory effects on soil microorganisms were aggravated. It is concluded that chlorpyrifos residues in soil had a temporary or short-term inhibitory effect on soil microbial functional diversity.

  9. Toxicity assessing for chlorpyrifos-contaminated soil with three different earthworm test methods

    Institute of Scientific and Technical Information of China (English)

    ZHOU Shi-ping; DUAN Chang-qun; FU Hui; CHEN Yu-hui; WANG Xue-hua; YU Ze-fen

    2007-01-01

    Earthworm toxicity tests are useful tools for terrestrial risk assessment but require a hierarchy of test designs that differ in effect levels (behavior, sublethal, lethal). In this study, the toxicity of chlorpyrifos contaminated soil on earthworms was assessed. In addition to the acute and chronic tests, an avoidance response test was applied. Earthworms were exposed to sublethal and lethal concentration of chlorpyrifos, and evaluated for acute toxicity, growth, fecundity and avoidance response after a certain exposure period. The test methods covered all important ecological relevant endpoints (acute, chronic, behavioral). Concentration of 78.91 mg/kg, chlorpyrifos caused significant toxic effects in all test methods, but at lower test concentrations, only significant chronic toxic effects could be observed. In the present study, chlorpyrifos had adverse effect on growth and fecundity in earthworm exposed to 5 mg/kg chlorpyrifos after eight weeks. The avoidance response test, however, showed significant repellent effects concentration of 40 mg/kg chlorpyrifos. For chlorpyrifos, concentration affecting avoidance response was far greater than growth and fecundity, it seemed likely that earthworms were not able to escape from pesticide-contaminated soil into the clean soil in field and hence were exposed continuously to elevated concentrations of pesticides.

  10. Pathophysiology of Manganese-Associated Neurotoxicity

    Science.gov (United States)

    Racette, Brad A.; Aschner, Michael; Guilarte, Tomas R.; Dydak, Ulrike; Criswell, Susan R.; Zheng, Wei

    2012-01-01

    Conference Summary Manganese (Mn) is a well established neurotoxin associated with specific damage to the basal ganglia in humans. The phenotype associated with Mn neurotoxicity was first described in two workers with occupational exposure to Mn oxide.(Couper, 1837) Although the description did not use modern clinical terminology, a parkinsonian illness characterized by slowness of movement (bradykinesia), masked facies, and gait impairment (postural instability) appears to have predominated. Nearly 100 years later an outbreak of an atypical parkinsonian illness in a Chilean Mn mine provided a phenotypic description of a fulminant neurologic disorder with parkinsonism, dystonia, and neuropsychiatric symptoms.(Rodier J, 1955) Exposures associated with this syndrome were massive and an order of magnitude greater than modern exposures.(Rodier J, 1955; Hobson et al., 2011) The clinical syndrome associated with Mn neurotoxicity has been called manganism. Modern exposures to Mn occur primarily through occupations in the steel industry and welding. These exposures are often chronic and varied, occurring over decades in the healthy workforce. Although the severe neurologic disorder described by Rodier and Couper are no longer seen, several reports have suggested a possible increased risk of neurotoxicity in these workers.(Racette et al., 2005b; Bowler et al., 2007; Harris et al., 2011) Based upon limited prior imaging and pathologic investigations into the pathophysiology of neurotoxicity in Mn exposed workers,(Huang et al., 2003) many investigators have concluded that the syndrome spares the dopamine system distinguishing manganism from Parkinson disease (PD), the most common cause of parkinsonism in the general population, and a disease with characteristic degenerative changes in the dopaminergic system.(Jankovic, 2005) The purpose of this symposium was to highlight recent advances in the understanding of the pathophysiology of Mn associated neurotoxicity from C. elegans

  11. Advanced Pre-clinical Research Approaches and Models to Studying Pediatric Anesthetic Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Cheng eWang

    2012-10-01

    Full Text Available Advances in pediatric and obstetric surgery have resulted in an increase in the duration and complexity of anesthetic procedures. A great deal of concern has recently arisen regarding the safety of anesthesia in infants and children. Because of obvious limitations, it is not possible to thoroughly explore the effects of anesthetic agents on neurons in vivo in human infants or children. However, the availability of some advanced pre-clinical research approaches and models, such as imaging technology both in vitro and in vivo, stem cell and nonhuman primate experimental models, have provided potentially invaluable tools for examining the developmental effects of anesthetic agents. This review discusses the potential application of some sophisticaled research approaches, e.g., calcium imaging, in stem cell-derived in vitro models, especially human embryonic neural stem cells, along with their capacity for proliferation and their potential for differentiation, to dissect relevant mechanisms underlying the etiology of the neurotoxicity associated with developmental exposures to anesthetic agents. Also, this review attempts to discuss several advantages for using the developing rhesus monkey models (in vivo, when combined with dynamic molecular imaging approaches, in addressing critical issues related to the topic of pediatric sedation/anesthesia. These include the relationships between anesthetic-induced neurotoxicity, dose response, time-course and developmental stage at time of exposure (in vivo studies, serving to provide the most expeditious platform toward decreasing the uncertainty in extrapolating pre-clinical data to the human condition.

  12. Assessment of Health Risk in Human Populations Due to Chlorpyrifos

    Directory of Open Access Journals (Sweden)

    Jeevani Marasinghe

    2014-04-01

    Full Text Available A wide ranging survey was carried out of the available data from ten different countries on human exposure to chlorpyrifos, in many different occupational and nonoccupational settings. Low levels of chlorpyrifos residues were found to be widely distributed in the global human population, but most of these do not constitute a public health risk, as evaluated using the U.S. Environmental Protection Agency (USEPA Guidelines. For example, the general populations in USA, Germany and Italy had detectable residue levels well below the guidelines. However, high levels of health risk were apparent in a specific group of pregnant mothers in the USA, at median exposure with a HQ0.50 of 26.6, suggesting that most of this population group was affected. Also the high exposure group (5% most exposed with occupationally exposed manufacturing workers in the USA had a HQ0.95 of 2.6 to 42.0, and pest control applicators in Australia and the USA both had a HQ0.95 of 5.2. Some farmers in Sri Lanka and Vietnam had a high level of risk after spraying applications, having a HQ0.95 of 2.2 and 19.5 respectively at the high exposure level. These results suggest that there is a possibility of adverse health effects in specific population groups in many different settings throughout the world.

  13. THC Prevents MDMA Neurotoxicity in Mice.

    Directory of Open Access Journals (Sweden)

    Clara Touriño

    Full Text Available The majority of MDMA (ecstasy recreational users also consume cannabis. Despite the rewarding effects that both drugs have, they induce several opposite pharmacological responses. MDMA causes hyperthermia, oxidative stress and neuronal damage, especially at warm ambient temperature. However, THC, the main psychoactive compound of cannabis, produces hypothermic, anti-inflammatory and antioxidant effects. Therefore, THC may have a neuroprotective effect against MDMA-induced neurotoxicity. Mice receiving a neurotoxic regimen of MDMA (20 mg/kg x 4 were pretreated with THC (3 mg/kg x 4 at room (21 degrees C and at warm (26 degrees C temperature, and body temperature, striatal glial activation and DA terminal loss were assessed. To find out the mechanisms by which THC may prevent MDMA hyperthermia and neurotoxicity, the same procedure was carried out in animals pretreated with the CB(1 receptor antagonist AM251 and the CB(2 receptor antagonist AM630, as well as in CB(1, CB(2 and CB(1/CB(2 deficient mice. THC prevented MDMA-induced-hyperthermia and glial activation in animals housed at both room and warm temperature. Surprisingly, MDMA-induced DA terminal loss was only observed in animals housed at warm but not at room temperature, and this neurotoxic effect was reversed by THC administration. However, THC did not prevent MDMA-induced hyperthermia, glial activation, and DA terminal loss in animals treated with the CB(1 receptor antagonist AM251, neither in CB(1 and CB(1/CB(2 knockout mice. On the other hand, THC prevented MDMA-induced hyperthermia and DA terminal loss, but only partially suppressed glial activation in animals treated with the CB(2 cannabinoid antagonist and in CB(2 knockout animals. Our results indicate that THC protects against MDMA neurotoxicity, and suggest that these neuroprotective actions are primarily mediated by the reduction of hyperthermia through the activation of CB(1 receptor, although CB(2 receptors may also contribute to

  14. Role of Ocimum sanctum as a Genoprotective Agent on Chlorpyrifos-Induced Genotoxicity

    OpenAIRE

    Khanna, Asha; Shukla, Poonam; Tabassum, Shajiya

    2011-01-01

    Protective effect of Ocimum sanctum was evaluated on chlorpyrifos-induced genotoxicity in in vivo and in vitro models. Two different concentrations of pesticide were taken, i.e., 1/5 and 1/15 of LD50 of chlorpyrifos for the in vivo study. Rats were pre-treated orally with O. sanctum extract (OE) at 50 mg/kg b.wt. For the in vitro studies, human lymphocyte cultures were exposed to 75 μg/ml chlorpyrifos with and without OE. Structural and numerical (both aneuploidy and euploidy types) chromosom...

  15. Mineralization of chlorpyrifos by co-culture of Serratia and Trichosporon spp.

    Science.gov (United States)

    Xu, Gangming; Li, Yingying; Zheng, Wei; Peng, Xiang; Li, Wen; Yan, Yanchun

    2007-10-01

    A bacterial strain (Serratia sp.) that could transform chlorpyrifos to 3,5,6-trichloro-2-pyridinol (TCP) and a TCP-mineralizing fungal strain (Trichosporon sp.) were isolated from activated sludge by enrichment culture technique. The fungus could also degrade 50 mg chlorpyrifos l(-1) within 7 days. Co-cultures completely mineralized 50 mg chlorpyrifos l(-1) within 18 h at 30 degrees C and pH 8 using a total inocula of 0.15 g biomass l(-1). PMID:17609859

  16. Non-accidental chlorpyrifos poisoning-an unusual cause of profound unconsciousness.

    Science.gov (United States)

    Lee, Jiun-Chang; Lin, Kuang-Lin; Lin, Jainn-Jim; Hsia, Shao-Hsuan; Wu, Chang-Teng

    2010-04-01

    Chlorpyrifos is an organophosphorus anticholinesterase insecticide, and organophosphate intoxication can induce symptoms such as miosis, urination, diarrhea, diaphoresis, lacrimation, excitation of central nervous system, salivation, and consciousness disturbance (MUDDLES). Although accidental poisoning of children with drugs and chemicals is a common cause for consciousness disturbance in children, the possibility of deliberate poisoning is rarely considered. We report on a healthy 5-year 6-month-old boy with recurrent organophosphate intoxication. Reports of chlorpyrifos intoxication in children are quite rare. This case report demonstrates decision-making process and how to disclose deliberate chlorpyrifos poisoning of the toddler by the stepmother, another example of Munchausen syndrome by proxy. PMID:19763618

  17. Glyphosate induces neurotoxicity in zebrafish.

    Science.gov (United States)

    Roy, Nicole M; Carneiro, Bruno; Ochs, Jeremy

    2016-03-01

    Glyphosate based herbicides (GBH) like Roundup(®) are used extensively in agriculture as well as in urban and rural settings as a broad spectrum herbicide. Its mechanism of action was thought to be specific only to plants and thus considered safe and non-toxic. However, mounting evidence suggests that GBHs may not be as safe as once thought as initial studies in frogs suggest that GBHs may be teratogenic. Here we utilize the zebrafish vertebrate model system to study early effects of glyphosate exposure using technical grade glyphosate and the Roundup(®) Classic formulation. We find morphological abnormalities including cephalic and eye reductions and a loss of delineated brain ventricles. Concomitant with structural changes in the developing brain, using in situ hybridization analysis, we detect decreases in genes expressed in the eye, fore and midbrain regions of the brain including pax2, pax6, otx2 and ephA4. However, we do not detect changes in hindbrain expression domains of ephA4 nor exclusive hindbrain markers krox-20 and hoxb1a. Additionally, using a Retinoic Acid (RA) mediated reporter transgenic, we detect no alterations in the RA expression domains in the hindbrain and spinal cord, but do detect a loss of expression in the retina. We conclude that glyphosate and the Roundup(®) formulation is developmentally toxic to the forebrain and midbrain but does not affect the hindbrain after 24h exposure. PMID:26773362

  18. Feasibility of constructed wetlands for removing chlorothalonil and chlorpyrifos from aqueous mixtures

    Energy Technology Data Exchange (ETDEWEB)

    Sherrard, R.M.; Bearr, J.S.; Murray-Gulde, C.L.; Rodgers, J.H.; Shah, Y.T

    2004-02-01

    Chlorpyrifos (an insecticide) and chlorothalonil (a fungicide) are transported in stormwater runoff and can be lethal to receiving aquatic system biota. This study determined removal rates of chlorpyrifos and chlorothalonil in simulated stormwater runoff treated in constructed wetland mesocosms. Using sentinel species, Ceriodaphnia dubia and Pimephales promelas, observed declines in toxicity of the simulated runoff after treatment were 98 and 100%, respectively. First order removal rates were 0.039/h for chlorpyrifos and 0.295/h for chlorothalonil in these experiments. Constructed wetland mesocosms were effective for decreasing concentrations of chlorpyrifos and chlorothalonil in simulated stormwater runoff, and decreasing P. promelas and C. dubia mortality resulting from these exposures. The results from this study indicate that constructed wetlands could be part of an efficient mitigation strategy for stormwater runoff containing these pesticides. - Constructed wetlands have potential for treatment of pesticide mixtures in stormwater runoff.

  19. 76 FR 39399 - Chlorpyrifos Registration Review; Preliminary Human Health Risk Assessment; Notice of Availability

    Science.gov (United States)

    2011-07-06

    ... AGENCY Chlorpyrifos Registration Review; Preliminary Human Health Risk Assessment; Notice of Availability AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: This notice announces the... human health or the environment. As part of the registration review process, the Agency has completed...

  20. INCREASED SUSCEPTIBILITY OF THE SPONTANEOUSLY HYPERTENSIVE RAT TO CHLORPYRIFOS, AN ORGANOPHOSPHATE PESTICIDE.

    Science.gov (United States)

    Hypertension and hypothermia are common symptoms in rats exposed to chlorpyrifos (CHP), an organophosphate (OP)-based pesticide. CHP inhibits acetylcholinesterase (AChE) activity resulting in central and peripheral stimulation of cholinergic pathways involved in blood pressure ...

  1. THE EFFECTS OF CHRONIC EXERCISE CONDITIONING ON THERMOREGULATORY RESPONSE TO CHLORPYRIFOS IN FEMALE RATS.

    Science.gov (United States)

    Chronic exercise conditioning has been shown to alter basal thermoregulatory processes (change in thermoregulatory set-point) as well as the response to infectious fever. Chlorpyrifos (CHP), an organophosphate pesticide, causes an acute period of hypothermia followed by a delaye...

  2. Feasibility of constructed wetlands for removing chlorothalonil and chlorpyrifos from aqueous mixtures

    International Nuclear Information System (INIS)

    Chlorpyrifos (an insecticide) and chlorothalonil (a fungicide) are transported in stormwater runoff and can be lethal to receiving aquatic system biota. This study determined removal rates of chlorpyrifos and chlorothalonil in simulated stormwater runoff treated in constructed wetland mesocosms. Using sentinel species, Ceriodaphnia dubia and Pimephales promelas, observed declines in toxicity of the simulated runoff after treatment were 98 and 100%, respectively. First order removal rates were 0.039/h for chlorpyrifos and 0.295/h for chlorothalonil in these experiments. Constructed wetland mesocosms were effective for decreasing concentrations of chlorpyrifos and chlorothalonil in simulated stormwater runoff, and decreasing P. promelas and C. dubia mortality resulting from these exposures. The results from this study indicate that constructed wetlands could be part of an efficient mitigation strategy for stormwater runoff containing these pesticides. - Constructed wetlands have potential for treatment of pesticide mixtures in stormwater runoff

  3. Integrated biomarker analysis of chlorpyrifos metabolism and toxicity in the earthworm Aporrectodea caliginosa.

    Science.gov (United States)

    Sanchez-Hernandez, Juan C; Narvaez, C; Sabat, P; Martínez Mocillo, S

    2014-08-15

    To increase our understanding about the mode of toxic action of organophosphorus pesticides in earthworms, a microcosm experiment was performed with Aporrectodea caliginosa exposed to chlorpyrifos-spiked soils (0.51 and 10 mg kg(-1) dry soil) for 3 and 21 d. Acetylcholinesterase (AChE), carboxylesterase (CbE), cytochrome P450-dependent monooxygenase (CYP450), and glutathione S-transferase (GST) activities were measured in the body wall of earthworms. With short-term exposure, chlorpyrifos inhibited CbE activity (51-89%) compared with controls in both treated groups, whereas AChE activity was depressed in the 10-mg kg(-1) group (87% inhibition). With long-term exposure, chlorpyrifos strongly inhibited all esterase activities (84-97%). Native electrophoresis revealed three AChE isozymes, two of which showed a decreased staining corresponding to the level of pesticide exposure. The impact of chlorpyrifos on CbE activity was also corroborated by zymography. CYP450 activity was low in unexposed earthworms, but it increased (1.5- to 2.4-fold compared to controls) in the earthworms exposed to both chlorpyrifos concentrations for 3d. Bioactivation of chlorpyrifos was determined by incubating the muscle homogenate in the presence of chlorpyrifos and NAD(H)2. The mean (±SD, n=40) bioactivation rate in the unexposed earthworms was 0.74±0.27 nmol NAD(H)2 oxidized min(-1) mg(-1) protein, and a significant induction was detected in the low/short-term exposure group. GST activity significantly increased (33-35% of controls) in earthworms short-term exposed to both chlorpyrifos concentrations. Current data showed that CYP450 and GST activities had a prominent role in the initial exposure to the organophosphorus. With short-term exposure, CbE activity was also a key enzyme in the non-catalytic detoxification of chlorpyrifos-oxon, thereby reducing its impact on AChE activity, before it became saturated at t=21 d. Results indicate that A. caliginosa detoxify efficiently

  4. Chlorpyrifos-induced Histopathological Alterations in Duttaphrynus melanostictus (Schneider 1799) Tadpoles: Evidence from Empirical Trials

    OpenAIRE

    M. G. D. K. Bandara; M. R. Wijesinghe; W D Ratnasooriya; A. A. H. Priyani

    2012-01-01

    This paper reports the histopathological responses of the gill, liver and tail muscle tissues in tadpoles of the Asian Common Toad Duttaphrynus melanostictus (Schneider, 1799) exposed to chlorpyrifos a common organophosphorus pesticide. Tadpoles of Gosner stages 24-26 were continuously exposed to low, mid and high (500, 1000 and 1500 µgl–1) concentrations of chlorpyrifos for two weeks. Histological alterations in the tissues of the surviving larvae were microscopically examined both at the en...

  5. Genotoxicity of Chlorpyrifos and the Antimutagenic Role of Lettuce Leaves in Male Mice

    Directory of Open Access Journals (Sweden)

    Kamilia Badrakhan Abdelaziz

    2010-11-01

    Full Text Available Chlorpyrifos [O O-diethyl-O-(3 5 6-trichloro-2-pyridyl-phosphorothioate] is one of the most widelyused organophosphate insecticides. Previous studies proved that chlorpyrifos, at different doses,induced genotoxicity. In Egyptian foods, the residual levels of pesticides are often higher than thosefound in developed country ones. So the aim of this research was to evaluate the genotoxicity of theinsecticide chlorpyrifos at doses equal to its maximum residue limit (MRL in the leafy vegetables, itsdouble and quadruple (0.5, 1 and 2 mg/kg body weight in somatic and germ cells of male mice.In addition to that, evaluating the role of lettuce leaves as antigenotoxic in reducing the genotoxiceffects of chlorpyrifos tested doses when concurrently administrated to these animals. The studywas conducted on adult male laboratory mice at three levels: bone marrow cells as a model formitotic chromosome aberrations, spermatocytes as a model for meiotic chromosomes and spermcount and morphology. The results of the present study indicate that the treatment of male micewith chlorpyrifos by oral gavages for three months induced significant increase in the frequencies oftotal chromosomal aberrations in both somatic and germ cells in relation to control groups. Resultsof the sperm analysis showed that chlorpyrifos induced significant decrease in the sperm countwhen compared to negative control. Furthermore, it induced significant increase in head and tailsperm abnormalities, among which coiled tail was considered the most obvious sperm abnormalityinduced by chlorpyrifos. At the same time, the present study indicated that lettuce leaves feedconcurrently with three doses of chlorpyrifos could not protect cells from damage.

  6. SEM study of ultrastructural changes in branchial architecture of Ctenopharyngodon idella (Cuvier & Valenciennes) exposed to chlorpyrifos

    OpenAIRE

    Kaur Mandeep; Jindal Rajinder

    2016-01-01

    We evaluated structural modifications in the branchial architecture of grass carp, Ctenopharyngodon idella, chronically exposed to chlorpyrifos (an organophosphate) using scanning electron microscopy (SEM). Static renewal tests were conducted for 96 h to determine the LC50 of chlorpyrifos to the fish. Physicochemical analysis of water was done using standard methods. To assess the effect of chronic toxicity, fish were exposed to two sublethal concentrations...

  7. Sub-lethal toxicity of chlorpyrifos on Common carp, Cyprinus carpio (Linnaeus, 1758): Biochemical response

    OpenAIRE

    Mahdi Banaee; Behzad Nematdoust Haghi; Ahmed Th. A. Ibrahim

    2014-01-01

    Chlorpyrifos, an organophosphate pesticide, is widely used to control pests in agriculture farms and orchards of fruit trees. In this study, the fish were exposed to sub-lethal concentrations of chlorpyrifos which were determined based on numerical value of 96 h LC50. Blood was sampled after 10, 20 and 30 days and biochemical parameters including glucose, total protein, albumin, globulin, triglyceride and cholesterol levels, and aspartate aminotransferase (AST), alanine aminotransferase (ALT)...

  8. Evaluating Oxidative Stress Factors Induced by Chlorpyrifos Poisoning in Plasma of Wistar Rat

    OpenAIRE

    Saberi, M; A Zare’i Mahmoudabadi; M Fasihi Ramandi; A. Kazemi; J Rasouli Vani

    2014-01-01

    Introduction: Chlorpyrifos (CPF) is a broad-spectrum organophosphorus insecticide that has been used abundantly over the globe during the past 40 years. Chemical pesticides may induce oxidative stress via generating free radicals and altering antioxidant levels of the free radical scavenging enzyme activity. Therefore, this study aimed to evaluate the toxicity of Chlorpyrifos-induced oxidative stress in the plasma samples of Wistar rat. Methods: Twenty-four male Wistar rats were selected r...

  9. Dissipation and Leachability of Formulated Chlorpyrifos and Atrazine in Organically-amended Soils

    OpenAIRE

    Xiao, Yunxiang III

    1997-01-01

    Dissipation and Leachability of Formulated Chlorpyrifos and Atrazine in Organically-amended Soils Yunxiang Xiao Dr. Donald E. Mullins, Chairperson Department of Entomology (ABSTRACT) Bioremediation was studied in soils containing high concentrations of formulated chlorpyrifos (5 mg kg-1 Dursban® 4E) and atrazine (5 mg kg-1 AAtrex® 4L) using amendments including lignocellulosic sorbents, microbial nutrients (vegetable oil, corn meal and fertilizers), and microbial e...

  10. Update of the morbidity experience of employees potentially exposed to chlorpyrifos

    OpenAIRE

    Burns, C J; Cartmill, J. B.; Powers, B. S.; Lee, M K

    1998-01-01

    OBJECTIVES: Chlorpyrifos, an organophosphate ingredient of several important insecticides, has been manufactured at The Dow Chemical Company for 25 years. A previous morbidity study among employees of The Dow Chemical Company found no increased prevalence of illness or symptoms among employees potentially exposed to chlorpyrifos from 1977 to 1985 compared with matched controls. The purpose of the current study was to update the original study to 1994, thereby increasing the statistical ...

  11. Residues of 14C-chlorpyrifos in coconut by radiotracer techniques

    International Nuclear Information System (INIS)

    A coconut tree was root-infused with 5 g a.i. chlorpyrifos (Lorsban plus 1.4 uCi of 14C-chlorpyrifos. Coconut samples both young and mature, were taken 24 h up to 60 days after root infusion. Analysis of the meat and water was done. The maximum uptake of chlorpyrifos equivalents was on the 13th day after root infusion both in mature and young fruit. The residue in water reached the peak on the 20th day after infusion and declined thereafter. A preharvest interval (PHI) of more than 60 days maybe recommended for safe consumption. The usual practice of storing copra in treated warehouses until it is processed into oil was simulated in the laboratory to determine the residues absorbed on the meat. Forty kg of copra with moisture content of 7-12% were stored in an improvised warehouse, i.e. 1 m x 1.5 m x 1 m wooden box, which was treated with 100 ml 1% a.i. Lorsban 50 WP plus 100 uCi 14C-chlorpyrifos for protection against insects. Analysis showed that 14C-chlorpyrifos equivalents ranged from 22.6 mg/kg on the 30th day to 8.2 mg/kg on the 90th day with a 63.7% reduction in residues. Bound residues were detected on samples stored for 60-90 days, with levels of 1.0 to 0.2 ug/g 14 C-chlorpyrifos equivalents. This is within the Maximum Residue Limit of 2 mg/kg set by FAO/WHO for chlorpyrifos in most agricultural commodities. Chlorpyrifos residues were also determined at various stages of refining and processing of crude coconut oil. It was subjected to alkali refining, bleaching and finally steaming. The residues were reduced by as much as 32.7%. (author). 18 refs.; 2 figs.; 3 tabs

  12. Persistence of chlorpyrifos, diazinon and dimethoate sprayed in the greenhouse environment during hydroponic cultivation of Gerbera

    OpenAIRE

    P. Hatzilazarou, Stefanos; Charizopoulos, Emmanouel; Papadopoulou-Mourkidou, Euphemia; S. Economou, Athanasios

    2005-01-01

    International audience The fate and behavior of chlorpyrifos, diazinon and dimethoate in a greenhouse installation during hydroponic cultivation of Gerbera was investigated. Their concentrations in the greenhouse air were related to their physicochemical properties. Thus, diazinon exhibited the highest concentration in the greenhouse air 2 hours after application, while chlorpyrifos and dimethoate were measured at lower concentrations. Afterwards, a rapid decrease was recorded. The concent...

  13. Neurotoxic aspects of porphyinopathies: lead and succinylacetone

    Energy Technology Data Exchange (ETDEWEB)

    Silbergeld, E.K. (National Inst. of Health, Bethesda, MD); Hruska, R.E.; Bradley, D.; Lamon, J.M.; Frykholm, B.C.

    1982-12-01

    Neurotoxic effects of heavy metals and polyhalogenated hydrocarbons frequently occur at low levels of exposure, in some cases below those levels where direct toxic actions of these compounds have been demonstrated. Rats with acute and chronic lead exposure were compared to rats whose heme synthesis was inhibited by succinylacetone, as a semichronic model of the hereditary heme synthesis disorder, acute intermittent porphyria. Both treatments produce significant inhibition in activity of the enzyme delta-aminolevulinic acid dehydrase and elevations in the heme precursor delta-aminolevulinic acid (ALA) in tissues and urine. Associated with increased ALA is a significant inhibition of neurotransmission utilizing the amino acid ..gamma..-aminobutyric acid (GABA), expressed chemically and behaviorally. The results suggest that in addition to their direct molecular neurotoxicity, porphyrinopathic compounds such as lead may, through altering heme synthesis, adversely affect the brain at low levels of exposure.

  14. Melatonin Attenuates Methamphetamine-Induced Neurotoxicity.

    Science.gov (United States)

    Wongprayoon, Pawaris; Govitrapong, Piyarat

    2016-01-01

    Methamphetamine (METH), an illegal psycho-stimulant, is widely known as a recreational drug. In addition to its addictive effect, METH induces neurotoxicity via multiple mechanisms. The major contributors to METH-induced neurotoxicity are reactive oxygen species, which lead to cell death through apoptotic pathway and disturbances in mitochondria, the generation of neuroinflammation, and autophagy. Melatonin, a neurohormone secreted by the pineal gland, is a potent antioxidant compound that plays a beneficial role by protecting against the oxidative stress caused by METH. Melatonin also plays a role in maintaining mitochondrial homeostasis. Nanomolar concentrations of melatonin have been shown to protect against the inflammation caused by METH and to prevent the decrease in neurogenesis caused by METH in progenitor cells obtained from adult rat hippocampal tissue. The intent of this review is to describe the underlying mechanisms involving melatonin that protect against the neurodegeneration caused by METH. PMID:25248807

  15. Clinical Neurotoxic Disorders : Past, Present and Future

    OpenAIRE

    Nag Devika

    2001-01-01

    Neurotoxins have existed on the earth from times immemorial. Old neurotoxic disorders were due to ingestion/ exposure of heavy metals and food like lathyrus sativus over a long period of time. The 20th Century with rapid industrialsation and expanding chemical and drug industry has spawned several new, hitherto unknown disorders. Old disorders continue to exist e.g. fluorosis, arsenicosis, lathyrism, manganism and lead neuropathy, along with new diseases like Minamata disease, subacute myelo ...

  16. Clinical Neurotoxic Disorders : Past, Present and Future

    Directory of Open Access Journals (Sweden)

    Nag Devika

    2001-01-01

    Full Text Available Neurotoxins have existed on the earth from times immemorial. Old neurotoxic disorders were due to ingestion/ exposure of heavy metals and food like lathyrus sativus over a long period of time. The 20th Century with rapid industrialsation and expanding chemical and drug industry has spawned several new, hitherto unknown disorders. Old disorders continue to exist e.g. fluorosis, arsenicosis, lathyrism, manganism and lead neuropathy, along with new diseases like Minamata disease, subacute myelo optic neuropathy (SMON, MPTP-Parkinsonian syndorme, triorthcresyl phosphate (TOCP neuroparalytic disease, pesticide induced seizures, tremor and neuropathy, solvent encephalopthy, antipileptic drug foetal syndrome and excitotoxin induced behavioural disorders. Studies on pesticides Organochlorine and organophosphates, synthetic pyrethrins, solvents, heavy metals and substances abuse in the Indian context confirm the neurotoxic nature of many synthetic substances. Future problems envisaged are of concern to clinical neurologists as many of these neurotoxic disorders mimic syndromes of well known neurological disease. The new millenium poses a challenge to the clinician as newer compounds in industry, food, drugs and chemical war agents are being developed. Molecular genetics has advanced rapidly with release of the human genome map. Animal cloning and genetically modified plant products have entered the food chain. How safe are these new inventions for the central nervous system is a big question? India cannot afford disasters like Union Carbide′s Bhopal gas leak nor be a silent spectator to manipulative biotechnology. Unless it is proven beyond all doubt to be a safe innovation, Chemicals have to be cautiously introduced in our environment. To Study, ascertain and confirm safety or neurotoxicity is an exciting challenge for the neuroscientists of the 21st century.

  17. Pathophysiology of Manganese-Associated Neurotoxicity

    OpenAIRE

    Racette, Brad A.; Aschner, Michael; Guilarte, Tomas R.; Dydak, Ulrike; Criswell, Susan R; Zheng, Wei

    2011-01-01

    Manganese (Mn) is a well established neurotoxin associated with specific damage to the basal ganglia in humans. The phenotype associated with Mn neurotoxicity was first described in two workers with occupational exposure to Mn oxide.(Couper, 1837) Although the description did not use modern clinical terminology, a parkinsonian illness characterized by slowness of movement (bradykinesia), masked facies, and gait impairment (postural instability) appears to have predominated. Nearly 100 years l...

  18. Toxicological effects of chlorpyrifos on growth, enzyme activity and chlorophyll a synthesis of freshwater microalgae.

    Science.gov (United States)

    Chen, Shangchao; Chen, Mindong; Wang, Zhuang; Qiu, Weijian; Wang, Junfeng; Shen, Yafei; Wang, Yajun; Ge, Shun

    2016-07-01

    This paper aims to acquire the experimental data on the eco-toxicological effects of agricultural pollutants on the aquatic plants and the data can support the assessment of toxicity on the phytoplankton. The pesticide of Chlorpyrifos used as a good model to investigate its eco-toxicological effect on the different microalgae in freshwater. In order to address the pollutants derived from forestry and agricultural applications, freshwater microalgae were considered as a good sample to investigate the impact of pesticides such as Chlorpyrifos on aquatic life species. Two microalgae of Chlorella pyrenoidosa and Merismopedia sp. were employed to evaluate toxicity of Chlorpyrifos in short time and long time by means of measuring the growth inhibition rate, the redox system and the content of chlorophyll a, respectively. In this study, the results showed that EC50 values ranging from 7.63 to 19.64mg/L, indicating the Chlorpyrifos had a relatively limited to the growth of algae during the period of the acute toxicity experiment. Moreover, when two kinds of algae were exposed to a medium level of Chlorpyrifos, SOD and CAT activities were importantly advanced. Therefore, the growth rate and SOD and CAT activities can be highly recommended for the eco-toxicological assessment. In addition, chlorophyll a also could be used as a targeted parameter for assessing the eco-toxicity of Chlorpyrifos on both Chlorella pyrenoidosa and Merismopedia sp. PMID:27314761

  19. Removal of chlorpyrifos by water lettuce (Pistia stratiotes L.) and duckweed (Lemna minor L.).

    Science.gov (United States)

    Prasertsup, Pichamon; Ariyakanon, Naiyanan

    2011-04-01

    The potential of water lettuce (Pistia stratiotes L.) and duckweed (Lemna minor L.) to remove chlorpyrifos in water was investigated under laboratory greenhouse conditions. At initial chlorpyrifos concentrations of 0.0, 0.1 and 0.5 mg/L, the relative growth rates (RGR) of L. minor and P. stratiotes were not significantly different. In contrast, in the presence of 1 mg/L chlorpyrifos the RGR was significantly inhibited, giving an observed fresh weight based RGR(FW) for P. stratiotes and L. minor from day 0 to 7 of -0.036 and -0.023 mg/g/day, respectively. The maximum removal of chlorpyrifos by P. stratiotes and L. minor, when chlorpyrifos was at an initial culture concentration of 0.5 mg/L, was 82% and 87%, respectively, with disappearance rate constants under these conditions of 2.94, 10.21 and 12.14 microg h(-1) for the control (no plants), and with P. stratiotes and L. minor, respectively, giving actual corrected plant removal rate constants of 7.27 and 9.20 microg h(-1) for P. stratiotes and L. minor, respectively. The bioconcentration factor (BCF) of L. minor was significantly greater than that for P. stratiotes and therefore, at least under these greenhouse-based conditions, L. minor was more efficient than P. stratiotes for the accelerated removal of chlorpyrifos from water. PMID:21598800

  20. Development of a freeze-dried fungal wettable powder preparation able to biodegrade chlorpyrifos on vegetables.

    Directory of Open Access Journals (Sweden)

    Jie Liu

    Full Text Available Continuous use of the pesticide chlorpyrifos has resulted in harmful contaminations in environment and species. Based on a chlorpyrifos-degrading fungus Cladosporium cladosporioides strain Hu-01 (collection number: CCTCC M 20711, a fungal wettable powder preparation was developed aiming to efficiently remove chlorpyrifos residues from vegetables. The formula was determined to be 11.0% of carboxymethyl cellulose-Na, 9.0% of polyethylene glycol 6000, 5.0% of primary alcohol ethoxylate, 2.5% of glycine, 5.0% of fucose, 27.5% of kaolin and 40% of freeze dried fungi by response surface methodology (RSM. The results of quality inspection indicated that the fungal preparation could reach manufacturing standards. Finally, the degradation of chlorpyrifos by this fungal preparation was determined on pre-harvest cabbage. Compared to the controls without fungal preparation, the degradation of chlorpyrifos on cabbages, which was sprayed with the fungal preparation, was up to 91% after 7 d. These results suggested this freeze-dried fungal wettable powder may possess potential for biodegradation of chlorpyrifos residues on vegetables and provide a potential strategy for food and environment safety against pesticide residues.

  1. Prenatal chlorpyrifos exposure alters motor behavior and ultrasonic vocalization in cd-1 mouse pups

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    Calamandrei Gemma

    2009-03-01

    Full Text Available Abstract Background Chlorpyrifos (CPF is a non-persistent organophosphate (OP largely used as pesticide. Studies from animal models indicate that CPF is a developmental neurotoxicant able to target immature central nervous system at dose levels well below the threshold of systemic toxicity. So far, few data are available on the potential short- and long-term adverse effects in children deriving from low-level exposures during prenatal life and infancy. Methods Late gestational exposure [gestational day (GD 14–17] to CPF at the dose of 6 mg/kg was evaluated in CD-1 mice during early development, by assessment of somatic and sensorimotor maturation [reflex-battery on postnatal days (PNDs 3, 6, 9, 12 and 15] and ultrasound emission after isolation from the mother and siblings (PNDs 4, 7 and 10. Pups' motor skills were assessed in a spontaneous activity test on PND 12. Maternal behavior of lactating dams in the home cage and in response to presentation of a pup previously removed from the nest was scored on PND 4, to verify potential alterations in maternal care directly induced by CPF administration. Results As for the effects on the offspring, results indicated that on PND 10, CPF significantly decreased number and duration of ultrasonic calls while increasing latency to emit the first call after isolation. Prenatal CPF also reduced motor behavior on PND 12, while a tendency to hyporeflexia was observed in CPF pups by means of reflex-battery scoring. Dams administered during gestation with CPF showed baseline levels of maternal care comparable to those of controls, but higher levels of both pup-directed (licking and explorative (wall rearing responses. Conclusion Overall our results are consistent with previous epidemiological data on OP neurobehavioral toxicity, and also indicate ultrasonic vocalization as an early marker of CPF exposure during development in rodent studies, with potential translational value to human infants.

  2. Neurotoxicity of artemether and its mechanism

    Institute of Scientific and Technical Information of China (English)

    ZhaoYH; WangTY

    2002-01-01

    It was reported that artemisinin derivatives in high does could lead to neurotoxicity in rat,dog and monkey.Using artemether as a representative,neurotoxicity and its mechanism of artemisinin derivatives was studied in vitro.MTT assay showed that artemether could affect MTT transformation of pheochromocytoma cell significantly.The morphologic result showed that artemisinin mainly injured mitochondria of pheochromocytoma cells and primary cultured rat neural cells with mitochondrial swelling and mitochondrial crista decreasing,rupturing and disappearing,and degeneration.Artemisinin could decrease mitochondrial transmembrane potential in both cell types in a dose-dependent manner and inhibit activity of the complex I and Ⅳ of mitochondria respiratory chain of rat brain.but the production of malondialdehyde in rat cerebral cortex mitochondria wasn't increased by artemether.Based on these experiments,it may infer that one of the neurotoxic mechanism of arfemether lies on its effects on the structure and function of mitochondria of neural cell.

  3. Neurotoxicity of Acrylamide in Exposed Workers

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    Mariano Malaguarnera

    2013-08-01

    Full Text Available Acrylamide (ACR is a water-soluble chemical used in different industrial and laboratory processes. ACR monomer is neurotoxic in humans and laboratory animals. Subchronic exposure to this chemical causes neuropathies, hands and feet numbness, gait abnormalities, muscle weakness, ataxia, skin and in some cases, cerebellar alterations. ACR neurotoxicity involves mostly the peripheral but also the central nervous system, because of damage to the nerve terminal through membrane fusion mechanisms and tubulovescicular alterations. Nevertheless, the exact action mechanism is not completely elucidated. In this paper we have reviewed the current literature on its neurotoxicity connected to work-related ACR exposure. We have analyzed not only the different pathogenetic hypotheses focusing on possible neuropathological targets, but also the critical behavior of ACR poisoning. In addition we have evaluated the ACR-exposed workers case studies. Despite all the amount of work which have being carried out on this topic more studies are necessary to fully understand the pathogenetic mechanisms, in order to propose suitable therapies.

  4. The role of multifunctional drug therapy as an antidote to combat experimental subacute neurotoxicity induced by organophosphate pesticides.

    Science.gov (United States)

    Singh, Satinderpal; Prakash, Atish; Kaur, Shamsherjit; Ming, Long Chiau; Mani, Vasudevan; Majeed, Abu Bakar Abdul

    2016-08-01

    Organophosphate pesticides are used in agriculture where they are associated with numerous cases of intentional and accidental misuse. These toxicants are potent inhibitors of cholinesterases leading to a massive build-up of acetylcholine which induces an array of deleterious effects, including convulsions, oxidative damage and neurobehavioral deficits. Antidotal therapies with atropine and oxime yield a remarkable survival rate, but fail to prevent neuronal damage and behavioral problems. It has been indicated that multifunction drug therapy with potassium channel openers, calcium channel antagonists and antioxidants (either single-agent therapy or combination therapy) may have the potential to prevent cell death and/or slow down the processes of secondary neuronal damage. The aim of the present study, therefore, was to make a relative assessment of the potential effects of nicorandil (2 mg/kg), clinidipine (10 mg/kg), and grape seed proanthocyanidin (GSPE) extract (200 mg/kg) individually against subacute chlorpyrifos induced toxicity. The test drugs were administered to Wistar rats 2 h after exposure to Chlorpyrifos (CPF). Different behavioral studies and biochemical estimation has been carried in the study. The results showed that chronic administration of CPF significantly impaired learning and memory, along with motor coordination, and produced a marked increase in oxidative stress along with significantly reduced acetylcholine esterase (AChE) activity. Treatment with nicorandil, clinidipine and GSPE was shown to significantly improve memory performance, attenuate oxidative damage and enhance AChE activity in rats. The present study also suggests that a combination of nicorandil, clinidipine, and GSPE has a better neuroprotective effect against subacute CPF induced neurotoxicity than if applied individually. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1017-1026, 2016. PMID:25864908

  5. Children's residential exposure to chlorpyrifos: Application of CPPAES field measurements of chlorpyrifos and TCPy within MENTOR/SHEDS-Pesticides model

    International Nuclear Information System (INIS)

    The comprehensive individual field-measurements on non-dietary exposure collected in the Children's-Post-Pesticide-Application-Exposure-Study (CPPAES) were used within MENTOR/SHEDS-Pesticides, a physically based stochastic human exposure and dose model. In this application, however, the model was run deterministically. The MENTOR/SHEDS-Pesticides employed the CPPAES as input variables to simulate the exposure and the dose profiles for seven children over a 2-week post-application period following a routine residential and professional indoor crack-and-crevice chlorpyrifos application. The input variables were obtained from a personal activity diary, microenvironmental measurements and personal biomonitoring data obtained from CPPAES samples collected from the individual children and in their homes. Simulation results were compared with CPPAES field measured values obtained from the children's homes to assess the utility of the different microenvironmental data collected in CPPAES, i.e. indicator toys and wipe samplers to estimate aggregate exposures that can be result from one or more exposure pathways and routes. The final analyses of the database involved comparisons of the actual data obtained from the individual biomarker samples of a urinary metabolite of chlorpyrifos (TCPy) and the values predicted by MENTOR/SHEDS-Pesticides using the CPPAES-derived variables. Because duplicate diet samples were not part of the CPPAES study design, SHEDs-Pesticides simulated dose profiles did not account for the dietary route. The research provided more confidence in the types of data that can be used in the inhalation and dermal contact modules of MENTOR/SHEDS-Pesticides to predict the pesticide dose received by a child. It was determined that we still need additional understanding about: (1) the types of activities and durations of activities that result in non-dietary ingestion of pesticides and (2) the influence of dietary exposures on the levels of TCPy found in the

  6. Propofol-Induced Neurotoxicity in the Fetal Animal Brain and Developments in Modifying These Effects—An Updated Review of Propofol Fetal Exposure in Laboratory Animal Studies

    Directory of Open Access Journals (Sweden)

    Ming Xiong

    2016-03-01

    Full Text Available In the past twenty years, evidence of neurotoxicity in the developing brain in animal studies from exposure to several general anesthetics has been accumulating. Propofol, a commonly used general anesthetic medication, administered during synaptogenesis, may trigger widespread apoptotic neurodegeneration in the developing brain and long-term neurobehavioral disturbances in both rodents and non-human primates. Despite the growing evidence of the potential neurotoxicity of different anesthetic agents in animal studies, there is no concrete evidence that humans may be similarly affected. However, given the growing evidence of the neurotoxic effects of anesthetics in laboratory studies, it is prudent to further investigate the mechanisms causing these effects and potential ways to mitigate them. Here, we review multiple studies that investigate the effects of in utero propofol exposure and the developmental agents that may modify these deleterious effects.

  7. A Human Life-Stage Physiologically Based Pharmacokinetic and Pharmacodynamic Model for Chlorpyrifos: Development and Validation

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Jordan N.; Hinderliter, Paul M.; Timchalk, Charles; Bartels, M. J.; Poet, Torka S.

    2014-08-01

    Sensitivity to chemicals in animals and humans are known to vary with age. Age-related changes in sensitivity to chlorpyrifos have been reported in animal models. A life-stage physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed to computationally predict disposition of CPF and its metabolites, chlorpyrifos-oxon (the ultimate toxicant) and 3,5,6-trichloro-2-pyridinol (TCPy), as well as B-esterase inhibition by chlorpyrifos-oxon in humans. In this model, age-dependent body weight was calculated from a generalized Gompertz function, and compartments (liver, brain, fat, blood, diaphragm, rapid, and slow) were scaled based on body weight from polynomial functions on a fractional body weight basis. Blood flows among compartments were calculated as a constant flow per compartment volume. The life-stage PBPK/PD model was calibrated and tested against controlled adult human exposure studies. Model simulations suggest age-dependent pharmacokinetics and response may exist. At oral doses ≥ 0.55 mg/kg of chlorpyrifos (significantly higher than environmental exposure levels), 6 mo old children are predicted to have higher levels of chlorpyrifos-oxon in blood and higher levels of red blood cell cholinesterase inhibition compared to adults from equivalent oral doses of chlorpyrifos. At lower doses that are more relevant to environmental exposures, the model predicts that adults will have slightly higher levels of chlorpyrifos-oxon in blood and greater cholinesterase inhibition. This model provides a computational framework for age-comparative simulations that can be utilized to predict CPF disposition and biological response over various postnatal life-stages.

  8. Chlorpyrifos exposure in farmers and urban adults: Metabolic characteristic, exposure estimation, and potential effect of oxidative damage.

    Science.gov (United States)

    Wang, Lei; Liu, Zhen; Zhang, Junjie; Wu, Yinghong; Sun, Hongwen

    2016-08-01

    Chlorpyrifos is a widely used organophosphorus pesticide that efficiently protects crops against pests. However, recent studies suggest that severe exposure to chlorpyrifos may present adverse health effects in human. To analyze the exposure level and metabolic characteristics of chlorpyrifos pesticide in urban adults and farmers with/without occupation pesticide contact, the occurrence of urinary chlorpyrifos and methyl chlorpyrifos (CP-me), as well as their metabolite, 3,5,6-trichloro-2-pyridinol (TCPy), was determined in farmers of an agricultural village in China, and in urban adults of a nearby town. The geometric mean (GM) concentrations of TCPy, which is the major marker of chlorpyrifos exposure, were 4.29 and 7.57μg/g-creatinine in urban adults and farmers before pesticide application, respectively. Chlorpyrifos spraying significantly increased the concentrations of urinary TCPy. In the first day after spraying, a GM concentration of 43.7μg/g-creatinine was detected in the urine specimens from farmers, which decreased to 38.1 and 22.8μg/g-creatinine in the second and third day after chlorpyrifos spraying. The ratio of TCPy and its parent compounds, i.e. chlorpyrifos and CP-me, was positively associated with the sum concentration of urinary chlorpyrifos, CP-me, and TCPy, suggesting the increasing metabolic efficiency of chlorpyrifos to TCPy at higher chlorpyrifos exposure levels. To estimate the farmers' occupational exposure to chlorpyrifos pesticide, a new model based on the fitted first-order elimination kinetics of TCPy was established. Occupational chlorpyrifos exposure in a farmer was estimated to be 3.70μg/kg-bw/day (GM), which is an exposure level that is higher than the recommended guideline levels. Significant increase of urinary 8-hydroxydeoxyguanosine (8-OHdG) was observed on the first day after chlorpyrifos spraying, which indicates a potential oxidative damage in farmers. However, urinary 8-OHdG returned to its baseline level within two

  9. Reappraisal of Vipera aspis venom neurotoxicity.

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    Elisabeth Ferquel

    Full Text Available BACKGROUND: The variation of venom composition with geography is an important aspect of intraspecific variability in the Vipera genus, although causes of this variability remain unclear. The diversity of snake venom is important both for our understanding of venomous snake evolution and for the preparation of relevant antivenoms to treat envenomations. A geographic intraspecific variation in snake venom composition was recently reported for Vipera aspis aspis venom in France. Since 1992, cases of human envenomation after Vipera aspis aspis bites in south-east France involving unexpected neurological signs were regularly reported. The presence of genes encoding PLA(2 neurotoxins in the Vaa snake genome led us to investigate any neurological symptom associated with snake bites in other regions of France and in neighboring countries. In parallel, we used several approaches to characterize the venom PLA(2 composition of the snakes captured in the same areas. METHODOLOGY/PRINCIPAL FINDINGS: We conducted an epidemiological survey of snake bites in various regions of France. In parallel, we carried out the analysis of the genes and the transcripts encoding venom PLA(2s. We used SELDI technology to study the diversity of PLA(2 in various venom samples. Neurological signs (mainly cranial nerve disturbances were reported after snake bites in three regions of France: Languedoc-Roussillon, Midi-Pyrénées and Provence-Alpes-Côte d'Azur. Genomes of Vipera aspis snakes from south-east France were shown to contain ammodytoxin isoforms never described in the genome of Vipera aspis from other French regions. Surprisingly, transcripts encoding venom neurotoxic PLA(2s were found in snakes of Massif Central region. Accordingly, SELDI analysis of PLA(2 venom composition confirmed the existence of population of neurotoxic Vipera aspis snakes in the west part of the Massif Central mountains. CONCLUSIONS/SIGNIFICANCE: The association of epidemiological studies to

  10. Developmental Disabilities

    Science.gov (United States)

    Developmental disabilities are severe, long-term problems. They may be physical, such as blindness. They may affect mental ability, such as learning disorders. Or the problem can be both physical and mental, such as Down ...

  11. Purification and characterization of a novel chlorpyrifos hydrolase from Cladosporium cladosporioides Hu-01.

    Directory of Open Access Journals (Sweden)

    Yan Gao

    Full Text Available Chlorpyrifos is of great environmental concern due to its widespread use in the past several decades and its potential toxic effects on human health. Thus, the degradation study of chlorpyrifos has become increasing important in recent years. A fungus capable of using chlorpyrifos as the sole carbon source was isolated from organophosphate-contaminated soil and characterized as Cladosporium cladosporioides Hu-01 (collection number: CCTCC M 20711. A novel chlorpyrifos hydrolase from cell extract was purified 35.6-fold to apparent homogeneity with 38.5% overall recovery by ammoniumsulfate precipitation, gel filtration chromatography and anion-exchange chromatography. It is a monomeric structure with a molecular mass of 38.3 kDa. The pI value was estimated to be 5.2. The optimal pH and temperature of the purified enzyme were 6.5 and 40°C, respectively. No cofactors were required for the chlorpyrifos-hydrolysis activity. The enzyme was strongly inhibited by Hg²⁺, Fe³⁺, DTT, β-mercaptoethanol and SDS, whereas slight inhibitory effects (5-10% inhibition were observed in the presence of Mn²⁺, Zn²⁺, Cu²⁺, Mg²⁺, and EDTA. The purified enzyme hydrolyzed various organophosphorus insecticides with P-O and P-S bond. Chlorpyrifos was the preferred substrate. The Km and Vmax values of the enzyme for chlorpyrifos were 6.7974 μM and 2.6473 μmol·min⁻¹, respectively. Both NH2-terminal sequencing and matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometer (MALDI-TOF-MS identified an amino acid sequence MEPDGELSALTQGANS, which shared no similarity with any reported organophosphate-hydrolyzing enzymes. These results suggested that the purified enzyme was a novel hydrolase and might conceivably be developed to fulfill the practical requirements to enable its use in situ for detoxification of chlorpyrifos. Finally, this is the first described chlorpyrifos hydrolase from fungus.

  12. Degradation of chlorpyrifos contaminated soil by bioslurry reactor operated in sequencing batch mode: bioprocess monitoring

    International Nuclear Information System (INIS)

    Bioslurry reactor (SS-SBR) was studied for the degradation of chlorpyrifos contaminated soil using native mixed microflora, by adopting sequencing batch mode (anoxic-aerobic-anoxic) operation. Reactor operation was monitored for a total cycle period of 72 h consisting of 3 h of FILL, 64 h REACT, 2 h of SETTLE, and 3 h of DECANT with chlorpyrifos concentrations of 3000 μg/g, 6000 μg/g and 12000 μg/g. At 3000 μg/g of chlorpyrifos concentration, 91% was degraded after 72 h of the cycle period, whereas in the case of 6000 μg/g of chlorpyrifos, 82.5% was degraded. However, for 12000 μg/g of chlorpyrifos, only 14.5% degradation was observed. The degradation rate was rapid at lower substrate concentration and 12000 μg/g of substrate concentration was found to be inhibitory. Chlorpyrifos removal rate was slow during the initial phase of the sequence operation. Half-life of chlorpyrifos degradation (t0.5) was estimated to be 6.3 h for 3000 μg/g of substrate, 17.5 h for 6000 μg/g and 732.2 h for 12000 μg/g. Process performance was assessed by monitoring chlorpyrifos concentration and biochemical process parameters viz., pH, oxidation and reduction potential (ORP), dissolved oxygen (DO), oxygen consumption rate (OCR) and microbial count (CFU) during sequence operation. From the experimental data obtained it can be concluded that the rate-limiting step with the bioslurry phase reactor in the process of chlorpyrifos degradation may be attributed to the concentration of substrate present in either soil or liquid phase. Periodic operations (SBR) by varying individual components of substrate with time in each process step place micro-organisms under nutritional changes from feast to famine and maintains a wide distribution in the population of micro-organisms resulting in high uptake of the substrate in the bioslurry reactor

  13. Genotoxic Effects of Chlorpyrifos in Freshwater Fish Cirrhinus mrigala Using Micronucleus Assay

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    Anita Bhatnagar

    2016-01-01

    Full Text Available The genotoxicity of pesticides is an issue of worldwide concern and chlorpyrifos is one of the largest selling organophosphate agrochemicals that has been widely detected in surface waters of India. The studies on long term genotoxic biomarkers are limited; therefore, present study was carried out to analyze the incidence of nuclear anomalies in the blood cells of fresh water fish Cirrhinus mrigala using micronucleus (MN assay as a potential tool for assessment of genotoxicity. Acute toxicity of chlorpyrifos was evaluated by exposing fingerlings to different doses of chlorpyrifos (1/20, 1/10, and 1/5 of LC50 and LC50 was calculated as 0.44 mg L−1 using probit analysis. Blood samples were taken on days 2, 4, 8, 12, 21, 28, and 35. In general, significant effects for both concentration and duration of exposure were observed in treated fish. It was found that MN induction was highest on day 14 at 0.08 mg L−1 concentration of chlorpyrifos. It was concluded that chlorpyrifos is genotoxic pesticide causing nuclear anomalies in Cirrhinus mrigala.

  14. Sub-lethal toxicity of chlorpyrifos on Common carp, Cyprinus carpio (Linnaeus, 1758: Biochemical response

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    Mahdi Banaee

    2014-01-01

    Full Text Available Chlorpyrifos, an organophosphate pesticide, is widely used to control pests in agriculture farms and orchards of fruit trees. In this study, the fish were exposed to sub-lethal concentrations of chlorpyrifos which were determined based on numerical value of 96 h LC50. Blood was sampled after 10, 20 and 30 days and biochemical parameters including glucose, total protein, albumin, globulin, triglyceride and cholesterol levels, and aspartate aminotransferase (AST, alanine aminotransferase (ALT, lactate dehydrogenase (LDH, creatine kinase (CK, alkaline phosphatase (ALP and acetylcholinsetrase (AChE activities were measured. Behavioral changes in the fish were also recorded during the experiment. Unbalanced swimming, swimming in the surface water and hyperglycemia, increased blood triglyceride, and increased levels of AST, LDH and CK activities as well as decreased levels of AChE activity were important changes that were observed in the specimens exposed to chlorpyrifos during experimental periods. The most important alterations in the blood biochemical parameters were measured in the specimens exposed to 40 µg/L chlorpyrifos on the 20th and 30th day of the trial. In conclusion, results of the present study indicated that exposure to sub-lethal concentrations of chlorpyrifos as low as 40 µg/L may cause biochemical and behavioral changes in Cyprinus carpio.

  15. Chlorpyrifos degradation in a Biomix: Effect of pre-incubation and water holding capacity

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    S Fernández-Alberti

    2012-12-01

    Full Text Available Biobed system is a simple method to minimize point source contamination during manipulation of pesticides and is based on the adsorption and degradation potential of a biomix composed by top soil, peat, and straw and covered with a grass layer. In our study, the biomix was prepared with Andisol, peat and straw in a volumetric proportion of 1:1:2, and adsorption and degradation studies were done. Degradation of chlorpyrifos (160 mg a.i. kg-1 and formation of TCP (3, 5, 6-trichloro-2-pyrinidol at different pre-incubation times (0, 15 and 30 days and with different moisture contents (40, 60 and 80 % of water holding capacity were evaluated, ligninolytic enzyme activity and microbial respiration in the biomix were periodically analyzed. Adsorption isotherms were fitted using Freundlich and linear models for Andisol and the biomix. The adsorption assays demonstrated that biomix has a higher capacity to retain chlorpyrifos than top soil. The pre-incubation period, WHC and the concentration of the chlorpyrifos of the biomix influenced the degradation of the contaminant and TCP formation as well as the biological activities in the biomix. The TCP was formed during the first steps of chlorpyrifos degradation and was later degraded in the biomix under all studied conditions. In conclusion, biomix with Andisol, peat and straw (1:1:2, pre-incubated by 15 days and incubated with 60% of WHC is capable to degrade chlorpyrifos efficiently.

  16. Sublethal effect of chlorpyrifos on the population dynamics of an experimental Tetranychus urticae Koch population%毒死蜱亚致死剂量对二斑叶螨实验种群动态的影响

    Institute of Scientific and Technical Information of China (English)

    涂洪涛; 张金勇; 陈汉杰

    2016-01-01

    significantly higher than those of the control, but the intrinsic rate of natural increase, finite rate of increase, and population doubling time, were not significantly different to those of the control. A dispersal test proved that chlorpyrifos strongly stimulated the dispersal ofT. urticae. [Conclusion] The results indicate that the sublethal effects of chlorpyrifos onT. urticaediffered according to developmental stage, and that the dispersal stimulus of chlorpyrifos may be a factor influencing the resurgence of this mite.

  17. Neurotoxicity of a polybrominated diphenyl ether mixture (DE-71) in mouse neurons and astrocytes is modulated by intracellular glutathione levels

    International Nuclear Information System (INIS)

    Polybrominated diphenyl ether (PBDE) flame retardants have become widespread environmental contaminants. Body burden in the U.S. population has been shown to be higher than in other countries, and infants and toddlers have highest exposure through maternal breast milk and household dust. The primary concern for adverse health effects of PBDEs relates to their potential developmental neurotoxicity, which has been found in a number of animal studies. Information on the possible mechanisms of PBDE neurotoxicity is limited, though some studies have suggested that PBDEs may elicit oxidative stress. The present study examined the in vitro neurotoxicity of DE-71, a penta-BDE mixture, in primary neurons and astrocytes obtained from wild-type and Gclm knockout mice, which lack the modifier subunit of glutamate-cysteine ligase and, as a consequence, have very low levels of glutathione (GSH). These experiments show that neurotoxicity of DE-71 in these cells is modulated by cellular GSH levels. Cerebellar granule neurons (CGNs) from Gclm (-/-) mice displayed a higher sensitivity to DE-71 toxicity compared to CGNs from wild-type animals. DE-71 neurotoxicity in CGNs from Gclm (+/+) mice was exacerbated by GSH depletion, and in CGNs from both genotypes it was antagonized by increasing GSH levels and by antioxidants. DE-71 caused an increase in reactive oxygen species and in lipid peroxidation in CGNs, that was more pronounced in Gclm (-/-) mice. Toxicity of DE-71 was mostly due to the induction of apoptotic cell death. An analysis of DE-71-induced cytotoxicity and apoptosis in neurons and astrocytes from different brain areas (cerebellum, hippocampus, cerebral cortex) in both mouse genotypes showed a significant correlation with intracellular GSH levels. As an example, DE-71 caused cytotoxicity in hippocampal neurons with IC50s of 2.2 and 0.3 μM, depending on genotype, and apoptosis with IC50s of 2.3 and 0.4 μM, respectively. These findings suggest that the developmental

  18. Multiparametric characterisation of neuronal network activity for in vitro agrochemical neurotoxicity assessment.

    Science.gov (United States)

    Alloisio, Susanna; Nobile, Mario; Novellino, Antonio

    2015-05-01

    The last few decades have seen the marketing of hundreds of new pesticide products with a forecasted expansion of the global agrochemical industry. As several pesticides directly target nervous tissue as their mechanism of toxicity, alternative methods to routine in vivo animal testing, such as the Multi Electrode Array (MEAs)-based approach, have been proposed as an in vitro tool to perform sensitive, quick and low cost neuro-toxicological screening. Here, we examined the effects of a training set of eleven active substances known to have neuronal or non-neuronal targets, contained in the most commonly used agrochemicals, on the spontaneous electrical activity of cortical neuronal networks grown on MEAs. A multiparametric characterisation of neuronal network firing and bursting was performed with the aim of investigating how this can contribute to the efficient evaluation of in vitro chemical-induced neurotoxicity. The analysis of MFR, MBR, MBD, MISI_B and % Spikes_B parameters identified four different groups of chemicals: one wherein only inhibition is observed (chlorpyrifos, deltamethrin, orysastrobin, dimoxystrobin); a second one in which all parameters, except the MISI_B, are inhibited (carbaryl, quinmerac); a third in which increases at low chemical concentration are followed by decreases at high concentration, with exception of MISI_B that only decreased (fipronil); a fourth in which no effects are observed (paraquat, glyphosate, imidacloprid, mepiquat). The overall results demonstrated that the multiparametric description of the neuronal networks activity makes MEA-based screening platform an accurate and consistent tool for the evaluation of the toxic potential of chemicals. In particular, among the bursting parameters the MISI_B was the best that correlates with potency and may help to better define chemical toxicity when MFR is affected only at relatively high concentration. PMID:25845298

  19. Prion protein oligomer and its neurotoxicity

    Institute of Scientific and Technical Information of China (English)

    Pei Huang; Fulin Lian; Yi Wen; Chenyun Guo; Donghai Lin

    2013-01-01

    The prion diseases,also known as transmissible spongiform encephalopathies,are fatal neurodegenerative disorders.According to the 'protein only' hypothesis,the key molecular event in the pathogenesis of prion disease is the conformational conversion of the host-derived cellular prion protein (PrPC) into a misfolded form (scrapie PrP,prpSc).Increasing evidence has shown that the most infectious factor is the smaller subfibrillar oligomers formed by prion proteins.Both the prion oligomer and PrPSc are rich in β-sheet structure and resistant to the proteolysis of proteinase K.The prion oligomer is soluble in physiologic environments whereas PrPSc is insoluble.Various prion oligomers are formed in different conditions.Prion oligomers exhibited more neurotoxicity both in vitro and in vivo than the fibrillar forms of PrPSc,implying that prion oligomers could be potential drug targets for attacking prion diseases.In this article,we describe recent experimental evidence regarding prion oligomers,with a special focus on prion oligomer formation and its neurotoxicity.

  20. VINCRISTINE INDUCED NEUROTOXICITY: STUDY OF 75 CASES

    Directory of Open Access Journals (Sweden)

    M.T. Arzanian

    2009-08-01

    Full Text Available ObjectiveConcern for side-effects of therapy related to treatment of childhood malignancies is becoming an increasingly important topic. In this study, we evaluated extent of vincristine (VCR induced neurotoxicity in a group of children who underwent chemotherapy, with VCR being part of the regimen.Materials & MethodsIn this investigation, for 75 children (54% boys, 46% girls, aged between 1 to 14 (mean 6.5±4.3 years, serial weekly neurological examinations were performed; of the 75, 70 had acute lymphoblastic leukemia and 5 Wilm's tumor. All patients were on a chemotherapy protocol of at least 4 consecutive VCR (1.5mg/m2 injections.ResultsDecreased deep tendons reflexes were seen in the Achilles reflex in 78%, and the patellar reflex in 53% of patients. Muscle weakness was found in 70% of patients, being mild in 76% of them. Four  percent of patients showed severe weakness. Petosis, jaw pain, hoarseness, abdominal pain and constipation were seen in 15%, 6%, 12%, 12% and 12% respectively. Paresthesia was observed in 32 of 52 patients, over 4 years old. No cases of foot drop, urinary retention or facial nerve palsy were seen in this patient group.ConclusionChildren on usual doses of vincristine regimen may have neuropathic side effects but most of these side effects are mild and not troublesome.Key words: Vincristine, neuropathy, neurotoxicity, side effect

  1. Molecular pathways of pannexin1-mediated neurotoxicity

    Directory of Open Access Journals (Sweden)

    Valery I. Shestopalov

    2014-02-01

    Full Text Available Pannexin1 (Panx1 forms nonselective membrane channels, structurally similar to gap junction hemichannels, that is permeable to ions, nucleotides and other small molecules below 900 Da. Panx1 activity is implicated in paracrine signaling and inflammasome regulation. Recent studies in different animal models showed that Panx1 overactivation correlates with a selective demise of several types of neurons, including retinal ganglion cells, brain pyramidal and enteric neurons. The list of Panx1 activators includes extracellular ATP, glutamate, high K+, Zn2+, fibroblast growth factors (FGFs, pro-inflammatory cytokines and elevation of intracellular Ca2+. Most of these molecules are released following mechanical, ischemic or inflammatory injury of the CNS, and rapidly activate this channel. As a result, prolonged opening of Panx1 channel induced by these danger signals trigger a cascade of neurotoxic events capable of killing cells. The most vulnerable cell type are neurons that express high levels of Panx1. Experimental evidence suggests that Panx1 channels mediate at least two distinct neurotoxic processes: increased permeability of the plasma membrane and activation of the inflammasome in neurons and glia. Importantly, either pharmacological or genetic inactivation of Panx1 suppresses both these processes, providing a marked protection in several disease and injury models. These findings indicate that external danger signals generated after diverse types of injuries converge to activate Panx1. In this review we discuss molecular mechanisms associated with Panx1 toxicity and the crosstalk between different pathways.

  2. Lithium-mediated protection against ethanol neurotoxicity

    Directory of Open Access Journals (Sweden)

    JiaLuo

    2010-06-01

    Full Text Available Lithium has long been used as a mood stabilizer in the treatment of manic-depressive (bipolar disorder. Recent studies suggest that lithium has neuroprotective properties and may be useful in the treatment of acute brain injuries such as ischemia and chronic neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis. One of the most important neuroprotective properties of lithium is its anti-apoptotic action. Ethanol is a neuroteratogen and fetal alcohol spectrum disorders (FASD are caused by maternal ethanol exposure during pregnancy. FASD is the leading cause of mental retardation. Ethanol exposure causes neuroapoptosis in the developing brain. Ethanol-induced loss of neurons in the central nervous system underlies many of the behavioral deficits observed in FASD. Excessive alcohol consumption is also associated with Wernicke–Korsakoff syndrome and neurodegeneration in the adult brain. Recent in vivo and in vitro studies indicate that lithium is able to ameliorate ethanol-induced neuroapoptosis. Lithium is an inhibitor of glycogen synthase kinase 3 (GSK3 which has recently been identified as a mediator of ethanol neurotoxicity. Lithium’s neuroprotection may be mediated by its inhibition of GSK3. In addition, lithium also affects many other signaling proteins and pathways that regulate neuronal survival and differentiation. This review discusses the recent evidence of lithium-mediated protection against ethanol neurotoxicity and potential underlying mechanisms.

  3. Neurotoxicity of Dietary Supplements from Annonaceae Species.

    Science.gov (United States)

    Höllerhage, Matthias; Rösler, Thomas W; Berjas, Magda; Luo, Rensheng; Tran, Kevin; Richards, Kristy M; Sabaa-Srur, Armando U; Maia, José Guilherme S; Moraes, Maria Rosa de; Godoy, Helena T; Höglinger, Günter U; Smith, Robert E

    2015-01-01

    Dietary supplements containing plant materials of Annonaceae species (Annona muricata L., A. squamosa L., A. mucosa JACQ., A. squamosa × cherimola Mabb.) were extracted by hot, pressurized ethyl acetate and analyzed for their effect in vitro on Lund human mesencephalic neurons. Cell viability was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cell death was determined by lactate dehydrogenase levels. Three supplements strongly decreased the cell viability at extract concentrations of 1 µg/mL, of which 1 decreased cell viability at 0.1 µg/µL. Also, strong neuronal toxicities of these supplements were found. Cell death was observed at concentrations of 10 µg/mL. The degree of toxicity was comparable to the ones found in Annonaceous fruit extracts. Two fruit pulps of Annonaceae (A. muricata and A. squamosa) showed a reduction in cell viability at lower concentrations. The fruit pulp extract of A. muricata revealed the strongest neurotoxic effect, with 67% cell death at a concentration of 1 µg/mL. A high reduction in cell viability coupled with pronounced cell death was found at 0.1 µg/mL for an Annonaceous seed extract. These results demonstrate that the intake of dietary supplements containing plant material from Annonaceae may be hazardous to health in terms of neurotoxicity. PMID:26405269

  4. Adverse effects of lactational exposure to chlorpyrifos in suckling rats.

    Science.gov (United States)

    Mansour, S A; Mossa, A H

    2010-02-01

    The present study was undertaken to evaluate the oxidative damage, biochemical and histopathological alterations in sucking rats whose mothers were exposed to the insecticide chlorpyrifos (CPF). Dams were administered CPF, via oral route. Doses equalled 0.01 mg kg(-1) body weight (b.wt.; acceptable daily intake, ADI), 1.00 mg kg(-1) b.wt. (no observed adverse effects level, NOAEL) and 1.35 mg kg(-1) b.wt. (1/100 lethal dose [LD(50)]) from postnatal day 1 until day 20 after delivery. At two high doses of CPF, the body weight gain and relative liver and kidney weight of suckling pups were significantly decreased. Exposure of the mothers to CPF caused increase in lipid peroxidation (LPO) and decrease in superoxide dismutase (SOD) and glutathione-s-transferase (GST) in lactating pups. CPF altered the level of the marker parameters related to the liver and kidneys. Consistent histological changes were found in the liver and kidneys of the subjected pups, especially at the higher doses. The results suggested that the transfer of CPF intoxication through the mother's milk has resulted in oxidative stress and biochemical and histopathological alterations in the suckling pups. The data of this study may be considered as a contribution to the problem of lactational transfer of the relatively less persistent OP pesticides, such as CPF. PMID:20028704

  5. Chlorpyrifos Exposure and Respiratory Health among Adolescent Agricultural Workers

    Directory of Open Access Journals (Sweden)

    Catherine L. Callahan

    2014-12-01

    Full Text Available Chlorpyrifos (CPF is a commonly used organophosphate insecticide (OP. In adults, exposure to OPs has been inconsistently associated with reduced lung function. OP exposure and lung function has not been assessed in adolescents. The objective of this study was to assess CPF exposure and lung function among Egyptian adolescents. We conducted a 10-month study of male adolescent pesticide applicators (n = 38 and non-applicators of similar age (n = 24. Urinary 3,5,6-trichloro-2-pyridinol (TPCy, a CPF-specific metabolite, was analyzed in specimens collected throughout the study. Spirometry was performed twice after pesticide application: day 146, when TCPy levels were elevated and day 269, when TCPy levels were near baseline. Applicators had higher levels of TCPy (mean cumulative TCPy day 146 = 33,217.6; standard deviation (SD = 49,179.3 than non-applicators (mean cumulative TCPy day 146 = 3290.8; SD = 3994.9. Compared with non-applicators, applicators had higher odds of reporting wheeze, odds ratio = 3.41 (95% CI: 0.70; 17.41. Cumulative urinary TCPy was inversely associated with spirometric measurements at day 146, but not at day 269. Although generally non-significant, results were consistent with an inverse association between exposure to CPF and lung function.

  6. Investigation of acute toxicity of chlorpyrifos-methyl on Nile tilapia (Oreochromis niloticus L.) larvae.

    Science.gov (United States)

    Gül, Ali

    2005-04-01

    Chlorpyrifos-methyl, a wide-spectrum organophosphorus insecticide and potential toxic pollutant contaminating aquatic ecosystems, was investigated for acute toxicity. Larvae of the freshwater fish Nile tilapia (Oreochromis niloticus L.) were selected for the bioassay experiments. The experiments were repeated three times and the 96 h LC50 was determined for the larvae. The static test method for assessing acute toxicity was used. Water temperature was maintained at 25+/-1 degrees C. In addition, behavioral changes at each chlorpyrifos-methyl concentration were observed for the individual fish. Data obtained from the chlorpyrifos-methyl acute toxicity tests were evaluated using Finney's probit analysis statistical method. The 96 h LC50 value for Nile tilapia larvae was calculated to be 1.57 mg/l. PMID:15722087

  7. Energetic Cost of Subacute Chlorpyrifos Intoxication in the German Cockroach (Dictyoptera: Blattellidae)

    DEFF Research Database (Denmark)

    Nielsen, Søren Achim; Jensen, Karl-Martin Vagn; Kristensen, Michael;

    2006-01-01

    The energetic cost of a sublethal treatment with chlorpyrifos was estimated by use of direct microcalorimetry to measure metabolic heat in susceptible and resistant strains of the German cockroach Blattella germanica L. Moreover, one of the detoxifcation enzyme systems known to be involved in...... detoxifcation of chlorpyrifos, glutathione-S-transferase, was measured. Individual cockroaches were exposed for 20 min on a glass-surfaces treated with 1.14 ...  g/cm2 of chlorpyrifos. There was no difference in glutathione-S-transferase activity of susceptible or resistant strains after the treatment. The heat...... production increased in the susceptible strain ...  30 min after exposure and declined again after ... 120 min to the basal level. The energetic cost of the exposure to the insecticide corresponds ... 5 h of normal metabolism. There were no signifcant differences in heat production after toxic treatment in...

  8. IN VITRO SCREENING OF DEVELOPMENTAL NEUROTOXICANTS IN RAT PRIMARY CORTICAL NEURONS USING HIGH CONTENT IMAGE

    Science.gov (United States)

    There is a need for more efficient and cost-effective methods for identifying, characterizing and prioritizing chemicals which may result in developmental neurotoxicity. One approach is to utilize in vitro test systems which recapitulate the critical processes of nervous system d...

  9. DEVELOPMENTAL NEUOTOXICITY EVALUATION OF MIXTURES OF MONO- AND DIMETHYL TIN IN DRINKING WATER OF RATS.

    Science.gov (United States)

    Developmental Neurotoxicity Evaluation of Mixtures of Mono- and Dimethyl Tin in Drinking Water of RatsV.C. Moser, K.L. McDaniel, P.M. PhillipsNeurotoxicology Division, NHEERL, ORD, US EPA, RTP, NC, USAOrganotins, especially monomethyl (MMT) and dimethyl (D...

  10. Ecotoxicity of two organophosphate pesticides chlorpyrifos and dichlorvos on non-targeting cyanobacteria Microcystis wesenbergii.

    Science.gov (United States)

    Sun, Kai-Feng; Xu, Xiang-Rong; Duan, Shun-Shan; Wang, You-Shao; Cheng, Hao; Zhang, Zai-Wang; Zhou, Guang-Jie; Hong, Yi-Guo

    2015-10-01

    Organophosphate pesticides (OPs), as a replacement for the organochlorine pesticides, are generally considered non-toxic to plants and algae. Chlorpyrifos and dichlorvos are two OPs used for pest control all over the world. In this study, the dose-response of cyanobacteria Microcystis wesenbergii on OPs exposure and the stimulating effect of OPs with and without phosphorus source were investigated. The results showed that high concentrations of chlorpyrifos and dichlorvos caused significant decrease of chlorophyll a content. The median inhibitory concentrations (EC50) of chlorpyrifos and dichlorvos at 96 h were 15.40 and 261.16 μmol L(-1), respectively. Growth of M. wesenbergii under low concentration of OPs (ranged from 1/10,000 to 1/20 EC50), was increased by 35.85 % (chlorpyrifos) and 41.83 % (dichlorvos) at 120 h, respectively. Correspondingly, the highest enhancement on the maximum quantum yield (F v/F m) was 4.20 % (24 h) and 9.70 % (48 h), respectively. Chlorophyll fluorescence kinetics, known as O-J-I-P transients, showed significant enhancements in the O-J, J-I, and I-P transients under low concentrations of dichlorvos at 144 h, while enhancements of chlorophyll fluorescence kinetics induced by low concentrations of chlorpyrifos were only observed in the J-I transient at 144 h. Significant decreases of chlorophyll content, F v/F m and O-J-I-P transients with OPs as sole phosphorus source were found when they were compared with inorganic phosphate treatments. The results demonstrated an evidently hormetic dose-response of M. wesenbergii to both chlorpyrifos and dichlorvos, where high dose (far beyond environmental concentrations) exposure caused growth inhibition and low dose exposure induced enhancement on physiological processes. The stimulating effect of two OPs on growth of M. wesenbergii was negligible under phosphate limitation. PMID:25854898

  11. Dissipation kinetics and assessment of processing factor for chlorpyrifos and lambda-cyhalothrin in cardamom.

    Science.gov (United States)

    George, Thomas; Beevi, S Naseema; Xavier, George; Kumar, N Pratheesh; George, Jayesh

    2013-06-01

    The dissipation kinetics and method for estimation of residues of chlorpyrifos and lambda-cyhalothrin in cardamom were studied and developed. The limit of detection and limit of quantitation arrived for the compounds were 0.01 and 0.025 μg g(-1), respectively. Gas chromatographic response of chlorpyrifos and lambda-cyhalothrin residues was linear in the range of 0.01-0.50 μg g(-1) and the mean recovery obtained was 97.3 % for chlorpyrifos and 98.9 % for lambda-cyhalothrin with satisfactory relative standard deviation values. The mean initial residues of chlorpyrifos applied at a concentration of 0.05 % in cardamom was 2.5 μg g(-1) and the residue was 8.1 μg g(-1) after processing, with a processing factor of 3.24, while lambda-cyhalothrin when applied at 0.0025 % resulted in initial residues of 1.63 μg g(-1) that magnified to 4.86 μg g(-1) on curing, with a processing factor of 2.98. The half-life of chlorpyrifos was in the range of 5.1-5.24 days while that of lambda-cyhalothrin was in the range of 4.40-4.55 days. The processing factor arrived at in the above experiment lead to the conclusion that the residues of chlorpyrifos got magnified to 3.24-3.68 times and that of lambda-cyhalothrin got magnified to 2.98-3.46 times of initial residues, consequent to loss of weight due to dehydration during curing. PMID:23079795

  12. Reactive oxygen species regulated mitochondria-mediated apoptosis in PC12 cells exposed to chlorpyrifos

    International Nuclear Information System (INIS)

    Reactive oxidative species (ROS) generated by environmental toxicants including pesticides could be one of the factors underlying the neuronal cell damage in neurodegenerative diseases. In this study we found that chlorpyrifos (CPF) induced apoptosis in dopaminergic neuronal components of PC12 cells as demonstrated by the activation of caspases and nuclear condensation. Furthermore, CPF also reduced the tyrosine hydroxylase-positive immunoreactivity in substantia nigra of the rat. In addition, CPF induced inhibition of mitochondrial complex I activity. Importantly, N-acetyl cysteine (NAC) treatment effectively blocked apoptosis via the caspase-9 and caspase-3 pathways while NAC attenuated the inhibition of mitochondrial complex I activity as well as the oxidative metabolism of dopamine (DA). These results demonstrated that CPF-induced apoptosis was involved in mitochondrial dysfunction through the production of ROS. In the response of cellular antioxidant systems to CPF, we found that CPF treatment increased HO-1 expression while the expression of CuZnSOD and MnSOD was reduced. In addition, we found that CPF treatment activated MAPK pathways, including ERK 1/2, the JNK, and the p38 MAP kinase in a time-dependent manner. NAC treatment abolished MAPK phosphorylation caused by CPF, indicating that ROS are upstream signals of MAPK. Interestingly, MAPK inhibitors abolished cytotoxicity and reduced ROS generation by CPF treatment. Our results demonstrate that CPF induced neuronal cell death in part through MAPK activation via ROS generation, suggesting its potential to generate oxidative stress via mitochondrial damage and its involvement in oxidative stress-related neurodegenerative disease. -- Highlights: ► Chlorpyrifos induces apoptosis. ► Chlorpyrifos inhibits mitochondrial complex I activity. ► ROS is involved in chlorpyrifos-induced apoptosis. ► Chlorpyrifos affects cellular antioxidant systems. ► Chlorpyrifos-induced apoptosis mediates activation of MAPK.

  13. Warming increases chlorpyrifos effects on predator but not anti-predator behaviours.

    Science.gov (United States)

    Dinh Van, Khuong; Janssens, Lizanne; Debecker, Sara; Stoks, Robby

    2014-07-01

    Recent insights indicate that negative effects of pesticides on aquatic biota occur at concentrations that current legislation considers environmentally protective. We here address two, potentially interacting, mechanisms that may contribute to the underestimation of the impact of sublethal pesticide effects in single species tests at room temperature: the impairment of predator and antipredator behaviours and the stronger impact of organophosphate pesticides at higher temperatures. To address these issues we assessed the effects of chlorpyrifos on the predator and antipredator behaviours of larvae of the damselfly Ischnura elegans, important intermediate predators in aquatic food webs, in a common-garden warming experiment with replicated low- and high-latitude populations along the latitudinal gradient of this species in Europe. Chlorpyrifos reduced the levels of predator behavioural endpoints, and this reduction was stronger at the higher temperature for head orientations and feeding strikes. Chlorpyrifos also impaired two key antipredator behavioural endpoints, activity reductions in response to predator cues were smaller in the presence of chlorpyrifos, and chlorpyrifos caused a lower escape swimming speed; these effects were independent of temperature. This suggests chlorpyrifos may impact food web interactions by changing predator-prey interactions both with higher (predators) and lower trophic levels (food). Given that only the interaction with the lower trophic level was more impaired at higher temperatures, the overall pesticide-induced changes in food web dynamics may be strongly temperature-dependent. These findings were consistent in damselflies from low- and high-latitude populations, illustrating that thermal adaptation will not mitigate the increased toxicity of pesticides at higher temperatures. Our study not only underscores the relevance of including temperature and prey-predator interactions in ecological risk assessment but also their potential

  14. Reactive oxygen species regulated mitochondria-mediated apoptosis in PC12 cells exposed to chlorpyrifos

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Eun [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Park, Jae Hyeon [Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of); Shin, In Chul [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Koh, Hyun Chul, E-mail: hckoh@hanyang.ac.kr [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of)

    2012-09-01

    Reactive oxidative species (ROS) generated by environmental toxicants including pesticides could be one of the factors underlying the neuronal cell damage in neurodegenerative diseases. In this study we found that chlorpyrifos (CPF) induced apoptosis in dopaminergic neuronal components of PC12 cells as demonstrated by the activation of caspases and nuclear condensation. Furthermore, CPF also reduced the tyrosine hydroxylase-positive immunoreactivity in substantia nigra of the rat. In addition, CPF induced inhibition of mitochondrial complex I activity. Importantly, N-acetyl cysteine (NAC) treatment effectively blocked apoptosis via the caspase-9 and caspase-3 pathways while NAC attenuated the inhibition of mitochondrial complex I activity as well as the oxidative metabolism of dopamine (DA). These results demonstrated that CPF-induced apoptosis was involved in mitochondrial dysfunction through the production of ROS. In the response of cellular antioxidant systems to CPF, we found that CPF treatment increased HO-1 expression while the expression of CuZnSOD and MnSOD was reduced. In addition, we found that CPF treatment activated MAPK pathways, including ERK 1/2, the JNK, and the p38 MAP kinase in a time-dependent manner. NAC treatment abolished MAPK phosphorylation caused by CPF, indicating that ROS are upstream signals of MAPK. Interestingly, MAPK inhibitors abolished cytotoxicity and reduced ROS generation by CPF treatment. Our results demonstrate that CPF induced neuronal cell death in part through MAPK activation via ROS generation, suggesting its potential to generate oxidative stress via mitochondrial damage and its involvement in oxidative stress-related neurodegenerative disease. -- Highlights: ► Chlorpyrifos induces apoptosis. ► Chlorpyrifos inhibits mitochondrial complex I activity. ► ROS is involved in chlorpyrifos-induced apoptosis. ► Chlorpyrifos affects cellular antioxidant systems. ► Chlorpyrifos-induced apoptosis mediates activation of MAPK.

  15. Behavioral Responses of the Freshwater Fish, Cyprinus carpio (Linnaeus) Following Sublethal Exposure to Chlorpyrifos

    OpenAIRE

    Halappa, Ramesh; David, Muniswamy

    2009-01-01

    Common carp fingerlings were exposed to different concentrations (0.120 to 0.200 mg/L) of an organophosphate pesticide, chlorpyrifos (20% EC) for 96 h. The acute toxicity (LC50) of chlorpyrifos by static renewal (semi-static) bioassay test was found to be 0.160 mg/L. One-seventh (0.0224 mg/L) and one-fourteenth (0.0112 mg/L) of the 96 h LC50 were selected as sublethal concentrations for subacute studies. The fish were exposed to both the sublethal concentrations for 1, 7 and 14 days and allow...

  16. Neurotoxicity of iodinated radiological contrast media

    International Nuclear Information System (INIS)

    We studied during the last ten years the neurotoxicity of artificial iodinated contrast media, with prospective clinical and experimental protocols. The experimental investigation in animals aimed to understand the relationship between the intracarotid injection, the subarachnoid application and the integrity of the blood-brain barrier function. The electro physiologic disturbances and the morphologic observation of pial circulation support the evidence that iodinated artificial contrast media induces significant alterations in brain metabolism and in the autoregulation of the blood flow of the encephalon. Even if many of such phenomena may not be apparent at the clinical level, we supposed that they are always present and that their clinical exteriorization is prevented by the immediate and effective action of homeostatic mechanisms. (author)

  17. Developmental Work

    DEFF Research Database (Denmark)

    Møller, Niels; Hvid, Helge; Kristensen, Tage Søndergaard;

    2003-01-01

    Human Deveoplment and Working Life - Work for Welfare explores whether the development of human resources at company level can improve individuals' quality of life, companies' possibilities of development, and welfare and democracy in society. Chapter two discuss the concept "developmental work...

  18. Mechanism of TiO2 nanoparticle-induced neurotoxicity in zebrafish (Danio rerio).

    Science.gov (United States)

    Sheng, Lei; Wang, Ling; Su, Mingyu; Zhao, Xiaoyang; Hu, Renping; Yu, Xiaohong; Hong, Jie; Liu, Dong; Xu, Bingqing; Zhu, Yunting; Wang, Han; Hong, Fashui

    2016-02-01

    Zebrafish (Danio rerio) has been used historically for evaluating the toxicity of environmental and aqueous toxicants, and there is an emerging literature reporting toxic effects of manufactured nanoparticles (NPs) in zebrafish embryos. Few researches, however, are focused on the neurotoxicity on adult zebrafish after subchronic exposure to TiO2 NPs. This study was designed to evaluate the morphological changes, alterations of neurochemical contents, and expressions of memory behavior-related genes in zebrafish brains caused by exposures to 5, 10, 20, and 40 μg/L TiO2 NPs for 45 consecutive days. Our data indicated that spatial recognition memory and levels of norepinephrine, dopamine, and 5-hydroxytryptamine were significantly decreased and NO levels were markedly elevated, and over proliferation of glial cells, neuron apoptosis, and TiO2 NP aggregation were observed after low dose exposures of TiO2 NPs. Furthermore, the low dose exposures of TiO2 NPs significantly activated expressions of C-fos, C-jun, and BDNF genes, and suppressed expressions of p38, NGF, CREB, NR1, NR2ab, and GluR2 genes. These findings imply that low dose exposures of TiO2 NPs may result in the brain damages in zebrafish, provide a developmental basis for evaluating the neurotoxicity of subchronic exposure, and raise the caution of aquatic application of TiO2 NPs. PMID:25059219

  19. Role of glutamate receptors in tetrabrominated diphenyl ether (BDE-47) neurotoxicity in mouse cerebellar granule neurons.

    Science.gov (United States)

    Costa, Lucio G; Tagliaferri, Sara; Roqué, Pamela J; Pellacani, Claudia

    2016-01-22

    The polybrominated diphenyl ether (PBDE) flame retardants are developmental neurotoxicants, as evidenced by numerous in vitro, animal and human studies. PBDEs can alter the homeostasis of thyroid hormone and directly interact with brain cells. Induction of oxidative stress, leading to DNA damage and apoptotic cell death is a prominent mechanism of PBDE neurotoxicity, though other mechanisms have also been suggested. In the present study we investigated the potential role played by glutamate receptors in the in vitro neurotoxicity of the tetrabromodiphenyl ether BDE-47, one of the most abundant PBDE congeners. Toxicity of BDE-47 in mouse cerebellar neurons was diminished by antagonists of glutamate ionotropic receptors, but not by antagonists of glutamate metabotropic receptors. Antagonists of NMDA and AMPA/Kainate receptors also inhibited BDE-47-induced oxidative stress and increases in intracellular calcium. The calcium chelator BAPTA-AM also inhibited BDE-47 cytotoxicity and oxidative stress. BDE-47 caused a rapid increase of extracellular glutamate levels, which was not antagonized by any of the compounds tested. The results suggest that BDE-47, by still unknown mechanisms, increases extracellular glutamate which in turn activates ionotropic glutamate receptors leading to increased calcium levels, oxidative stress, and ultimately cell death. PMID:26640238

  20. Toxicity of chlorpyrifos and chlorpyrifos oxon in a transgenic mouse model of the human paraoxonase (PON1) Q192R polymorphism

    Energy Technology Data Exchange (ETDEWEB)

    Cole, Toby B.; Walter, Betsy J.; Shih, Diana M.; Tward, Aaron D.; Lusis, Aldons J.; Timchalk, Chuck; Richter, Rebecca J.; Costa, Lucio G.; Furlong, Clement E.

    2005-08-01

    The Q192R polymorphism of paraoxonase (PON1) has been shown to affect hydrolysis of organophosphorus compounds. The Q192 and R192 alloforms exhibit equivalent catalytic efficiencies of hydrolysis for diazoxon, the oxon form of the pesticide (DZ). However, the R192 alloform has a higher catalytic efficiency of hydrolysis than does the Q192 alloform for chlorpyrifos oxon (CPO), the oxon form of the pesticide chlorpyrifos (CPS). The current study examined the relevance of these observations for in-vivo exposures to chlorpyrifos and chlorpyrifos oxon. Methods Using a transgenic mouse model we examined the relevance of the Q192R polymorphism for exposure to CPS and CPO in vivo. Transgenic mice were generated that expressed either human PON1Q192 or PON1R192 at equivalent levels, in the absence of endogenous mouse PON1. Dose-response and time course experiments were performed on adult mice exposed dermally to CPS or CPO. Morbidity and acetylcholinesterase (AChE) activity in the brain and diaphragm were determined in the first 24 h following exposure. Results Mice expressing PON1Q192 were significantly more sensitive to CPO, and to a lesser extent CPS, than were mice expressing PON1R192. The time course of inhibition following exposure to 1.2 mg/kg CPO revealed maximum inhibition of brain AChE at 6?12 h, with PON1R192, PON1Q192, and PON1? /? mice exhibiting 40, 70 and 85% inhibition, respectively, relative to control mice. The effect of PON1 removal on the dose?response curve for CPS exposure was remarkably consistent with a PBPK/PD model of CPS exposure. Conclusion These results indicate that individuals expressing only the PON1Q192 allele would be more sensitive to the adverse effects of CPO or CPS exposure, especially if they are expressing a low level of plasma PON1Q192.

  1. The Effect of The Pesticides Chlorpyrifos and Alphacypermethrin on The Development of Cutaneous Leishmaniasis Lesion in BALB/c Mice

    International Nuclear Information System (INIS)

    Three groups of BALB/c mice were treated orally with 0.6, 1.0 and 6.0mg/kg body weight of chlorpyrifos (CPF), and 3 other groups were treated with 2.5, 6.25 and 25mg/kg bodyweight of alphacypermethrin (ACM), respectively, every other day for 1 week. Six other groups were treated similarly for 2 weeks. The treated groups and a control group for each pesticide were inoculated in the dorsum with Leishmania major promastigotes at their stationary phase. Lesions started to appear 2-3 weeks post-inoculation and their diameters were measured in all groups 1, 5, 9 and 14 days post-appearance (PA). The mean diameter of lesions (MDL) only in the 6.0mg group treated with CPF for 1 week was larger than that of the control group. In the groups treated for 2 weeks, the MDL of the 1.0 and 6.0mg groups were larger than those of the control group 5, 9 and 14 days PA while MLD of the 0.6mg group was larger than that of the control group only 5 days PA. MLD was larger in the 0.6mg group treated for 2 weeks than that in the group treated for 1 week 1 and 5 days PA. MLD was larger in the 1.0mg group treated for 2 weeks than that treated for 1 week 9 days PA. MLD was similar in the 6.0mg group treated for 1 and 2 weeks. The MDL only in the 25mg group treated with ACM for 1 week was larger than that of the control group 9 and 14 days PA. The MDL of the 6.25 and 25mg groups treated for 2 weeks were larger than those of the control groups 5 days PA and the MLD of the 25mg group was larger than that of the control group 9 and 14 days PA. The MLD was larger in the 2.5mg group treated for 2 weeks than that in the group treated for 1 week 5 days PA. The MLD was larger in the 6.25 and 25.0mg groups treated for 2 weeks than those treated for 1 week 1 and 5 days PA. Immunotoxicity and/or peripheral neurotoxicity caused by CPF and ACM might have caused aggravation of lesions in mice particularly those treated with the pesticides for 2 weeks. (author)

  2. Effects of chlorpyrifos in freshwater model ecosystems: the influence of experimental conditions on ecotoxicological thresholds

    NARCIS (Netherlands)

    Wijngaarden, van R.P.A.; Brock, T.C.M.; Douglas, M.T.

    2005-01-01

    Three experiments were conducted to determine the impact of the insecticide chlorpyrifos (single applications of 0.01 to 10 µg AI litre-1) in plankton-dominated nutrient-rich microcosms. The microcosms (water volume approximately 14 litres) were established in the laboratory under temperature, light

  3. SEM study of ultrastructural changes in branchial architecture of Ctenopharyngodon idella (Cuvier & Valenciennes exposed to chlorpyrifos

    Directory of Open Access Journals (Sweden)

    Kaur Mandeep

    2016-01-01

    Full Text Available We evaluated structural modifications in the branchial architecture of grass carp, Ctenopharyngodon idella, chronically exposed to chlorpyrifos (an organophosphate using scanning electron microscopy (SEM. Static renewal tests were conducted for 96 h to determine the LC50 of chlorpyrifos to the fish. Physicochemical analysis of water was done using standard methods. To assess the effect of chronic toxicity, fish were exposed to two sublethal concentrations (1.44 μg/L and 2.41 μg/L of chlorpyrifos for 15, 30 and 60 days, after which gills were examined by SEM, which revealed changes in gill ultrastructure. Branchial alterations included distorted secondary lamellae in the form of curling and shortening, erosion in a few primary filaments and a wrinkled and denuded epithelial surface. Excessive mucosal openings (mucoid hyperplasia on the surface were observed in the gills of fish exposed to both concentrations of chlorpyrifos. Alteration in the microridge pattern of pavement cells and cracks on the gill rakers were also observed, and the intensity of the damage was found to be directly related to the toxicant concentration and exposure period. The present study revealed that the assessment of surface morphology can serve as a novel bioindicator of pollution, disease and toxicity.

  4. Effects of chronic low concentrations of pesticides chlorpyrifos and atrazine in indoor freshwater microcosms.

    NARCIS (Netherlands)

    Brink, van den P.J.; Donk, van E.; Gylstra, R.; Crum, S.J.H.; Brock, T.C.M.

    1995-01-01

    Standards for pesticide concentrations in water are based on the laboratory toxicity of the most susceptible standard test organisms (algae, crustaceans or fish). Field studies have shown that the standards for the insecticide chlorpyrifos and the herbicide atrazine will protect aquatic ecosystems a

  5. Effects of chlorpyrifos, carbendazim and linuron on the ecology of a small indoor aquatic microcosm

    NARCIS (Netherlands)

    Daam, M.A.; Brink, van den P.J.

    2007-01-01

    To validate the use of small indoor microcosms for the risk assessment of pesticides, the fate and effects of chlorpyrifos, carbendazim, and linuron were studied in 8.5¿liter indoor freshwater microcosms. Functional and structural responses to selected concentrations were evaluated and compared with

  6. CHANGES IN THE RAT EEG SPECTRA AND CORE TEMPERATURE AFTER EXPOSURE TO DIFFERENT DOSES OF CHLORPYRIFOS.

    Science.gov (United States)

    Our previous study showed that single exposure to 25 mg/kg (p.o.) of organophsphate pesticide chlorpyrifos (CHP) led to significant alterations in all EEG frequency bands within 0.1-50 Hz range, reduction in core temperature (Tc) and motor activity (MA). The alterations in EEG pe...

  7. THERMOREGULATION IN THE RAT DURING CHRONIC, DIETARY EXPOSURE TO CHLORPYRIFOS, AN ORGANOPHOSPHATE INSECTICIDE.

    Science.gov (United States)

    Administration of chlorpyrifos (CHP) at a dose of 25 to 80 mg/kg (p.o.) To rats results in hypothermia followed by a fever lasting for several days. To understand if chronic, low level exposure to CHP affects thermoregulation in a comparable manner to acute administration, male L...

  8. Specific surface area effect on adsorption of chlorpyrifos and TCP by soils and modeling

    Science.gov (United States)

    The adsorption of chlorpyrifos and TCP (3,5,6, trichloro-2-pyridinol) was determined in four soils (Mollisol, Inceptisol, Entisol, Alfisol) having different specific surface areas (19–84 m2/g) but rather similar organic matter content (2.4–3.5%). Adsorption isotherms were derived from batch equilibr...

  9. Dissipation of chlorpyrifos in pakchoi-vegetated soil in a greenhouse

    Institute of Scientific and Technical Information of China (English)

    FANG Hua; YU Yun-long; WANG Xiao; SHAN Min; WU Xiao-mao; YU Jing-quan

    2006-01-01

    The dissipation of chlorpyrifos in pakchoi-vegetated soil was investigated in the summer and autumn in a greenhouse and field, respectively. The dissipation of chlorpyrifos in pakchoi-grown soil was comparatively described by fitting the residue data to seven models (1st-order, 1.5th-order, 2nd-order, RF 1st-order, RF 1.5th-order, RF 2nd-order, and bi-exponential or two-compartment models). Statistical analysis was performed using the SPSS 11.5 statistical package. The bi-exponential model was selected as the optimal model according to the coefficient of determination r2. The dissipation half-lives (DT50) of chlorpyrifos in pakchoi-vegetated soil at the recommended dose in the summer and autumn, calculated by the bi-exponential model, were 0.6 and 1.2 d in a greenhouse,0.4 and 1.0 d in a field, respectively; the corresponding values at double dose were 1.2 and 2.1 d in a greenhouse, 0.5 and 1.3 d in a field, respectively. The kinetic data indicate the dissipation of chlorpyrifos in pakchoi-grown soil in a greenhouse is slower than that in a field, and dissipates slower in the autumn than in the summer.

  10. The effects of chlorpyrifos on cholinesterase activity and foraging behavior in the dragonfly, Anax junius (Odonata)

    Science.gov (United States)

    Brewer, S.K.; Atchison, G.J.

    1999-01-01

    We examined head capsule cholinesterase (ChE) and foraging behavior in nymphs of the dragonfly, Anax junius, exposed for 24 h to 0.2, 0.6 and 1.0 ??g l-1 of the organophosphorus (OP) insecticide, chlorpyrifos [O,O-diethyl O-(3,5,6-trichloro-2-pyridyl) phosphorothioate]. The invertebrate community is an important component of the structure and function of wetland ecosystems, yet the potential effects of insecticides on wetland ecosystems are largely unknown. Our objectives were to determine if exposure to environmentally realistic concentrations of chlorpyrifos affected foraging behavior and ChE activity in head capsules of dragonfly nymphs. Nymphs were exposed to different concentrations of chlorpyrifos and different prey densities in a factorial design. ChE activities and foraging behaviors of treated nymphs were not statistically different (p ??? 0.05) from control groups. Prey density effects exerted a greater effect on dragonfly foraging than toxicant exposures. Nymphs offered higher prey densities exhibited more foraging behaviors but also missed their prey more often. High variability in ChE activities within the control group and across treated groups precluded determination of relationships between ChE and foraging behaviors. It appears that A. junius is relatively tolerant of chlorpyrifos, although the concentrations we tested have been shown in other work to adversely affect the prey base; therefore the introduction of this insecticide may have indirect adverse affects on top invertebrate predators such as Odonata.

  11. Changes of Field Incurred Chlorpyrifos and Its Toxic Metabolite Residues in Rice during Food Processing from-RAC-to-Consumption

    OpenAIRE

    Zhang, Zhiyong; Wayne W Jiang; Jian, Qiu; Song, Wencheng; Zheng, Zuntao; Wang, Donglan; Liu, Xianjin

    2015-01-01

    The objectives of this study were to determine the effects of food processing on field incurred residues levels of chlorpyrifos and its metabolite 3,5,6-Trichloro-2-pyridinol (TCP) in rice. The chlorpyrifos and TCP were found to be 1.27 and 0.093 mg kg-1 in straw and 0.41 and 0.073 mg kg-1 in grain, respectively. It is observed that the sunlight for 2 hours does not decrease the chlorpyrifos and TCP residues in grain significantly. Their residues in rice were reduced by up to 50% by hulling. ...

  12. Neurotoxic effects during vidarabine therapy for herpes zoster.

    OpenAIRE

    Burdge, D R; Chow, A W; Sacks, S L

    1985-01-01

    Two cases of neurotoxic effects resulting from therapy with vidarabine are described. Both patients were undergoing treatment for cutaneously disseminated herpes zoster complicating therapy for solid malignant tumours. Both had normal renal function. The serum levels of hepatic enzymes were normal in one patient and slightly elevated in the other. Neurotoxicity was first manifested in both patients by the development of intention tremors that progressed to gross tremors. Obtundation, coma and...

  13. Problems of neurotoxicity assessment with using of electroretinography

    OpenAIRE

    R. A. Tkachuk; B. І. Yavorskyy; A. F. Yanenko

    2015-01-01

    Introduction. An actual problem of detection neurotoxication from getting nanoparticles into the human body in its initial stage, the identification of toxicant, determine its amount (dose) is considered. Formulation of the problem. The solving of the basic problems which encountered during improving electroretinography means and methods in its application to risk assessment person neurotoxication are considered in this article. Directions of retinographia improvement. We propose a method to ...

  14. Minocycline Attenuates Iron Neurotoxicity in Cortical Cell Cultures

    OpenAIRE

    Chen-Roetling, Jing; Chen, Lifen; Regan, Raymond F.

    2009-01-01

    Iron neurotoxicity may contribute to the pathogenesis of intracerebral hemorrhage (ICH). The tetracycline derivative minocycline is protective in ICH models, due putatively to inhibition of microglial activation. Although minocycline also chelates iron, its effect on iron neurotoxicity has not been reported, and was examined in this study. Cortical cultures treated with 10 μM ferrous sulfate for 24h sustained loss of most neurons and an increase in malondialdehyde. Minocycline prevented this ...

  15. Donepezil markedly potentiates memantine neurotoxicity in the adult rat brain

    OpenAIRE

    Creeley, Catherine E.; Wozniak, David F.; Nardi, Anthony; Farber, Nuri B.; Olney, John W.

    2006-01-01

    The NMDA antagonist, memantine (Namenda), and the cholinesterase inhibitor, donepezil (Aricept), are currently being used widely, either individually or in combination, for treatment of Alzheimer’s disease (AD). NMDA antagonists have both neuroprotective and neurotoxic properties; the latter is augmented by drugs, such as pilocarpine, that increase cholinergic activity. Whether donepezil, by increasing cholinergic activity, might augment memantine’s neurotoxic potential has not been investiga...

  16. Neurotoxicity testing: a discussion of in vitro alternatives.

    OpenAIRE

    Costa, L. G.

    1998-01-01

    A large number of chemicals may exert adverse effects on the central and/or peripheral nervous system. A commonly recommended strategy for neurotoxicity testing is that of a tiered approach aimed at identifying and characterizing the neurotoxicity of a compound. Guidelines exist in the United States and other countries that define the tests to be utilized in tier 1 testing. To address problems related to the increasing cost and time required for toxicity testing, the increasing number of chem...

  17. Neurotoxicity in snakebite--the limits of our knowledge.

    Directory of Open Access Journals (Sweden)

    Udaya K Ranawaka

    Full Text Available Snakebite is classified by the WHO as a neglected tropical disease. Envenoming is a significant public health problem in tropical and subtropical regions. Neurotoxicity is a key feature of some envenomings, and there are many unanswered questions regarding this manifestation. Acute neuromuscular weakness with respiratory involvement is the most clinically important neurotoxic effect. Data is limited on the many other acute neurotoxic manifestations, and especially delayed neurotoxicity. Symptom evolution and recovery, patterns of weakness, respiratory involvement, and response to antivenom and acetyl cholinesterase inhibitors are variable, and seem to depend on the snake species, type of neurotoxicity, and geographical variations. Recent data have challenged the traditional concepts of neurotoxicity in snake envenoming, and highlight the rich diversity of snake neurotoxins. A uniform system of classification of the pattern of neuromuscular weakness and models for predicting type of toxicity and development of respiratory weakness are still lacking, and would greatly aid clinical decision making and future research. This review attempts to update the reader on the current state of knowledge regarding this important issue.

  18. High chlorpyrifos resistance in Culex pipiens mosquitoes: strong synergy between resistance genes.

    Science.gov (United States)

    Alout, H; Labbé, P; Berthomieu, A; Makoundou, P; Fort, P; Pasteur, N; Weill, M

    2016-02-01

    We investigated the genetic determinism of high chlorpyrifos resistance (HCR), a phenotype first described in 1999 in Culex pipiens mosquitoes surviving chlorpyrifos doses ⩾1 mg l(-1) and more recently found in field samples from Tunisia, Israel or Indian Ocean islands. Through chlorpyrifos selection, we selected several HCR strains that displayed over 10 000-fold resistance. All strains were homozygous for resistant alleles at two main loci: the ace-1 gene, with the resistant ace-1(R) allele expressing the insensitive G119S acetylcholinesterase, and a resistant allele of an unknown gene (named T) linked to the sex and ace-2 genes. We constructed a strain carrying only the T-resistant allele and studied its resistance characteristics. By crossing this strain with strains harboring different alleles at the ace-1 locus, we showed that the resistant ace-1(R) and the T alleles act in strong synergy, as they elicited a resistance 100 times higher than expected from a simple multiplicative effect. This effect was specific to chlorpyrifos and parathion and was not affected by synergists. We also examined how HCR was expressed in strains carrying other ace-1-resistant alleles, such as ace-1(V) or the duplicated ace-1(D) allele, currently spreading worldwide. We identified two major parameters that influenced the level of resistance: the number and the nature of the ace-1-resistant alleles and the number of T alleles. Our data fit a model that predicts that the T allele acts by decreasing chlorpyrifos concentration in the compartment targeted in insects. PMID:26463842

  19. Concentration-dependent interactions of the organophosphates chlorpyrifos oxon and methyl paraoxon with human recombinant acetylcholinesterase

    International Nuclear Information System (INIS)

    For many decades it has been thought that oxygen analogs (oxons) of organophosphorus insecticides phosphorylate the catalytic site of acetylcholinesterase by a mechanism that follows simple Michaelis-Menten kinetics. More recently, the interactions of at least some oxons have been shown to be far more complex and likely involve binding of oxons to a second site on acetylcholinesterase that modulates the inhibitory capacity of other oxon molecules at the catalytic site. The current study has investigated the interactions of chlorpyrifos oxon and methyl paraoxon with human recombinant acetylcholinesterase. Both chlorpyrifos oxon and methyl paraoxon were found to have k i's that change as a function of oxon concentration. Furthermore, 10 nM chlorpyrifos oxon resulted in a transient increase in acetylthiocholine hydrolysis, followed by inhibition. Moreover, in the presence of 100 nM chlorpyrifos oxon, acetylthiocholine was found to influence both the K d (binding affinity) and k 2 (phosphorylation constant) of this oxon. Collectively, these results demonstrate that the interactions of chlorpyrifos oxon and methyl paraoxon with acetylcholinesterase cannot be described by simple Michaelis-Menten kinetics but instead support the hypothesis that these oxons bind to a secondary site on acetylcholinesterase, leading to activation/inhibition of the catalytic site, depending on the nature of the substrate and inhibitor. Additionally, these data raise questions regarding the adequacy of estimating risk of low levels of insecticide exposure from direct extrapolation of insecticide dose-response curves since the capacity of individual oxon molecules at low oxon levels could be greater than individual oxon molecules in vivo associated with the dose-response curve

  20. Protection against neurotoxicity by an autophagic mechanism

    Directory of Open Access Journals (Sweden)

    Kangyong Liu

    2012-05-01

    Full Text Available The objective of the present study was to investigate the effects of 3-n-butylphthalide (NBP on a 1-methyl-4-phenylpyridinium (MPP+-induced cellular model of Parkinson’s disease (PD and to illustrate the potential mechanism of autophagy in this process. For this purpose, rat PC12 pheochromocytoma cells were treated with MPP+ (1 mM for 24 h following pretreatment with NBP (0.1 mM. Cell metabolic viability was determined by the MTT assay and cell ultrastructure was examined by transmission electron microscopy. The intracellular distribution and expression of α-synuclein and microtubule-associated protein light chain 3 (LC3 were detected by immunocytochemistry and Western blotting. Our results demonstrated that: 1 NBP prevented MPP+-induced cytotoxicity in PC12 cells by promoting metabolic viability. 2 NBP induced the accumulation of autophagosomes in MPP+-treated PC12 cells. 3 Further study of the molecular mechanism demonstrated that NBP enhanced the colocalization of α-synuclein and LC3 and up-regulated the protein level of LC3-II. These results demonstrate that NBP protects PC12 cells against MPP+-induced neurotoxicity by activating autophagy-mediated α-synuclein degradation, implying that it may be a potential effective therapeutic agent for the treatment of PD.

  1. Role of Prion Protein Aggregation in Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Tullio Florio

    2012-07-01

    Full Text Available In several neurodegenerative diseases, such as Parkinson, Alzheimer’s, Huntington, and prion diseases, the deposition of aggregated misfolded proteins is believed to be responsible for the neurotoxicity that characterizes these diseases. Prion protein (PrP, the protein responsible of prion diseases, has been deeply studied for the peculiar feature of its misfolded oligomers that are able to propagate within affected brains, inducing the conversion of the natively folded PrP into the pathological conformation. In this review, we summarize the available experimental evidence concerning the relationship between aggregation status of misfolded PrP and neuronal death in the course of prion diseases. In particular, we describe the main findings resulting from the use of different synthetic (mainly PrP106-126 and recombinant PrP-derived peptides, as far as mechanisms of aggregation and amyloid formation, and how these different spatial conformations can affect neuronal death. In particular, most data support the involvement of non-fibrillar oligomers rather than actual amyloid fibers as the determinant of neuronal death.

  2. Neurotoxic Alkaloids: Saxitoxin and Its Analogs

    Directory of Open Access Journals (Sweden)

    Troco K. Mihali

    2010-07-01

    Full Text Available Saxitoxin (STX and its 57 analogs are a broad group of natural neurotoxic alkaloids, commonly known as the paralytic shellfish toxins (PSTs. PSTs are the causative agents of paralytic shellfish poisoning (PSP and are mostly associated with marine dinoflagellates (eukaryotes and freshwater cyanobacteria (prokaryotes, which form extensive blooms around the world. PST producing dinoflagellates belong to the genera Alexandrium, Gymnodinium and Pyrodinium whilst production has been identified in several cyanobacterial genera including Anabaena, Cylindrospermopsis, Aphanizomenon Planktothrix and Lyngbya. STX and its analogs can be structurally classified into several classes such as non-sulfated, mono-sulfated, di-sulfated, decarbamoylated and the recently discovered hydrophobic analogs—each with varying levels of toxicity. Biotransformation of the PSTs into other PST analogs has been identified within marine invertebrates, humans and bacteria. An improved understanding of PST transformation into less toxic analogs and degradation, both chemically or enzymatically, will be important for the development of methods for the detoxification of contaminated water supplies and of shellfish destined for consumption. Some PSTs also have demonstrated pharmaceutical potential as a long-term anesthetic in the treatment of anal fissures and for chronic tension-type headache. The recent elucidation of the saxitoxin biosynthetic gene cluster in cyanobacteria and the identification of new PST analogs will present opportunities to further explore the pharmaceutical potential of these intriguing alkaloids.

  3. Protection against neurotoxicity by an autophagic mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Kangyong; Huang, Jiankang; Chen, Rongfu; Zhang, Ting [Department of Neurology, Affiliated Sixth People' s Hospital, Shanghai Jiaotong University, Shanghai (China); Shen, Liwei [Department of Neurology, Fifth People' s Hospital, Fudan University, Shanghai (China); Yang, Jiajun; Sun, Xiaojiang [Department of Neurology, Affiliated Sixth People' s Hospital, Shanghai Jiaotong University, Shanghai (China)

    2012-03-23

    The objective of the present study was to investigate the effects of 3-n-butylphthalide (NBP) on a 1-methyl-4-phenylpyridinium (MPP{sup +})-induced cellular model of Parkinson's disease (PD) and to illustrate the potential mechanism of autophagy in this process. For this purpose, rat PC12 pheochromocytoma cells were treated with MPP{sup +} (1 mM) for 24 h following pretreatment with NBP (0.1 mM). Cell metabolic viability was determined by the MTT assay and cell ultrastructure was examined by transmission electron microscopy. The intracellular distribution and expression of α-synuclein and microtubule-associated protein light chain 3 (LC3) were detected by immunocytochemistry and Western blotting. Our results demonstrated that: 1) NBP prevented MPP{sup +}-induced cytotoxicity in PC12 cells by promoting metabolic viability. 2) NBP induced the accumulation of autophagosomes in MPP{sup +}-treated PC12 cells. 3) Further study of the molecular mechanism demonstrated that NBP enhanced the colocalization of α-synuclein and LC3 and up-regulated the protein level of LC3-II. These results demonstrate that NBP protects PC12 cells against MPP{sup +}-induced neurotoxicity by activating autophagy-mediated α-synuclein degradation, implying that it may be a potential effective therapeutic agent for the treatment of PD.

  4. Protection against neurotoxicity by an autophagic mechanism

    International Nuclear Information System (INIS)

    The objective of the present study was to investigate the effects of 3-n-butylphthalide (NBP) on a 1-methyl-4-phenylpyridinium (MPP+)-induced cellular model of Parkinson's disease (PD) and to illustrate the potential mechanism of autophagy in this process. For this purpose, rat PC12 pheochromocytoma cells were treated with MPP+ (1 mM) for 24 h following pretreatment with NBP (0.1 mM). Cell metabolic viability was determined by the MTT assay and cell ultrastructure was examined by transmission electron microscopy. The intracellular distribution and expression of α-synuclein and microtubule-associated protein light chain 3 (LC3) were detected by immunocytochemistry and Western blotting. Our results demonstrated that: 1) NBP prevented MPP+-induced cytotoxicity in PC12 cells by promoting metabolic viability. 2) NBP induced the accumulation of autophagosomes in MPP+-treated PC12 cells. 3) Further study of the molecular mechanism demonstrated that NBP enhanced the colocalization of α-synuclein and LC3 and up-regulated the protein level of LC3-II. These results demonstrate that NBP protects PC12 cells against MPP+-induced neurotoxicity by activating autophagy-mediated α-synuclein degradation, implying that it may be a potential effective therapeutic agent for the treatment of PD

  5. Inhibition of recombinant human carboxylesterase 1 and 2 and monoacylglycerol lipase by chlorpyrifos oxon, paraoxon and methyl paraoxon

    Energy Technology Data Exchange (ETDEWEB)

    Crow, J. Allen; Bittles, Victoria; Herring, Katye L.; Borazjani, Abdolsamad [Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762 (United States); Potter, Philip M. [Department of Chemical Biology and Therapeutics, St. Jude Children' s Research Hospital, 332 N. Lauderdale, Memphis, TN 38105 (United States); Ross, Matthew K., E-mail: mross@cvm.msstate.edu [Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762 (United States)

    2012-01-01

    Oxons are the bioactivated metabolites of organophosphorus insecticides formed via cytochrome P450 monooxygenase-catalyzed desulfuration of the parent compound. Oxons react covalently with the active site serine residue of serine hydrolases, thereby inactivating the enzyme. A number of serine hydrolases other than acetylcholinesterase, the canonical target of oxons, have been reported to react with and be inhibited by oxons. These off-target serine hydrolases include carboxylesterase 1 (CES1), CES2, and monoacylglycerol lipase. Carboxylesterases (CES, EC 3.1.1.1) metabolize a number of xenobiotic and endobiotic compounds containing ester, amide, and thioester bonds and are important in the metabolism of many pharmaceuticals. Monoglyceride lipase (MGL, EC 3.1.1.23) hydrolyzes monoglycerides including the endocannabinoid, 2-arachidonoylglycerol (2-AG). The physiological consequences and toxicity related to the inhibition of off-target serine hydrolases by oxons due to chronic, low level environmental exposures are poorly understood. Here, we determined the potency of inhibition (IC{sub 50} values; 15 min preincubation, enzyme and inhibitor) of recombinant CES1, CES2, and MGL by chlorpyrifos oxon, paraoxon and methyl paraoxon. The order of potency for these three oxons with CES1, CES2, and MGL was chlorpyrifos oxon > paraoxon > methyl paraoxon, although the difference in potency for chlorpyrifos oxon with CES1 and CES2 did not reach statistical significance. We also determined the bimolecular rate constants (k{sub inact}/K{sub I}) for the covalent reaction of chlorpyrifos oxon, paraoxon and methyl paraoxon with CES1 and CES2. Consistent with the results for the IC{sub 50} values, the order of reactivity for each of the three oxons with CES1 and CES2 was chlorpyrifos oxon > paraoxon > methyl paraoxon. The bimolecular rate constant for the reaction of chlorpyrifos oxon with MGL was also determined and was less than the values determined for chlorpyrifos oxon with CES1

  6. Inhibition of recombinant human carboxylesterase 1 and 2 and monoacylglycerol lipase by chlorpyrifos oxon, paraoxon and methyl paraoxon

    International Nuclear Information System (INIS)

    Oxons are the bioactivated metabolites of organophosphorus insecticides formed via cytochrome P450 monooxygenase-catalyzed desulfuration of the parent compound. Oxons react covalently with the active site serine residue of serine hydrolases, thereby inactivating the enzyme. A number of serine hydrolases other than acetylcholinesterase, the canonical target of oxons, have been reported to react with and be inhibited by oxons. These off-target serine hydrolases include carboxylesterase 1 (CES1), CES2, and monoacylglycerol lipase. Carboxylesterases (CES, EC 3.1.1.1) metabolize a number of xenobiotic and endobiotic compounds containing ester, amide, and thioester bonds and are important in the metabolism of many pharmaceuticals. Monoglyceride lipase (MGL, EC 3.1.1.23) hydrolyzes monoglycerides including the endocannabinoid, 2-arachidonoylglycerol (2-AG). The physiological consequences and toxicity related to the inhibition of off-target serine hydrolases by oxons due to chronic, low level environmental exposures are poorly understood. Here, we determined the potency of inhibition (IC50 values; 15 min preincubation, enzyme and inhibitor) of recombinant CES1, CES2, and MGL by chlorpyrifos oxon, paraoxon and methyl paraoxon. The order of potency for these three oxons with CES1, CES2, and MGL was chlorpyrifos oxon > paraoxon > methyl paraoxon, although the difference in potency for chlorpyrifos oxon with CES1 and CES2 did not reach statistical significance. We also determined the bimolecular rate constants (kinact/KI) for the covalent reaction of chlorpyrifos oxon, paraoxon and methyl paraoxon with CES1 and CES2. Consistent with the results for the IC50 values, the order of reactivity for each of the three oxons with CES1 and CES2 was chlorpyrifos oxon > paraoxon > methyl paraoxon. The bimolecular rate constant for the reaction of chlorpyrifos oxon with MGL was also determined and was less than the values determined for chlorpyrifos oxon with CES1 and CES2 respectively

  7. Transferable residues from dog fur and plasma cholinesterase inhibition in dogs treated with a flea control dip containing chlorpyrifos.

    OpenAIRE

    Boone, J S; Tyler, J. W.; Chambers, J. E.

    2001-01-01

    We studied chlorpyrifos, an insecticide present in a commercial dip for treating ectoparasites in dogs, to estimate the amount of transferable residues that children could obtain from their treated pets. Although the chlorpyrifos dip is no longer supported by the manufacturer, the methodology described herein can help determine transferable residues from other flea control insecticide formulations. Twelve dogs of different breeds and weights were dipped using the recommended guidelines with a...

  8. Emblica officinalis Garten fruits extract ameliorates reproductive injury and oxidative testicular toxicity induced by chlorpyrifos in male rats

    OpenAIRE

    Dutta, Abir Lal; Sahu, Chitta Ranjan

    2013-01-01

    Organophosphate pesticides have destroying properties on male reproduction and chlorpyrifos adversely affects the male reproductive system. Emblica offcinalis Garten plays a vital role to challenge many diseases in human body. We investigated the induction of oxidative stress in the male reproductive system of adult rats (Wistar Strain) exposed to widely used organophosphate pesticide, Chlorpyrifos, and tried to establish the ameliorative properties of Emblica officinalis Garten with respect ...

  9. Developmental Scaffolding

    DEFF Research Database (Denmark)

    Giorgi, Franco; Bruni, Luis Emilio

    2015-01-01

    The concept of scaffolding has wide resonance in several scientific fields. Here we attempt to adopt it for the study of development. In this perspective, the embryo is conceived as an integral whole, comprised of several hierarchical modules as in a recurrent circularity of emerging patterns...... molecular signalling to the complexity of sign recognition proper of a cellular community. In this semiotic perspective, the apparent goal directness of any developmental strategy should no longer be accounted for by a predetermined genetic program, but by the gradual definition of the relationships...

  10. Changes of field incurred chlorpyrifos and its toxic metabolite residues in rice during food processing from-RAC-to-consumption.

    Directory of Open Access Journals (Sweden)

    Zhiyong Zhang

    Full Text Available The objectives of this study were to determine the effects of food processing on field incurred residues levels of chlorpyrifos and its metabolite 3,5,6-Trichloro-2-pyridinol (TCP in rice. The chlorpyrifos and TCP were found to be 1.27 and 0.093 mg kg-1 in straw and 0.41 and 0.073 mg kg-1 in grain, respectively. It is observed that the sunlight for 2 hours does not decrease the chlorpyrifos and TCP residues in grain significantly. Their residues in rice were reduced by up to 50% by hulling. The cooking reduced the chlorpyrifos and TCP in rice to undetectable level (below 0.01 mg kg-1. Processing factors (PFs of chlorpyrifos and TCP residues in rice during food processing were similar. Various factors have impacts on the fates of chlorpyrifos and TCP residues and the important steps to reduce their residues in rice were hulling and cooking. The results can contribute to assure the consumer of a safe wholesome food supply.

  11. The expression profile of detoxifying enzyme of tomato leaf miner, Tuta absoluta Meyrik (Lepidoptera: Gelechiidae to chlorpyrifos

    Directory of Open Access Journals (Sweden)

    Idin Zibaee

    2016-06-01

    Full Text Available The tomato leafminer, Tuta absoluta (Meyrich (Lepidoptera: Gelechiidae is an important pest of tomato crops worldwide. The persistent use of organophosphate insecticide to control this pest has led to resistance. However, there is no report on the susceptibility and resistance mechanism of field population of Tuta absoluta (Meyrik from Iran. Furthermore, the toxicity and impact of chlorpyrifos on metabolic enzymes in this pest remains unknown. The populations of T. absoluta from Rasht in Iran displayed LC30; 4332, LC50; 5010 and LC90; 7027 μg larva-1 to chlorpyrifos. The toxicity of chlorpyrifos could be synergized more bydiethyl maleate (DEM and triphenylphosphate (TPP whereas the synergistic effect of piperonylbutoxide (PBO was not efficient as well as two other synergists. The synergistic effect ranged from 1.3 to 1.9-fold in 24 h and 1.2 to 1.5-fold in 48 h. The exposure with chlorpyrifos for 24 and 48 h significantly increased the activities of esterase and cytochrome P450-dependent monooxygenases, while there were no significant changes in glutathione-S-transferase. Field populations of T. absoluta from Iran displayed less susceptibility to chlorpyrifos and had a relatively high LC50 in compare to other previous studies. Esterases and cytochrome P450 monooxygenase might be involved in the metabolism, and hence resistance to, chlorpyrifos in this pest.

  12. Effects of developmental exposure to a Commercial PBDE mixture (DE-71) on protein networks in the rat Cerebellum and Hippocampus

    Science.gov (United States)

    Title (20 words): Effects of developmental exposure to a Commercial PBDE mixture (DE-71) on protein networks in the rat Cerebellum and Hippocampus. Introduction (120 words): Polybrominated diphenyl ethers (PBDE5) possess neurotoxic effects similar to those of PCBs. The cellular a...

  13. The fungicide imazalil induces developmental abnormalities and alters locomotor activity during early developmental stages in zebrafish.

    Science.gov (United States)

    Jin, Yuanxiang; Zhu, Zhihong; Wang, Yueyi; Yang, Enlu; Feng, Xiayan; Fu, Zhengwei

    2016-06-01

    The fungicide imazalil (IMZ) is used extensively to protect vegetable fields, fruit plantations and post-harvest crops from rot. Likely due to its wide-spread use, IMZ is frequently detected in vegetable, fruit, soil and even surface water samples. Even though several previous studies have reported on the neurotoxicity of IMZ, its effects on the neurobehavior of zebrafish have received little attention to date. In this study, we show that the heartbeat and hatchability of zebrafish were significantly influenced by IMZ concentrations of 300 μg L(-1) or higher. Moreover, in zebrafish larvae, locomotor behaviors such as average swimming speed and swimming distance were significantly decreased after exposure to 300 μg L(-1) IMZ for 96 h, and acetylcholinesterase (AChE) expression and activity were consistently inhibited in IMZ-treated fish. Our results further suggest that IMZ could act as a neuroendocrine disruptor by decreasing the expression of neurotoxicity-related genes such as Glial fibrillary acidic protein (Gfap), Myelin basic protein (Mbp) and Sonic hedgehog a (Shha) during early developmental stages of zebrafish. In conclusion, we show that exposure to IMZ has the potential to induce developmental toxicity and locomotor behavior abnormalities during zebrafish development. PMID:27035382

  14. Acrylamide neurotoxicity on the cerebrum of weaning rats

    Directory of Open Access Journals (Sweden)

    Su-min Tian

    2015-01-01

    Full Text Available The mechanism underlying acrylamide-induced neurotoxicity remains controversial. Previous studies have focused on acrylamide-induced toxicity in adult rodents, but neurotoxicity in weaning rats has not been investigated. To explore the neurotoxic effect of acrylamide on the developing brain, weaning rats were gavaged with 0, 5, 15, and 30 mg/kg acrylamide for 4 consecutive weeks. No obvious neurotoxicity was observed in weaning rats in the low-dose acrylamide group (5 mg/kg. However, rats from the moderate- and high-dose acrylamide groups (15 and 30 mg/kg had an abnormal gait. Furthermore, biochemical tests in these rats demonstrated that glutamate concentration was significantly reduced, and γ-aminobutyric acid content was significantly increased and was dependent on acrylamide dose. Immunohistochemical staining showed that in the cerebral cortex, γ-aminobutyric acid, glutamic acid decarboxylase and glial fibrillary acidic protein expression increased remarkably in the moderate- and high-dose acrylamide groups. These results indicate that in weaning rats, acrylamide is positively associated with neurotoxicity in a dose-dependent manner, which may correlate with upregulation of γ-aminobutyric acid and subsequent neuronal degeneration after the initial acrylamide exposure.

  15. Is Neurotoxicity of Metallic Nanoparticles the Cascades of Oxidative Stress?

    Science.gov (United States)

    Song, Bin; Zhang, YanLi; Liu, Jia; Feng, XiaoLi; Zhou, Ting; Shao, LongQuan

    2016-12-01

    With the rapid development of nanotechnology, metallic (metal or metal oxide) nanoparticles (NPs) are widely used in many fields such as cosmetics, the food and building industries, and bio-medical instruments. Widespread applications of metallic NP-based products increase the health risk associated with human exposures. Studies revealed that the brain, a critical organ that consumes substantial amounts of oxygen, is a primary target of metallic NPs once they are absorbed into the body. Oxidative stress (OS), apoptosis, and the inflammatory response are believed to be the main mechanisms underlying the neurotoxicity of metallic NPs. Other studies have disclosed that antioxidant pretreatment or co-treatment can reverse the neurotoxicity of metallic NPs by decreasing the level of reactive oxygen species, up-regulating the activities of antioxidant enzymes, decreasing the proportion of apoptotic cells, and suppressing the inflammatory response. These findings suggest that the neurotoxicity of metallic NPs might involve a cascade of events following NP-induced OS. However, additional research is needed to determine whether NP-induced OS plays a central role in the neurotoxicity of metallic NPs, to develop a comprehensive understanding of the correlations among neurotoxic mechanisms and to improve the bio-safety of metallic NP-based products. PMID:27295259

  16. Is Neurotoxicity of Metallic Nanoparticles the Cascades of Oxidative Stress?

    Science.gov (United States)

    Song, Bin; Zhang, YanLi; Liu, Jia; Feng, XiaoLi; Zhou, Ting; Shao, LongQuan

    2016-06-01

    With the rapid development of nanotechnology, metallic (metal or metal oxide) nanoparticles (NPs) are widely used in many fields such as cosmetics, the food and building industries, and bio-medical instruments. Widespread applications of metallic NP-based products increase the health risk associated with human exposures. Studies revealed that the brain, a critical organ that consumes substantial amounts of oxygen, is a primary target of metallic NPs once they are absorbed into the body. Oxidative stress (OS), apoptosis, and the inflammatory response are believed to be the main mechanisms underlying the neurotoxicity of metallic NPs. Other studies have disclosed that antioxidant pretreatment or co-treatment can reverse the neurotoxicity of metallic NPs by decreasing the level of reactive oxygen species, up-regulating the activities of antioxidant enzymes, decreasing the proportion of apoptotic cells, and suppressing the inflammatory response. These findings suggest that the neurotoxicity of metallic NPs might involve a cascade of events following NP-induced OS. However, additional research is needed to determine whether NP-induced OS plays a central role in the neurotoxicity of metallic NPs, to develop a comprehensive understanding of the correlations among neurotoxic mechanisms and to improve the bio-safety of metallic NP-based products.

  17. Neurotoxicity Caused by the Treatment with Platinum Analogues

    Directory of Open Access Journals (Sweden)

    Sousana Amptoulach

    2011-01-01

    Full Text Available Platinum agents (cisplatin, carboplatin, and oxaliplatin are a class of chemotherapy agents that have a broad spectrum of activity against several solid tumors. Toxicity to the peripheral nervous system is the major dose-limiting toxicity of at least some of the platinum drugs of clinical interest. Among the platinum compounds in clinical use, cisplatin is the most neurotoxic, inducing mainly sensory neuropathy of the upper and lower extremities. Carboplatin is generally considered to be less neurotoxic than cisplatin, but it is associated with a higher risk of neurological dysfunction if administered at high dose or in combination with agents considered to be neurotoxic. Oxaliplatin induces two types of peripheral neuropathy, acute and chronic. The incidence of oxaliplatin-induced neuropathy is related to various risk factors such as treatment schedule, cumulative dose, and time of infusion. To date, several neuroprotective agents including thiol compounds, vitamin E, various anticonvulsants, calcium-magnesium infusions, and other nonpharmacological strategies have been tested for their ability to prevent platinum-induced neurotoxicity with controversial results. Further studies on the prevention and treatment of neurotoxicity of platinum analogues are warranted.

  18. Developmental dyslexia.

    Science.gov (United States)

    Démonet, Jean-François; Taylor, Margot J; Chaix, Yves

    2004-05-01

    Developmental dyslexia, or specific reading disability, is a disorder in which children with normal intelligence and sensory abilities show learning deficits for reading. Substantial evidence has established its biological origin and the preponderance of phonological disorders even though important phenotypic variability and comorbidity have been recorded. Diverse theories have been proposed to account for the cognitive and neurological aspects of dyslexia. Findings of genetic studies show that different loci affect specific reading disability although a direct relation has not been established between symptoms and a given genomic locus. In both children and adults with dyslexia, results of neuroimaging studies suggest defective activity and abnormal connectivity between regions crucial for language functions--eg, the left fusiform gyrus for reading--and changes in brain activity associated with performance improvement after various remedial interventions. PMID:15121410

  19. Developmental dyslexia.

    Science.gov (United States)

    Peterson, Robin L; Pennington, Bruce F

    2015-01-01

    This review uses a levels-of-analysis framework to summarize the current understanding of developmental dyslexia's etiology, brain bases, neuropsychology, and social context. Dyslexia is caused by multiple genetic and environmental risk factors as well as their interplay. Several candidate genes have been identified in the past decade. At the brain level, dyslexia is associated with aberrant structure and function, particularly in left hemisphere reading/language networks. The neurocognitive influences on dyslexia are also multifactorial and involve phonological processing deficits as well as weaknesses in other oral language skills and processing speed. We address contextual issues such as how dyslexia manifests across languages and social classes as well as what treatments are best supported. Throughout the review, we highlight exciting new research that cuts across levels of analysis. Such work promises eventually to provide a comprehensive explanation of the disorder as well as its prevention and remediation. PMID:25594880

  20. Synthesis and Characterization of Microcapsules with Chlorpyrifos Cores and Polyurea Walls

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Microcapsules with chlorpyrifos cores and polyurea walls were synthesized with 2,4-tolylene diisocyanate as an oil-soluble monomer and ethylenediamine as a water-soluble monomer via an interfacial polycondensation reaction.The products were characterized by means of Fourier transform infrared spectrometry, 13C NMR spectrometry and 31P NMR spectrometry. The morphology, the particle size and the particle size distribution, and the thermal properties were also evaluated. The prepared microcapsules exhibit clear and smooth surfaces and have a mean diameter of 28. 13 μm. These microcapsules also have a good thermal stability for long-term use, and have potential applications in minimizing the toxicity of chlorpyrifos through controlled release.

  1. Effects of processing of crude soybean oil on 14C-chlorpyrifos residues

    International Nuclear Information System (INIS)

    Under conditions similar to those used in practice, soybean seeds were treated postharvest with 14C-chlorpyrifos. After 3 months in storage, total residues declined to 7.34 mg/kg. The major portion of this residue (67%) could be washed off with water; methanol-extractable and bound residues accounted for 31% and 2% respectively. The crude oil was gained from the seeds by n-hexane extraction, and subjected to four processes used commercially for the refinement of the oil. While the degumming removed 5% of the residue, alkali treatment removed 50%. Bleaching had practically no effect on the residue while steam distillation (deodorization) reduced the residue by a further 25%; total > 80%. In the refined oil, < 5% of the residue was in the form of the hydrolysis product 3,5,6-trichloro-2-pyridinol. It is concluded that industrial processes are highly effective in removing chlorpyrifos residues from crude soybean oil. (author). 3 refs, 3 tabs

  2. Effect of processing on residues of 14C-chlorpyrifos in coconut oil

    International Nuclear Information System (INIS)

    A coconut tree was root infused with 5 g of 14C-chlorpyrifos (51.8 kBq) and residues in the young and mature fruits were determined at various intervals up to 60 days. After 2 months the mature fruits retained much higher residues in the meat (11 mg/kg) than the young fruit (0.6 mg/kg). Under simulated agricultural practice, a post harvest single treatment of mature coconut meat (copra) resulted in a mean residue value of 8.2 mg/kg copra meat after three months. After gaining the crude oil by extraction with n-hexane, the efficiency of processes used commercially in refining the oil were tested. For post harvest treatment, aged residues lost only 23% after subjecting the crude oil to alkali treatment, bleaching and steam distillation, while chlorpyrifos-spiked samples lost 30%. (author). 5 refs, 3 tabs

  3. Non-fibrillar amyloid-β peptide reduces NMDA-induced neurotoxicity, but not AMPA-induced neurotoxicity

    International Nuclear Information System (INIS)

    Amyloid-β peptide (Aβ) is thought to be linked to the pathogenesis of Alzheimer's disease. Recent studies suggest that Aβ has important physiological roles in addition to its pathological roles. We recently demonstrated that Aβ42 protects hippocampal neurons from glutamate-induced neurotoxicity, but the relationship between Aβ42 assemblies and their neuroprotective effects remains largely unknown. In this study, we prepared non-fibrillar and fibrillar Aβ42 based on the results of the thioflavin T assay, Western blot analysis, and atomic force microscopy, and examined the effects of non-fibrillar and fibrillar Aβ42 on glutamate-induced neurotoxicity. Non-fibrillar Aβ42, but not fibrillar Aβ42, protected hippocampal neurons from glutamate-induced neurotoxicity. Furthermore, non-fibrillar Aβ42 decreased both neurotoxicity and increases in the intracellular Ca2+ concentration induced by N-methyl-D-aspartate (NMDA), but not by α-amino-3-hydrozy-5-methyl-4-isoxazole propionic acid (AMPA). Our results suggest that non-fibrillar Aβ42 protects hippocampal neurons from glutamate-induced neurotoxicity through regulation of the NMDA receptor.

  4. In vitro protection of human lymphocytes from toxic effects of chlorpyrifos by selenium-enriched medicines

    OpenAIRE

    Navaei-Nigjeh, Mona; Asadi, Hamidreza; Baeeri, Maryam; Pedram, Sahar; Rezvanfar, Mohammad Amin; Mohammadirad, Azadeh; Abdollahi, Mohammad

    2015-01-01

    Objective(s): Chlorpyrifos (CP) is a broad-spectrum organophosphorus pesticide used extensively in agricultural and domestic pest control, accounting for 50% of the global insecticidal use. In the present study, protective effects of two selenium-enriched strong antioxidative medicines IMOD and Angipars were examined in human lymphocytes treated with CP in vitro. Materials and Methods: Isolated lymphocytes were exposed to 12 µg/ml CP either alone or in combination with effective doses (ED50) ...

  5. Environmental distribution of acetochlor, atrazine, chlorpyrifos, and propisochlor under field conditions.

    Science.gov (United States)

    Konda, L N; Pásztor, Z

    2001-08-01

    The environmental behavior, movement, distribution, persistence, and runoff by rainfall of the pesticides acetochlor, atrazine, chlorpyrifos, and propisochlor were studied under field conditions during a five-month period at normal weather conditions. The pesticide concentrations in soil depths of 0-5 and 5-20 cm, and in sediment and runoff water samples (collected from an artificial reservoir built in the lower part of the experimental plot) were measured every second week and following every runoff event. The contamination of a stream running across the lowest part of the plot was also monitored. The weather conditions were also recorded at the experimental site. The pesticide residues were quantified by a capillary gas chromatograph equipped with a nitrogen phosphorus selective detector (GC-NPD). There was a consistent decrease in pesticide residues in the 0-5 cm soil layer with time after spaying. At 140 days after treatment only atrazine and chlorpyrifos were present; acetochlor and propisochlor were not detected in this soil layer. Atrazine and chlorpyrifos in the soil at a depth of 5-20 cm were detectable during the whole experimental interval, whereas acetochlor and propisochlor concentrations were below the limit of detection. Pesticide losses by the surface runoff process and the contamination of the stream were closely related to the time of rainfall elapsed after treatment and amount of rain at the experimental plots. Losses were primarily dependent on surface rainfall volume and intensity. The maximum detected residues of atrazine and acetochlor in stream water were 1 order of magnitude higher than the maximum residue limit specified by the European Union (EU) for environmental and drinking water (0.1 microg/L for individual compounds and 0.5 microg/L for total pesticides). Chlorpyrifos and propisochlor were not detected in this matrix. PMID:11513679

  6. An evaluation of the inhibition of human butyrylcholinesterase and acetylcholinesterase by the organophosphate chlorpyrifos oxon

    International Nuclear Information System (INIS)

    Acetylcholinesterase (EC 3.1.1.7) and butyrylcholinesterase (EC 3.1.1.8) are enzymes that belong to the superfamily of α/β-hydrolase fold proteins. While they share many characteristics, they also possess many important differences. For example, whereas they have about 54% amino acid sequence identity, the active site gorge of acetylcholinesterase is considerably smaller than that of butyrylcholinesterase. Moreover, both have been shown to display simple and complex kinetic mechanisms, depending on the particular substrate examined, the substrate concentration, and incubation conditions. In the current study, incubation of butyrylthiocholine in a concentration range of 0.005-3.0 mM, with 317 pM human butyrylcholinesterase in vitro, resulted in rates of production of thiocholine that were accurately described by simple Michaelis-Menten kinetics, with a Km of 0.10 mM. Similarly, the inhibition of butyrylcholinesterase in vitro by the organophosphate chlorpyrifos oxon was described by simple Michaelis-Menten kinetics, with a ki of 3048 nM-1 h-1, and a KD of 2.02 nM. In contrast to inhibition of butyrylcholinesterase, inhibition of human acetylcholinesterase by chlorpyrifos oxon in vitro followed concentration-dependent inhibition kinetics, with the ki increasing as the inhibitor concentration decreased. Chlorpyrifos oxon concentrations of 10 and 0.3 nM gave kis of 1.2 and 19.3 nM-1 h-1, respectively. Although the mechanism of concentration-dependent inhibition kinetics is not known, the much smaller, more restrictive active site gorge of acetylcholinesterase almost certainly plays a role. Similarly, the much larger active site gorge of butyrylcholinesterase likely contributes to its much greater reactivity towards chlorpyrifos oxon, compared to acetylcholinesterase.

  7. Genotoxic Effects of Chlorpyrifos in Freshwater Fish Cirrhinus mrigala Using Micronucleus Assay

    OpenAIRE

    Anita Bhatnagar; Abhay Singh Yadav; Navneet Cheema

    2016-01-01

    The genotoxicity of pesticides is an issue of worldwide concern and chlorpyrifos is one of the largest selling organophosphate agrochemicals that has been widely detected in surface waters of India. The studies on long term genotoxic biomarkers are limited; therefore, present study was carried out to analyze the incidence of nuclear anomalies in the blood cells of fresh water fish Cirrhinus mrigala using micronucleus (MN) assay as a potential tool for assessment of genotoxicity. Acute toxicit...

  8. Effects of chlorpyrifos, carbendazim and linuron on the ecology of a small indoor aquatic microcosm

    OpenAIRE

    Daam, M.A.; Brink, van den, R.B.A.

    2007-01-01

    To validate the use of small indoor microcosms for the risk assessment of pesticides, the fate and effects of chlorpyrifos, carbendazim, and linuron were studied in 8.5¿liter indoor freshwater microcosms. Functional and structural responses to selected concentrations were evaluated and compared with responses observed in larger-scale model ecosystem studies. Overall, the microcosms adequately displayed the chain of effects resulting from the application, although they did not always predict t...

  9. Efficiency of the intestinal bacteria in the degradation of the toxic pesticide, chlorpyrifos

    OpenAIRE

    Harishankar, M. K.; C Sasikala; Ramya, M.

    2012-01-01

    Chlorpyrifos (CP) is the most commonly used pesticide throughout the world. Its widespread use in agriculture and its potential toxicity to humans from ingestion of CP contaminated food have raised concerns about its risk to health. Human intestinal microflora has the ability to degrade pesticides, but the exact mechanisms involved and the metabolite end-products formed are not well understood. The primary objective of this work was to analyse the in vitro degradation of CP by five model inte...

  10. PON1 Status Does Not Influence Cholinesterase Activity in Egyptian Agricultural Workers Exposed to Chlorpyrifos

    OpenAIRE

    Ellison, Corie A.; Crane, Alice L.; Bonner, Matthew R; Knaak, James B.; Browne, Richard W; Lein, Pamela J; Olson, James R.

    2012-01-01

    Animal studies have shown that paraoxonase 1 (PON1) genotype can influence susceptibility to the organophosphorus pesticide chlorpyrifos (CPF). However, Monte Carlo analysis suggests that PON1 genotype may not affect CPF-related toxicity at low exposure conditions in humans. The current study sought to determine the influence of PON1 genotype on the activity of blood cholinesterase as well as the effect of CPF exposure on serum PON1 in workers occupationally exposed to CPF. Saliva, blood and ...

  11. Lethal and Demographic Impact of Chlorpyrifos and Spinosad on the Ectoparasitoid Habrobracon hebetor (Say) (Hymenoptera: Braconidae).

    Science.gov (United States)

    Mahdavi, V; Saber, M; Rafiee-Dastjerdi, H; Kamita, S G

    2015-12-01

    The appropriate use of biological agents and chemical compounds is necessary to establish successful integrated pest management (IPM) programs. Thus, the off-target effects of pesticides on biological control agents are essential considerations of IPM. In this study, the effects of lethal and sublethal concentrations of chlorpyrifos and spinosad on the demographic parameters of Habrobracon hebetor (Say) (Hymenoptera: Braconidae) were assessed. Bioassays were carried out on immature and adult stages by using dipping and contact exposure of dry pesticide residue on an inert material, respectively. The lethal concentration (LC)50 values of chlorpyrifos and spinosad were 3.69 and 151.37 ppm, respectively, on the larval stage and 1.75 and 117.37 ppm, respectively, on adults. Hazard quotient (HQ) values for chlorpyrifos and spinosad were 400 and 2.2, respectively, on the larval stage and 857.14 and 2.84, respectively, on adults. A low lethal concentration (LC30) was used to assess the sublethal effects of both pesticides on the surviving females. In each treatment, 25 survivors were randomly selected and transferred into 6-cm Petri dishes. Adults were provided daily with last instars of Anagasta kuehniella (Zeller) as a host until all of the females died. The number of eggs laid, percent of larvae hatched, longevity, and sex ratio were recorded. Stable population growth parameters were estimated by the Jackknife method. In control, chlorpyrifos, and spinosad treatments, the intrinsic rates of increase (r m) values were 0.23, 0.10, and 0.21, respectively. The results of this study suggest a relative compatibility between spinosad use and H. hebetor. Finally, further studies should be conducted under natural conditions to verify the compatibility of spinosad with H. hebetor in IPM programs. PMID:26280986

  12. Potential chlorpyrifos exposure to residents following standard crack and crevice treatment.

    OpenAIRE

    Byrne, S L; Shurdut, B A; Saunders, D G

    1998-01-01

    Multipathway exposures were evaluated for residents of houses over a 10-day period following a crack and crevice application of a chlorpyrifos-based formulation. Three multiroom houses with two adults each were treated. Air concentration, total deposition, and dislodgeable residues on horizontal surfaces were measured to assess potential respiratory, oral, and dermal exposures, respectively, in treated and untreated high activity rooms. In addition, urine samples collected from the adults wer...

  13. Effects of Nickel, Chlorpyrifos and Their Mixture on the Dictyostelium discoideum Proteome

    Directory of Open Access Journals (Sweden)

    Francesco Marsano

    2012-11-01

    Full Text Available Mixtures of chemicals can have additive, synergistic or antagonistic interactions. We investigated the effects of the exposure to nickel, the organophosphate insecticide chlorpyrifos at effect concentrations (EC of 25% and 50% and their binary mixture (Ec25 + EC25 on Dictyostelium discoideum amoebae based on lysosomal membrane stability (LMS. We treated D. discoideum with these compounds under controlled laboratory conditions and evaluated the changes in protein levels using a two-dimensional gel electrophoresis (2DE proteomic approach. Nickel treatment at EC25 induced changes in 14 protein spots, 12 of which were down-regulated. Treatment with nickel at EC50 resulted in changes in 15 spots, 10 of which were down-regulated. Treatment with chlorpyrifos at EC25 induced changes in six spots, all of which were down-regulated; treatment with chlorpyrifos at EC50 induced changes in 13 spots, five of which were down-regulated. The mixture corresponding to EC25 of each compound induced changes in 19 spots, 13 of which were down-regulated. The data together reveal that a different protein expression signature exists for each treatment, and that only a few proteins are modulated in multiple different treatments. For a simple binary mixture, the proteomic response does not allow for the identification of each toxicant. The protein spots that showed significant differences were identified by mass spectrometry, which revealed modulations of proteins involved in metal detoxification, stress adaptation, the oxidative stress response and other cellular processes.

  14. Bird predation on cutworms (Lepidoptera: Noctuidae) in wheat fields and chlorpyrifos effects on brain cholinesterase activity

    Science.gov (United States)

    McEwen, L.C.; DeWeese, L.R.; Schladweiler, P.

    1986-01-01

    Horned larks, Eremophila alpestris (L.), and McCown's longspurs, Calcarius mccownii (Lawrence), were collected at intervals from two winter wheat fields in Montana [USA] after aerial application of chlorpyrifos to control cutworms. Both bird species had a high (95-100%) incidence of Lepidoptera, mostly pale western cutworms, Agrotis orthogonia Morrison, in their stomachs at 3 days postspray. Incidence of cutworms and other insects in stomachs of birds from sprayed fields was lower at 9 and 16 days postspray than in control birds, presumably due to insecticide-caused reduction of insects. Effects of birds on population dynamics of insect pests in wheat are unknown, but birds do contribute to cutworm mortality. Predation is one of the limiting factors to cutworm increase and can supplement insecticidal control. Brain cholinesterase activity in horned larks collected from the sprayed fields at 3 and 9 days postspray was significantly lower than in unexposed larks, but at 16 days the difference was not significant. Although nontarget birds clearly were exposed to chlorpyrifos and manifested a sublethal physiological response, toxic effects were less severe than those resulting from endrin application for cutworm control in wheat. More study is needed of larger chlorpyrifos-treated fields under a variety of conditions to fully assess effects on nontarget life.

  15. A comparison of a laboratory scale experiment with a field trial treatment using chlorpyrifos-methyl

    International Nuclear Information System (INIS)

    An experiment was carried out in which a field treatment of a small bulk of grain with chlorpyrifos-methyl was compared with a laboratory treatment of 1 kg of grain with 14C radiolabelled chlorpyrifos-methyl. The conditions under which the grain was maintained in the laboratory mimicked those of the field trial as closely as possible, with sampling and analysis being carried out at the same time and in a similar manner in both. The results from the two experiments were in general agreement with approx. 60% of the chlorpyrifos-methyl remaining intact at the end. A satisfactory level of biological control was achieved in the field trial. The use of the radio-label enabled more information about the fate of the degraded insecticide to be obtained from the laboratory experiment. The majority of this radioactivity comprised a fraction which remained within the grain tissue after solvent extraction. The level of activity in the grain tissues gradually increased with time but its nature is as yet unknown. The good agreement obtained between the residue profile and the breakdown patterns in both experiments would suggest that a laboratory scale experiment is a satisfactory model for the situation pertaining in a large scale field trial. (author)

  16. Neonatal Anesthesia Neurotoxicity: A Review for Cleft and Craniofacial Surgeons.

    Science.gov (United States)

    Laub, Donald R; Williams, Robert K

    2015-07-01

    There is growing evidence that the commonly used anesthetic agents cause some degree of damage to the early developing brain. The animal evidence for anesthetic neurotoxicity is compelling. Numerous confounders in human research prevent researchers from drawing definitive conclusions about the degree of risk. For every surgery, it should be assessed whether the benefits of an early surgical procedure justify a potential but unquantifiable risk of neurotoxicity of anesthetic agents. The timing and number of surgeries in our treatment protocols may need to be reevaluated to account for these potential risks. PMID:24941351

  17. Cancer Treatment-Induced Neurotoxicity: A Focus on Newer Treatments

    Science.gov (United States)

    Stone, Jacqueline B.; DeAngelis, Lisa M.

    2016-01-01

    Neurotoxicity from traditional chemotherapy and radiotherapy is widely recognized. The adverse effects of newer therapeutics such as biological and immunotherapeutic agents are less familiar and they are also associated with significant neurotoxicity in the central and peripheral nervous systems. This review addresses the main toxicities of cancer treatment by symptom with a focus on the newer therapeutics. Recognition of these patterns of toxicity is important as drug discontinuation or dose adjustment may prevent further neurologic injury. Also, knowledge of these toxicities helps to differentiate treatment-related symptoms from progression of cancer or its involvement of the nervous system. PMID:26391778

  18. Applications of quantitative measurements for assessing glutamate neurotoxicity.

    OpenAIRE

    Finkbeiner, S.; Stevens, C F

    1988-01-01

    The role of the N-methyl-D-aspartate receptor channel in glutamate neurotoxicity was investigated in cultured hippocampal neurons of the CA1 region. An equation, the survival function, was developed to quantify the effects of putative modulators of neurotoxicity. 2-Amino-5-phosphonovaleric acid (30 microM) reduced the neuronal sensitivity to glutamate by a factor greater than 20, whereas glycine (1 microM) enhanced it by a factor of 7.5 +/- 2.5. Neurons were protected by increasing Mg2+ conce...

  19. Translational Biomarkers of Neurotoxicity: A Health and Environmental Sciences Institute Perspective on The Way Forward

    Science.gov (United States)

    Neurotoxicity has been linked to a number of common drugs and chemicals, yet efficient and accurate methods to detect it are lacking. There is a need for more sensitive and specific biomarkers of neurotoxicity that can help diagnose and predict neurotoxicity that are relevant acr...

  20. Developmental dyspraxia and developmental coordination disorder.

    Science.gov (United States)

    Miyahara, M; Möbs, I

    1995-12-01

    This article discusses the role developmental dyspraxia plays in developmental coordination disorder (DCD), based upon a review of literature on apraxia, developmental dyspraxia, and DCD. Apraxia and dyspraxia have often been equated with DCD. However, it is argued that apraxia and dyspraxia primarily refer to the problems of motor sequencing and selection, which not all children with DCD exhibit. The author proposes to distinguish developmental dyspraxia from DCD. Other issues discussed include the assessment, etiology, and treatment of developmental dyspraxia and DCD, and the relationship between DCD and learning disabilities. A research agenda is offered regarding future directions to overcome current limitation. PMID:8866511

  1. The effect of consequent exposure of stress and dermal application of low doses of chlorpyrifos on the expression of glial fibrillary acidic protein in the hippocampus of adult mice

    Directory of Open Access Journals (Sweden)

    Nadarajah Vishna

    2011-03-01

    Full Text Available Abstract Background Chlorpyrifos (CPF, a commonly used pesticide worldwide, has been reported to produce neurobehavioural changes. Dermal exposure to CPF is common in industries and agriculture. This study estimates changes in glial fibrillary acidic protein (GFAP expression in hippocampal regions and correlates with histomorphometry of neurons and serum cholinesterase levels following dermal exposure to low doses of CPF with or without swim stress. Methods Male albino mice were separated into control, stress control and four treatment groups (n = 6. CPF was applied dermally over the tails under occlusive bandage (6 hours/day at doses of 1/10th (CPF 0.1 and 1/5th dermal LD50 (CPF 0.2 for seven days. Consequent treatment of swim stress followed by CPF was also applied. Serum cholinesterase levels were estimated using spectroflurometric methods. Paraffin sections of the left hippocampal regions were stained with 0.2% thionin followed by the counting of neuronal density. Right hippocampal sections were treated with Dako Envision GFAP antibodies. Results CPF application in 1/10th LD50 did not produce significant changes in serum cholinesterase levels and neuronal density, but increased GFAP expression significantly (p Conclusions Findings suggest GFAP expression is upregulated with dermal exposure to low dose of CPF. Stress combined with sub-toxic dermal CPF exposure can produce neurotoxicity.

  2. Targeting neurotrophic factors and their receptors, but not cholinesterase or neurotransmitter, in the neurotoxicity of TDCPP in Chinese rare minnow adults (Gobiocypris rarus).

    Science.gov (United States)

    Yuan, Lilai; Li, Jiasu; Zha, Jinmiao; Wang, Zijian

    2016-01-01

    Organophosphate flame retardants (OPFRs) have been detected at high concentrations in various environmental and biotic samples, but little is known about their toxicity. In this study, the potential neurotoxicity of three OPFRs (TCEP, TDCPP, and TPP) and Chlorpyrifos (CPF, an organophosphate pesticide) were compared in Chinese rare minnow using an acute toxicity test and a 21-day fish assay. The acute test demonstrated significant inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) by CPF. Although significant AChE inhibition at high concentration of TPP was also observed, none of the OPFRs had effects similar to CPF on these enzymes, indicating that their acute toxicities to Chinese rare minnow may be unrelated to cholinesterase inhibition. In addition, the 21-day fish assay with TDCPP demonstrated no significant effects on cholinesterase activities or neurotransmitter levels. Nonetheless, this OPFR exhibited widespread effects on the neurotrophic factors and their receptors (e.g., ntf3, ntrk1, ntrk2, ngfr, and fgf2, fgf11, fgf22, fgfr4), indicating that TDCPP or other OPFRs may elicit neurological effects by targeting neurotrophic factors and their receptors in Chinese rare minnow. PMID:26552522

  3. Research advances on potential neurotoxicity of quantum dots.

    Science.gov (United States)

    Wu, Tianshu; Zhang, Ting; Chen, Yilu; Tang, Meng

    2016-03-01

    With rapid development of nanotechnology, quantum dots (QDs) as advanced nanotechnology products have been widely used in biological and biomedical studies, including neuroscience, due to their superior optical properties. In recent years, there has been intense concern regarding the toxicity of QDs with a growing number of studies. However, the knowledge of neurotoxic consequences of QDs applied in living organisms is lagging behind their development, while a potential risk of neurotoxicity arises if mass production of QDs leads to increased exposure and distribution in the nervous system. Owing to the quantum size effect of QDs, they are capable of crossing the blood-brain barrier or moving along neural pathways and entering the brain. Nevertheless, the interactions of QDs with cells and tissues in the central nervous system are not well understood. This review highlighted research advances on the neurotoxicity of QDs in the central nervous system, including oxidative stress injury, elevated cytoplasmic Ca(2+) levels and autophagy to damage in vitro neural cells, and impairments of synaptic transmission and plasticity as well as brain functions in tested animals, with the hope of throwing light on future research directions of QD neurotoxicity, which is a demanding topic that requires further exploration. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26364743

  4. Potential Role of Epigenetic Mechanism in Manganese Induced Neurotoxicity

    Science.gov (United States)

    Tarale, Prashant; Chakrabarti, Tapan; Sivanesan, Saravanadevi; Naoghare, Pravin; Bafana, Amit; Krishnamurthi, Kannan

    2016-01-01

    Manganese is a vital nutrient and is maintained at an optimal level (2.5–5 mg/day) in human body. Chronic exposure to manganese is associated with neurotoxicity and correlated with the development of various neurological disorders such as Parkinson's disease. Oxidative stress mediated apoptotic cell death has been well established mechanism in manganese induced toxicity. Oxidative stress has a potential to alter the epigenetic mechanism of gene regulation. Epigenetic insight of manganese neurotoxicity in context of its correlation with the development of parkinsonism is poorly understood. Parkinson's disease is characterized by the α-synuclein aggregation in the form of Lewy bodies in neuronal cells. Recent findings illustrate that manganese can cause overexpression of α-synuclein. α-Synuclein acts epigenetically via interaction with histone proteins in regulating apoptosis. α-Synuclein also causes global DNA hypomethylation through sequestration of DNA methyltransferase in cytoplasm. An individual genetic difference may also have an influence on epigenetic susceptibility to manganese neurotoxicity and the development of Parkinson's disease. This review presents the current state of findings in relation to role of epigenetic mechanism in manganese induced neurotoxicity, with a special emphasis on the development of Parkinson's disease. PMID:27314012

  5. NEUROTOXICITY OF PARATHION-INDUCED ACETYLCHOLINESTERASE INHIBITION IN NEONATAL RATS

    Science.gov (United States)

    The biochemical and morphological neurotoxic effects of postnatal acetylcholinesterase (AChE) inhibition were examined in rat pups dosed with parathion, at time points critical to hippocampal neurogenesis and synaptogenesis (i.e., D5-20). ippocampal cytopathology as assessed by l...

  6. Problems of neurotoxicity assessment with using of electroretinography

    Directory of Open Access Journals (Sweden)

    R. A. Tkachuk

    2015-06-01

    Full Text Available Introduction. An actual problem of detection neurotoxication from getting nanoparticles into the human body in its initial stage, the identification of toxicant, determine its amount (dose is considered. Formulation of the problem. The solving of the basic problems which encountered during improving electroretinography means and methods in its application to risk assessment person neurotoxication are considered in this article. Directions of retinographia improvement. We propose a method to improve of the standard electroretinography tools for assessment of risk of neurotoxicity. On the basis of the concept of applying with low intense pulsed light exposure on to the retina leads to a large resolution and less recovery time of the retina. A negative effect of reducing the intensity of the light obtained in the form of decrease of ratio energies of electroretino - signal to noise (ER-SNR. The application of the optimal Kalman filter to estimate the electroretinosignal in the selected from the retina its mixture with noise is based. The main results cited as simulation, and the field experiment. The statistical test of whether the alternative hypothesis achieves the predetermined significance level in order to be accepted in preference to the null hypothesis was applied. The formulas for entropy expressions in stationary and periodical correlated models of ERS are proposed. Conclusion. The results are used in development of an expert system for detecting of neurotoxicity, identification of nanoparticle type, and estimation of their dose in the nervous system of an organism, including at cases of a priori unknown particle.

  7. Berberine Reduces Neurotoxicity Related to Nonalcoholic Steatohepatitis in Rats

    Directory of Open Access Journals (Sweden)

    Doaa A. Ghareeb

    2015-01-01

    Full Text Available Berberine is a plant alkaloid that has several pharmacological effects such as antioxidant, antilipidemic, and anti-inflammatory effects. Nonalcoholic steatohepatitis (NASH triggers different aspects of disorders such as impaired endogenous lipid metabolism, hypercholesterolemia, oxidative stress, and neurotoxicity. In this study, we examined the mechanism by which NASH induces neurotoxicity and the protective effect of berberine against both NASH and its associated neurotoxicity. NASH induced rats showed significant impairments in lipid metabolism with increased serum triglycerides, cholesterol, and low-density lipoprotein (LDL. The NASH induced group also demonstrated a significant oxidative stress which is characterized by increased TBARs level and decreased antioxidant capacity such as GSH and SOD levels. Moreover, the NASH induction was associated with inflammation which was demonstrated by increased TNFα and nitric oxide levels. Hyperglycemia and hyperinsulinemia were observed in the NASH induced group. Also, our results showed a significant increase in the expression of the acetylcholine esterase (AChE and amyloid beta precursor protein (AβPP. These changes were significantly correlated with decreased insulin degrading enzyme (IDE and beta-amyloid40 (Aβ40 and increased beta-amyloid42 (Aβ42 in the hippocampal region. Daily administration of berberine (50 mg/kg for three weeks ameliorated oxidative stress, inflammation, hyperlipidemia, hyperglycemia, hyperinsulinemia, and the observed neurotoxicity.

  8. Respiratory strategy is a major determinant of [3H]water and [14C]chlorpyrifos uptake in aquatic insects

    Science.gov (United States)

    Buchwalter, D.B.; Jenkins, J.J.; Curtis, L.R.

    2002-01-01

    Despite the extensive use of aquatic insects to evaluate freshwater ecosystem health, little is known about the underlying factors that result in sensitivity differences between taxa. Organismal characteristics (respiratory strategy and body size) were used to explore the rates of [3H]H2O and [14)C]chlorpyrifos accumulation in aquatic insects. Ten aquatic insect taxa, including ephemeropteran, trichopteran, dipteran, hemipteran, and coleopteran species, were exposed to [14C]chlorpyrifos (240 ng??L-1) and [3H]H2O for up to 12 h. Because exchange epithelial surfaces on the)integument are permeable to water, [3H]H2O was used as a quantitative surrogate for exposed cellular surface area.) [14C]Chlorpyrifos uptake rates were highly correlated with water permeability in all 10 taxa tested and largely covaried with body size and respiratory strategy. Rates were highest among smaller organisms on a per-weight basis and in taxa with relatively large external cellular surfaces such as gills. Air-breathing taxa were significantly less permeable to both [3)HH20 and [14C)C]chlorpyrifos. A method for labeling exposed epithelial surfaces with a fluorescent dye was developed. This technique allowed discrimination between exchange epithelium and barrier tissue on the integument. Fluorescent dye distributions on the body surface provided a rapid method for estimating exposed epithelium consistent with [3H]H2O and [14)C]chlorpyrifos accumulation.

  9. Removal of Chlorpyrifos by Water Hyacinth (Eichhornia crassipes) and the Role of a Plant-Associated Bacterium.

    Science.gov (United States)

    Anudechakul, Choochai; Vangnai, Alisa S; Ariyakanon, Naiyanan

    2015-01-01

    The objective of this research was to study the efficiency of water hyacinth (Eichhornia crassipes) and the role of any plant-associated bacteria in removing chlorpyrifos from water. The relative growth rate (RGR) of E. crassipes in the presence of 0.1 mg/L chlorpyrifos was not significantly different from that in its absence and only slightly decreased at concentrations of 0.5 and 1.0 mg/L by ∼1.1- and ∼1.2-fold, respectively, with an observed dry weight based RGRDW for E. crassipes of 0.036-0.041 mg/g/d. The removal rate constants of chlorpyrifos in the absence of plants were low at 3.52, 2.29 and 1.84 h(-1) for concentrations of 0.1, 0.5 and 1.0 mg/L, respectively, but were some 3.89- to 4.87-fold higher in the presence of E. crassipes. Chlorpyrifos removal was markedly facilitated by the presence of a root-associated bacterium, preliminarily identified as Acinetobacter sp. strain WHA. The interaction of E. crassipes and Acinetobacter sp. strain WHA provide an efficient and ecological alternative to accelerate the removal and degradation of chlorpyrifos pollution from aquatic systems including wastewater. PMID:25976881

  10. CHLORPYRIFOS ACCUMULATION PATTERNS FOR CHILD ACCESSIBLE SURFACES AND OBJECTIVES AND URINARY METABOLITE EXCRETION BY CHILDREN FOR TWO-WEEKS AFTER CRACK-AND-CREVICE APPLICATION

    Science.gov (United States)

    The Children's-Post-Pesticide-Application-Exposure-Study (CPPAES) was conducted to look at the distribution of chlorpyrifos within a home environment for a 2-week period following a routine professional crack-and-crevice application, and to determine the amount of the chlorpyrifo...

  11. Effects of the insecticide Dursban 4E (active ingredient chlorpyrifos) in outdoor experimental ditches: I. comparison of short-term toxicity between the laboratory and the field

    NARCIS (Netherlands)

    Wijngaarden, van R.P.A.; Brink, van den P.J.; Crum, S.J.H.; Oude Voshaar, J.H.; Brock, T.C.M.; Leeuwangh, P.

    1996-01-01

    By means of the insecticide chlorpyrifos, results of acute single-species toxicity tests were compared with direct effects in outdoor mesocosms. In the mesocosms, chlorpyrifos concentrations between 0.1 and 44 Šg/l were sprayed once. Acute effects were observed on arthropods. Effects could be quanti

  12. Diffusion abnormalities of the globi pallidi in manganese neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    McKinney, Alexander M.; Filice, Ross W.; Teksam, Mehmet; Casey, Sean; Truwit, Charles; Clark, H. Brent; Woon, Carolyn; Liu, Hai Ying [Department of Radiology, Medical School, Box 292, 420 Delaware Street S.E., 55455, Minneapolis, MN (United States)

    2004-04-01

    Manganese is an essential trace metal required for normal central nervous system function, which is toxic when in excess amounts in serum. Manganese neurotoxicity has been demonstrated in patients with chronic liver/biliary failure where an inability to excrete manganese via the biliary system causes increased serum levels, and in patients on total parenteral nutrition (TPN), occupational/inhalational exposure, or other source of excess exogenous manganese. Manganese has been well described in the literature to deposit selectively in the globi pallidi and to induce focal neurotoxicity. We present a case of a 53-year-old woman who presented for a brain MR 3 weeks after liver transplant due to progressively decreasing level of consciousness. The patient had severe liver failure by liver function tests and bilirubin levels, and had also been receiving TPN since the transplant. The MR demonstrated symmetric hyperintensity on T1-weighted images in the globi pallidi. Apparent diffusion coefficient (ADC) map indicated restricted diffusion in the globi pallidi bilaterally. The patient eventually succumbed to systemic aspergillosis 3 days after the MR. The serum manganese level was 195 mcg/l (micrograms per liter) on postmortem exam (over 20 times the upper limits of normal). The patient was presumed to have suffered from manganese neurotoxicity since elevated serum manganese levels have been shown in the literature to correlate with hyperintensity on T1-weighted images, neurotoxicity symptoms, and focal concentration of manganese in the globi pallidi. Neuropathologic sectioning of the globi pallidi at autopsy was also consistent with manganese neurotoxicity. (orig.)

  13. Developmental neurotoxicity of ortho-phthalate diesters: review of human and experimental evidence.

    Science.gov (United States)

    Miodovnik, Amir; Edwards, Andrea; Bellinger, David C; Hauser, Russ

    2014-03-01

    Ortho-phthalate diesters, or phthalates, are widely used synthetic chemicals found primarily in consumer products and polyvinyl chloride plastics. Experimental evidence suggests that several phthalates possess antiandrogenic properties and may disrupt endocrine pathways resulting in abnormal reproductive outcomes. Low-level exposure to phthalates has been well documented in humans, with higher levels found in children and women of childbearing age. Recent epidemiologic studies postulate that prenatal exposure to measurable urine phthalate concentrations may be associated with altered genital and pubertal development in infants and children. This review addresses the emerging evidence that some phthalates may have an adverse impact on the developing brain. The supporting animal studies and proposed mechanisms underlying the deleterious properties of phthalates in relation to neurodevelopmental outcomes are also discussed. While the observed associations are based on limited studies with a broad range of endpoints, the implications of such outcomes are of concern from a public health standpoint and merit further investigation given the widespread nature of the exposure. PMID:24486776

  14. A Retrospective Performance Assessment of the Developmental Neurotoxicity Study in Support of OECD Test Guideline 426

    DEFF Research Database (Denmark)

    Makris, Susan L.; Raffaele, Kathleen; Allen, Sandra; Bowers, Wayne J.; Hass, Ulla; Alleva, Enrico; Calamandrei, Gemma; Sheets, Larry; Amcoff, Patric; Delrue, Nathalie; Crofton, Kevin M.

    2009-01-01

    this review we summarize extensive scientific efforts that form the foundation for this testing paradigm, including basic neurotoxicology research, interlaboratory collaborative studies, expert workshops, and validation studies, and we address the relevance, applicability, and use of the DNT study in...... validation and international acceptance of new or updated test methods for hazard characterization. Multiple independent, expert scientific peer reviews affirm these conclusions....

  15. EVALUATION OF DEVELOPMENTAL NEUROTOXICITY OF ORGANOTINS VIA DRINKING WATER IN RATS: MONOMETHYL TIN

    Science.gov (United States)

    Organotins such as monomethyltin (MMT) are widely used as heat stabilizers in PVC and CPVC piping. Because human exposure to organotins is widespread via drinking water and the health consequences unknown, organotins were listed on the US EPA Candidate Contaminant List. Particu...

  16. International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes

    DEFF Research Database (Denmark)

    Bal-Price, Anna; Crofton, Kevin M.; Leist, Marcel;

    2015-01-01

    of regulatory needs on the one hand and the opportunities provided by new test systems and methods on the other hand. Alignment of academically and industrially driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISTNET) in DNT testing...

  17. Effects of chlorpyrifos on life cycle parameters, cytochrome P450S expression, and antioxidant systems in the monogonont rotifer Brachionus koreanus.

    Science.gov (United States)

    Kim, Ryeo-Ok; Kim, Bo-Mi; Jeong, Chang-Bum; Lee, Jae-Seong; Rhee, Jae-Sung

    2016-06-01

    Chlorpyrifos is a widely used organophosphorus insecticide for controlling diverse insect pests of crops. In the monogonont rotifer Brachionus koreanus, population growth retardation with the inhibition of lifespan, fecundity, and individual body size of ovigerous females was shown over 10 d in response to chlorpyrifos exposure. At the molecular and biochemical levels, the rotifer B. koreanus defensome, composed of cytochrome P450 complements, heat shock protein 70, and antioxidant enzymatic systems (i.e., glutathione, glutathione peroxidase, glutathione reductase, and glutathione S-transferase), was significantly induced in response to different concentrations of chlorpyrifos. Thus, chlorpyrifos strongly induced a defensome system to mitigate the deleterious effects of chlorpyrifos at in vivo and in vitro levels as a trade-off in fitness costs. Environ Toxicol Chem 2016;35:1449-1457. © 2015 SETAC. PMID:26496856

  18. Chemicals in the environment and developmental toxicity to children: a public health and policy perspective.

    OpenAIRE

    Goldman, L R; Koduru, S

    2000-01-01

    There are numerous pesticides and toxic chemicals in the environment that have yet to be evaluated for potential to cause developmental neurotoxicity. Recent legislation and testing initiatives provide an impetus to generating more information about potential hazards to children. In the United States, the 1996 Food Quality Protection Act (FQPA) required the U.S. Environmental Protection Agency (U.S. EPA) to make a finding that a pesticide food use is safe for children. In addition, the law re...

  19. Comparative effects of parathion and chlorpyrifos on endocannabinoid and endocannabinoid-like lipid metabolites in rat striatum.

    Science.gov (United States)

    Liu, Jing; Parsons, Loren; Pope, Carey

    2015-09-01

    Parathion and chlorpyrifos are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE). The endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) are endogenous neuromodulators that regulate presynaptic neurotransmitter release in neurons throughout the central and peripheral nervous systems. While substantial information is known about the eCBs, less is known about a number of endocannabinoid-like metabolites (eCBLs, e.g., N-palmitoylethanolamine, PEA; N-oleoylethanolamine, OEA). We report the comparative effects of parathion and chlorpyrifos on AChE and enzymes responsible for inactivation of the eCBs, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), and changes in the eCBs AEA and 2AG and eCBLs PEA and OEA, in rat striatum. Adult, male rats were treated with vehicle (peanut oil, 2 ml/kg, sc), parathion (27 mg/kg) or chlorpyrifos (280 mg/kg) 6-7 days after surgical implantation of microdialysis cannulae into the right striatum, followed by microdialysis two or four days later. Additional rats were similarly treated and sacrificed for evaluation of tissue levels of eCBs and eCBLs. Dialysates and tissue extracts were analyzed by LC-MS/MS. AChE and FAAH were extensively inhibited at both time-points (85-96%), while MAGL activity was significantly but lesser affected (37-62% inhibition) by parathion and chlorpyrifos. Signs of toxicity were noted only in parathion-treated rats. In general, chlorpyrifos increased eCB levels while parathion had no or lesser effects. Early changes in extracellular AEA, 2AG and PEA levels were significantly different between parathion and chlorpyrifos exposures. Differential changes in extracellular and/or tissue levels of eCBs and eCBLs could potentially influence a number of signaling pathways and contribute to selective neurological changes following acute OP intoxications. PMID:26215119

  20. Children's residential exposure to chlorpyrifos: Application of CPPAES field measurements of chlorpyrifos and TCPy within MENTOR/SHEDS-Pesticides model

    Energy Technology Data Exchange (ETDEWEB)

    Hore, Paromita [Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University and the University of Medicine and Dentistry of New Jersey (UMDNJ), Robert Wood Johnson Medical School, 170 Frelinghuysen Road, Piscataway, NJ 08855 (United States)]|[New York City Department of Health, 253 Broadway New York, New York 10007 (United States); Zartarian, Valerie; Xue Jianping; Ozkaynak, Haluk [National Exposure Research Laboratory, U.S. EPA, 109 TW Alexander Drive, Research Triangle Park, NC 27709 (United States); Wang, S.-W.; Yang, Y.-C.; Chu, P.-Ling; Robson, Mark; Georgopoulos, Panos [Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University and the University of Medicine and Dentistry of New Jersey (UMDNJ), Robert Wood Johnson Medical School, 170 Frelinghuysen Road, Piscataway, NJ 08855 (United States); Sheldon, Linda [National Exposure Research Laboratory, U.S. EPA, 109 TW Alexander Drive, Research Triangle Park, NC 27709 (United States); Needham, Larry Barr, Dana [Contemporary Pesticide Laboratory, Centers for Disease Control, 4770 Buford Highway, Atlanta, GA 30341 (United States); Freeman, Natalie [Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University and the University of Medicine and Dentistry of New Jersey (UMDNJ), Robert Wood Johnson Medical School, 170 Frelinghuysen Road, Piscataway, NJ 08855 (United States)]|[University of Florida, Gainesville, FL 32611 (United States); Lioy, Paul J. [Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University and the University of Medicine and Dentistry of New Jersey (UMDNJ), Robert Wood Johnson Medical School, 170 Frelinghuysen Road, Piscataway, NJ 08855 (United States)]. E-mail: plioy@eohsi.rutgers.edu

    2006-08-01

    The comprehensive individual field-measurements on non-dietary exposure collected in the Children's-Post-Pesticide-Application-Exposure-Study (CPPAES) were used within MENTOR/SHEDS-Pesticides, a physically based stochastic human exposure and dose model. In this application, however, the model was run deterministically. The MENTOR/SHEDS-Pesticides employed the CPPAES as input variables to simulate the exposure and the dose profiles for seven children over a 2-week post-application period following a routine residential and professional indoor crack-and-crevice chlorpyrifos application. The input variables were obtained from a personal activity diary, microenvironmental measurements and personal biomonitoring data obtained from CPPAES samples collected from the individual children and in their homes. Simulation results were compared with CPPAES field measured values obtained from the children's homes to assess the utility of the different microenvironmental data collected in CPPAES, i.e. indicator toys and wipe samplers to estimate aggregate exposures that can be result from one or more exposure pathways and routes. The final analyses of the database involved comparisons of the actual data obtained from the individual biomarker samples of a urinary metabolite of chlorpyrifos (TCPy) and the values predicted by MENTOR/SHEDS-Pesticides using the CPPAES-derived variables. Because duplicate diet samples were not part of the CPPAES study design, SHEDs-Pesticides simulated dose profiles did not account for the dietary route. The research provided more confidence in the types of data that can be used in the inhalation and dermal contact modules of MENTOR/SHEDS-Pesticides to predict the pesticide dose received by a child. It was determined that we still need additional understanding about: (1) the types of activities and durations of activities that result in non-dietary ingestion of pesticides and (2) the influence of dietary exposures on the levels of TCPy found

  1. Acute toxicity of chlorpyrifos, cadusafos and diazinon to three Indian major carps (Catla catla, Labeo rohita and Cirrhinus mrigala) fingerlings

    OpenAIRE

    Hossain, Z; Haldar, G.C.; Mollah, M.F.A.

    2000-01-01

    Fingerlings of three Indian major carps, viz. Catla catla (Hamilton-Buchanon), Labeo rohita (Hamilton-Buchanon) and Cirrhinus mrigala (Hamilton-Buchanon), were exposed to different concentrations of chlorpyrifos (lorsban 10 G), cadusafos (rugby 10 G) and diazinon (basudin 10 G) for a period of 96h with a view to determine the median lethal concentrations (LC sub50) values for each of chemicals. Of the tested concentrations, chlorpyrifos at a dose of 6.65 ppm, cadusafos at 2.0 ppm and diazinon...

  2. Chlorpyrifos-induced Histopathological Alterations in Duttaphrynus melanostictus (Schneider 1799 Tadpoles: Evidence from Empirical Trials

    Directory of Open Access Journals (Sweden)

    M. G. D. K. Bandara

    2012-10-01

    Full Text Available This paper reports the histopathological responses of the gill, liver and tail muscle tissues in tadpoles of the Asian Common Toad Duttaphrynus melanostictus (Schneider, 1799 exposed to chlorpyrifos a common organophosphorus pesticide. Tadpoles of Gosner stages 24-26 were continuously exposed to low, mid and high (500, 1000 and 1500 µgl–1 concentrations of chlorpyrifos for two weeks. Histological alterations in the tissues of the surviving larvae were microscopically examined both at the end of the exposure period and after a week following the final exposure. Several histological alterations were noted in the gills, liver and tail muscles of the larvae exposed to 1500 µgl–1 of chlorpyrifos. The gills of exposed larvae showed architectural distortion resulting from reduced primary and secondary gill lamellae and blood vessels, and alterations in the gill epithelium. In the liver sinusoidal congestion and dilation, cytoplasmic vacuolation and changes in hepatocytes such as hyperchromatic nuclei and nuclear fragmentation were observed.  The tail muscle tissue suffered from severe atrophy and myotomal disintegration. Although histological alterations in the gill and liver tissues were noted only at the high concentration, changes in the muscle tissue i.e. muscle degeneration and atrophy, were apparent at both low and mid concentrations. The degree of damage in surviving larvae in a week following the final exposure was lower than that observed during the exposure, probably indicating recovery or resistance. The findings of the present study emphasize the need to investigate possible sublethal damage induced by pesticides in amphibians inhabiting agricultural habitats.

  3. Cold Stress Offered Modulation on Chlorpyrifos Toxicity in Aging Rat Central Nervous System

    OpenAIRE

    Basha, Mahaboob; Poojary, Annappa

    2012-01-01

    The adverse effects produced by chlorpyrifos (CPF) or cold stress alone in humans and animals are well documented, but there is no information available relating to the consequences of their co- exposure in an age-related manner. In this study, effects of sublethal doses of CPF were carried out in vivo, for 48 h to assess the biochemical perturbations in relation to interactions with cold stress (15°C and 20°C) in different age group rat CNS. A positive interaction of CPF with age of animal a...

  4. Swimming impairment and acetylcholinesterase inhibition in zebrafish exposed to copper or chlorpyrifos separately, or as mixtures

    OpenAIRE

    Tilton, Fred A.; Bammler, Theo K.; Gallagher, Evan P.

    2010-01-01

    Pesticides such as chlorpyrifos (CPF) and metals such as copper can impair swimming behavior in fish. However, the impact to swimming behavior from exposure to mixtures of neurotoxicants has received little attention. In the current study, we analyzed spontaneous swimming rates of adult zebrafish (Danio rerio) to investigate in vivo mixture interactions involving two chemical classes. Zebrafish were exposed to the neurotoxicants copper chloride (CuCl, 0.1 μM, 0.25 μM, 0.6 μM, or 6.3, 16, 40 p...

  5. Comparative effects of chlorpyrifos in wild type and cannabinoid Cb1 receptor knockout mice

    Energy Technology Data Exchange (ETDEWEB)

    Baireddy, Praveena; Liu, Jing; Hinsdale, Myron; Pope, Carey, E-mail: carey.pope@okstate.edu

    2011-11-15

    Endocannabinoids (eCBs) modulate neurotransmission by inhibiting the release of a variety of neurotransmitters. The cannabinoid receptor agonist WIN 55.212-2 (WIN) can modulate organophosphorus (OP) anticholinesterase toxicity in rats, presumably by inhibiting acetylcholine (ACh) release. Some OP anticholinesterases also inhibit eCB-degrading enzymes. We studied the effects of the OP insecticide chlorpyrifos (CPF) on cholinergic signs of toxicity, cholinesterase activity and ACh release in tissues from wild type (+/+) and cannabinoid CB1 receptor knockout (-/-) mice. Mice of both genotypes (n = 5-6/treatment group) were challenged with CPF (300 mg/kg, 2 ml/kg in peanut oil, sc) and evaluated for functional and neurochemical changes. Both genotypes exhibited similar cholinergic signs and cholinesterase inhibition (82-95% at 48 h after dosing) in cortex, cerebellum and heart. WIN reduced depolarization-induced ACh release in vitro in hippocampal slices from wild type mice, but had no effect in hippocampal slices from knockouts or in striatal slices from either genotype. Chlorpyrifos oxon (CPO, 100 {mu}M) reduced release in hippocampal slices from both genotypes in vitro, but with a greater reduction in tissues from wild types (21% vs 12%). CPO had no significant in vitro effect on ACh release in striatum. CPF reduced ACh release in hippocampus from both genotypes ex vivo, but reduction was again significantly greater in tissues from wild types (52% vs 36%). In striatum, CPF led to a similar reduction (20-23%) in tissues from both genotypes. Thus, while CB1 deletion in mice had little influence on the expression of acute toxicity following CPF, CPF- or CPO-induced changes in ACh release appeared sensitive to modulation by CB1-mediated eCB signaling in a brain-regional manner. -- Highlights: Black-Right-Pointing-Pointer C57Bl/6 mice showed dose-related cholinergic toxicity following subcutaneous chlorpyrifos exposure. Black-Right-Pointing-Pointer Wild type and

  6. Toxicity persistence following an experimental cypermethrin and chlorpyrifos application in Pampasic surface waters (Buenos Aires, Argentina).

    Science.gov (United States)

    Mugni, H; Demetrio, P; Marino, D; Ronco, A; Bonetto, C

    2010-05-01

    The Pampa plain is intensively cultivated, the genetically modified glyphosate-resistant soybean being the main culture. A small first-order stream draining a cultured farm was studied. During the dry 2007 spring, the channel became a wetland with remnant intercalated shallow pools. Toxicity persistence of cypermethrin and chlorpyrifos to the amphipod Hyallela curvispina was assessed following a simulated plane application in the recently formed pools. In situ exposures and laboratory toxicity tests were performed. An ephemeral toxicity pulse lasting 4 h after the application and mortality cessation following that was observed. PMID:20396865

  7. Developmental reading disorder

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/001406.htm Developmental reading disorder To use the sharing features on this page, please enable JavaScript. Developmental reading disorder is a reading disability that occurs when ...

  8. A review on potential neurotoxicity of titanium dioxide nanoparticles

    OpenAIRE

    SONG, BIN; Liu, Jia; Feng, Xiaoli; Wei, Limin; Shao, Longquan

    2015-01-01

    As the rapid development of nanotechnology in the past three decades, titanium dioxide nanoparticles (TiO2 NPs), for their peculiar physicochemical properties, are widely applied in consumer products, food additives, cosmetics, drug carriers, and so on. However, little is known about their potential exposure and neurotoxic effects. Once NPs are unintentionally exposed to human beings, they could be absorbed, and then accumulated in the brain regions by passing through the blood–brain barrier ...

  9. Bilirubin Neurotoxicity in Preterm Infants: Risk and Prevention

    OpenAIRE

    Bhutani, Vinod K.; Wong, Ronald J

    2013-01-01

    Hemolytic conditions in preterm neonates, including Rhesus (Rh) disease, can lead to mortality and long-term impairments due to bilirubin neurotoxicity. Universal access to Rh immunoprophylaxis, coordinated perinatal-neonatal care, and effective phototherapy has virtually eliminated the risk of kernicterus in many countries. In the absence of jaundice due to isoimmunization and without access to phototherapy or exchange transfusion (in 1955), kernicterus was reported at 10.1%, 5.5%, and 1.2% ...

  10. Neurotoxic effects of levobupivacaine and fentanyl on rat spinal cord

    OpenAIRE

    2015-01-01

    BACKGROUND: The purpose of the study was to compare the neurotoxic effects of intrathecally administered levobupivacaine, fentanyl and their mixture on rat spinal cord. METHODS: In experiment, there were four groups with medication and a control group. Rats were injected 15 µL saline or fentanyl 0.0005 µg/15 µL, levobupivacaine 0.25%/15 µL and fentanyl 0.0005 µg + le...

  11. Protein adduct formation as a molecular mechanism in neurotoxicity.

    Science.gov (United States)

    Lopachin, Richard M; Decaprio, Anthony P

    2005-08-01

    Chemicals that cause nerve injury and neurological deficits are a structurally diverse group. For the majority, the corresponding molecular mechanisms of neurotoxicity are poorly understood. Many toxicants (e.g., hepatotoxicants) of other organ systems and/or their oxidative metabolites have been identified as electrophiles and will react with cellular proteins by covalently binding nucleophilic amino acid residues. Cellular toxicity occurs when adduct formation disrupts protein structure and/or function, which secondarily causes damage to submembrane organelles, metabolic pathways, or cytological processes. Since many neurotoxicants are also electrophiles, the corresponding pathophysiological mechanism might involve protein adduction. In this review, we will summarize the principles of covalent bond formation that govern reactions between xenobiotic electrophiles and biological nucleophiles. Because a neurotoxicant can form adducts with multiple nucleophilic residues on proteins, the challenge is to identify the mechanistically important adduct. In this regard, it is now recognized that despite widespread chemical adduction of tissue proteins, neurotoxicity can be mediated through binding of specific target nucleophiles in key neuronal proteins. Acrylamide and 2,5-hexanedione are prototypical neurotoxicants that presumably act through the formation of protein adducts. To illustrate both the promise and the difficulty of adduct research, these electrophilic chemicals will be discussed with respect to covalent bond formation, suspected protein sites of adduction, and proposed mechanisms of neurotoxicity. The goals of future investigations are to identify and quantify specific protein adducts that play a causal role in the generation of neurotoxicity induced by electrophilic neurotoxicants. This is a challenging but critical objective that will be facilitated by recent advances in proteomic methodologies. PMID:15901921

  12. Squalestatin alters the intracellular trafficking of a neurotoxic prion peptide

    Directory of Open Access Journals (Sweden)

    Williams Alun

    2007-11-01

    Full Text Available Abstract Background Neurotoxic peptides derived from the protease-resistant core of the prion protein are used to model the pathogenesis of prion diseases. The current study characterised the ingestion, internalization and intracellular trafficking of a neurotoxic peptide containing amino acids 105–132 of the murine prion protein (MoPrP105-132 in neuroblastoma cells and primary cortical neurons. Results Fluorescence microscopy and cell fractionation techniques showed that MoPrP105-132 co-localised with lipid raft markers (cholera toxin and caveolin-1 and trafficked intracellularly within lipid rafts. This trafficking followed a non-classical endosomal pathway delivering peptide to the Golgi and ER, avoiding classical endosomal trafficking via early endosomes to lysosomes. Fluorescence resonance energy transfer analysis demonstrated close interactions of MoPrP105-132 with cytoplasmic phospholipase A2 (cPLA2 and cyclo-oxygenase-1 (COX-1, enzymes implicated in the neurotoxicity of prions. Treatment with squalestatin reduced neuronal cholesterol levels and caused the redistribution of MoPrP105-132 out of lipid rafts. In squalestatin-treated cells, MoPrP105-132 was rerouted away from the Golgi/ER into degradative lysosomes. Squalestatin treatment also reduced the association between MoPrP105-132 and cPLA2/COX-1. Conclusion As the observed shift in peptide trafficking was accompanied by increased cell survival these studies suggest that the neurotoxicity of this PrP peptide is dependent on trafficking to specific organelles where it activates specific signal transduction pathways.

  13. The dopamine transporter: role in neurotoxicity and human disease

    International Nuclear Information System (INIS)

    The dopamine transporter (DAT) is a plasma membrane transport protein expressed exclusively within a small subset of CNS neurons. It plays a crucial role in controlling dopamine-mediated neurotransmission and a number of associated behaviors. This review focuses on recent data elucidating the role of the dopamine transporter in neurotoxicity and a number of CNS disorders, including Parkinson disease, drug abuse, and attention deficit hyperactivity disorder (ADHD)

  14. Effects of sildenafil on isoniazid and streptomycin neurotoxicity in rats

    OpenAIRE

    Abdullah Acar; Uğur Fırat; Ertuğrul Uzar; Adalet Arıkanoğlu; Adnan Tüfek; Ayşenur Keleş; Mehmet Uğur Çevik; Yavuz Yücel; Harun Alp; Osman Gökalp

    2011-01-01

    Neurotoxicity due to isoniazide (INH) and streptomycin has been reported. Experimental studies reported that sildenafil can reduce toxic effects of some drugs. The aim of this study was to investigate the possible toxic effects of long-term streptomycin and INH use and probable protective effects of sildenafil on the rat brain and cerebellum.Materials and methods: In this study, 78 rats were divided into eight groups as follows; control group (n=10), INH group (n=10), streptomycin group (n=10...

  15. In vitro neurotoxic hazard characterisation of dinitrophenolic herbicides.

    Science.gov (United States)

    Heusinkveld, Harm J; van Vliet, Arie C; Nijssen, Peter C G; Westerink, Remco H S

    2016-06-11

    Dinitrophenolic compounds are powerful toxicants with a long history of use in agriculture and industry. While (high) human exposure levels are not uncommon, in particular for agricultural workers during the spraying season, the neurotoxic mechanism(s) that underlie the human health effects are largely unknown. We therefore investigated the in vitro effects of two dinitrophenolic herbicides (DNOC and dinoseb) on a battery of neurotoxicity endpoints in (dopaminergic) rat PC12 cells. Cell viability, mitochondrial activity, oxidative stress and caspase activation were assessed using fluorescence-based bioassays (CFDA, alamar Blue, H2DCFDA and Ac-DEVD-AMC, respectively), whereas changes in intracellular [Ca(2+)]i were assessed using single-cell fluorescence microscopy with Fura-2AM. The combined results demonstrate that exposure to both DNOC and dinoseb is linked to calcium release from the endoplasmic reticulum and activation of caspase-mediated apoptotic pathways. In subsequent experiments, immunofluorescent labelling with specific antibodies was used to determine changes in intracellular α-synuclein levels, demonstrating that both DNOC and dinoseb increase levels of intracellular α-synuclein. The combined results indicate that in vitro exposure to DNOC and dinoseb activates pathways that are not only involved in acute neurotoxicity but also in long-term effects as seen in neurodegeneration. PMID:27106277

  16. The WD40 domain is required for LRRK2 neurotoxicity.

    Directory of Open Access Journals (Sweden)

    Nathan D Jorgensen

    Full Text Available BACKGROUND: Mutations in leucine-rich repeat kinase 2 (LRRK2 are the most common genetic cause of Parkinson disease (PD. LRRK2 contains an "enzymatic core" composed of GTPase and kinase domains that is flanked by leucine-rich repeat (LRR and WD40 protein-protein interaction domains. While kinase activity and GTP-binding have both been implicated in LRRK2 neurotoxicity, the potential role of other LRRK2 domains has not been as extensively explored. PRINCIPAL FINDINGS: We demonstrate that LRRK2 normally exists in a dimeric complex, and that removing the WD40 domain prevents complex formation and autophosphorylation. Moreover, loss of the WD40 domain completely blocks the neurotoxicity of multiple LRRK2 PD mutations. CONCLUSION: These findings suggest that LRRK2 dimerization and autophosphorylation may be required for the neurotoxicity of LRRK2 PD mutations and highlight a potential role for the WD40 domain in the mechanism of LRRK2-mediated cell death.

  17. Oxidative damage and neurodegeneration in manganese-induced neurotoxicity

    International Nuclear Information System (INIS)

    Exposure to excessive manganese (Mn) levels results in neurotoxicity to the extrapyramidal system and the development of Parkinson's disease (PD)-like movement disorder, referred to as manganism. Although the mechanisms by which Mn induces neuronal damage are not well defined, its neurotoxicity appears to be regulated by a number of factors, including oxidative injury, mitochondrial dysfunction and neuroinflammation. To investigate the mechanisms underlying Mn neurotoxicity, we studied the effects of Mn on reactive oxygen species (ROS) formation, changes in high-energy phosphates (HEP), neuroinflammation mediators and associated neuronal dysfunctions both in vitro and in vivo. Primary cortical neuronal cultures showed concentration-dependent alterations in biomarkers of oxidative damage, F2-isoprostanes (F2-IsoPs) and mitochondrial dysfunction (ATP), as early as 2 h following Mn exposure. Treatment of neurons with 500 μM Mn also resulted in time-dependent increases in the levels of the inflammatory biomarker, prostaglandin E2 (PGE2). In vivo analyses corroborated these findings, establishing that either a single or three (100 mg/kg, s.c.) Mn injections (days 1, 4 and 7) induced significant increases in F2-IsoPs and PGE2 in adult mouse brain 24 h following the last injection. Quantitative morphometric analyses of Golgi-impregnated striatal sections from mice exposed to single or three Mn injections revealed progressive spine degeneration and dendritic damage of medium spiny neurons (MSNs). These findings suggest that oxidative stress, mitochondrial dysfunction and neuroinflammation are underlying mechanisms in Mn-induced neurodegeneration.

  18. Early Neurodevelopment of Sea Urchin and Neurotoxic Effects of Organophosphate Pesticides on It%海胆早期神经发育及有机磷农药对其神经毒性作用的研究进展

    Institute of Scientific and Technical Information of China (English)

    汝少国; 许磊

    2012-01-01

    早期发育阶段是有机磷农药神经毒性作用最敏感的时期,海胆的胚胎和幼虫为研究有机磷农药对早期发育阶段的神经毒性作用提供了一种理想的模型.本文介绍了海胆的早期神经发育过程,综述了神经系统对海胆早期发育的调控作用,结合近年来国内外的研究,阐述了有机磷农药对海胆早期发育的影响及其神经毒性作用机制,并展望了该领域的研究方向.%Despite their widespread use, organophosphate pesticides cause developmental neurotoxicity through a mechanism based on their function as an acetylcholinesterase inhibitor. Animals in early developmental stages are especially vulnerable to developmental neurotoxicity induced by organophosphate pesticides. The embryos and larvae of sea urchin provide a promising invertebrate model system for evaluating developmental neurotoxicity induced by organophosphate pesticides, as they develop quickly with well -characterized morphological and biochemical features, possess similar processes of neurogenesis and signaling cascades to chordates, and are vulnerable to pollutants. Both the neurodevelpment of sea urchin during early development stage and the regulation on the early development were included. Particularly, the neurotoxic effects of organophosphate pesticides on the early development and its potential neurotoxicity mechanism for sea urchin are discussed, and future prospects of this field are provided.

  19. A Drosophila model to investigate the neurotoxic side effects of radiation exposure

    Directory of Open Access Journals (Sweden)

    Lisa J. Sudmeier

    2015-07-01

    Full Text Available Children undergoing cranial radiation therapy (CRT for pediatric central nervous system malignancies are at increased risk for neurological deficits later in life. We have developed a model of neurotoxic damage in adult Drosophila following irradiation during the juvenile stages with the goal of elucidating underlying neuropathological mechanisms and of ultimately identifying potential therapeutic targets. Wild-type third-instar larvae were irradiated with single doses of γ-radiation, and the percentage that survived to adulthood was determined. Motor function of surviving adults was examined with a climbing assay, and longevity was assessed by measuring lifespan. Neuronal cell death was assayed by using immunohistochemistry in adult brains. We also tested the sensitivity at different developmental stages by irradiating larvae at various time points. Irradiating late third-instar larvae at a dose of 20 Gy or higher impaired the motor activity of surviving adults. A dose of 40 Gy or higher resulted in a precipitous reduction in the percentage of larvae that survive to adulthood. A dose-dependent decrease in adult longevity was paralleled by a dose-dependent increase in activated Death caspase-1 (Dcp1 in adult brains. Survival to adulthood and adult lifespan were more severely impaired with decreasing larval age at the time of irradiation. Our initial survey of the Drosophila Genetic Reference Panel demonstrated that differences in genotype can confer phenotypic differences in radio-sensitivity for developmental survival and motor function. This work demonstrates the usefulness of Drosophila to model the toxic effects of radiation during development, and has the potential to unravel underlying mechanisms and to facilitate the discovery of novel therapeutic interventions.

  20. Presynaptic mechanisms of lead neurotoxicity: effects on vesicular release, vesicle clustering and mitochondria number.

    Science.gov (United States)

    Zhang, Xiao-Lei; Guariglia, Sara R; McGlothan, Jennifer L; Stansfield, Kirstie H; Stanton, Patric K; Guilarte, Tomás R

    2015-01-01

    Childhood lead (Pb2+) intoxication is a global public health problem and accounts for 0.6% of the global burden of disease associated with intellectual disabilities. Despite the recognition that childhood Pb2+ intoxication contributes significantly to intellectual disabilities, there is a fundamental lack of knowledge on presynaptic mechanisms by which Pb2+ disrupts synaptic function. In this study, using a well-characterized rodent model of developmental Pb2+ neurotoxicity, we show that Pb2+ exposure markedly inhibits presynaptic vesicular release in hippocampal Schaffer collateral-CA1 synapses in young adult rats. This effect was associated with ultrastructural changes which revealed a reduction in vesicle number in the readily releasable/docked vesicle pool, disperse vesicle clusters in the resting pool, and a reduced number of presynaptic terminals with multiple mitochondria with no change in presynaptic calcium influx. These studies provide fundamental knowledge on mechanisms by which Pb2+ produces profound inhibition of presynaptic vesicular release that contribute to deficits in synaptic plasticity and intellectual development. PMID:26011056

  1. Presynaptic mechanisms of lead neurotoxicity: effects on vesicular release, vesicle clustering and mitochondria number.

    Directory of Open Access Journals (Sweden)

    Xiao-Lei Zhang

    Full Text Available Childhood lead (Pb2+ intoxication is a global public health problem and accounts for 0.6% of the global burden of disease associated with intellectual disabilities. Despite the recognition that childhood Pb2+ intoxication contributes significantly to intellectual disabilities, there is a fundamental lack of knowledge on presynaptic mechanisms by which Pb2+ disrupts synaptic function. In this study, using a well-characterized rodent model of developmental Pb2+ neurotoxicity, we show that Pb2+ exposure markedly inhibits presynaptic vesicular release in hippocampal Schaffer collateral-CA1 synapses in young adult rats. This effect was associated with ultrastructural changes which revealed a reduction in vesicle number in the readily releasable/docked vesicle pool, disperse vesicle clusters in the resting pool, and a reduced number of presynaptic terminals with multiple mitochondria with no change in presynaptic calcium influx. These studies provide fundamental knowledge on mechanisms by which Pb2+ produces profound inhibition of presynaptic vesicular release that contribute to deficits in synaptic plasticity and intellectual development.

  2. The Domain of Developmental Psychopathology.

    Science.gov (United States)

    Sroufe, L. Alan; Rutter, Michael

    1984-01-01

    Describes how developmental psychopathology differs from related disciplines, including abnormal psychology, psychiatry, clinical child psychology, and developmental psychology. Points out propositions underlying a developmental perspective and discusses implications for research in developmental psychopathology. (Author/RH)

  3. Comparative toxicity of chlorpyrifos, diazinon, malathion and their oxon derivatives to larval Rana boylii

    International Nuclear Information System (INIS)

    Organophosphorus pesticides (OPs) are ubiquitous in the environment and are highly toxic to amphibians. They deactivate cholinesterase, resulting in neurological dysfunction. Most chemicals in this group require oxidative desulfuration to achieve their greatest cholinesterase-inhibiting potencies. Oxon derivatives are formed within liver cells but also by bacterial decay of parental pesticides. This study examines the toxicity of chlorpyrifos, malathion and diazinon and their oxons on the foothill yellow-legged frog (Rana boylii). R. boylii is exposed to agricultural pesticides in the California Central Valley. Median lethal concentrations of the parental forms during a 96 h exposure were 3.00 mg/L (24 h) for chlorpyrifos, 2.14 mg/L for malathion and 7.49 mg/L for diazinon. Corresponding oxons were 10 to 100 times more toxic than their parental forms. We conclude that environmental concentrations of these pesticides can be harmful to R. boylii populations. - Laboratory tests on the toxicity of OP insecticides and their oxons suggest that they may be acutely lethal to amphibians at ecologically relevant concentrations

  4. Peak centiles of chlorpyrifos surface-water concentrations in the NAWQA and NASQAN programs.

    Science.gov (United States)

    Mosquin, Paul L; Aldworth, Jeremy; Poletika, Nicholas N

    2015-02-01

    We provide upper bound estimates for peak centiles of surface water chlorpyrifos concentration readings within spatial, temporal, and land-use domains of the United States Geological Survey (USGS) National Water-Quality Assessment (NAWQA) and National Stream Quality Accounting Network (NASQAN) programs. These datasets have large overall sample sizes but variable sampling frequencies and, for chlorpyrifos, extremely high levels of non-detections. Point and interval estimates are provided for the 90th, 95th, 99th, and the 99.9th centiles, given sufficient sample size. Overall upper bound estimates for the NAWQA program over the period 1992-2011 for the 90th, 95th, 99th, and 99.9th centiles are approach, finding centiles of pooled data across aggregates of site-years. Although the population quantity estimated by a pooled data centile is not the easily interpretable average of population site-year centiles, we provide strong support that it bounds this average by a combination of theory, comparison of NAWQA aggregate and direct estimates, and using modeled populations. PMID:25497425

  5. Chlorpyrifos causes decreased organic matter decomposition by suppressing earthworm and termite communities in tropical soil

    Energy Technology Data Exchange (ETDEWEB)

    De Silva, P. Mangala C.S., E-mail: msilva@falw.vu.n [Department of Animal Ecology, VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Department of Zoology, Faculty of Science, University of Ruhuna, Matara (Sri Lanka); Pathiratne, Asoka [Department of Zoology, Faculty of Science, University of Kelaniya, Kelaniya (Sri Lanka); Straalen, Nico M. van; Gestel, Cornelis A.M. van [Department of Animal Ecology, VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands)

    2010-10-15

    Effects of pesticides on structural and functional properties of ecosystems are rarely studied under tropical conditions. In this study litterbag and earthworm field tests were performed simultaneously at the same tropical field site sprayed with chlorpyrifos (CPF). The recommended dose of CPF (0.6 kg a.i. ha{sup -1}) and two higher doses (4.4-8.8 kg a.i. ha{sup -1}) significantly decreased litter decomposition during the first 3 months after application, which could be explained from lower earthworm and termite abundances during this period. Species-specific effects of CPF on organism abundance and biomass were observed, with termites being mostly affected followed by the earthworm Perionyx excavatus; the earthworm Megascolex sp. was least affected. Recovery was completed within 6 months. Decomposition in the controls and lowest two treatments was completed within 4 months, which suggests the need for modification of standard test guidelines to comply with faster litter degradation under tropical conditions. - Effects of chlorpyrifos on functional and structural endpoints in soil.

  6. Comparative toxicity of chlorpyrifos, diazinon, malathion and their oxon derivatives to larval Rana boylii

    Energy Technology Data Exchange (ETDEWEB)

    Sparling, D.W. [Cooperative Wildlife Research Laboratory, Department of Zoology and Center for Ecology, Southern Illinois University, LS II, MS6504, Carbondale, IL 62901 (United States)]. E-mail: dsparl@siu.edu; Fellers, G. [Western Ecology Research Center, U.S. Geological Survey, Point Reyes National Seashore, Point Reyes, CA 94956 (United States)

    2007-06-15

    Organophosphorus pesticides (OPs) are ubiquitous in the environment and are highly toxic to amphibians. They deactivate cholinesterase, resulting in neurological dysfunction. Most chemicals in this group require oxidative desulfuration to achieve their greatest cholinesterase-inhibiting potencies. Oxon derivatives are formed within liver cells but also by bacterial decay of parental pesticides. This study examines the toxicity of chlorpyrifos, malathion and diazinon and their oxons on the foothill yellow-legged frog (Rana boylii). R. boylii is exposed to agricultural pesticides in the California Central Valley. Median lethal concentrations of the parental forms during a 96 h exposure were 3.00 mg/L (24 h) for chlorpyrifos, 2.14 mg/L for malathion and 7.49 mg/L for diazinon. Corresponding oxons were 10 to 100 times more toxic than their parental forms. We conclude that environmental concentrations of these pesticides can be harmful to R. boylii populations. - Laboratory tests on the toxicity of OP insecticides and their oxons suggest that they may be acutely lethal to amphibians at ecologically relevant concentrations.

  7. Chronic exposure to chlorpyrifos reveals two modes of action in the springtail Folsomia candida

    International Nuclear Information System (INIS)

    Organophosphates are popular insecticides, but relatively little is known about their chronic effects on ecologically relevant endpoints. In this paper, we examine a life-cycle experiment with the springtail Folsomia candida, exposed via food to chlorpyrifos (CPF). The results for all endpoints (survival, growth and reproduction) were analyzed using the DEBtox model. Growth was unaffected by CPF, even at concentrations causing severe effects on survival and reproduction. Model analysis suggests that CPF directly affects the process of egg production. For the short-term response (45 days), this single mode of action accurately agreed with the data. However, the full data set (120 days) revealed a dose-related decrease in reproduction at low concentrations after prolonged exposure, not covered by the same mechanism. It appears that CPF interacts with senescence by increasing oxidative damage. This assumption fits the data well, but has little consequences for the predicted response at the population level. - Exposure to chlorpyrifos in food affects reproduction in springtails according to two distinct toxic mechanisms

  8. Chlorpyrifos Determined in Human Blood by UPLC-MS/MS and Its Application in Poisoning Cases

    Institute of Scientific and Technical Information of China (English)

    QIAO Zheng; YAN Hui; ZHUO Xian-yi; SHEN Bao-hua

    2015-01-01

    Objective To determine the chlorpyrifos in human blood by liquid chromatography-tandemmass spectrometry and to validate its application in poisoning cases. Methods The samples were extracted by a simple one-step protein precipitation procedure. Chromatography was performed on a Capcell Pack C18 mG II column (250 mm×2.0 mm, 5μm) using an isocratic elution of solvent A (0.1% formic acid-water with 2 mmol/L ammoniumacetate) and solvent B (methanol with 2 mmol/L ammoniumacetate) at 5∶95 (V∶V).Results The linearranged from5 to 500ng/mL (r=0.9987).Thelimitofdetection (LOD) and the lower limit of quantification (LLOQ ) were 2 ng/mL and 4 ng/mL , respectively. For this method, the precision and accuracy of intra-day and inter-day were <10% and 97.44%-101.10%, respectively. The re-sults in stability test of long-termfrozen were satisfied. The matrix effect, recovery and process efficien-cy were 64.97%-86.81%, 76.70%-85.52%, and 55.57%-66.58%, respectively. Conclusion This method can provide a rapid approach to chlorpyrifos extraction and determination in toxicological analysis of forensic and clinical treatment.

  9. Pilot biomonitoring of adults and children following use of chlorpyrifos shampoo and flea collars on dogs.

    Science.gov (United States)

    Dyk, Melinda Bigelow; Chen, Zhenshan; Mosadeghi, Sasan; Vega, Helen; Krieger, Robert

    2011-01-01

    Pesticide handlers and pet owners who use products such as shampoos and dips and insecticide-impregnated collars to treat and control fleas on companion animals are exposed to a variety of active ingredients. Chlorpyrifos exposures of adults and children were measured using urine biomonitoring following use of over-the-counter products on dogs. Age and gender-specific measurements of urinary 3, 5, 6-trichloro-2-pyridinol (TCPy) revealed modest elevations of biomarker excretion following shampoo/dips. Smaller TCPy increments were measured following application of impregnated dog collars. The extent of indoor activity and potential pet contact were important determinants of urine biomarker level. Children without direct pet contact excreted more TCPy following collar application. Pet collars may be a source of indoor surface contamination and human exposure. Children excreted up to 4 times more TCPy than adults when urine volumes were adjusted using age-specific creatinine excretion levels. Although chlorpyrifos is no longer used in the United States in pet care products, results of this research provide perspective on the extent of human exposure from similar pet care products. These pilot studies demonstrated that pet care products such as insecticidal shampoos and dips and impregnated collars may expose family members to low levels of insecticide relative to toxic levels of concern. PMID:21240711

  10. Chlorpyrifos causes decreased organic matter decomposition by suppressing earthworm and termite communities in tropical soil

    International Nuclear Information System (INIS)

    Effects of pesticides on structural and functional properties of ecosystems are rarely studied under tropical conditions. In this study litterbag and earthworm field tests were performed simultaneously at the same tropical field site sprayed with chlorpyrifos (CPF). The recommended dose of CPF (0.6 kg a.i. ha-1) and two higher doses (4.4-8.8 kg a.i. ha-1) significantly decreased litter decomposition during the first 3 months after application, which could be explained from lower earthworm and termite abundances during this period. Species-specific effects of CPF on organism abundance and biomass were observed, with termites being mostly affected followed by the earthworm Perionyx excavatus; the earthworm Megascolex sp. was least affected. Recovery was completed within 6 months. Decomposition in the controls and lowest two treatments was completed within 4 months, which suggests the need for modification of standard test guidelines to comply with faster litter degradation under tropical conditions. - Effects of chlorpyrifos on functional and structural endpoints in soil.

  11. Crocin reduced acrylamide-induced neurotoxicity in Wistar rat through inhibition of oxidative stress

    OpenAIRE

    Soghra Mehri; Khalil Abnous; Alireza Khooei; Seyed Hadi Mousavi; Vahideh Motamed Shariaty; Hossein Hosseinzadeh

    2015-01-01

    Objective(s):Acrylamide (ACR) has many applications in different industries. ACR damages the central and the peripheral nervous system in human and animals. Importance of ACR-induced neurotoxicity encouraged researchers to find both different mechanisms involved in ACR neurotoxicity and potent neuroprotective agents. Therefore, this study was designed to investigate the protective effect of crocin, an active constituent of Crocus sativus L. (saffron) on ACR-induced neurotoxicity in Wistar rat...

  12. Acetylcholinesterase from Human Erythrocytes as a Surrogate Biomarker of Lead Induced Neurotoxicity

    OpenAIRE

    Vivek Kumar Gupta; Rajnish Pal; Nikhat Jamal Siddiqi; Bechan Sharma

    2015-01-01

    Lead induced neurotoxicity in the people engaged in different occupations has received wide attention but very little studies have been carried out to monitor occupational neurotoxicity directly due to lead exposure using biochemical methods. In the present paper an endeavour has been made in order to assess the lead mediated neurotoxicity by in vitro assay of the activity of acetylcholinesterase (AChE) from human erythrocytes in presence of different concentrations of lead. The results sugge...

  13. Cyanobacterial Xenobiotics as Evaluated by a Caenorhabditis elegans Neurotoxicity Screening Test

    OpenAIRE

    Jingjuan Ju; Nadine Saul; Cindy Kochan; Anke Putschew; Yuepu Pu; Lihong Yin; Steinberg, Christian E. W.

    2014-01-01

    In fresh waters cyanobacterial blooms can produce a variety of toxins, such as microcystin variants (MCs) and anatoxin-a (ANA). ANA is a well-known neurotoxin, whereas MCs are hepatotoxic and, to a lesser degree, also neurotoxic. Neurotoxicity applies especially to invertebrates lacking livers. Current standardized neurotoxicity screening methods use rats or mice. However, in order to minimize vertebrate animal experiments as well as experimental time and effort, many investigators have prop...

  14. The Dynamics of Autism Spectrum Disorders: How Neurotoxic Compounds and Neurotransmitters Interact

    OpenAIRE

    Margot van de Bor; Ilona Quaak; Brouns, Madeleine R.

    2013-01-01

    In recent years concern has risen about the increasing prevalence of Autism Spectrum Disorders (ASD). Accumulating evidence shows that exposure to neurotoxic compounds is related to ASD. Neurotransmitters might play a key role, as research has indicated a connection between neurotoxic compounds, neurotransmitters and ASD. In the current review a literature overview with respect to neurotoxic exposure and the effects on neurotransmitter systems is presented. The aim was to identify mechanisms ...

  15. A sensitive monoclonal antibody-based enzyme-linked immunosorbent assay for chlorpyrifos residue determination in Chinese agricultural smaples

    Science.gov (United States)

    A monoclonal antibody-based competitive antibody-coated enzyme-linked immunosorbent assay (ELISA) was developed and optimized for determining chlorpyrifos residue in agricultural products. The IC50 and IC10 of this ELISA were 3.3 ng/mL and 0.1 ng/mL respectively. The average recoveries recovery rate...

  16. Dietary predictors of young children’s exposures to chlorpyrifos, permethrin, and 2,4-D using urinary biomonitoring

    Science.gov (United States)

    Few data exist on the association between dietary habits and urinary biomarker concentrations of pesticides in children. The objective was to examined the association between the weekly intake frequency of 65 food items and urinary biomarkers of exposure to chlorpyrifos (3,5,6-tr...

  17. Effectiveness of personal protective equipment: Relevance of dermal and inhalation exposure to chlorpyrifos among pest control operators

    NARCIS (Netherlands)

    Jagt, K. van der; Tielemans, E.; Links, I.; Brouwer, D.; Hemmen, J. van

    2004-01-01

    This study assessed the effectiveness of a custom fit personal protective equipment (PPE) program aimed at reducing occupational exposure to pesticides. The intervention study was carried out on 15 pest control operators (PCOs) during mixing/loading and application of chlorpyrifos. Each worker was m

  18. Effects of chlorpyrifos ethyl on acetylcholinesterase activity in climbing perch cultured in rice fields in the Mekong Delta, Vietnam.

    Science.gov (United States)

    Nguyen, Tam Thanh; Berg, Håkan; Nguyen, Hang Thi Thuy; Nguyen, Cong Van

    2015-07-01

    Climbing perch is commonly harvested in rice fields and associated wetlands in the Mekong Delta. Despite its importance in providing food and income to local households, there is little information how this fish species is affected by the high use of pesticides in rice farming. Organophosphate insecticides, such as chlorpyrifos ethyl, which are highly toxic to aquatic organisms, are commonly used in the Mekong Delta. This study shows that the brain acetylcholinesterase (AChE) activity in climbing perch fingerlings cultured in rice fields, was significantly inhibited by a single application of chlorpyrifos ethyl, at doses commonly applied by rice farmers (0.32-0.64 kg/ha). The water concentration of chlorpyrifos ethyl decreased below the detection level within 3 days, but the inhibition of brain AChE activity remained for more than 12 days. In addition, the chlorpyrifos ethyl treatments had a significant impact on the survival and growth rates of climbing perch fingerlings, which were proportional to the exposure levels. The results indicate that the high use of pesticides among rice farmers in the Mekong Delta could have a negative impact on aquatic organisms and fish yields, with implications for the aquatic biodiversity, local people's livelihoods and the aquaculture industry in the Mekong Delta. PMID:25828891

  19. What is developmental dyspraxia?

    Science.gov (United States)

    Dewey, D

    1995-12-01

    The idea of developmental dyspraxia has been discussed in the research literature for almost 100 years. However, there continues to be a lack of consensus regarding both the definition and description of this disorder. This paper presents a neuropsychologically based operational definition of developmental dyspraxia that emphasizes that developmental dyspraxia is a disorder of gesture. Research that has investigated the development of praxis is discussed. Further, different types of gestural disorders displayed by children and different mechanisms that underlie developmental dyspraxia are compared to and contrasted with adult acquired apraxia. The impact of perceptual-motor, language, and cognitive impairments on children's gestural development and the possible associations between these developmental disorders and developmental dyspraxia are also examined. Also, the relationship among limb, orofacial, and verbal dyspraxia is discussed. Finally, problems that exist in the neuropsychological assessment of developmental dyspraxia are discussed and recommendations concerning what should be included in such an assessment are presented. PMID:8838385

  20. The expression of proteins involved in digestion and detoxification are regulated in Helicoverpa armigera to cope up with chlorpyrifos insecticide.

    Science.gov (United States)

    Dawkar, Vishal V; Chikate, Yojana R; More, Tushar H; Gupta, Vidya S; Giri, Ashok P

    2016-02-01

    Helicoverpa armigera is a key pest in many vital crops, which is mainly controlled by chemical strategies. To manage this pest is becoming challenging due to its ability and evolution of resistance against insecticides. Further, its subsequent spread on nonhost plant is remarkable in recent times. Hence, decoding resistance mechanism against phytochemicals and synthetic insecticides is a major challenge. The present work describes that the digestion, defense and immunity related enzymes are associated with chlorpyrifos resistance in H. armigera. Proteomic analysis of H. armigera gut tissue upon feeding on chlorpyrifos containing diet (CH) and artificial diet (AD) using nano-liquid chromatography-mass spectrometry identified upregulated 23-proteins in CH fed larvae. Database searches combined with gene ontology analysis revealed that the identified gut proteins engrossed in digestion, proteins crucial for immunity, adaptive responses to stress, and detoxification. Biochemical and quantitative real-time polymerase chain reaction analysis of candidate proteins indicated that insects were struggling to get nutrients and energy in presence of CH, while at the same time endeavoring to metabolize chlorpyrifos. Moreover, we proposed a potential processing pathway of chlorpyrifos in H. armigera gut by examining the metabolites using gas chromatography-mass spectrometry. H. armigera exhibit a range of intriguing behavioral, morphological adaptations and resistance to insecticides by regulating expression of proteins involved in digestion and detoxification mechanisms to cope up with chlorpyrifos. In these contexts, as gut is a rich repository of biological information; profound analysis of gut tissues can give clues of detoxification and resistance mechanism in insects. PMID:25284010

  1. On the protective effect of omega-3 against propionic acid-induced neurotoxicity in rat pups

    Directory of Open Access Journals (Sweden)

    El-Gezeery Amina R

    2011-08-01

    Full Text Available Abstract Backgrounds The investigation of the environmental contribution for developmental neurotoxicity is very important. Many environmental chemical exposures are now thought to contribute to the development of neurological disorders, especially in children. Results from animal studies may guide investigations of human populations toward identifying environmental contaminants and drugs that produce or protect from neurotoxicity and may help in the treatment of neurodevelopmental disorders. Objective To study the protective effects of omega-3 polyunsaturated fatty acid on brain intoxication induced by propionic acid (PPA in rats. Methods 24 young male Western Albino rats were enrolled in the present study. They were grouped into three equal groups; oral buffered PPA-treated group given a nuerotoxic dose of 250 mg/Kg body weight/day for 3 days; omega-3 - protected group given a dose of 100 mg/kg body weight/day omega-3 orally daily for 5 days followed by PPA for 3 days, and a third group as control given only phosphate buffered saline. Tumor necrosis factor-α, caspase-3, interlukin-6, gamma amino-buteric acid (GABA, serotonin, dopamine and phospholipids were then assayed in the rats brain's tissue of different groups. Results The obtained data showed that PPA caused multiple signs of brain toxicity as measured by depletion of gamaaminobyteric acid (GABA, serotonin (5HT and dopamine (DA as three important neurotransmitters that reflect brain function. A high significant increase of interlukin-6 (Il-6, tumor necrosis factor-α (TNF-α as excellent markers of proinflammation and caspase-3 as a proapotic marker were remarkably elevated in the intoxicated group of rats. Moreover, brain phospholipid profile was impaired in PPA-treated young rats recording lower levels of phosphatidylethanolamine (PE, phosphatidylserine (PS and phosphatidylcholine (PC. Conclusions Omega-3 fatty acids showed a protective effects on PPA - induced changes in rats as

  2. PON1 status does not influence cholinesterase activity in Egyptian agricultural workers exposed to chlorpyrifos

    International Nuclear Information System (INIS)

    Animal studies have shown that paraoxonase 1 (PON1) genotype can influence susceptibility to the organophosphorus pesticide chlorpyrifos (CPF). However, Monte Carlo analysis suggests that PON1 genotype may not affect CPF-related toxicity at low exposure conditions in humans. The current study sought to determine the influence of PON1 genotype on the activity of blood cholinesterase as well as the effect of CPF exposure on serum PON1 in workers occupationally exposed to CPF. Saliva, blood and urine were collected from agricultural workers (n = 120) from Egypt's Menoufia Governorate to determine PON1 genotype, blood cholinesterase activity, serum PON1 activity towards chlorpyrifos-oxon (CPOase) and paraoxon (POase), and urinary levels of the CPF metabolite 3,5,6-trichloro-2-pyridinol (TCPy). The PON1 55 (P ≤ 0.05) but not the PON1 192 genotype had a significant effect on CPOase activity. However, both the PON1 55 (P ≤ 0.05) and PON1 192 (P ≤ 0.001) genotypes had a significant effect on POase activity. Workers had significantly inhibited AChE and BuChE after CPF application; however, neither CPOase activity nor POase activity was associated with ChE depression when adjusted for CPF exposure (as determined by urinary TCPy levels) and stratified by PON1 genotype. CPOase and POase activity were also generally unaffected by CPF exposure although there were alterations in activity within specific genotype groups. Together, these results suggest that workers retained the capacity to detoxify chlorpyrifos-oxon under the exposure conditions experienced by this study population regardless of PON1 genotype and activity and that effects of CPF exposure on PON1 activity are minimal. -- Highlights: ► CPF exposure resulted in an increase in TCPy and decreases in BuChE and AChE. ► CPOase activity decreased in subjects with the PON1 55LM and PON1 55 MM genotypes. ► Neither PON1 genotype nor CPOase activity had an effect on BuChE or AChE inhibition.

  3. PON1 status does not influence cholinesterase activity in Egyptian agricultural workers exposed to chlorpyrifos

    Energy Technology Data Exchange (ETDEWEB)

    Ellison, Corie A., E-mail: cellison@buffalo.edu [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Crane, Alice L., E-mail: alcrane@buffalo.edu [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Bonner, Matthew R., E-mail: mrbonner@buffalo.edu [Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Knaak, James B., E-mail: jbknaak@aol.com [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Browne, Richard W., E-mail: rwbrowne@buffalo.edu [Department of Biotechnical and Clinical Laboratory Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Lein, Pamela J., E-mail: pjlein@ucdavis.edu [Department of Molecular Biosciences, University of California School of Veterinary Medicine, Davis, CA 95618 (United States); Olson, James R., E-mail: jolson@buffalo.edu [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY 14214 (United States)

    2012-12-15

    Animal studies have shown that paraoxonase 1 (PON1) genotype can influence susceptibility to the organophosphorus pesticide chlorpyrifos (CPF). However, Monte Carlo analysis suggests that PON1 genotype may not affect CPF-related toxicity at low exposure conditions in humans. The current study sought to determine the influence of PON1 genotype on the activity of blood cholinesterase as well as the effect of CPF exposure on serum PON1 in workers occupationally exposed to CPF. Saliva, blood and urine were collected from agricultural workers (n = 120) from Egypt's Menoufia Governorate to determine PON1 genotype, blood cholinesterase activity, serum PON1 activity towards chlorpyrifos-oxon (CPOase) and paraoxon (POase), and urinary levels of the CPF metabolite 3,5,6-trichloro-2-pyridinol (TCPy). The PON1 55 (P ≤ 0.05) but not the PON1 192 genotype had a significant effect on CPOase activity. However, both the PON1 55 (P ≤ 0.05) and PON1 192 (P ≤ 0.001) genotypes had a significant effect on POase activity. Workers had significantly inhibited AChE and BuChE after CPF application; however, neither CPOase activity nor POase activity was associated with ChE depression when adjusted for CPF exposure (as determined by urinary TCPy levels) and stratified by PON1 genotype. CPOase and POase activity were also generally unaffected by CPF exposure although there were alterations in activity within specific genotype groups. Together, these results suggest that workers retained the capacity to detoxify chlorpyrifos-oxon under the exposure conditions experienced by this study population regardless of PON1 genotype and activity and that effects of CPF exposure on PON1 activity are minimal. -- Highlights: ► CPF exposure resulted in an increase in TCPy and decreases in BuChE and AChE. ► CPOase activity decreased in subjects with the PON1 55LM and PON1 55 MM genotypes. ► Neither PON1 genotype nor CPOase activity had an effect on BuChE or AChE inhibition.

  4. CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FALLS TO ALTER SOMATOSENSORY EVOKED POTENTIALS, COMPOUND NERVE ACTION POTENTIALS, OR NERVE CONDUCTION VELOCITY IN RATS.

    Science.gov (United States)

    Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Cholinergic transmission is involved in sensory modulation in the cortex and cerebellum, and therefore may be altered following chlorpyrifos (CPF) exposure...

  5. Biodegradation characteristics of chlorpyrifos by sodium alginate immobilized bacteria%海藻酸钠固定化细菌对毒死蜱的降解特性

    Institute of Scientific and Technical Information of China (English)

    段海明

    2012-01-01

    Chlorpyrifos [(O,O-diethyl-O-3,5,6-trichloro-2-pyridinyl) phosphorothioate] is a broad spectrum of moderately toxic organophosphorus pesticide used as insecticide on a large variety of crops including fruits, vegetables, cotton, corn and wheat. With especially the recent elimination of five highly toxic organophosphorus pesticides, chlorpyrifos has been widely used in China. Consequently, large quantities of wastewater containing chlorpyrifos have been generated from pesticide industry and lot more chlorpyrifos scattered in the depths of soils and waters in the fields. Moreover, various reports have noted that chlorpyrifos have had visible toxicity in mammalians. Therefore the high degree of persistence of chlorpyrifos in the environment and the toxic effects on humans had necessitated removal. Biodegradation has received increasing attention as an efficient and cheap biotechnological approach to cleaning up polluted environments. Several chemicals have been successfully removed from soil and aquatic environments using degrading microbes. Similarly, biodegradation has been the major mechanism for removing chlorpyrifos residues, especially for treatments of discharged wastewater from the processes of chlorpyrifos production. Previous successes in isolating Bacillus cereus strain from chlorpyrifos degradation have augmented scarce literatures on this strain of chlorpyrifos biodegradation. In order to enhance degradation efficiency, B. cereus HY-1 strain was immobilized with sodium alginate using the syringe titration method. Also biodegradation characteristics of chlorpyrifos by immobilized B. cereus strain were further investigated. While the optimal reaction time was obtained, the effects of the various parameters (e.g., amounts of immobilized biomass, pH and chlorpyrifos initial concentration) of biodegradation were studied. The results showed that chlorpyrifos were readily degraded by sodium alginateimmobilized B.cereus. The appropriate concentration of sodium

  6. Neurotoxicity of perfluorooctane sulfonate to hippocampal cells in adult mice.

    Directory of Open Access Journals (Sweden)

    Yan Long

    Full Text Available Perfluorooctane sulfonate (PFOS is a ubiquitous pollutant and found in the environment and in biota. The neurotoxicity of PFOS has received much concern among its various toxic effects when given during developing period of brain. However, little is known about the neurotoxic effects and potential mechanisms of PFOS in the mature brain. Our study demonstrated the neurotoxicity and the potential mechanisms of PFOS in the hippocampus of adult mice for the first time. The impairments of spatial learning and memory were observed by water maze studies after exposure to PFOS for three months. Significant apoptosis was found in hippocampal cells after PFOS exposure, accompanied with a increase of glutamate in the hippocampus and decreases of dopamine (DA and 3,4-dihydrophenylacetic acid (DOPAC in Caudate Putamen in the 10.75 mg/kg PFOS group. By two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE analysis, seven related proteins in the hippocampus that responded to PFOS exposure were identified, among which, Mib1 protein (an E3 ubiquitin-protein ligase, Herc5 (hect domain and RLD 5 isoform 2 and Tyro3 (TYRO3 protein tyrosine kinase 3 were found down-regulated, while Sdha (Succinate dehydrogenase flavoprotein subunit, Gzma (Isoform HF1 of Granzyme A precursor, Plau (Urokinase-type plasminogen activator precursor and Lig4 (DNA ligase 4 were found up-regulated in the 10.75 mg/kg PFOS-treated group compare with control group. Furthermore, we also found that (i increased expression of caspase-3 protein and decreased expression of Bcl-2, Bcl-XL and survivin proteins, (ii the increased glutamate release in the hippocampus. All these might contribute to the dysfunction of hippocampus which finally account for the impairments of spatial learning and memory in adult mice.

  7. Enhancement of endocannabinoid signaling protects against cocaine-induced neurotoxicity

    International Nuclear Information System (INIS)

    Cocaine is an addictive substance with a potential to cause deleterious effects in the brain. The strategies for treating its neurotoxicity, however, are limited. Evidence suggests that the endocannabinoid system exerts neuroprotective functions against various stimuli. Thus, we hypothesized that inhibition of fatty acid amide hydrolase (FAAH), the main enzyme responsible for terminating the actions of the endocannabinoid anandamide, reduces seizures and cell death in the hippocampus in a model of cocaine intoxication. Male Swiss mice received injections of endocannabinoid-related compounds followed by the lowest dose of cocaine that induces seizures, electroencephalographic activity and cell death in the hippocampus. The molecular mechanisms were studied in primary cell culture of this structure. The FAAH inhibitor, URB597, reduced cocaine-induced seizures and epileptiform electroencephalographic activity. The cannabinoid CB1 receptor selective agonist, ACEA, mimicked these effects, whereas the antagonist, AM251, prevented them. URB597 also inhibited cocaine-induced activation and death of hippocampal neurons, both in animals and in primary cell culture. Finally, we investigated if the PI3K/Akt/ERK intracellular pathway, a cell surviving mechanism coupled to CB1 receptor, mediated these neuroprotective effects. Accordingly, URB597 injection increased ERK and Akt phosphorylation in the hippocampus. Moreover, the neuroprotective effect of this compound was reversed by the PI3K inhibitor, LY294002. In conclusion, the pharmacological facilitation of the anandamide/CB1/PI3K signaling protects the brain against cocaine intoxication in experimental models. This strategy may be further explored in the development of treatments for drug-induced neurotoxicity. - Highlights: • Cocaine toxicity is characterized by seizures and hippocampal cell death. • The endocannabinoid anandamide acts as a brain protective mechanism. • Inhibition of anandamide hydrolysis attenuates

  8. Enhancement of endocannabinoid signaling protects against cocaine-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Vilela, Luciano R. [Graduate Program in Neuroscience, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Gobira, Pedro H.; Viana, Thercia G. [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Medeiros, Daniel C.; Ferreira-Vieira, Talita H. [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Doria, Juliana G. [Graduate Program in Neuroscience, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Rodrigues, Flávia [Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Aguiar, Daniele C. [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Pereira, Grace S.; Massessini, André R. [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Ribeiro, Fabíola M. [Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Oliveira, Antonio Carlos P. de [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Moraes, Marcio F.D., E-mail: mfdm@icb.ufmg.br [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Moreira, Fabricio A., E-mail: fabriciomoreira@icb.ufmg.br [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

    2015-08-01

    Cocaine is an addictive substance with a potential to cause deleterious effects in the brain. The strategies for treating its neurotoxicity, however, are limited. Evidence suggests that the endocannabinoid system exerts neuroprotective functions against various stimuli. Thus, we hypothesized that inhibition of fatty acid amide hydrolase (FAAH), the main enzyme responsible for terminating the actions of the endocannabinoid anandamide, reduces seizures and cell death in the hippocampus in a model of cocaine intoxication. Male Swiss mice received injections of endocannabinoid-related compounds followed by the lowest dose of cocaine that induces seizures, electroencephalographic activity and cell death in the hippocampus. The molecular mechanisms were studied in primary cell culture of this structure. The FAAH inhibitor, URB597, reduced cocaine-induced seizures and epileptiform electroencephalographic activity. The cannabinoid CB{sub 1} receptor selective agonist, ACEA, mimicked these effects, whereas the antagonist, AM251, prevented them. URB597 also inhibited cocaine-induced activation and death of hippocampal neurons, both in animals and in primary cell culture. Finally, we investigated if the PI3K/Akt/ERK intracellular pathway, a cell surviving mechanism coupled to CB{sub 1} receptor, mediated these neuroprotective effects. Accordingly, URB597 injection increased ERK and Akt phosphorylation in the hippocampus. Moreover, the neuroprotective effect of this compound was reversed by the PI3K inhibitor, LY294002. In conclusion, the pharmacological facilitation of the anandamide/CB1/PI3K signaling protects the brain against cocaine intoxication in experimental models. This strategy may be further explored in the development of treatments for drug-induced neurotoxicity. - Highlights: • Cocaine toxicity is characterized by seizures and hippocampal cell death. • The endocannabinoid anandamide acts as a brain protective mechanism. • Inhibition of anandamide hydrolysis

  9. 3-Nitropropionic acid neurotoxicity in organotypic striatal and corticostriatal slice cultures is dependent on glucose and glutamate

    DEFF Research Database (Denmark)

    Storgaard, J; Kornblit, B T; Zimmer, J;

    2000-01-01

    Mitochondrial inhibition by 3-nitropropionic acid (3-NPA) causes striatal degeneration reminiscent of Huntington's disease. We studied 3-NPA neurotoxicity and possible indirect excitotoxicity in organotypic striatal and corticostriatal slice cultures. Neurotoxicity was quantified by assay of lact...

  10. BIOCHEMICAL, FUNCTIONAL AND MORPHOLOGICAL INDICATORS OF NEUROTOXICITY: EFFECTS OF ACUTE ADMINISTRATION OF TRIMETHYLTIN TO THE DEVELOPING RAT

    Science.gov (United States)

    The neurotoxic organometal, trimethyltin (TMT), was administered to rats on postnatal day (PND)5. Neurotoxicity was assessed throughout subsequent development using morphological, biochemical and functional endpoints. These consisted of brain weight measures and histology (morpho...

  11. The unfolded protein response protects from tau neurotoxicity in vivo.

    Directory of Open Access Journals (Sweden)

    Carin A Loewen

    Full Text Available The unfolded protein response is a critical system by which the cell handles excess misfolded protein in the secretory pathway. The role of the system in modulating the effects of aggregation prone cytosolic proteins has received less attention. We use genetic reporters to demonstrate activation of the unfolded protein response in a transgenic Drosophila model of Alzheimer's disease and related tauopathies. We then use loss of function genetic reagents to support a role for the unfolded protein response in protecting from tau neurotoxicity. Our findings suggest that the unfolded protein response can ameliorate the toxicity of tau in vivo.

  12. Individual and combined toxic effects of cypermethrin and chlorpyrifos on earthworm

    Institute of Scientific and Technical Information of China (English)

    Shiping Zhou; Changqun Duan; Wong Hang Gi Michelle; Fazhong Yang; Xuehua Wang

    2011-01-01

    Toxicities were assessed for a pyrethroid (cypermethrin) and an organophosphate insecticide (chlorpyrifos) individually and in combination. A series of tests were conducted on different responses (acute, chronic, behavioral) of earthworms of species Eisenia fetida andrei in the ecological risk assessment of these pesticides. The results showed that the toxicity of the mixture of cypermethrin and chiorpyfifos was significantly higher than either of these pesticides individually, especially on the earthworm's chronic responses.At a concentration of 5 mg/kg, the mixture caused significant reductions on the growth and reproduction rates of earthworms, but did not cause any significant effect when the individual was tested. The increase in toxicity of the pesticide mixture means that the use of toxicity data obtained exclusively from single-pesticide experiments may underestimate the ecological risk of pesticides that actually present in the field.

  13. Chlorpyrifos induced testicular damage in rats: ameliorative effect of glutathione antioxidant.

    Science.gov (United States)

    Elsharkawy, Eman E; Yahia, Doha; El-Nisr, Neveen A

    2014-09-01

    This study investigated the induction of oxidative stress in the testes of adult rats exposed to chlorpyrifos (CPF). CPF was administered orally, in a dose of 30 mg/kg body weight to male rats for 90 days, twice weekly. Coadministration of water-soluble nonenzymatic antioxidant glutathione (GSH) was performed in a dose of 100 mg/kg body weight, orally, for the same period. Another two groups of male rats were administered GSH and corn oil, respectively. The activities of superoxide dismutase and GSH reductase were decreased while the levels of lipid peroxidation were increased in the testicular tissues of the exposed animals. Testosterone level in the serum was significantly decreased. A decrease in the histochemical determination of testicular alkaline phosphatase was observed in CPF-treated rats. A significant decrease in all stages of spermatogenesis in the seminiferous tubules was recorded in the exposed animals. Coadministration of GSH restored these parameters. PMID:23172834

  14. Fate of 14C-Chlorpyrifos Insecticide in Sunflower Seeds and Oil and the Effect of Processing According to Industrial Practice

    International Nuclear Information System (INIS)

    Ethyl -1- 14C-chlorpyrifos and some of its degradation products have been prepared for the present investigation. Sunflower plants were treated with 14C-chlorpyrifos under conditions simulating local agricultural practice. 14C-residue in seeds were determined at different time intervals. At harvest time about 8 % of 14C-activity was associated with oil. The methanol soluble 14C-residues accounted for 0.8 % of the total seed residues, while the cake contained about 80 % of the total residues. About 46 % of the 14C-activity in the crude oil could be eliminated by simulated commercial processes locally used for oil refining. The refined oil had a 14C- residue level of about 21 ppm. Chromatographic analysis of crude and refined oil revealed the presence of the parent compound together with three metabolites which were identified as chlorpyrifos oxon, desethyl chlorpyrifos, and desethyl chlorpyrifos oxon in addition to an unknown compound. Methanol extract of the cake revealed the presence of the parent compound and its oxon as free compounds. Acid hydrolysis of the conjugated metabolites in the methanol extract yielded desethyl chlorpyrifos and 3, 5, 6- trichloro-2-hydroxypyridine

  15. Hormetic response of cholinesterase from Daphnia magna in chronic exposure to triazophos and chlorpyrifos

    Institute of Scientific and Technical Information of China (English)

    Shaonan Li; Yajun Tan

    2011-01-01

    In vivo activity of cholinesterase (ChE) in Daphnia magna was measured at different time points during 21-day exposure to triazophos and chlorpyrifos ranging from 0.05 to 2.50 μg/L and 0.01 to 2.00 μg/L, respectively.For exposure to triazophos, ChE was induced up to 176.5% at 1.5 μg/L and day 10 when measured by acetylthiocholine (ATCh), whereas it was induced up to 174.2% at 0.5 μg/L and day 10 when measured by butyrylthiocholine (BTCh).For exposure to chlorpyrifos, ChE was induced up to 134.0% and 160.5% when measured by ATCh and BTCh, respectivly, with both maximal inductions detected at 0.l μg/L and day 8.Obvious induction in terms of ChE activity was also detected in daphnia removed from exposures 24 hr after their birth and kept in a recovery culture for 21 days.Results indicated that the enzyme displayed symptoms of hormesis, a characteristic featured by conversion from low-dose stimulation to high-dose inhibition.In spite of that, no promotion in terms of reproduction rate and body size was detected at any tested concentrations regardless of whether the daphnia were collected at end of the 21-day exposure or at end of a 21-day recovery culture.This suggested that induction of ChE caused by anticholinesterases had nothing to do with the prosperity of the daphnia population.

  16. Hormetic response of cholinesterase from Daphnia magna in chronic exposure to triazophos and chlorpyrifos.

    Science.gov (United States)

    Li, Shaonan; Tan, Yajun

    2011-01-01

    In vivo activity of cholinesterase (ChE) in Daphnia magna was measured at different time points during 21-day exposure to triazophos and chlorpyrifos ranging from 0.05 to 2.50 microg/L and 0.01 to 2.00 microg/L, respectively. For exposure to triazophos, ChE was induced up to 176.5% at 1.5 microg/L and day 10 when measured by acetylthiocholine (ATCh), whereas it was induced up to 174.2% at 0.5 microg/L and day 10 when measured by butyrylthiocholine (BTCh). For exposure to chlorpyrifos, ChE was induced up to 134.0% and 160.5% when measured by ATCh and BTCh, respectively, with both maximal inductions detected at 0.1 microg/L and day 8. Obvious induction in terms of ChE activity was also detected in daphnia removed from exposures 24 hr after their birth and kept in a recovery culture for 21 days. Results indicated that the enzyme displayed symptoms of hormesis, a characteristic featured by conversion from low-dose stimulation to high-dose inhibition. In spite of that, no promotion in terms of reproduction rate and body size was detected at any tested concentrations regardless of whether the daphnia were collected at end of the 21-day exposure or at end of a 21-day recovery culture. This suggested that induction of ChE caused by anticholinesterases had nothing to do with the prosperity of the daphnia population. PMID:21790060

  17. Impact of Location, Cropping History, Tillage, and Chlorpyrifos on Soil Arthropods in Peanut.

    Science.gov (United States)

    Cardoza, Yasmin J; Drake, Wendy L; Jordan, David L; Schroeder-Moreno, Michelle S; Arellano, Consuelo; Brandenburg, Rick L

    2015-08-01

    Demand for agricultural production systems that are both economically viable and environmentally conscious continues to increase. In recent years, reduced tillage systems, and grass and pasture rotations have been investigated to help maintain or improve soil quality, increase crop yield, and decrease labor requirements for production. However, documentation of the effects of reduced tillage, fescue rotation systems as well as other management practices, including pesticides, on pest damage and soil arthropod activity in peanut production for the Mid-Atlantic US region is still limited. Therefore, this project was implemented to assess impacts of fescue-based rotation systems on pests and other soil organisms when compared with cash crop rotation systems over four locations in eastern North Carolina. In addition, the effects of tillage (strip vs. conventional) and soil chlorpyrifos application on pod damage and soil-dwelling organisms were also evaluated. Soil arthropod populations were assessed by deploying pitfall traps containing 50% ethanol in each of the sampled plots. Results from the present study provide evidence that location significantly impacts pest damage and soil arthropod diversity in peanut fields. Cropping history also influenced arthropod diversity, with higher diversity in fescue compared with cash crop fields. Corn rootworm damage to pods was higher at one of our locations (Rocky Mount) compared with all others. Cropping history (fescue vs. cash crop) did not have an effect on rootworm damage, but increased numbers of hymenopterans, acarina, heteropterans, and collembolans in fescue compared with cash crop fields. Interestingly, there was an overall tendency for higher number of soil arthropods in traps placed in chlorpyrifos-treated plots compared with nontreated controls. PMID:26314040

  18. The chemical substances and the neurotoxic effect on workers

    Directory of Open Access Journals (Sweden)

    Rosa Morales

    2013-12-01

    Full Text Available (Received: 2013/10/02 - Accepted: 2013/12/13Tens of thousands of workers are exposed to pollution by the neurotoxicity found in their different workplaces, small businesses, handcrafting industries and even at home. The problem gets worst due to the lack of information on the risks posed by these substances and the safety controls to be taken during its use, on the other hand, the overconfidence that exists about the abstraction of this danger when it comes to the exposure to small doses of toxicity by ignoring the cumulative effects of these substances every time they enter the body. In Ecuador, nowadays there are few studies that distinguish this exposure to these substances, and none on the incidence of the neurotoxic syndrome, considering it an important field to research. Workers who are exposed to chemical toxic substances are now associated to adverse human health effects, due to its aggression and because of the worker´s safety before breaking health directly. They enter the body by the respiratory, dermal or digestive system, and show a great affinity with the body grease so that it accumulates and affects the different organs, tissues, the central nervous system, the bone marrow and liver. Immediate acute and chronic long-term effects were detected due to the intensity and duration of the exposure. Some symptoms include drowsiness, loss of appetite, headache, dizziness, depression, anxiety, nervousness, fatigue, irritability, memory problems, mental sluggishness, apathy, seizures, motor skills incoordination, genetic alterations, among others.

  19. Lead neurotoxicity: In vitro and in vivo effects

    Energy Technology Data Exchange (ETDEWEB)

    Rowles, T.K.

    1989-01-01

    Neuroglial cells, in particular astroglia, are thought to play a role in the neurotoxicity of lead. Two hypotheses have been proposed as possible cellular mechanism of this neurotoxicity: (1) lead affects intracellular levels of metals which mediate the toxic effects noted, and (2) lead affects intracellular heme biosynthesis which is then toxic to the cells. Zinc was found to have a profound effect on both intracellular lead levels and on cell numbers in lead-treated rat astroglia. A comparison of bovine and rat astroglia in culture indicated that the bovine cell cultures were not more sensitive to lead, even though calves are more sensitive. Lead was also shown to affect intracellular heme biosynthesis by a decrease in {sup 14}C aminolevulinic acid incorporation into extractable heme in lead-treated rat astroglia. Finally, low levels of lead in immature guinea pigs caused changes in tissue levels of lead, iron, copper, and zinc with no change in weight gain or body:brain weight ratios.

  20. Subchronic organophosphorus ester-induced delayed neurotoxicity in mallards

    Science.gov (United States)

    Hoffman, D.J.; Sileo, L.; Murray, H.C.

    1984-01-01

    Eighteen-week-old mallard hens received 0, 10, 30, 90, or 270 ppm technical grade EPN (phenylphosphonothioic acid O-ethyl-O-4-nitrophenyl ester) in the diet for 90 days. Ataxia was first observed in the 270-ppm group after 16 days, in the 90-ppm group after 20 days, in the 30-ppm group after 38 days; 10 ppm failed to produce ataxia. By the end of 90 days all 6 birds in the 270-ppm group exhibited ataxia or paralysis whereas 5 of 6 birds in the 90-ppm group and 2 of 6 birds in the 30-ppm group were visibly affected. Treatment with 30 ppm or more resulted in a significant reduction in body weight. Brain neurotoxic esterase activity was inhibited by averages of 16, 69, 73, and 74% in the 10-, 30-, 90-, and 270-ppm groups, respectively. Brain acetylcholinesterase, plasma cholinesterase, and plasma alkaline phosphatase were significantly inhibited as well. Distinct histopathological effects were seen in the 30-, 90-, and 270-ppm groups which included demyelination and degeneration of axons of the spinal cord. Additional ducks were exposed in a similar manner to 60-, 270-, or 540-ppm leptophos (phosphonothioic acid O-4-bromo-2,5-dichlorophenyl-O-methylphenyl ester) which resulted in similar behavioral, biochemical, and histopathological alterations. These findings indicate that adult mallards are probably somewhat less sensitive than chickens to subchronic dietary exposure to organophosphorus insecticides that induce delayed neurotoxicity.

  1. Evidence for neurotoxicity associated with amoxicillin in juvenile rats.

    Science.gov (United States)

    Atli, O; Demir-Ozkay, U; Ilgin, S; Aydin, T H; Akbulut, E N; Sener, E

    2016-08-01

    Amoxicillin (AMX) is one of the most commonly prescribed antibiotics for children, and childhood is the period to have the highest risk for toxicity cases including drug-induced adverse reactions. Some neurological adverse effects (anxiety, hyperactivity, confusion, convulsions, and behavioral changes) have been reported related to AMX treatment. In the present study, we aimed to determine the neurotoxic effects of AMX administration at clinically relevant doses in female juvenile rats. AMX was administered in single oral daily doses of 25 and 50 mg/kg for 14 days. According to our results, while AMX administration caused a significant increase in the immobility time of animals, swimming time of these animals significantly decreased. AMX administration significantly reduced the onset of pentylenetetrazole-induced convulsions. The serotonin levels of brain tissues in the AMX-administered groups were decreased significantly, which is thought to be related to depression. The glutamate levels in brain tissues increased significantly in AMX-administered groups, which is thought to be related to convulsion. Otherwise, superoxide dismutase and catalase activities were significantly decreased in brain tissues of AMX-administered groups. In conclusion, AMX administration triggered depression and shortened the time of the appearance of first seizure in juvenile rats. Also, altered brain neurotransmitter levels and increased oxidative stress observed in our study were thought to be the possible underlying mechanisms of AMX-induced neurotoxicity. PMID:26429924

  2. Drugs That Bind to α-Synuclein: Neuroprotective or Neurotoxic?

    Science.gov (United States)

    Kakish, Joe; Lee, Dongsoo; Lee, Jeremy S

    2015-12-16

    The misfolding of α-synuclein is a critical event in the death of dopaminergic neurons and the progression of Parkinson's disease. Drugs that bind to α-synuclein and form a loop structure between the N- and C-terminus tend to be neuroprotective, whereas others that cause a more compact structure tend to be neurotoxic. The binding of several natural products and other drugs that are involved in dopamine metabolism were investigated by nanopore analysis and isothermal titration calorimetry. The antinausea drugs, cinnarizine and metoclopramide, do not bind to α-synuclein, whereas amphetamine and the herbicides, paraquat and rotenone, bind tightly and cause α-synuclein to adopt a more compact conformation. The recreational drug, cocaine, binds to α-synuclein, whereas heroin and methadone do not. Metformin, which is prescribed for diabetes and is neuroprotective, binds well without causing α-synuclein to adopt a more compact conformation. Methylphenidate (ritalin) binds to sites in both the N- and C-terminus and causes α-synuclein to adopt a loop conformation. In contrast, amphetamine only binds to the N-terminus. Except for cinnarizine and metoclopramide, there is a good correlation between the mode of binding to α-synuclein and whether a drug is neuroprotective or neurotoxic. PMID:26378986

  3. Transcriptional response of zebrafish embryos exposed to neurotoxic compounds reveals a muscle activity dependent hspb11 expression.

    Directory of Open Access Journals (Sweden)

    Nils Klüver

    Full Text Available Acetylcholinesterase (AChE inhibitors are widely used as pesticides and drugs. Their primary effect is the overstimulation of cholinergic receptors which results in an improper muscular function. During vertebrate embryonic development nerve activity and intracellular downstream events are critical for the regulation of muscle fiber formation. Whether AChE inhibitors and related neurotoxic compounds also provoke specific changes in gene transcription patterns during vertebrate development that allow them to establish a mechanistic link useful for identification of developmental toxicity pathways has, however, yet not been investigated. Therefore we examined the transcriptomic response of a known AChE inhibitor, the organophosphate azinphos-methyl (APM, in zebrafish embryos and compared the response with two non-AChE inhibiting unspecific control compounds, 1,4-dimethoxybenzene (DMB and 2,4-dinitrophenol (DNP. A highly specific cluster of APM induced gene transcripts was identified and a subset of strongly regulated genes was analyzed in more detail. The small heat shock protein hspb11 was found to be the most sensitive induced gene in response to AChE inhibitors. Comparison of expression in wildtype, ache and sop(fixe mutant embryos revealed that hspb11 expression was dependent on the nicotinic acetylcholine receptor (nAChR activity. Furthermore, modulators of intracellular calcium levels within the whole embryo led to a transcriptional up-regulation of hspb11 which suggests that elevated intracellular calcium levels may regulate the expression of this gene. During early zebrafish development, hspb11 was specifically expressed in muscle pioneer cells and Hspb11 morpholino-knockdown resulted in effects on slow muscle myosin organization. Our findings imply that a comparative toxicogenomic approach and functional analysis can lead to the identification of molecular mechanisms and specific marker genes for potential neurotoxic compounds.

  4. Genetics and Developmental Psychology

    Science.gov (United States)

    Plomin, Robert

    2004-01-01

    One of the major changes in developmental psychology during the past 50 years has been the acceptance of the important role of nature (genetics) as well as nurture (environment). Past research consisting of twin and adoption studies has shown that genetic influence is substantial for most domains of developmental psychology. Present research…

  5. Efeito da interação do nicosulfuron e chlorpyrifos sobre o banco de sementes e os atributos microbianos do solo Effect of sequential nicosulfuron and chlorpyrifos application on seed bank and soil microbial characteristics

    Directory of Open Access Journals (Sweden)

    Taciane Almeida de Oliveira

    2009-06-01

    Full Text Available Considerando o período de competição de plantas daninhas e a incidência da lagarta-do-cartucho na cultura do milho, há necessidade de aplicação, em curto intervalo de tempo, de herbicidas e de inseticidas, principalmente o nicosulfuron e o chlorpyrifos. O objetivo deste estudo foi avaliar o efeito da aplicação sequencial do nicosulfuron e do chlorpyrifos sobre a emergência de plântulas do banco de sementes, a taxa de desprendimento de CO2 (respiração basal e o C da biomassa microbiana (CBM do solo. Foi realizada aplicação sequencial, em solo, do nicosulfuron (doses de 0 a 64 g ha-1 associado ou não ao chlorpyrifos (0 e 240 g ha-1. Aos 20, 40 e 60 dias após a aplicação (DAA dos produtos, todas as plântulas emergidas do banco de sementes foram identificadas em nível de espécie, sendo estimadas a frequência, densidade e abundância, além do índice de valor de importância (IVI. Aos 60 DAA, determinou-se também a taxa de desprendimento de CO2, o CBM e o quociente metabólico (qCO2, por meio da relação entre o CO2 acumulado e o CBM total do solo. A aplicação alterou severamente a massa de plântulas secas e o número de espécies nas doses superiores a 20 g ha-1 do nicosulfuron. Na presença do herbicida, as espécies com maior IVI foram Boehavia diffusa e Commelina benghalensis. Quanto aos bioindicadores do solo, foi observado decréscimo na taxa da respiração basal do solo com o aumento da dose aplicada do nicosulfuron associado ao chlorpyrifos, sem efeito na ausência do inseticida. Houve decréscimo linear no CBM em todos os casos, independentemente da aplicação do chlorpyrifos; entretanto, observou-se uma taxa de decréscimo 4,5 vezes maior para o solo que recebeu esse inseticida em conjunto com o nicosulfuron. A avaliação do qCO2 confirmou o efeito negativo da aplicação do inseticida e do herbicida. Conclui-se que a aplicação de chlorpyrifos + nicosulfuron promove impacto negativo sobre o banco de

  6. The expression profile of detoxifying enzyme of tomato leaf miner, Tuta absoluta Meyrik (Lepidoptera: Gelechiidae) to chlorpyrifos

    OpenAIRE

    Idin Zibaee; Ali Reza Bandani; Ghodratollah Sabahi

    2016-01-01

    The tomato leafminer, Tuta absoluta (Meyrich) (Lepidoptera: Gelechiidae) is an important pest of tomato crops worldwide. The persistent use of organophosphate insecticide to control this pest has led to resistance. However, there is no report on the susceptibility and resistance mechanism of field population of Tuta absoluta (Meyrik) from Iran. Furthermore, the toxicity and impact of chlorpyrifos on metabolic enzymes in this pest remains unknown. The populations of T. absoluta from Rasht in I...

  7. Synergistic effects of chlorpyrifos with piperonyl butoxide (pbo) against the lesser mealworm, Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae)

    OpenAIRE

    Akter Mst Yeasmin; Talukdar Muhammad Waliullah; ASM Shafiqur Rahman

    2014-01-01

    Objective: To investigate the co-toxicity and co-efficient activity of Chlorpyrifos (Dursban 20EC), an organophosphate and Piperonyl butoxide (PBO) against the lesser meal worm Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae) (A. diaperinus). Methods: The repellent activity was carried out by the residual film assay technique. Statistically the dose mortality relationship was expressed as a median lethal dose (LD50) by the probit analysis. The regression lines and isoboles were ...

  8. COMPARATIVE EFFECTS OF PARATHION AND CHLORPYRIFOS ON EXTRACELLULAR ENDOCANNABINOID LEVELS IN RAT HIPPOCAMPUS: INFLUENCE ON CHOLINERGIC TOXICITY

    OpenAIRE

    Liu, Jing; Parsons, Loren; Pope, Carey

    2013-01-01

    Parathion (PS) and chlorpyrifos (CPF) are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE). Endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) can modulate neurotransmission by inhibiting neurotransmitter release. We proposed that differential inhibition of eCB-degrading enzymes (fatty acid amide hydrolase, FAAH, and monoacylglycerol lipase, MAGL) by PS and CPF lead to differences in extracellular eCB l...

  9. Fitness Effects of Chlorpyrifos in the Damselfly Enallagma cyathigerum Strongly Depend upon Temperature and Food Level and Can Bridge Metamorphosis

    OpenAIRE

    Lizanne Janssens; Robby Stoks

    2013-01-01

    Interactions between pollutants and suboptimal environmental conditions can have severe consequences for the toxicity of pollutants, yet are still poorly understood. To identify patterns across environmental conditions and across fitness-related variables we exposed Enallagma cyathigerum damselfly larvae to the pesticide chlorpyrifos at two food levels or at two temperatures and quantified four fitness-related variables (larval survival, development time, mass at emergence and adult cold resi...

  10. Investigation of in vitro effects of ethephon and chlorpyrifos, either alone or in combination, on rat intestinal muscle contraction

    OpenAIRE

    Çetinkaya, Mustafa Alp; Baydan, Emine

    2010-01-01

    A range of pesticides is widely used in pest management and the chances of exposure to multiple organophosphorus (OP) compounds simultaneously are high, especially from dietary and other sources. Although health hazards of individual OP insecticides have been relatively well characterized, there is lesser information on the interactive toxicity of multiple OP insecticides. The aim of this study is to elicit the possible interactions in case combined exposure of an OP pesticide chlorpyrifos (C...

  11. Residual toxicity of abamectin, chlorpyrifos, cyromazine, indoxacarb and spinosad on Liriomyza trifolii (Burgess) (Diptera: Agromyzidae) in greenhouse conditions

    OpenAIRE

    Ghasem Askari Saryazdi; Mir Jalil Hejazi; Moosa Saber

    2012-01-01

    Liriomyza trifolii is an important pest of vegetable crops in many parts of the world including Iran. In this study potted bean plants were sprayed with recommended field rates of abamectin, chlorpyrifos, cyromazine, indoxacarb and spinosad. To assess the residual activities of these insecticides, the plants were infested with L. trifolii adults 2 hours; 1, 3, 5, 7, 10, 15, 20, 25 and 35 days after insecticidal treatments. The adults were allowed to stay on...

  12. Chlorpyrifos Induces the Expression of the Epstein-Barr Virus Lytic Cycle Activator BZLF-1 via Reactive Oxygen Species

    OpenAIRE

    Ling Zhao; Fei Xie; Ting-ting Wang; Meng-yu Liu; Jia-la Li; Lei Shang; Zi-xuan Deng; Peng-xiang Zhao; Xue-mei Ma

    2015-01-01

    Organophosphate pesticides (OPs) are among the most widely used synthetic chemicals for the control of a wide variety of pests, and reactive oxygen species (ROS) caused by OPs may be involved in the toxicity of various pesticides. Previous studies have demonstrated that a reactivation of latent Epstein-Barr virus (EBV) could be induced by oxidative stress. In this study, we investigated whether OPs could reactivate EBV through ROS accumulation. The Raji cells were treated with chlorpyrifos (C...

  13. Alterations in Central Nervous System Serotonergic and Dopaminergic Synaptic Activity in Adulthood after Prenatal or Neonatal Chlorpyrifos Exposure

    OpenAIRE

    Aldridge, Justin E; Meyer, Armando; Seidler, Frederic J; Slotkin, Theodore A.

    2005-01-01

    Exposure to chlorpyrifos (CPF) alters neuronal development of serotonin (5HT) and dopamine systems, and we recently found long-term alterations in behaviors related to 5HT function. To characterize the synaptic mechanisms underlying these effects, we exposed developing rats to CPF regimens below the threshold for systemic toxicity, in three treatment windows: gestational days (GD) 17–20, postnatal days (PN) 1–4, or PN11–14. In early adulthood (PN60), we assessed basal neurotransmitter content...

  14. Repeated exposures to low-level chlorpyrifos results in impairments in sustained attention and increased impulsivity in rats

    OpenAIRE

    Middlemore-Risher, M.L.; Buccafusco, J.J.; Terry, A.V.

    2010-01-01

    Organophosphates such as chlorpyrifos (CPF) are among the most commonly used pesticides in the world. Therefore, it is not surprising that measurable levels of organophosphates (including CPF) are found in over 50% of fresh fruits, vegetables and grains that we consume and that approximately 80% of adults in the US have detectable levels of CPF metabolites in their urine. It is well known that acute exposure to organophosphates can cause cognitive deficits; however, the effects of daily or in...

  15. Residual Toxicity of Abamectin, Chlorpyrifos, Cyromazine, Indoxacarb and Spinosad on Liriomyza trifolii (Burgess (Diptera: Agromyzidae in Greenhouse Conditions

    Directory of Open Access Journals (Sweden)

    Ghasem Askari Saryazdi

    2012-01-01

    Full Text Available Liriomyza trifolii is an important pest of vegetable crops in many parts of the worldincluding Iran. In this study potted bean plants were sprayed with recommended fieldrates of abamectin, chlorpyrifos, cyromazine, indoxacarb and spinosad. To assess the residualactivities of these insecticides, the plants were infested with L. trifolii adults 2 hours; 1, 3,5, 7, 10, 15, 20, 25 and 35 days after insecticidal treatments. The adults were allowed to stayon treated plants for eight hours. The treated plants were kept in a greenhouse. Numberof feeding stipples and larval mines on leaves, as well as pupation and adult eclosion rateswere assessed. Two-way ANOVA procedure of SAS was used for statistical analysis andthe treatment means were separated using Duncan’s multiple range test. Abamectin andspinosad severely affected egg hatching and embryonic development. Eggs oviposited inleaves with residues of chlorpyrifos up to 5 days old, had reduced hatching. Larval developmentwas also, affected by residues of chlorpyrifos up to four weeks old. Indoxacarbreduced larval development and adult eclosion in treatments with up to 20 days old residues.Cyromazine had no effect on the number of larval mines, but, pupation was severelyhampered and adult eclosion was completely ceased even in treatments with five weeksold residues. Determining the residual activity of insecticides used for controlling this pestis useful in avoiding unnecessary treatments.

  16. Remediation of Chlorpyrifos-Contaminated Soils by Laboratory-Synthesized Zero-Valent Nano Iron Particles: Effect of pH and Aluminium Salts

    Directory of Open Access Journals (Sweden)

    A. Vijaya Bhaskar Reddy

    2013-01-01

    Full Text Available Degradation of the insecticide chlorpyrifos in contaminated soils was investigated using laboratory synthesized zero-valent nano iron (ZVNI particles. The synthesized ZVNI particles were characterized as nanoscale sized by scanning electron microscopy (SEM and transmission electron microscopy (TEM. The zero-valent state (Fe0 of iron was confirmed by EDAX analysis and the morphology of the ZVNI particles was studied by XRD. Batch experiments were conducted by treating the chlorpyrifos contaminated soil with ZVNI, our results indicate that 90% of chlorpyrifos was degraded after 10 days of incubation. Only 32% degradation was observed with micro zero-valent iron (mZVI and no considerable degradation was attained without ZVNI. The degradation of chlorpyrifos followed the first-order kinetics with a rate constant and a half-life of 0.245 day−1 and 2.82 days, respectively. Degradation was monitored at two different pH values, that is, pH 10 and pH 4. Chlorpyrifos degradation rate constant increased as the pH decreases from 10 to 4. The corresponding rate constant and half-lives were 0.43 day−1 and 1.57days for pH 4, 0.18 day−1 and 3.65 days for pH 10. In addition, an attempt was made by augmenting Al2(SO43 with ZVNI and it was found that the degradation rate of chlorpyrifos was greatly enhanced and the rate constant was rapidly increased from 0.245 day−1 to 0.60 day−1. Hydrolysis and stepwise dechlorination pathway of chlorpyrifos with ZVNI was the dominant reaction.

  17. Life Span Developmental Approach

    Directory of Open Access Journals (Sweden)

    Ali Eryilmaz

    2011-03-01

    Full Text Available The Life Span Developmental Approach examines development of individuals which occurs from birth to death. Life span developmental approach is a multi-disciplinary approach related with disciplines like psychology, psychiatry, sociology, anthropology and geriatrics that indicates the fact that development is not completed in adulthood, it continues during the life course. Development is a complex process that consists of dying and death. This approach carefully investigates the development of individuals with respect to developmental stages. This developmental approach suggests that scientific disciplines should not explain developmental facts only with age changes. Along with aging, cognitive, biological, and socioemotional development throughout life should also be considered to provide a reasonable and acceptable context, guideposts, and reasonable expectations for the person. There are three important subjects whom life span developmental approach deals with. These are nature vs nurture, continuity vs discontinuity, and change vs stability. Researchers using life span developmental approach gather and produce knowledge on these three most important domains of individual development with their unique scientific methodology.

  18. Neurotoxicity and Biomarkers of Lead Exposure:a Review

    Institute of Scientific and Technical Information of China (English)

    Kang-sheng Liu; Jia-hu Hao; Yu Zeng; Fan-chun Dai; Ping-qing Gu

    2013-01-01

    Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes, public health decision making, and primary prevention synthesis. Lead is one of the neurotoxicants that seems to be involved in the etiology of psychologies. Biomarkers are generally classified into three groups:biomarkers of exposure, effect, and susceptibility.The main body compartments that store lead are the blood, soft tissues, and bone;the half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone. Within the brain, lead-induced damage in the prefrontal cerebral cortex, hippocampus, and cerebellum can lead to a variety of neurological disorders, such as brain damage, mental retardation, behavioral problems, nerve damage, and possibly Alzheimer’s disease, Parkinson’s disease, and schizophrenia. This paper presents an overview of biomarkers of lead exposure and discusses the neurotoxic effects of lead with regard to children and adults.

  19. A plastic stabilizer dibutyltin dilaurate induces subchronic neurotoxicity in rats

    Institute of Scientific and Technical Information of China (English)

    Minghua Jin; Peilin Song; Na Li; Xuejun Li; Jiajun Chen

    2012-01-01

    Dibutyltin dilaurate functions as a stabilizer for polyvinyl chloride.In this study,experimental rats were intragastrically administered 5,10,or 20 mg/kg dibutyltin dilaurate to model sub-chronic poisoning.After exposure,our results showed the activities of superoxide dismutase and glutathione peroxidase decreased in rat brain tissue,while the malondialdehyde and nitric oxide content,as well as nitric oxide synthase activity in rat brain tissue increased.The cell cycle in the right parietal cortex was disordered and the rate of apoptosis increased.DNA damage was aggravated in the cerebral cortex,and the ultrastructure of the right parietal cortex tissues was altered.The above changes became more apparent with exposure to increasing doses of dibutyltin dilaurate.Our experimental findings confirmed the neurotoxicity of dibutyltin dilaurate in rat brain tissues,and demonstrated that the poisoning was dose-dependent.

  20. Trimethyltin (TMT) neurotoxicity in organotypic rat hippocampal slice cultures

    DEFF Research Database (Denmark)

    Noraberg, J; Gramsbergen, J B; Fonnum, F;

    1998-01-01

    neurotoxicological studies, including further studies of neurotoxic mechanisms of TMT. Four-week-old cultures, derived from 7-day-old donor rats and grown in serum-free medium, were exposed to TMT (0.5-100 microM) for 24 h followed by 24 h in normal medium. TMT-induced neurodegeneration was then monitored by (a......) propidium iodide (PI) uptake, (b) lactate dehydrogenase (LDH) efflux into the culture medium, (c) cellular cobalt uptake as an index of calcium influx, (d) ordinary Nissl cell staining, and (e) immunohistochemical staining for microtubule-associated protein 2 (MAP-2). Cellular degeneration as assessed by...... vivo cell stain observations of rats acutely exposed to TMT. The mean PI uptake of the cultures and the LDH efflux into the medium were highly correlated. The combined results obtained by the different markers indicate that the hippocampal slice culture method is a feasible model for further studies of...

  1. Neurotoxicity of general anesthetics: A modern view of the problem

    Directory of Open Access Journals (Sweden)

    A. M. Ovezov

    2015-01-01

    Full Text Available All general anesthetics routinely used in clinical practice are noted to have a neurotoxic effect on the brain in different animal species including primates. The negative effects observed both in young and sexually mature animals include apoptotic neuronal cell death, suppression of neurogenesis and gliogenesis, neuroinflammation, as well as learning and memory impairments. A number of epidemiologic surveys have established an association between anesthesia in patients younger than 3 to 4 years and subsequent learning disabilities and language disorders whereas others have not found this link. In middle-aged and elderly patients, anesthesia is frequently associated with the development of postoperative cognitive dysfunction. The key component of its pathogenesis (general anesthesia itself or other factors, such as operative injury, an inflammatory response, pain syndrome, intraoperative complications, underlying disease in a patient remains unelucidated. It is concluded that there is a need for additional experimental and clinical studies of the pathogenesis of these undesirable phenomena to be prevented and corrected.

  2. PROTECTIVE EFFECT OF GREEN TEA FROM PAF-INDUCED NEUROTOXITY

    Institute of Scientific and Technical Information of China (English)

    Han Enji; Hah Xuefei; Joseph Rajiv

    2000-01-01

    Objective The protective effect of chinese green tea from PAF-induced neurotoxity was investigated Method LaN1 ( neuroblastoma cell line) was used as neuron. Lactate dehydrogenase (LDH) -release was an indicator of cell death. Cytoplasmic calcium was measured with Aequouin-loaded method. Results When applied to LaN1 cells, green tea in concentration 2mg/ml or stronger obviously damaged cells. If lower concentration (0. 5mg/ml and l.Omg/ml) of green tea were applied, green tea inhibited the elevation of intracellular calcium and reduced the cytotoxity induced by PAF in neurons. Conclusion PAF plays an important role in brain injury and stroke, the protective effect of green tea could be a basis to explore weather green tea or its derivative may have preventive and therapeutic potential for neuronal injury.

  3. Changing the Face of Kynurenines and Neurotoxicity: Therapeutic Considerations

    Directory of Open Access Journals (Sweden)

    Zsuzsanna Bohár

    2015-04-01

    Full Text Available Kynurenines are the products of tryptophan metabolism. Among them, kynurenine and kynurenic acid are generally thought to have neuroprotective properties, while 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid are considered neurotoxic. They participate in immunoregulation and inflammation and possess pro- or anti-excitotoxic properties, and their involvement in oxidative stress has also been suggested. Consequently, it is not surprising that kynurenines have been closely related to neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis and multiple sclerosis. More information about the less-known metabolites, picolinic and cinnabarinic acid, evaluation of new receptorial targets, such as aryl-hydrocarbon receptors, and intensive research on the field of the immunomodulatory function of kynurenines delineated the high importance of this pathway in general homeostasis. Emerging knowledge about the kynurenine pathway provides new target points for the development of therapeutical solutions against neurodegenerative diseases.

  4. Subarachnoid hemorrhage associated with cyclosporine A neurotoxicity in a bone-marrow transplant recipient

    Energy Technology Data Exchange (ETDEWEB)

    Teksam, M.; Casey, S.O.; Michel, E.; Truwit, C.L. [Minnesota Univ., Minneapolis, MN (United States). Dept. of Radiology

    2001-03-01

    We report subarachnoid hemorrhage associated with cyclosporine A (CSA) neurotoxicity after bone-marrow transplantation for chronic myelogenous leukemia. CT showed occipital subarachnoid hemorrhage. MRI confirmed this, and demonstrated cortical and subcortical edema in the posterior temporal, occipital, and posterior frontal lobes bilaterally, which was typical of CSA neurotoxicity. Recognition of CSA neurotoxicity as the cause of the subarachnoid hemorrhage obviated angiographic investigation. After cessation of cyclosporine therapy, the cortical and subcortical edema resolved on follow-up MRI with some residual blood products in the subarachnoid space. (orig.)

  5. In vitro oxidation of MPTP by primate neural tissue: A potential model of MPTP neurotoxicity.

    Science.gov (United States)

    Johannessen, J N; Kelner, L; Hanselman, D; Shih, M C; Markey, S P

    1985-01-01

    The compound 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces a parkinsonian syndrome in humans and primates. We have previously found that metabolism of MPTP to a quaternary species is necessary for the expression of its neurotoxic effects. We now report that the metabolism of MPTP occurs in primate brain tissue in vitro , and present a model of MPTP neurotoxicity which incorporates our findings to date. Since the toxicity of MPTP is metabolism dependent, we propose that the in vitro metabolism of MPTP by brain tissue should provide a useful model for studying selected aspects of MPTP neurotoxicity. PMID:20492913

  6. Subarachnoid hemorrhage associated with cyclosporine A neurotoxicity in a bone-marrow transplant recipient

    International Nuclear Information System (INIS)

    We report subarachnoid hemorrhage associated with cyclosporine A (CSA) neurotoxicity after bone-marrow transplantation for chronic myelogenous leukemia. CT showed occipital subarachnoid hemorrhage. MRI confirmed this, and demonstrated cortical and subcortical edema in the posterior temporal, occipital, and posterior frontal lobes bilaterally, which was typical of CSA neurotoxicity. Recognition of CSA neurotoxicity as the cause of the subarachnoid hemorrhage obviated angiographic investigation. After cessation of cyclosporine therapy, the cortical and subcortical edema resolved on follow-up MRI with some residual blood products in the subarachnoid space. (orig.)

  7. A review on potential neurotoxicity of titanium dioxide nanoparticles

    Science.gov (United States)

    Song, Bin; Liu, Jia; Feng, Xiaoli; Wei, Limin; Shao, Longquan

    2015-08-01

    As the rapid development of nanotechnology in the past three decades, titanium dioxide nanoparticles (TiO2 NPs), for their peculiar physicochemical properties, are widely applied in consumer products, food additives, cosmetics, drug carriers, and so on. However, little is known about their potential exposure and neurotoxic effects. Once NPs are unintentionally exposed to human beings, they could be absorbed, and then accumulated in the brain regions by passing through the blood-brain barrier (BBB) or through the nose-to-brain pathway, potentially leading to dysfunctions of central nerve system (CNS). Besides, NPs may affect the brain development of embryo by crossing the placental barrier. A few in vivo and in vitro researches have demonstrated that the morphology and function of neuronal or glial cells could be impaired by TiO2 NPs which might induce cell necrosis. Cellular components, such as mitochondrial, lysosome, and cytoskeleton, could also be influenced as well. The recognition ability, spatial memory, and learning ability of TiO2 NPs-treated rodents were significantly impaired, which meant that accumulation of TiO2 NPs in the brain could lead to neurodegeneration. However, conclusions obtained from those studies were not consistent with each other as researchers may choose different experimental parameters, including administration ways, dosage, size, and crystal structure of TiO2 NPs. Therefore, in order to fully understand the potential risks of TiO2 NPs to brain health, figure out research areas where further studies are required, and improve its bio-safety for applications in the near future, how TiO2 NPs interact with the brain is investigated in this review by summarizing the current researches on neurotoxicity induced by TiO2 NPs.

  8. Neurotoxic effects of levobupivacaine and fentanyl on rat spinal cord

    Directory of Open Access Journals (Sweden)

    Yesim Cokay Abut

    2015-02-01

    Full Text Available BACKGROUND: The purpose of the study was to compare the neurotoxic effects of intrathecally administered levobupivacaine, fentanyl and their mixture on rat spinal cord. METHODS: In experiment, there were four groups with medication and a control group. Rats were injected 15 µL saline or fentanyl 0.0005 µg/15 µL, levobupivacaine 0.25%/15 µL and fentanyl 0.0005 µg + levobupivacaine 0.25%/15 µL intrathecally for four days. Hot plate test was performed to assess neurologic function after each injection at 5th, 30th and 60th min. Five days after last lumbal injection, spinal cord sections between the T5 and T6 vertebral levels were obtained for histologic analysis. A score based on subjective assessment of number of eosinophilic neurons - Red neuron - which means irreversible neuronal degeneration. They reflect the approximate number of degenerating neurons present in the affected neuroanatomic areas as follows: 1, none; 2, 1-20%; 3, 21-40%; 4, 41-60%; and 5, 61-100% dead neurons. An overall neuropathologic score was calculated for each rat by summating the pathologic scores for all spinal cord areas examined. RESULTS: In the results of HPT, comparing the control group, analgesic latency statistically prolonged for all four groups.In neuropathologic investment, the fentanyl and fentanyl + levobupivacaine groups have statistically significant high degenerative neuron counts than control and saline groups. CONCLUSIONS: These results suggest that, when administered intrathecally in rats, fentanyl and levobupivacaine behave similar for analgesic action, but fentanyl may be neurotoxic for spinal cord. There was no significant degeneration with levobupivacaine, but fentanyl group has had significant degeneration.

  9. Role of endolysosomes in HIV-1 Tat-induced neurotoxicity

    Directory of Open Access Journals (Sweden)

    Liang Hui

    2012-06-01

    Full Text Available Combined anti-retroviral therapeutic drugs effectively increase the lifespan of HIV-1-infected individuals who then have a higher prevalence of HAND (HIV-1 associated neurocognitive disorder. Soluble factors including HIV-1 proteins released from HIV-1-infected cells have been implicated in the pathogenesis of HAND, and particular attention has been paid to the HIV-1 Tat (transactivator of transcription protein because of its ability to directly excite neurons and cause neuronal cell death. Since HIV-1 Tat enters cells by receptor-mediated endocytosis and since endolysosomes play an important role in neuronal cell life and death, we tested here the hypothesis that HIV-1 Tat neurotoxicity is associated with changes in the endolysosome structure and function and also autophagy. Following the treatment of primary cultured rat hippocampal neurons with HIV-1 Tat or as controls mutant-Tat or PBS, neuronal viability was determined using a triple staining method. Preceding observations of HIV-1 Tat-induced neuronal cell death, we observed statistically significant changes in the structure and membrane integrity of endolysosomes, endolysosome pH and autophagy. As early as 24 h after HIV-1 Tat was applied to neurons, HIV-1 Tat accumulated in endolysosomes, endolysosome morphology was affected and their size increased, endolysosome membrane integrity was disrupted, endolysosome pH increased, specific activities of endolysosome enzymes decreased and autophagy was inhibited, as indicated by the significant changes in three markers for autophagy. In contrast, statistically significant levels of HIV-1 Tat-induced neuronal cell death were observed only after 48 h of HIV-1 Tat treatment. Our findings suggest that endolysosomes are involved in HIV-1 Tat-induced neurotoxicity and may represent a target for therapeutic intervention against HAND.

  10. Rodent neurotoxicity bioassays for screening contaminated Great Lakes fish

    Energy Technology Data Exchange (ETDEWEB)

    Beattie, M.K.; Hoffman, R. [Univ. of Minnesota, Duluth, MN (United States); Gerstenberger, S. [Univ. of Illinois, Urbana, IL (United States). Dept. of Veterinary Biosciences; Dellinger, J.A. [Medical Coll. of Wisconsin, Milwaukee, MI (United States). Dept. of Preventive Medicine

    1996-03-01

    Standard laboratory rat neurotoxicity protocols were used to study the consequences resulting from the consumption of walleye (Stizostedion vitreum), whitefish (Coregonus clupeaformis), and lake trout (Salvelinus namaycush) from Lake Superior (LS) and the consumption of carp (Cyprinus carpio) from Little Lake Butte des Morte (LLBM) near Oshkosh, Wisconsin, USA. Two 90-d subchronic studies are described, including a 45-d exposure to fish diets using male Sprague-Dawley hooded rats, and a 90-d exposure to fish diets using female rats of the same species. Behavioral alterations were tested using a battery of behavioral tests. In addition, pharmacologic challenges using apomorphine and D-amphetamine were administered to the rats to reveal latent neurotoxic effects. Cumulative fish consumption data were recorded daily, weight gain recorded weekly, and behavior data collected prior to exposure, and on days 7, 14, 55 {+-} 2, 85 {+-} 2. Motor activity data were collected on days 30 {+-} 2, 60 {+-} 2, and 90 {+-} 2 of the feeding protocols. Brain tissue from rodents fed these fish were subsequently analyzed for either mercury (Hg) or polychlorinated biphenyls (PCB). Mercury concentrations were increased in the brains of the walleye-fed rats, and PCB concentrations ranged from 0.5 nl/L to 10 nl/L in the brains of rats fed carp from LLBM, a Lake Michigan tributary. Adult male rats fed LLBM carp for 45 d exhibited the greatest behavior responses to the dopaminergic agonist apomorphine on the accelerating rotarod, although these differences were not significant. The 90-d exposure of LS walleye or Hg-spiked LS walleye resulted in behavior alterations on tactile startle response and second footsplay. D-Amphetamine challenge caused changes in tactile startle response, second footsplay, and accelerating rotarod performance after consuming walleye diets. Rats fed LLBM carp had altered behavioral responses to apomorphine on the accelerating rotarod.

  11. Inhibitors of histone deacetylases enhance neurotoxicity of DNA damage.

    Science.gov (United States)

    Vashishta, A; Hetman, M

    2014-12-01

    The nonselective inhibitors of class I/II histone deacetylases (HDACs) including trichostatin A and the clinically used suberoylanilide hydroxamic acid (SAHA, vorinostat) are neuroprotective in several models of neuronal injury. Here, we report that in cultured cortical neurons from newborn rats and in the cerebral cortex of whole neonate rats, these HDAC inhibitors exacerbated cytotoxicity of the DNA double-strand break (DSB)-inducing anticancer drug etoposide by enhancing apoptosis. Similar neurotoxic interactions were also observed in neurons that were treated with other DNA damaging drugs including cisplatin and camptothecin. In addition, in rat neonates, SAHA increased cortical neuron apoptosis that was induced by a single injection of the NMDA receptor antagonist dizocilpine (MK801). In etoposide-treated neurons, the nonselective HDAC inhibition resulted in more DSBs. It also potentiated etoposide-induced accumulation and phosphorylation of the pro-apoptotic transcription factor p53. Moreover, nonselective HDAC inhibition exacerbated neuronal apoptosis that was induced by the overexpressed p53. Importantly, such effects cannot be fully explained by inhibition of HDAC1, which is known to play a role in DSB repair and regulation of p53. The specific HDAC1 inhibitor MS275 only moderately enhanced etoposide-induced neuronal death. Although in etoposide-treated neurons MS275 increased DSBs, it did not affect activation of p53. Our findings suggest that besides HDAC1, there are other class I/II HDACs that participate in neuronal DNA damage response attenuating neurotoxic consequences of genotoxic insults to the developing brain. PMID:25063076

  12. Comparative chlorpyrifos pharmacokinetics via multiple routes of exposure and vehicles of administration in the adult rat

    International Nuclear Information System (INIS)

    Chlorpyrifos (CPF) is a commonly used organophosphorus pesticide. A number of toxicity and mechanistic studies have been conducted in animals, where CPF has been administered via a variety of different exposure routes and dosing vehicles. This study compared chlorpyrifos (CPF) pharmacokinetics using oral, intravenous (IV), and subcutaneous (SC) exposure routes and corn oil, saline/Tween 20, and dimethyl sulfoxide (DMSO) as dosing vehicles. Two groups of rats were co-administered target doses (5 mg/kg) of CPF and isotopically labeled CPF (L-CPF). One group was exposed by both oral (CPF) and IV (L-CPF) routes using saline/Tween 20 vehicle; whereas, the second group was exposed by the SC route using two vehicles, corn oil (CPF) and DMSO (L-CPF). A third group was only administered CPF by the oral route in corn oil. For all treatments, blood and urine time course samples were collected and analyzed for 3,5,6-trichloro-2-pyridinol (TCPy), and isotopically labeled 3,5,6-trichloro-2-pyridinol (L-TCPy). Peak TCPy/L-TCPy concentrations in blood (20.2 μmol/l), TCPy/L-TCPy blood AUC (94.9 μmol/l h), and percent of dose excreted in urine (100%) were all highest in rats dosed orally with CPF in saline/Tween 20 and second highest in rats dosed orally with CPF in corn oil. Peak TCPy concentrations in blood were more rapidly obtained after oral administration of CPF in saline/Tween 20 compared to all other dosing scenarios (>1.5 h). These results indicate that orally administered CPF is more extensively metabolized than systemic exposures of CPF (SC and IV), and vehicle of administration also has an effect on absorption rates. Thus, equivalent doses via different routes and/or vehicles of administration could potentially lead to different body burdens of CPF, different rates of bioactivation to CPF-oxon, and different toxic responses. Simulations using a physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model for CPF are consistent with these possibilities

  13. Pervasive Developmental Disorders

    Science.gov (United States)

    ... ultimately cure this and similar disorders. NIH Patient Recruitment for Pervasive Developmental Disorders Clinical Trials At NIH ... 1055 (TTY) National Institute of Child Health and Human Information Resource Center P.O. Box 3006 Rockville, MD 20847 ...

  14. Facts about Developmental Disabilities

    Science.gov (United States)

    ... do if you’re concerned » Developmental Monitoring and Screening A child’s growth and development are followed through ... to prevent illness. Some health conditions, such as asthma, gastrointestinal symptoms, eczema and skin allergies, and migraine ...

  15. Developmental Effects of Ghrelin

    OpenAIRE

    Steculorum, Sophie M.; Bouret, Sebastien G.

    2011-01-01

    Ghrelin is a pleiotropic hormone that was originally described as promoting feeding and stimulating growth hormone release in adults. A growing body of evidence suggests that ghrelin may also exert developmental and organizational effects during perinatal life. The perinatal actions of ghrelin include the regulation of early developmental events such as blastocyst development and perinatal growth. Moreover, alterations in perinatal ghrelin levels result in structural differences in various pe...

  16. Life Span Developmental Approach

    OpenAIRE

    Eryılmaz, Ali

    2011-01-01

    The Life Span Developmental Approach examines development of individuals which occurs from birth to death. Life span developmental approach is a multi-disciplinary approach related with disciplines like psychology, psychiatry, sociology, anthropology and geriatrics that indicates the fact that development is not completed in adulthood, it continues during the life course. Development is a complex process that consists of dying and death. This approach carefully investigates the development of...

  17. Towards Deep Developmental Learning

    OpenAIRE

    Sigaud, Olivier; Droniou, Alain

    2016-01-01

    International audience Deep learning techniques are having an undeniable impact on general pattern recognition issues. In this paper, from a developmental robotics perspective, we scrutinize deep learning techniques under the light of their capability to construct a hierarchy of meaningful multimodal representations from the raw sensors of robots. These investigations reveal the differences between the methodological constraints of pattern recognition and those of developmental robotics. I...

  18. Cholinergic and behavioral neurotoxicity of carbaryl and cadmium to larval rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Beauvais, S L; Jones, S B; Parris, J T; Brewer, S K; Little, E E

    2001-05-01

    Pesticides and heavy metals are common environmental contaminants that can cause neurotoxicity to aquatic organisms, impairing reproduction and survival. Neurotoxic effects of cadmium and carbaryl exposures were estimated in larval rainbow trout (RBT; Oncorhynchus mykiss) using changes in physiological endpoints and correlations with behavioral responses. Following exposures, RBT were videotaped to assess swimming speed. Brain tissue was used to measure cholinesterase (ChE) activity, muscarinic cholinergic receptor (MChR) number, and MChR affinity. ChE activity decreased with increasing concentrations of carbaryl but not of cadmium. MChR were not affected by exposure to either carbaryl or cadmium. Swimming speed correlated with ChE activity in carbaryl-exposed RBT, but no correlation occurred in cadmium-exposed fish. Thus, carbaryl exposure resulted in neurotoxicity reflected by changes in physiological and behavioral parameters measured, while cadmium exposure did not. Correlations between behavior and physiology provide a useful assessment of neurotoxicity. PMID:11386719

  19. Evaluation of misonidazole peripheral neurotoxicity in rats by analysis of nerve trains evoked response

    International Nuclear Information System (INIS)

    The clinical use of misonidazole and other nitroimidazole radiosensitizing agents is limited by the peripheral and central neurotoxicity that is produced in animals and humans. In a blinded study, rats treated with misonidazole at either 100 mg/kg or 300 mg/kg, 5 days/week for 3 weeks, were evaluated for peripheral neurotoxicity using nerve trains evoked responses. Only one rat treated at a dose of 100 mg/kg developed symptoms and signs of neurotoxicity, while all rats treated at 300 mg/kg developed these signs and symptoms. Nerve trains analysis made possible a diagnosis of neurotoxicity before overt clinical signs appeared. This test is non-invasive and may be useful for evaluating patients receiving nitroimidazole radiosensitizers as part of a radiation therapy regimen

  20. A novel antagonistic role of natural compound icariin on neurotoxicity of amyloid β peptide

    Directory of Open Access Journals (Sweden)

    Jianhui Liu

    2015-01-01

    Interpretation & conclusions: The results indicated a novel antagonistic role of icariin in the neurotoxicity of Aβ1-42 via inhibiting its aggregation, suggesting that icariin might have potential therapeutic benefits to delay or modify the progression of AD.

  1. Age-related differences in neurotoxicity produced by organophosphorus and N-methyl carbamate pesticides

    Science.gov (United States)

    Potential pesticide effects in infants and toddlers have received much attention in the scientific literature and the public media, including the concern for increased response to acute or shortterm exposures. Age-related differences in the acute neurotoxicity of acetylcholinest...

  2. Effect of the application of chlorpyrifos to maize on pests and beneficial arthropods in Nicaragua

    International Nuclear Information System (INIS)

    Field experiments were performed between 1994 and 1997 to evaluate the effect of chlorpyrifos insecticide on arthropods in maize agroecosystem. The experiments were carried out in Boaco (Central zone) and Managua (Pacific zone) areas. Experiments were set up according to randomized block design, with large plots (750 m2) and four replications. The treatments were 1L/ha Lorsban 4E (containing 480 g a.i../L) and control. Visual sampling, pitfall traps and yellow traps were used to estimate numbers of pest insects and beneficial arthropods. Chlorpiryfos had a measureable affect on fall armyworm (Spodoptera frugiperda) and Dalbulus maidis. The plots sprayed with the insecticide had the lowest population of S. frugiperda and the highest population of D. maidis. Beneficials insects, mainly parasitoids were more affected than pests by the insecticide sprays. The highest parasitism was found in the unsprayed plots. Overall, the lowest population of arthropods was found in the sprayed plots, except that in Managua the highest number of D. maidis were found in the sprayed plots. (author)

  3. Utilization of microbial community potential for removal of chlorpyrifos: a review.

    Science.gov (United States)

    Yadav, Maya; Shukla, Awadhesh Kumar; Srivastva, Navnita; Upadhyay, Siddh Nath; Dubey, Suresh Kumar

    2016-08-01

    Chlorpyrifos (CP) is the most commonly used pesticide in agricultural fields worldwide. Exposure to CP and its metabolites creates severe neuron-disorders in human beings. Improper handling and uncontrolled application of CP by farmers have lead to the contamination of surface and ground water bodies. Biodegradation offers an efficient and cost effective method for the removal of CP and other toxic organophosphorus pesticides from the contaminated environment. The degradation of CP by various microorganisms has been investigated by several researchers over the past few years. This review presents a critical summary of the recent published results on the biodegradation of CP. A diverse range of bacterial species such as Agrobacterium sp., Alcaligenes faecalis, Enterobacter sp. Arthrobacter sp. Bacillus pumilus, Pseudomonas sp. etc., fungal species like Trichoderma viridae, Aspergillus niger, Verticillium sp., Acremonium sp. Cladosporium cladosporiodes, etc. and certain algal species viz. Chlorella vulgaris, Spirulina platensis, Synechocystis sp., etc., have been shown to degrade CP. The efficacy of these communities for CP degradation in batch and continuous modes has also been discussed but more studies are required on continuous reactors. Also, the available published information on kinetics of biodegradation of CP along with the available results on molecular biological approaches are discussed in this work. PMID:25782532

  4. How safe is the use of chlorpyrifos: Revelations through its effect on layer birds

    Directory of Open Access Journals (Sweden)

    P. P. Singh

    2016-07-01

    Full Text Available Aim: The present study was aimed to investigate the immunological competence of chlorpyrifos (CPF insecticide after oral administration in layer chickens. Materials and Methods: A total of 20 White Leghorn birds were given CPF in drinking water at 0.3 ppm/bird/day (no observable effect level dose for a period of 3-month. Immune competence status of layer birds and chicks hatched from CPF-treated birds were estimated at 15 days interval in layer birds and monthly interval in chicks using immunological and biochemical parameters. Results: There was a significant decrease in values of total leukocytes count, absolute lymphocyte count, absolute heterophil count, total serum protein, serum albumin, serum globulin, and serum gamma globulin in the birds treated with CPF as compared to control. Similarly, immune competence tests such as lymphocyte stimulation test, oxidative burst assay, and enzyme-linked immunosorbent assay tests indicated lower immunity in birds treated with CPF as compared to control. Subsequently, chicks produced from CPF-treated birds were also examined for immune competence, but no significant difference was observed between chicks of both the groups. Conclusion: The exposure to CPF produced hemo-biochemical and other changes that could be correlated with changes in the immunological profile of layer chickens suggesting total stoppage of using CPF in poultry sheds.

  5. Effect of pulse frequency and interval on the toxicity of chlorpyrifos to Daphnia magna.

    Science.gov (United States)

    Naddy, R B; Klaine, S J

    2001-11-01

    Due to the episodic nature in which organisms are exposed to non-point source pollutants, it is necessary to understand how they are affected by pulsed concentrations of contaminants. This is essential, as standard toxicity tests may not adequately simulate exposure scenarios for short-lived hydrophobic compounds, such as chlorpyrifos (CPF), a broad-spectrum organophosphate insecticide. Studies were conducted with 7-day old Daphnia magna for 7 days to evaluate the effect of pulse frequency and interval among multiple CPF exposures. Daphnids were exposed to a total exposure of either 12 h at 0.5 microg/l or 6 h at 1.0 microg/l nominal CPF, respectively, in all studies. For interval studies, D. magna were exposed to two pulses of CPF at each concentration, with 0-96-h intervals between pulses. For frequency studies, D. magna were exposed to each CPF concentration altering the pulse scheme by decreasing the exposure duration but increasing the number of pulses, keeping the total exposure time the same. The pulse interval between multiple pulses in these experiments was 24 h. Our results suggest that D. magna can withstand an acutely lethal CPF exposure provided that there is adequate time for recovery between exposures. PMID:11680745

  6. An engineered microorganism can simultaneously detoxify cadmium, chlorpyrifos, and γ-hexachlorocyclohexane.

    Science.gov (United States)

    Yang, Chao; Yu, Huilei; Jiang, Hong; Qiao, Chuanling; Liu, Ruihua

    2016-07-01

    Many ecosystems are currently co-contaminated with heavy metals such as cadmium (Cd(2+) ) and pesticides such as chlorpyrifos (CP) and γ-hexachlorocyclohexane (γ-HCH). A feasible approach to remediate the combined pollution of heavy metals and pesticides is the use of γ-HCH degrading bacteria endowed with CP hydrolysis and heavy metal biosorption capabilities. In this work, a recombinant microorganism capable of simultaneously detoxifying Cd(2+) , CP, and γ-HCH was constructed by display of synthetic phytochelatins (EC20) and methyl parathion hydrolase (MPH) fusion protein on the cell surface of the γ-HCH degrading Sphingobium japonicum UT26 using the truncated ice nucleation protein (INPNC) as an anchoring motif. The surface localization of INPNC-EC20-MPH was verified by cell fractionation, Western blot analysis, immunofluorescence microscopy, and proteinase accessibility experiment. Expression of EC20 on the cell surface not only improved Cd(2+) binding but also alleviated the cellular toxicity of Cd(2+) . As expected, the rates of CP and γ-HCH degradation were reduced in the presence of Cd(2+) for cells without EC20 expression. However, expression of EC20 (higher Cd(2+) accumulation) significantly restored the levels of CP and γ-HCH degradation. These results demonstrated that surface display of EC20 enhanced not only Cd(2+) accumulation but also protected the recombinant strain against the toxic effects of Cd(2+) on CP and γ-HCH degradation. PMID:26648050

  7. Bacterial assisted degradation of chlorpyrifos: The key role of environmental conditions, trace metals and organic solvents.

    Science.gov (United States)

    Khalid, Saira; Hashmi, Imran; Khan, Sher Jamal

    2016-03-01

    Wastewater from pesticide industries, agricultural or surface runoff containing pesticides and their residues has adverse environmental impacts. Present study demonstrates effect of petrochemicals and trace metals on chlorpyrifos (CP) biotransformation often released in wastewater of agrochemical industry. Biodegradation was investigated using bacterial strain Pseudomonas kilonensis SRK1 isolated from wastewater spiked with CP. Optimal environmental conditions for CP removal were CFU (306 × 10(6)), pH (8); initial CP concentration (150 mg/L) and glucose as additional carbon source. Among various organic solvents (petrochemicals) used in this study toluene has stimulatory effect on CP degradation process using SRK1, contrary to this benzene and phenol negatively inhibited degradation process. Application of metal ions (Cu (II), Fe (II) Zn (II) at low concentration (1 mg/L) took part in biochemical reaction and positively stimulated CP degradation process. Metal ions at high concentrations have inhibitory effect on degradation process. A first order growth model was shown to fit the data. It could be concluded that both type and concentration of metal ions and petrochemicals can affect CP degradation process. PMID:26692411

  8. Characterization of the interaction between cadmium and chlorpyrifos with integrative techniques in incurring synergistic hepatoxicity.

    Directory of Open Access Journals (Sweden)

    Liqun Chen

    Full Text Available Mixture toxicity is an important issue for the risk assessment of environmental pollutants, for which an extensive amount of data are necessary in evaluating their potential adverse health effects. However, it is very hard to decipher the interaction between compounds due to limited techniques. Contamination of heavy metals and organophosphoric insecticides under the environmental and biological settings poses substantial health risk to humans. Although previous studies demonstrated the co-occurrence of cadmium (Cd and chlorpyrifos (CPF in environmental medium and food chains, their interaction and potentially synergistic toxicity remain elusive thus far. Here we integrated the approaches of thin-layer chromatography and (1H NMR to study the interaction between Cd(2+ and CPF in inducing hepatoxicity. A novel interaction was identified between Cd(2+ and CPF, which might be the bonding between Cd(2+ and nitrogen atom in the pyridine ring of CPF, or the chelation formation between one Cd(2+ and two CPF molecules. The Cd-CPF complex was conferred with distinct biological fate and toxicological performances from its parental components. We further demonstrated that the joint hepatoxicity of Cd ion and CPF was chiefly due to the Cd-CPF complex-facilitated intracellular transport associated with oxidative stress.

  9. Acetylcholinesterase inhibition and micronucleus frequency in oysters (Crassostrea corteziensis exposed to chlorpyrifos

    Directory of Open Access Journals (Sweden)

    AB Benitez-Trinidad1

    2014-09-01

    Full Text Available Chlorpyrifos (CPF is an Organophosphorous pesticide (OP that has been widely used for both agricultural and domestic pest control. To date, there is little information regarding the effects of this pesticide on aquatic organisms, particularly oysters. The aim of this study was to evaluate Acetylcholinesterase (AChE activity and Micronucleus (MN frequency in the oyster Crassostrea corteziensis in laboratory exposure with CPF (20, 40, 60, 80, and 160 μg/L and in a field study. The results showed that AChE was reduced 60 - 82 % in oysters exposed to CPF, relative to the negative control. Similar AChE results were observed in oysters collected from the Boca de Camichín Estuary in Nayarit, Mexico; with respect to genetic damage, evaluated through MN, treatment with CPF did not induce the MN frequency, nor did the oyster from the field study exhibit an increase in this biomarker. These results suggest that C. corteziensis is a sensitive model for evaluating the acute toxicity of OP in laboratory studies as well in the field. In addition, it generates prospects on studying mechanisms through which the oyster could possess resistance to genotoxic agents, as well as its being a reliable model for evaluating the genotoxic effects of xenobiotics through the MN technique.

  10. A model of chlorpyrifos distribution and its biochemical effects on the liver and kidneys of rats.

    Science.gov (United States)

    Tanvir, E M; Afroz, R; Chowdhury, Maz; Gan, S H; Karim, N; Islam, M N; Khalil, M I

    2016-09-01

    This study investigated the main target sites of chlorpyrifos (CPF), its effect on biochemical indices, and the pathological changes observed in rat liver and kidney function using gas chromatography/mass spectrometry. Adult female Wistar rats (n = 12) were randomly assigned into two groups (one control and one test group; n = 6 each). The test group received CPF via oral gavage for 21 days at 5 mg/kg daily. The distribution of CPF was determined in various organs (liver, brain, heart, lung, kidney, ovary, adipose tissue, and skeletal muscle), urine and stool samples using GCMS. Approximately 6.18% of CPF was distributed in the body tissues, and the highest CPF concentration (3.80%) was found in adipose tissue. CPF also accumulated in the liver (0.29%), brain (0.22%), kidney (0.10%), and ovary (0.03%). Approximately 83.60% of CPF was detected in the urine. CPF exposure resulted in a significant increase in plasma transaminases, alkaline phosphatase, and total bilirubin levels, a significant reduction in total protein levels and an altered lipid profile. Oxidative stress due to CPF administration was also evidenced by a significant increase in liver malondialdehyde levels. The detrimental effects of CPF on kidney function consisted of a significant increase in plasma urea and creatinine levels. Liver and kidney histology confirmed the observed biochemical changes. In conclusion, CPF bioaccumulates over time and exerts toxic effects on animals. PMID:26519480

  11. The effect of chlorpyrifos on thermogenic capacity of bank voles selected for increased aerobic exercise metabolism.

    Science.gov (United States)

    Dheyongera, Geoffrey; Grzebyk, Katherine; Rudolf, Agata M; Sadowska, Edyta T; Koteja, Paweł

    2016-04-01

    Agro-chemicals potentially cause adverse effects in non-target organisms. The rate of animal energy metabolism can influence their susceptibility to pesticides by influencing food consumption, biotransformation and elimination rates of toxicants. We used experimental evolution to study the effects of inherent differences in energy metabolism rate and exposure to the organophosphate insecticide, chlorpyrifos (CPF) on thermogenic capacity in a wild rodent, the bank vole (Myodes = Clethrionomys glareolus). The voles were sampled from four replicate lines selected for high swim-induced aerobic metabolism (A) and four unselected control (C) lines. Thermogenic capacity, measured as the maximum cold-induced rate of oxygen consumption (VO2cold), was higher in the A - than C lines, and it decreased after continuous exposure to CPF via food or after a single dose administered via oral gavage, but only when measured shortly after exposure. VO2cold measured 24 h after repeated exposure was not affected. In addition, gavage with a single dose led to decreased food consumption and loss in body mass. Importantly, the adverse effects of CPF did not differ between the selected and control lines. Therefore, exposure to CPF has adverse effects on thermoregulatory performance and energy balance in this species. The effects are short-lived and their magnitude is not associated with the inherent level of energy metabolism. Even without severe symptoms of poisoning, fitness can be compromised under harsh environmental conditions, such as cold and wet weather. PMID:26878110

  12. Modulation of macrophage functionality induced in vitro by chlorpyrifos and carbendazim pesticides.

    Science.gov (United States)

    Helali, Imen; Ferchichi, Saiida; Maaouia, Amal; Aouni, Mahjoub; Harizi, Hedi

    2016-09-01

    The immune response is the first defense against pathogens; however, it is very sensitive and can be impacted on by agrochemicals such as carbamate and organophosphate pesticides widely present in the environment. To understand how pesticides can affect immune cell function in vitro, this study investigated the effects of chlorpyrifos (CPF) and carbendazim (CBZ), the most commonly used pesticides worldwide, on murine immune cell (i.e. macrophage) functions, including lysosomal enzyme activity and pro-inflammatory cytokines (IL-1β and TNFα) and nitric oxide (NO) production by isolated mouse peritoneal macrophages. This study showed for the first time that CPF and CBZ dose-relatedly reduced macrophage lysosomal enzyme activity and LPS-induced production of IL-1β, TNFα and NO. In general, the effects caused by CPF appeared more pronounced than those by CBZ. Collectively, these results demonstrated that CPF and CBZ exhibited marked immunomodulatory effects and could act as potent immunosuppressive factors in vitro. This inhibition of macrophage pro-inflammatory function may be an integral part of the underlying mode of action related to pesticide-induced immunosuppression. PMID:27429139

  13. Neurobehavioral and biochemical changes in Nauphoeta cinerea following dietary exposure to chlorpyrifos.

    Science.gov (United States)

    Adedara, Isaac A; Rosemberg, Denis B; de Souza, Diego; Farombi, Ebenezer O; Aschner, Michael; Souza, Diogo O; Rocha, Joao B T

    2016-06-01

    The present study aimed to increase our understanding about the mode of toxic action of organophosphate pesticides in insects by evaluating the biochemical and neurobehavioral characteristics in Nauphoeta cinerea exposed to chlorpyrifos (CPF)-contaminated diet. The insects were exposed for 35 consecutive days to CPF at 0.078, 0.15625, 0.3125 and 0.625μg/g feed. Locomotor behavior was assessed for a 10-min trial in a novel arena and subsequently, biochemical analyses were carried out using the cockroaches' heads. In comparison to control, CPF-exposed cockroaches showed significant decreases in the total distance traveled, body rotation, turn angle and meandering, along with significant increase in the number of falls, time and episodes of immobility. The marked decrease in the exploratory profiles of CPF-exposed cockroaches was confirmed by track plots, whereas occupancy plot analyses showed a progressive dispersion at 0.15625μg/g feed group. Moreover, the heads of CPF-exposed cockroaches showed marked decrease in acetylcholinesterase activity and antioxidant status with concomitant significant elevation in dichlorofluorescein oxidation and lipid peroxidation levels in CPF-treated cockroaches. Gas Chromatography-Mass Spectrometry analyses revealed bioaccumulation of CPF in cockroaches exposed to concentrations above 0.078μg/g feed. The findings from this investigation showed N. cinerea as a value model organism for the risk assessment of environmental organophosphate contamination in insects. PMID:27155480

  14. 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings

    OpenAIRE

    Baumann, Michael H.; Wang, Xiaoying; Rothman, Richard B.

    2006-01-01

    Rationale 3,4-Methylenedioxymethamphetamine (MDMA) is a widely abused illicit drug. In animals, high-dose administration of MDMA produces deficits in serotonin (5-HT) neurons (e.g., depletion of forebrain 5-HT) that have been interpreted as neurotoxicity. Whether such 5-HT deficits reflect neuronal damage is a matter of ongoing debate. Objective The present paper reviews four specific issues related to the hypothesis of MDMA neurotoxicity in rats: (1) the effects of MDMA on monoamine neurons,...

  15. Neurotoxicity of advanced glycation endproducts during focal stroke and neuroprotective effects of aminoguanidine.

    OpenAIRE

    Zimmerman, G A; Meistrell, M; Bloom, O.; Cockroft, K M; Bianchi, M.; Risucci, D; Broome, J.; Farmer, P; Cerami, A; Vlassara, H.

    1995-01-01

    Cerebral infarction (stroke) is a potentially disastrous complication of diabetes mellitus, principally because the extent of cortical loss is greater in diabetic patients than in nondiabetic patients. The etiology of this enhanced neurotoxicity is poorly understood. We hypothesized that advanced glycation endproducts (AGEs), which have previously been implicated in the development of other diabetic complications, might contribute to neurotoxicity and brain damage during ischemic stroke. Usin...

  16. The Molecular Mechanisms of Zinc Neurotoxicity and the Pathogenesis of Vascular Type Senile Dementia

    OpenAIRE

    Masahiro Kawahara; Dai Mizuno

    2013-01-01

    Zinc (Zn) is an essential trace element that is abundantly present in the brain. Despite its importance in normal brain functions, excess Zn is neurotoxic and causes neurodegeneration following transient global ischemia and plays a crucial role in the pathogenesis of vascular-type dementia (VD). We have investigated the molecular mechanisms of Zn-induced neurotoxicity using immortalized hypothalamic neurons (GT1–7 cells) and found that carnosine (β-alanyl histidine) and histidine (His) inhibi...

  17. Genotoxic, neurotoxic and neuroprotective activities of apomorphine and its oxidized derivative 8-oxo-apomorphine

    OpenAIRE

    Picada J.N.; Roesler R.; Henriques J.A.P.

    2005-01-01

    Apomorphine is a dopamine receptor agonist proposed to be a neuroprotective agent in the treatment of patients with Parkinson's disease. Both in vivo and in vitro studies have shown that apomorphine displays both antioxidant and pro-oxidant actions, and might have either neuroprotective or neurotoxic effects on the central nervous system. Some of the neurotoxic effects of apomorphine are mediated by its oxidation derivatives. In the present review, we discuss recent studies from our laborator...

  18. Evaluation of the neurotoxical effect of aluminum on the Wistar rat

    Directory of Open Access Journals (Sweden)

    Martać L.

    2010-01-01

    Full Text Available Our previous investigations on an animal model of neurotoxicity show that increased power in the delta range is connected with the neurotoxic effect of aluminum exposure. In this study we used several aluminum-treated animals as a reliable model for the evaluation of the neurotoxic effects of aluminum on neurons, and compared it with a control group. We conclude that spectral analysis and the ratio between the delta and theta ranges might be reliable for a qualitative description of the neurotoxic effect of aluminum, and that the t test might be used to evaluate the change in brain activity between the treated and control groups of animals. The animal model under anesthesia was used to describe the state of brain activity with neurotoxicity with suppressed functional connectivity in the brain structure. We also performed fractal analysis to quantitatively describe neurotoxic effect in different pathophysiological states of animals treated with different doses of aluminum. A decrease in the fractal dimension is an indicator of neurodegeneration in the state of stress. This animal model is suitable for evaluation of the neurodegenerative processes in Alzheimer's dementia and Parkinson's disease. .

  19. Developmental Heptachlor Exposure Increases Susceptibility of Dopamine Neurons to N-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP)in a Gender-Specific Manner

    OpenAIRE

    Richardson, Jason R.; Caudle, W Michael; Wang, Min Zheng; Dean, E. Danielle; Pennell, Kurt D.; Miller, Gary W.

    2008-01-01

    Parkinson’s disease (PD) is primarily thought of as a disease of aging. However recent evidence points to the potential for exposure to xenobiotics during development to increase risk of PD. Here, we report that developmental exposure to the organochlorine pesticide heptachlor alters the dopamine system and increases neurotoxicity in an animal model of PD. Exposure of pregnant mice to heptachlor led to increased levels of the dopamine transporter (DAT) and vesicular monoamine transporter 2 (V...

  20. Protective role of glutathione reductase in paraquat induced neurotoxicity.

    Science.gov (United States)

    Djukic, Mirjana M; Jovanovic, Marina D; Ninkovic, Milica; Stevanovic, Ivana; Ilic, Katarina; Curcic, Marijana; Vekic, Jelena

    2012-08-30

    Paraquat (PQ), a widely used herbicide is a well-known free radical producing agent. The mechanistic pathways of PQ neurotoxicity were examined by assessing oxidative/nitrosative stress markers. Focus was on the role of glutathione (GSH) cycle and to examine whether the pre-treatment with enzyme glutathione reductase (GR) could protect the vulnerable brain regions (VBRs) against harmful oxidative effect of PQ. The study was conducted on Wistar rats, randomly divided in five groups: intact-control group, (n = 8) and four experimental groups (n = 24). All tested compounds were administered intrastriatally (i.s.) in one single dose. The following parameters of oxidative status were measured in the striatum, hippocampus and cortex, at 30 min, 24 h and 7 days post treatment: superoxide anion radical (O₂·⁻), nitrate (NO₃⁻), malondialdehyde (MDA), superoxide dismutase (SOD), total GSH (tGSH) and its oxidized, disulfide form (GSSG) and glutathione peroxidase (GPx). Results obtained from the intact and the sham operated groups were not statistically different, confirming that invasive i.s. route of administration would not influence the reliability of results. Also, similar pattern of changes were observed between ipsi- and contra- lateral side of examined VBRs, indicating rapid spatial spreading of oxidative stress. Mortality of the animals (10%), within 24h, along with symptoms of Parkinsonism, after awakening from anesthesia for 2-3 h, were observed in the PQ group, only. Increased levels of O₂·⁻, NO₃⁻ and MDA, increased ratio of GSSG/GSH and considerably high activity of GPx were measured at 30 min after the treatment. Cytotoxic effect of PQ was documented by drastic drop of all measured parameters and extremely high peak of the ratio GSSG/GSH at 24th hrs after the PQ i.s. injection. In the GR+PQ group, markedly low activity of GPx and low content of NO₃⁻ (in striatum and cortex) were measured during whole experiment, while increase value was

  1. Time-resolved fluorescence sensing of pesticides chlorpyrifos, crotoxyphos and endosulfan by the luminescent Eu(III)-8-allyl-3-carboxycoumarin probe

    Science.gov (United States)

    Azab, Hassan A.; Khairy, Gasser M.; Kamel, Rasha M.

    2015-09-01

    This work describes the application of time resolved fluorescence in microtiter plates for investigating the interactions of europium-allyl-3-carboxycoumarin with pesticides chlorpyrifos, endosulfan and crotoxyphos. Stern-Volmer studies at different temperatures for chlorpyrifos and crotoxyphos shows dynamic and static quenching mechanisms respectively. Direct methods for the determination of the pesticides under investigation have been developed using the luminescence variations of the probe in solution. The detection limits are 6.53, 0.004, 3.72 μmol/L for chlorpyrifos, endosulfan, and crotoxyphos, respectively. The binding constants and thermodynamic parameters of the pesticides with probe were evaluated. A thermodynamic analysis showed that the reaction is spontaneous with negative ΔG. Effect of some relevant interferents on the detection of pesticides has been investigated. The new method was applied to the determination of the pesticides in different types of water samples (tap, mineral, and waste water).

  2. Determination of selected pesticides in water samples adjacent to agricultural fields and removal of organophosphorus insecticide chlorpyrifos using soil bacterial isolates

    Science.gov (United States)

    Hossain, M. S.; Chowdhury, M. Alamgir Zaman; Pramanik, Md. Kamruzzaman; Rahman, M. A.; Fakhruddin, A. N. M.; Alam, M. Khorshed

    2015-06-01

    The use of pesticide for crops leads to serious environmental pollution, therefore, it is essential to monitor and develop approaches to remove pesticide from contaminated environment. In this study, water samples were collected to monitor pesticide residues, and degradation of chlorpyrifos was also performed using soil bacteria. Identification of pesticide residues and determination of their levels were performed by high-performance liquid chromatography with photodiode array detector. Among 12 samples, 10 samples were found contaminated with pesticides. Chlorpyrifos was detected in four tested samples and concentrations ranged from 3.27 to 9.31 μg/l whereas fenitrothion ranging from (Below Detection Limit, pesticide residues in water, to protect the aquatic environment. Chlorpyrifos degrading bacterial isolates can be used to clean up environmental samples contaminated with the organophosphate pesticides.

  3. Selenium protects neonates against neurotoxicity from prenatal exposure to manganese.

    Directory of Open Access Journals (Sweden)

    Xin Yang

    Full Text Available Manganese (Mn exposure can affect brain development. Whether Selenium (Se can protect neonates against neurotoxicity from Mn exposure remains unclear. We investigated this issue in 933 mother-newborn pairs in Shanghai, China, from 2008 through 2009. Umbilical cord serum concentrations of Mn and Se were measured and Neonatal Behavioral Neurological Assessment (NBNA tests were conducted. The scores <37 were defined as the low NBNA. The median concentrations of cord serum Mn and Se were 4.0 µg/L and 63.1 µg/L, respectively. After adjusting for potential confounders, the interaction between Se and Mn was observed. Cord blood Mn levels had different effects on NBNA scores stratified by different cord blood Se levels. With Seneurotoxicity from prenatal exposure to Mn. Se supplementation should be considered during pregnancy, especially in areas with low natural Se.

  4. Fitness Effects of Chlorpyrifos in the Damselfly Enallagma cyathigerum Strongly Depend upon Temperature and Food Level and Can Bridge Metamorphosis.

    Directory of Open Access Journals (Sweden)

    Lizanne Janssens

    Full Text Available Interactions between pollutants and suboptimal environmental conditions can have severe consequences for the toxicity of pollutants, yet are still poorly understood. To identify patterns across environmental conditions and across fitness-related variables we exposed Enallagma cyathigerum damselfly larvae to the pesticide chlorpyrifos at two food levels or at two temperatures and quantified four fitness-related variables (larval survival, development time, mass at emergence and adult cold resistance. Food level and temperature did not affect survival in the absence of the pesticide, yet the pesticide reduced survival only at the high temperature. Animals reacted to the pesticide by accelerating their development but only at the high food level and at the low temperature; at the low food level, however, pesticide exposure resulted in a slower development. Chlorpyrifos exposure resulted in smaller adults except in animals reared at the high food level. Animals reared at the low food level and at the low temperature had a higher cold resistance which was not affected by the pesticide. In summary our study highlight that combined effects of exposure to chlorpyrifos and the two environmental conditions (i were mostly interactive and sometimes even reversed in comparison with the effect of the environmental condition in isolation, (ii strongly differed depending on the fitness-related variable under study, (iii were not always predictable based on the effect of the environmental condition in isolation, and (iv bridged metamorphosis depending on which environmental condition was combined with the pesticide thereby potentially carrying over from aquatic to terrestrial ecosystems. These findings are relevant when extrapolating results of laboratory tests done under ideal environmental conditions to natural communities.

  5. Neurotoxic effects of iron overload under high glucose concentration

    Institute of Scientific and Technical Information of China (English)

    Shi Zhao; Lin Zhang; Zihui Xu; Weiqun Chen

    2013-01-01

    Iron overload can lead to cytotoxicity, and it is a risk factor for diabetic peripheral neuropathy. However, the underlying mechanism remains unclear. We conjectured that iron overload-induced neurotoxicity might be associated with oxidative stress and the NF-E2-related factor 2 (Nrf2)/ARE signaling pathway. As an in vitro cellular model of diabetic peripheral neuropathy, PC12 cells ex-posed to high glucose concentration were used in this study. PC12 cells were cultured with ferric ammonium citrate at different concentrations to create iron overload. PC12 cells cultured in ferric ammonium citrate under high glucose concentration had significantly low cellviability, a high rate of apoptosis, and elevated reactive oxygen species and malondialdehyde levels. These changes were dependent on ferric ammonium citrate concentration. Nrf2 mRNA and protein expression in the fer-ric ammonium citrate groups were inhibited markedly in a dose-dependent manner. Al changes could be inhibited by addition of deferoxamine. These results indicate that iron overload aggravates oxidative stress injury in neural cells under high glucose concentration and that the Nrf2/ARE sig-naling pathway might play an important role in this process.

  6. Gender differences in the neurotoxicity of metals in children

    International Nuclear Information System (INIS)

    Gender-related differences in susceptibility to chemical exposure to neurotoxicants have not received sufficient attention. Although a significant number of epidemiological studies on the neurodevelopmental effects of metal exposure has been published in the last twenty years, not many of them have considered the possible gender-specific effects of such exposure. This review is focused on studies where the gender differences in pre- and/or postnatal exposure/s to five metals (mercury, lead, manganese, cadmium, and arsenic) and neurodevelopment were evaluated. We conducted a PubMed search in December 2012 and retrieved 20 studies that met the inclusion criteria. A large body of literature on potential neurodevelopment effects in children due to mercury exposure is available, but, a clear pattern regarding gender differences in neurotoxicity is not elucidated. There is also abundant available information on the gender-specific health effects of lead, and exposure to this metal seems to affect boys more than girls. Information regarding gender differences in susceptibility of manganese, cadmium, and arsenic is still too scarce to draw any definite conclusion. More research is highly warranted about this matter. Environmental epidemiological studies should be designed to quantify differential gender-based exposures and outcomes, and this may provide new insights into prevention strategies

  7. Pharmacological imaging as a tool to visualise dopaminergic neurotoxicity.

    Science.gov (United States)

    Schrantee, A; Reneman, L

    2014-09-01

    Dopamine abnormalities underlie a wide variety of psychopathologies, including ADHD and schizophrenia. A new imaging technique, pharmacological magnetic resonance imaging (phMRI), is a promising non-invasive technique to visualize the dopaminergic system in the brain. In this review we explore the clinical potential of phMRI in detecting dopamine dysfunction or neurotoxicity, assess its strengths and weaknesses and identify directions for future research. Preclinically, phMRI is able to detect severe dopaminergic abnormalities quite similar to conventional techniques such as PET and SPECT. phMRI benefits from its high spatial resolution and the possibility to visualize both local and downstream effects of dopaminergic neurotransmission. In addition, it allows for repeated measurements and assessments in vulnerable populations. The major challenge is the complex interpretation of phMRI results. Future studies in patients with dopaminergic abnormalities need to confirm the currently reviewed preclinical findings to validate the technique in a clinical setting. Eventually, based on the current review we expect that phMRI can be of use in a clinical setting involving vulnerable populations (such as children and adolescents) for diagnosis and monitoring treatment efficacy. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'. PMID:23851258

  8. Walnut consumption protects rats against cisplatin-induced neurotoxicity.

    Science.gov (United States)

    Shabani, Mohammad; Nazeri, Masoud; Parsania, Shahrnaz; Razavinasab, Moazamehosadat; Zangiabadi, Nasser; Esmaeilpour, Khadije; Abareghi, Fatemeh

    2012-10-01

    Walnut is extensively used in traditional medicine for treatment of various ailments. It is described as an anticancer, anti-inflammatory, blood purifier and antioxidant agent. In this study, we investigated whether or not Walnut could protect neurons against cisplatin-induced neurotoxicity in rats. Dietary walnut (6%) was assessed for its neuroprotective effects through the alteration in performance of hippocampus- and cerebellum-related behaviors following chronic cisplatin treatment (5 mg/kg/week for 5 consecutive weeks) in male rats. We also evaluated the effect of cisplatin and walnut administration on nociception. We showed that exposure of adolescent rats to cisplatin resulted in significant decrease in explorative behaviors and memory retention. Walnut consumption improved memory and motor abilities in cisplatin treated rats, while walnut alone did not show any significant changes in these abilities compared to saline. Cisplatin increased latency of response to nociception, and walnut reversed this effect of cisplatin. We conclude that walnuts in the diet following anticancer drugs such as cisplatin might have a protective effect against cisplatin-induced disruptions in motor and cognitive function. However, further studies are needed to elucidate the exact mechanisms of this protective effect of walnut and to explore underlying mechanisms. PMID:22935099

  9. Evaluation of large-sized brains for neurotoxic endpoints.

    Science.gov (United States)

    Garman, Robert H

    2003-01-01

    Sampling of large-sized brains (eg, dog, primate) for microscopic examination is frequently inadequate to detect localized neurotoxic injury. Furthermore, the examination of H&E-stained sections alone will often be insufficient for the detection of subtle neuropathogic alteration. It is imperative for any pathologist evaluating brain sections to have knowledge of microscopic neuroanatomy and to also have some understanding of basic neurochemistry. When a focus of degeneration is detected within the brain, the pathologist needs to ascertain not only the specific anatomic location of this focus but also the neuroanatomic regions that project to and receive output from the injured focus. Because of the complexity of brain circuitry and the fact that the brain contains many distinctive neuron populations, many more brain sections are required for adequate microscopic evaluation than for any other body organ. Deciding which and how many areas should be examined, microscopically, from a large size brain is often problematic. Although any sampling protocol will be influenced by what is known about the test chemical, it has been well established that certain regions of the brain (eg, hippocampus and other components of the limbic system, basal ganglia, Purkinje neurons) are more susceptible than others to a variety of physical, metabolic, and chemical insults. Knowledge of these regional sensitivities will assist in guiding the pathologist in the development of an adequate sampling protocol. PMID:12597429

  10. Catalytic Metalloporphyrin Protects Against Paraquat Neurotoxicity in vivo

    Institute of Scientific and Technical Information of China (English)

    PING CHEN; ZHEN CHEN; ANG LI; XIAO-CHU LOU; XIAO-KANG WU; CHUN-JUN ZHAO; SHI-LONG WANG; LI-PING LIANG

    2008-01-01

    Objective To examine the neuroprotective effects of a novel manganese porphyrin, manganese (Ⅲ) meso-tetrakis(N,N'-diethylimidazolium-2-yl) porphyrin (MnTDM), in the mouse model of Parkinson's disease (PD) induced by paraquat (PQ). Methods Male C57BL/6 mice were subcutaneously injected with either saline or PQ at 2-day intervals for a total of 10 doses, MnTDM was subcutaneously injected with the PQ 2 h before treatment. Performance on the pole and swim test were measured 7 days after the last injection and animals were sacrificed one day later. Levels of dopamine (DA) and its metabolites in the striatum were measured by high-performance liquid chromatography with an electrochemical detector (HPLC-ECD).Thiobarbituric acid (TBA) method was used to assay the lipid peroxidation product, malondialdehyde (MDA), and the number of tyrosine hydroxylase (TH) positive neurons was estimated using immunohistochemistry. Results Pretreatment with MnTDM significantly attenuated PQ-impaired behavioral performance, depleted dopamine content in striata, increased MDA, and dopaminergic neuron loss in the substantia nigra. Conclusions Oxidative stress plays an important role in PQ-induced neurotoxicity which can be potentially prevented by manganese porphyrin. These findings also propose a possible therapeutical strategy for neurodegenerative disorders associated with oxidative stress such as PD.

  11. Health assessment of gasoline and fuel oxygenate vapors: neurotoxicity evaluation.

    Science.gov (United States)

    O'Callaghan, James P; Daughtrey, Wayne C; Clark, Charles R; Schreiner, Ceinwen A; White, Russell

    2014-11-01

    Sprague-Dawley rats were exposed via inhalation to vapor condensates of either gasoline or gasoline combined with various fuel oxygenates to assess potential neurotoxicity of evaporative emissions. Test articles included vapor condensates prepared from "baseline gasoline" (BGVC), or gasoline combined with methyl tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA). Target concentrations were 0, 2000, 10,000 or 20,000mg/mg(3) and exposures were for 6h/day, 5days/week for 13weeks. The functional observation battery (FOB) with the addition of motor activity (MA) testing, hematoxylin and eosin staining of brain tissue sections, and brain regional analysis of glial fibrillary acidic protein (GFAP) were used to assess behavioral changes, traditional neuropathology and astrogliosis, respectively. FOB and MA data for all agents, except G/TBA, were negative. G/TBA behavioral effects resolved during recovery. Neuropathology was negative for all groups. Analyses of GFAP revealed increases in multiplebrain regions largely limited to males of the G/EtOH group, findings indicative of minor gliosis, most significantly in the cerebellum. Small changes (both increases and decreases) in GFAP were observed for other test agents but effects were not consistent across sex, brain region or exposure concentration. PMID:24879970

  12. Neurotoxicity of a methylated analog of MPTP in mice

    International Nuclear Information System (INIS)

    Under conditions in which the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was relatively ineffective, (2 injections per day at 6-hr intervals on 2 successive days; total dose of 0.45 mmoles/kg) a methylated analog of MPTP, namely 2'CH3-MPTP, produced a marked depletion in the neostriatal content of dopamine (DA) and its metabolites, a corresponding reduction of 3H-DA uptake into neostriatal synaptosomes, and an extensive loss of neurons in the pars compacta of the substantia nigra. 2'CH3-MPTP is oxidized in vitro by monoamine oxidase-B in brain mitochondrial preparations, although at a much faster rate than is MPTP. And like the MPTP metabolite (MPP+), 1-methyl-4-(2'methylphenyl)pyridinium (2'CH3-MPP+) is an excellent substrate for the DA transport system (as evidenced by its ability to release previously accumulated 3H-DA from synaptosomes, and the ability of the dopamine uptake inhibitor, mazindol, to prevent this release). In vivo, the pretreatment of mice with DA uptake inhibitors or monoamine oxidase-B inhibitors attenuated the above-mentioned biochemical changes induced by 2'CH3-MPTP. It appears as if 2'CH3-MPTP produces neurotoxicity in a manner similar to MPTP. That 2'CH3-MPTP is oxidized at a faster rate than MPTP likely contributes to the fact that it is more potent than MPTP, although most certainly, other unknown considerations also are relevant

  13. Developmental manganese exposure in combination with developmental stress and iron deficiency: Effects on behavior and monoamines.

    Science.gov (United States)

    Amos-Kroohs, Robyn M; Davenport, Laurie L; Gutierrez, Arnold; Hufgard, Jillian R; Vorhees, Charles V; Williams, Michael T

    2016-01-01

    Manganese (Mn) is an essential element but neurotoxic at higher exposures, however, Mn exposure seldom occurs in isolation. It often co-occurs in populations with inadequate dietary iron (Fe) and limited resources that result in stress. Subclinical FeD affects up to 15% of U.S. children and exacerbates Mn toxicity by increasing Mn bioavailability. Therefore, we investigated Mn overexposure (MnOE) in rats in combination with Fe deficiency (FeD) and developmental stress, for which we used barren cage rearing. For barren cage rearing (BAR), rats were housed in cages with a wire grid floor or standard bedding material (STD) from embryonic day (E)7 through postnatal day (P)28. For FeD, dams were fed a 90% Fe-deficient NIH-07 diet from E15 through P28. Within each litter, different offspring were treated with 100mg/kg Mn (MnOE) or vehicle (VEH) by gavage every other day from P4-28. Behavior was assessed at two ages and consisted of: open-field, anxiety tests, acoustic startle response (ASR) with prepulse inhibition (PPI), sociability, sucrose preference, tapered beam crossing, and the Porsolt's forced swim test. MnOE had main effects of decreasing activity, ASR, social preference, and social novelty. BAR and FeD transiently modified MnOE effects. BAR groups weighed less and showed decreased anxiety in the elevated zero maze, had increased ASR and decreased PPI, and exhibited reduced sucrose preference compared with the STD groups. FeD animals also weighed less and had increased slips on the tapered beam. Most of the monoamine effects were dopaminergic and occurred in the MnOE groups. The results showed that Mn is a pervasive developmental neurotoxin, the effects of which are modulated by FeD and/or BAR cage rearing. PMID:27302314

  14. Evaluation of chronic chlorpyrifos-induced reproductive toxicity in male Wistar rat: protective effects of vitamin C

    OpenAIRE

    Mohammed M. Sulaiman; Mohammed Y. Fatihu; Joseph O. Ayo; Suleiman F. Ambali; Muftau Shittu; Lukuman S. Yaqub

    2013-01-01

    The aim of the present study was to evaluate the effect of vitamin C on reproductive toxicity, induced by chronic chlorpyrifos (CPF) exposure in male Wistar rats. Twenty adult male Wistar rats were divided into 4 groups of 5 animals in each group. Group I received soya oil (2 ml/kg); group II was given vitamin C only (100 mg/kg); group III was administered CPF only (10.6 mg/kg; ~1/8th LD50), while group IV was pretreated with vitamin C and then exposed to CPF, 30 min later. The regimens were ...

  15. Chlorpyrifos for control of the short-nosed cattle louse, Haematopinus eurysternus (Nitzsch) (Anoplura, Haematopinidae) during winter.

    OpenAIRE

    Khan, M. A.; Schaalje, G. B.

    1985-01-01

    Two groups (A and C) of range cows were treated in February with chlorpyrifos (16 mL Dursban 44/cow) for the control of heavy infestations of the short-nosed cattle louse. Group A was treated in 1977 and group C in 1979 and each treated group was compared with a separate untreated group. Some of the treated cows were identified as carriers of louse infestation (subgroups A1 and C1), while others were noncarriers (subgroups A2 and C2). The maximum level of reduction in louse populations was 99...

  16. Comparative effects of parathion and chlorpyrifos on extracellular endocannabinoid levels in rat hippocampus: Influence on cholinergic toxicity

    International Nuclear Information System (INIS)

    Parathion (PS) and chlorpyrifos (CPF) are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE). Endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) can modulate neurotransmission by inhibiting neurotransmitter release. We proposed that differential inhibition of eCB-degrading enzymes (fatty acid amide hydrolase, FAAH, and monoacylglycerol lipase, MAGL) by PS and CPF leads to differences in extracellular eCB levels and toxicity. Microdialysis cannulae were implanted into hippocampus of adult male rats followed by treatment with vehicle (peanut oil, 2 ml/kg, sc), PS (27 mg/kg) or CPF (280 mg/kg) 6–7 days later. Signs of toxicity, AChE, FAAH and MAGL inhibition, and extracellular levels of AEA and 2AG were measured 2 and 4 days later. Signs were noted in PS-treated rats but not in controls or CPF-treated rats. Cholinesterase inhibition was extensive in hippocampus with PS (89–90%) and CPF (78–83%) exposure. FAAH activity was also markedly reduced (88–91%) by both OPs at both time-points. MAGL was inhibited by both OPs but to a lesser degree (35–50%). Increases in extracellular AEA levels were noted after either PS (about 2-fold) or CPF (about 3-fold) while lesser treatment-related 2-AG changes were noted. The cannabinoid CB1 receptor antagonist/inverse agonist AM251 (3 mg/kg, ip) had no influence on functional signs after CPF but markedly decreased toxicity in PS-treated rats. The results suggest that extracellular eCBs levels can be markedly elevated by both PS and CPF. CB1-mediated signaling appears to play a role in the acute toxicity of PS but the role of eCBs in CPF toxicity remains unclear. - Highlights: • Chlorpyrifos and parathion both extensively inhibited hippocampal cholinesterase. • Functional signs were only noted with parathion. • Chlorpyrifos and parathion increased hippocampal extracellular anandamide levels. • 2-Arachidonoylglycerol levels were

  17. Comparative effects of parathion and chlorpyrifos on extracellular endocannabinoid levels in rat hippocampus: Influence on cholinergic toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jing [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK (United States); Parsons, Loren [Committee on Neurobiology of Affective Disorders, The Scripps Research Institute, La Jolla, CA (United States); Pope, Carey, E-mail: carey.pope@okstate.edu [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK (United States)

    2013-11-01

    Parathion (PS) and chlorpyrifos (CPF) are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE). Endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) can modulate neurotransmission by inhibiting neurotransmitter release. We proposed that differential inhibition of eCB-degrading enzymes (fatty acid amide hydrolase, FAAH, and monoacylglycerol lipase, MAGL) by PS and CPF leads to differences in extracellular eCB levels and toxicity. Microdialysis cannulae were implanted into hippocampus of adult male rats followed by treatment with vehicle (peanut oil, 2 ml/kg, sc), PS (27 mg/kg) or CPF (280 mg/kg) 6–7 days later. Signs of toxicity, AChE, FAAH and MAGL inhibition, and extracellular levels of AEA and 2AG were measured 2 and 4 days later. Signs were noted in PS-treated rats but not in controls or CPF-treated rats. Cholinesterase inhibition was extensive in hippocampus with PS (89–90%) and CPF (78–83%) exposure. FAAH activity was also markedly reduced (88–91%) by both OPs at both time-points. MAGL was inhibited by both OPs but to a lesser degree (35–50%). Increases in extracellular AEA levels were noted after either PS (about 2-fold) or CPF (about 3-fold) while lesser treatment-related 2-AG changes were noted. The cannabinoid CB1 receptor antagonist/inverse agonist AM251 (3 mg/kg, ip) had no influence on functional signs after CPF but markedly decreased toxicity in PS-treated rats. The results suggest that extracellular eCBs levels can be markedly elevated by both PS and CPF. CB1-mediated signaling appears to play a role in the acute toxicity of PS but the role of eCBs in CPF toxicity remains unclear. - Highlights: • Chlorpyrifos and parathion both extensively inhibited hippocampal cholinesterase. • Functional signs were only noted with parathion. • Chlorpyrifos and parathion increased hippocampal extracellular anandamide levels. • 2-Arachidonoylglycerol levels were

  18. Diploid and triploid African catfish (Clarias gariepinus) differ in biomarker responses to the pesticide chlorpyrifos.

    Science.gov (United States)

    Karami, Ali; Goh, Yong-Meng; Jahromi, Mohammad Faseleh; Lazorchak, James M; Abdullah, Maha; Courtenay, Simon C

    2016-07-01

    The impacts of environmental stressors on polyploid organisms are largely unknown. This study investigated changes in morphometric, molecular, and biochemical parameters in full-sibling diploid and triploid African catfish (Clarias gariepinus) in response to chlorpyrifos (CPF) exposures. Juvenile fish were exposed to three concentrations of CPF (mean measured μg/L (SD): 9.71 (2.27), 15.7 (3.69), 31.21 (5.04)) under a static-renewal condition for 21days. Diploid control groups had higher hepatosomatic index (HSI), plasma testosterone (T), and brain GnRH and cyp19a2 expression levels than triploids. In CPF-exposed groups, changes in HSI, total weight and length were different between the diploid and triploid fish. In contrast, condition factor did not alter in any of the treatments, while visceral-somatic index (VSI) changed only in diploids. In diploid fish, exposure to CPF did not change brain 11β-hsd2, ftz-f1, foxl2, GnRH or cyp19a2 mRNA levels, while reduced tph2 transcript levels compared to the control group. In contrast, 11β-hsd2 and foxl2 expression levels were changed in triploids following CPF exposures. In diploids, plasma T levels showed a linear dose-response reduction across CPF treatments correlating with liver weight and plasma total cholesterol concentrations. In contrast, no changes in plasma cholesterol and T concentrations were observed in triploids. Plasma cortisol and 17-β estradiol (E2) showed no response to CPF exposure in either ploidy. Results of this first comparison of biomarker responses to pesticide exposure in diploid and polyploid animals showed substantial differences between diploid and triploid C. gariepinus. PMID:26994807

  19. Biotreatment of chlorpyrifos in a bench scale bioreactor using Psychrobacter alimentarius T14.

    Science.gov (United States)

    Khalid, Saira; Hashmi, Imran

    2016-01-01

    Bacteria tolerant to high pesticide concentration could be used for designing an efficient treatment technology. Bacterial strains T14 was isolated from pesticide-contaminated soil in mineral salt medium (MSM) and identified as Psychrobacter alimentarius T14 using 16S rRNA gene sequence analysis. Bench scale bioreactor was evaluated for biotreatment of high Chlorpyrifos (CP) concentration using P. alimentarius T14. Effect of various parameters on bioreactor performance was examined and optimum removal was observed at optical density (OD600 nm): 0.8; pH: 7.2; CP concentration: 300 mg L(-1) and hydraulic retention time: 48 h. At optimum conditions, 70.3/79% of CP/chemical oxygen demand (COD) removal was achieved in batch bioreactors. In addition, P. alimentarius T14 achieved 95/91, 62.3/75, 69.8/64% CP/COD removal efficiency with addition of CS (co-substrates), CS1 (yeast extract + synthetic wastewater), CS2 (glucose + synthetic wastewater) and CS3 (yeast extract), respectively. Addition of CS1 to bioreactor could accelerate CP removal rate up to many cycles with considerable efficiency. However, accumulation of 3, 5, 6-trichloro-2-pyridinol affects reactor performance in cyclic mode. First-order rate constant k1 0.062 h(-1) and t1/2 11.1 h demonstrates fast degradation. Change in concentration of total chlorine and nitrogen could be the result of complete mineralization. Photodegradation of CP in commercial product was more than its pure form. Commercial formulation accelerated photodegradation process; however no effect on biodegradation process was observed. After bio-photodegradation, negligible toxicity for seeds of Triticum aestivum was observed. Study suggests an efficient treatment of wastewater containing CP and its metabolites in batch bioreactors could be achieved using P. alimentarius. PMID:26144866

  20. In Vitro Rat Hepatic and Intestinal Metabolism of the Organophosphate Pesticides Chlorpyrifos and Diazinon

    Energy Technology Data Exchange (ETDEWEB)

    Poet, Torka S.(BATTELLE (PACIFIC NW LAB)); Wu, Hong (BATTELLE (PACIFIC NW LAB)); Kousba, Ahmed A.(BATTELLE (PACIFIC NW LAB)); Timchalk, Charles (Pacific Northwest National Laboratory)

    2003-04-01

    Chlorpyrifos (CPF) and diazinon (DZN) are thionophosphorus organophosphate, insecticides; their toxicity is mediated through CYP450 metabolism to CPF-oxon and DZN-oxon, respectively. Conversely, CYP450s also detoxify these OPs to trichloropyridinol (TCP) and 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMHP), respectively. In addition, A-esterase metabolism of CPF- and DZN-oxon also form TCP and IMHP. This study evaluated the role intestinal and hepatic metabolism may play in the first-pass elimination of CPF and DZN. Similar CYP450- and A-esterase-mediated metabolic profiles were demonstrated in microsomes from liver or isolated intestinal enterocytes. In enterocyte microsomes, the CYP450 metabolic efficiency (Vmax/Km) for metabolism to the oxon metabolites was~5-fold greater for CPF than DZN. Compared on a per nmol P450 basis, the Vmax for CPF in enterocytes was~2-3 times higher than in liver microsomes for the production of CPF-oxon and TCP. The affinity (Km) for the metabolism of CPF to CPF-oxon was comparable in liver and enterocyte microsomes, however the enterocyte Km for TCP production was higher (lower affinity). The smaller volume of intestine, lower amount of CYP450, and higher Km for TCP in the enterocyte microsomes, resulted in a lower catalytic efficiency (2 and 62 times) than in liver for oxon and TCP. A-esterase-mediated metabolism of CPF- and DZN-oxon was also demonstrated in liver and enterocyte microsomes. Although A-esterase affinity for the substrates were comparable in hepatic and enterocyte microsomes, the Vmax were 48 - to 275-fold, in the liver. These results suggest that intestinal metabolism may impact first-pass metabolism of CPF and DZN, especially following low-dose oral exposures.

  1. Fluorescent Chemosensors for Selective and Sensitive Detection of Phosmet/Chlorpyrifos with Octahedral Ni(2+) Complexes.

    Science.gov (United States)

    Raj, Pushap; Singh, Amanpreet; Kaur, Kamalpreet; Aree, Thammarat; Singh, Ajnesh; Singh, Narinder

    2016-05-16

    The hexadentate ligands H2L1-L3 with mixed S, N, O donor sites and possessing substituents having either "no" or electron-releasing/withdrawing nature at terminal ends are synthesized. The ligands H2L1-L3 were tested for binding with library of metal ions, wherein maximum efficiency was observed with Ni(2+), and it motivated us to prepare the Ni(2+) complexes. The ligand H2L1 underwent deprotonation and formed binuclear complex when interacted with Ni(2+) as evident from its crystal structure. The H2L2 and H2L3 having electron-withdrawing/electron releasing groups, respectively, were also deprotonated; however, they afforded mononuclear complexes with Ni(2+) ion. This signifies the importance of steric parameters instead of electronic factors in these particular cases. Impressed by differential behavior of complexes of H2L1 and H2L2/H2L3 with Ni(2+) and their photophysical and electrochemical properties, all the metal complexes were studied for their chemosensing ability. Nowadays with increased use of organophosphate, there is alarming increase of these agents in the environment, and thus we require efficient technique to estimate the level of these agents with high sensitivity and selectivity in aqueous medium. The Ni(2+) complexes with hydrophobic nature were suspended into aqueous medium for testing them as sensor for organophosphate. The (L1)2.(Ni(2+))2 could sense phosmet with detection limit of 44 nM, whereas L2.Ni(2+) and L3.Ni(2+) exhibited the detection limits of 62 and 71 nM, respectively, for chlorpyrifos. PMID:27115348

  2. Co-treatment of chlorpyrifos and lead induce serum lipid disorders in rats: Alleviation by taurine.

    Science.gov (United States)

    Akande, Motunrayo G; Aliu, Yusuf O; Ambali, Suleiman F; Ayo, Joseph O

    2016-07-01

    The aim of this study was to investigate the effects of taurine (TA) on serum lipid profiles following chronic coadministration of chlorpyrifos (CP) and lead acetate (Pb) in male Wistar rats. Fifty rats randomly distributed into five groups served as subjects. Distilled water (DW) was given to DW group, while soya oil (SO; 1 mL kg(-1)) was given to SO group. The TA group was treated with TA (50 mg kg(-1)). The CP + Pb group was administered sequentially with CP (4.25 mg kg(-1); 1/20th median lethal dose (LD50)) and Pb at 233.25 mg kg(-1) (1/20th LD50), while the TA + CP + Pb group received TA (50 mg kg(-1)), CP (4.25 mg kg(-1)), and Pb (233.25 mg kg(-1)) sequentially. The treatments were administered once daily by oral gavage for 16 weeks. The rats were euthanised, and the blood samples were collected at the termination of the study. Sera obtained from the blood samples were analyzed for total cholesterol, high-density lipoprotein cholesterol, triglycerides, and malondialdehyde, and also the activities of serum antioxidant enzymes including superoxide dismutase, catalase and glutathione peroxidase were analyzed. The low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and atherogenic index were calculated. The results showed that CP and Pb induced alterations in the serum lipid profiles and evoked oxidative stress. TA alleviated the disruptions in the serum lipid profiles of the rats partially by mitigating oxidative stress. It was concluded that TA may be used for prophylaxis against serum lipid disorders in animals that were constantly co-exposed to CP and Pb in the environment. PMID:25537622

  3. Arguments from Developmental Order.

    Science.gov (United States)

    Stöckle-Schobel, Richard

    2016-01-01

    In this article, I investigate a special type of argument regarding the role of development in theorizing about psychological processes and cognitive capacities. Among the issues that developmental psychologists study, discovering the ontogenetic trajectory of mechanisms or capacities underpinning our cognitive functions ranks highly. The order in which functions are developed or capacities are acquired is a matter of debate between competing psychological theories, and also philosophical conceptions of the mind - getting the role and the significance of the different steps in this order right could be seen as an important virtue of such theories. Thus, a special kind of strategy in arguments between competing philosophical or psychological theories is using developmental order in arguing for or against a given psychological claim. In this article, I will introduce an analysis of arguments from developmental order, which come in two general types: arguments emphasizing the importance of the early cognitive processes and arguments emphasizing the late cognitive processes. I will discuss their role in one of the central tools for evaluating scientific theories, namely in making inferences to the best explanation. I will argue that appeal to developmental order is, by itself, an insufficient criterion for theory choice and has to be part of an argument based on other core explanatory or empirical virtues. I will end by proposing a more concerted study of philosophical issues concerning (cognitive) development, and I will present some topics that also pertain to a full-fledged 'philosophy of development.' PMID:27242648

  4. Arguments from Developmental Order

    Science.gov (United States)

    Stöckle-Schobel, Richard

    2016-01-01

    In this article1, I investigate a special type of argument regarding the role of development in theorizing about psychological processes and cognitive capacities. Among the issues that developmental psychologists study, discovering the ontogenetic trajectory of mechanisms or capacities underpinning our cognitive functions ranks highly. The order in which functions are developed or capacities are acquired is a matter of debate between competing psychological theories, and also philosophical conceptions of the mind – getting the role and the significance of the different steps in this order right could be seen as an important virtue of such theories. Thus, a special kind of strategy in arguments between competing philosophical or psychological theories is using developmental order in arguing for or against a given psychological claim. In this article, I will introduce an analysis of arguments from developmental order, which come in two general types: arguments emphasizing the importance of the early cognitive processes and arguments emphasizing the late cognitive processes. I will discuss their role in one of the central tools for evaluating scientific theories, namely in making inferences to the best explanation. I will argue that appeal to developmental order is, by itself, an insufficient criterion for theory choice and has to be part of an argument based on other core explanatory or empirical virtues. I will end by proposing a more concerted study of philosophical issues concerning (cognitive) development, and I will present some topics that also pertain to a full-fledged ‘philosophy of development.’ PMID:27242648

  5. The Developmental Work

    DEFF Research Database (Denmark)

    Møller, Niels; Hvid, Helge

    2001-01-01

    AbstractIn the nineties, the concept of the developmental work (DW) has become a significant point of orientation for the actors on Danish labour market. The DW has moved the focus of the labour market from wages and working time towards work and production. For employees, the DW promises...

  6. Developmental paediatric anaesthetic pharmacology

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing

    2015-01-01

    Safe and effective drug therapy in neonates, infants and children require detailed knowledge about the ontogeny of drug disposition and action as well how these interact with genetics and co-morbidity of children. Recent advances in developmental pharmacology in children follow the increased...

  7. Mammary Glands: Developmental Changes

    Science.gov (United States)

    The mammary gland progresses from the accumulation of a few cells in the embryonic ectoderm to a highly arborescent tubulo-alveolar gland capable of secreting a highly nutritious product for consumption. Throughout this progression, various changes occur during each developmental stage: prenatal, pr...

  8. Qualitative methodology in developmental psychology

    DEFF Research Database (Denmark)

    Demuth, Carolin; Mey, Günter

    2015-01-01

    Qualitative methodology presently is gaining increasing recognition in developmental psychology. Although the founders of developmental psychology to a large extent already used qualitative procedures, the field was long dominated by a (post) positivistic quantitative paradigm. The increasing...

  9. L-DOPA neurotoxicity is mediated by up-regulation of DMT1-IRE expression.

    Directory of Open Access Journals (Sweden)

    Fang Du

    Full Text Available BACKGROUND: The mechanisms underlying neurotoxicity caused by L-DOPA are not yet completely known. Based on recent findings, we speculated that the increased expression of divalent metal transporter 1 without iron-response element (DMT1-IRE induced by L-DOPA might play a critical role in the development of L-DOPA neurotoxicity. To test this hypothesis, we investigated the effects of astrocyte-conditioned medium (ACM and siRNA DMT-IRE on L-DOPA neurotoxicity in cortical neurons. METHODS AND FINDINGS: We demonstrated that neurons treated with L-DOPA have a significant dose-dependent decrease in neuronal viability (MTT Assay and increase in iron content (using a graphite furnace atomic absorption spectrophotometer, DMT1-IRE expression (Western blot analysis and ferrous iron (55Fe(II uptake. Neurons incubated in ACM with or without L-DOPA had no significant differences in their morphology, Hoechst-33342 staining or viability. Also, ACM significantly inhibited the effects of L-DOPA on neuronal iron content as well as DMT1-IRE expression. In addition, we demonstrated that infection of neurons with siRNA DMT-IRE led to a significant decrease in DMT1-IRE expression as well as L-DOPA neurotoxicity. CONCLUSION: The up-regulation of DMT1-IRE and the increase in DMT1-IRE-mediated iron influx play a key role in L-DOPA neurotoxicity in cortical neurons.

  10. Environmental enrichment does not reduce the rewarding and neurotoxic effects of methamphetamine.

    Science.gov (United States)

    Thiriet, Nathalie; Gennequin, Benjamin; Lardeux, Virginie; Chauvet, Claudia; Decressac, Mickael; Janet, Thierry; Jaber, Mohamed; Solinas, Marcello

    2011-01-01

    Abuse of amphetamine analogues, such as methamphetamine (METH), represents an important health problem because of their powerful addictive and neurotoxic effects. Abuse of METH induces dopamine neuron terminals loss and cell death in the striatum similar to what is found in other neurodegenerative processes. Exposing mice and rats to enriched environments (EE) has been shown to produce significant protective effects against drug-induced reward as well as against neurodegenerative processes. Here, we investigated whether exposure to EE could reduce the METH-induced reward and neurotoxicity. For this, we reared mice for 2 months during early stages of life in standard environments or EE and then, at adulthood, we tested the ability of METH to induce conditioned place preference and neurotoxicity. We found that, contrary to what we found with other drugs such as cocaine and heroin, EE was unable to reduce the rewarding effects of METH. In addition, contrary to what we found with other toxins such as MPTP, EE did not diminish the striatal neurotoxicity induced by METH (4 x 10 mg/kg) as measured by dopamine content, tyrosine hydroxylase protein levels and apoptosis. Our results demonstrate that the rewarding and neurotoxic effects of METH are not reduced by EE and highlight the great risks associated with the increased popularity of this drug amongst the young population. PMID:20143198

  11. The in vitro protective effect of salicylic acid against paclitaxel and cisplatin-induced neurotoxicity.

    Science.gov (United States)

    Cetin, Damla; Hacımuftuoglu, Ahmet; Tatar, Abdulgani; Turkez, Hasan; Togar, Basak

    2016-08-01

    Paclitaxel (PAC) and cisplatin (CIS) are two established chemotherapeutic drugs used in combination for the treatment of various solid tumors. However, the usage of PAC and CIS are limited because of the incidence of their moderate or severe neurotoxic side effects. In this study, we aimed to assess the protective role of salicylic acid (SA) against neurotoxicity caused by PAC and CIS. For this purpose, newborn Sprague Dawley rats were decapitated in sterile atmosphere and primary cortex neuron cultures were established. On the 10th day SA was added into culture plates. PAC and CIS were added on the 12th day. The cytotoxicity was determined by using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Oxidative alterations were assessed using total antioxidant capacity and total oxidative stress assays in rat primary neuron cell cultures. It was shown that both concentrations of PAC and CIS treatments caused neurotoxicity. Although SA decreased the neurotoxicity by CIS and PAC, it was more effective against the toxicity caused by CIS rather than the toxicity caused by PAC. In conclusion it was clearly revealed that SA decreased the neurotoxic effect of CIS and PAC in vitro. PMID:26199062

  12. Ascorbic acid glucoside reduces neurotoxicity and glutathione depletion in mouse brain induced by nitrotriazole radiosensitazer

    Directory of Open Access Journals (Sweden)

    Nadezda V Cherdyntseva

    2013-01-01

    Full Text Available Aim: To investigate the potential of the anti-oxidant ascorbic acid glucoside (AA-2G to modulate neurotoxicity induced by high doses of nitrotriazole radiosensitizer. Materials and Methods: Male and female C56Bl/6xCBA hybrid mice aged 8-14 weeks (weight 18-24 g were used. Nitrotriazole drug radiosensitizer sanazole at a high dose of 2, 1 g/kg was per os administered to induce neurotoxicity at mice. Ascorbic acid glucoside was given 30 min before the sanazole administration. Serum ascorbic acid, brain glutathione level, as well as behavioral performance using open field apparatus were measured. Results: Administration of high (non-therapeutic doses of the nitrotriazole drug sanazole results in neurotoxicity in mice as evidenced from behavioral performance, emotional activity and depletion of the cellular antioxidant, glutathione, in the brain. The serum levels of ascorbic acid was also found reduced in high dose sanazole treated animals. Per os administration of ascorbic acid glucoside significantly reduced the neurotoxicity. This effect was associated with the prevention of glutathione depletion in mouse brain and restoring the ascorbic acid level in serum. Conclusion: Administration of ascorbic acid glucoside, but not ascorbic acid, before sanazole administration protected from sanazole-induced neurotoxicity by preventing the decrease in the brain reduced glutathione level and providing high level of ascorbic acid in plasma.

  13. Oxidative stress related to chlorpyrifos exposure in rainbow trout: Acute and medium term effects on genetic biomarkers.

    Science.gov (United States)

    Benedetto, A; Brizio, P; Squadrone, S; Scanzio, T; Righetti, M; Gasco, L; Prearo, M; Abete, M C

    2016-05-01

    Organophosphates (OPs) are derivatives of phosphoric acid widely used in agriculture as pesticides. Chlorpyrifos (CPF) is an OP that is extremely toxic to aquatic organisms. Rainbow trout (Oncorhynchus mykiss) is considered as a sentinel model species for ecotoxicology assessment in freshwater ecosystems. An exposure study was carried out on rainbow trout to investigate genetic responses to CPF-induced oxidative stress by Real-Time PCR, and to determine the accumulation dynamics of CPF and toxic metabolite chlorpyrifos-oxon (CPF-ox) in edible parts, by HPLC-MS/MS. Among the genes considered to be related to oxidative stress, a significant increase in HSP70 mRNA levels was observed in liver samples up to 14days after CPF exposure (0.05mg/L). CPF concentrations in muscle samples reach mean values of 285.25ng/g within 96hours of exposure, while CPF-ox concentrations were always under the limit of quantification (LOQ) of the applied method. Our findings lead us to consider HSP70 as a suitable genetic marker in rainbow trout for acute and medium-term monitoring of CPF exposure, complementary to analytical determinations. PMID:27017883

  14. Inhibition, recovery and oxime-induced reactivation of muscle esterases following chlorpyrifos exposure in the earthworm Lumbricus terrestris

    Energy Technology Data Exchange (ETDEWEB)

    Collange, B. [Universite d' Avignon et des Pays de Vaucluse, UMR 406 Abeilles et Environnement, Site AGROPARC, F-84914, Avignon Cede 09 (France); Wheelock, C.E. [Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 171 77, Stockholm (Sweden); Rault, M.; Mazzia, C. [Universite d' Avignon et des Pays de Vaucluse, UMR 406 Abeilles et Environnement, Site AGROPARC, F-84914, Avignon Cede 09 (France); Capowiez, Y. [INRA, Unite PSH, Site AGROPARC, F-84914 Avignon Cedex 09 (France); Sanchez-Hernandez, J.C., E-mail: juancarlos.sanchez@uclm.e [Laboratory of Ecotoxicology, Faculty of Environmental Science, University of Castilla-La Mancha, Avda. Carlos III s/n, 45071, Toledo (Spain)

    2010-06-15

    Assessment of wildlife exposure to organophosphorus (OP) pesticides generally involves the measurement of cholinesterase (ChE) inhibition, and complementary biomarkers (or related endpoints) are rarely included. Herein, we investigated the time course inhibition and recovery of ChE and carboxylesterase (CE) activities in the earthworm Lumbricus terrestris exposed to chlorpyrifos, and the ability of oximes to reactivate the phosphorylated ChE activity. Results indicated that these esterase activities are a suitable multibiomarker scheme for monitoring OP exposure due to their high sensitivity to OP inhibition and slow recovery to full activity levels following pesticide exposure. Moreover, oximes reactivated the inhibited ChE activity of the earthworms exposed to 12 and 48 mg kg{sup -1} chlorpyrifos during the first week following pesticide exposure. This methodology is useful for providing evidence for OP-mediated ChE inhibition in individuals with a short history of OP exposure (<=1 week); resulting a valuable approach for assessing multiple OP exposure episodes in the field. - Esterase inhibition combined with oxime reactivation methods is a suitable approach for monitoring organophosphate contamination

  15. Genome-wide gene expression analysis in response to organophosphorus pesticide chlorpyrifos and diazinon in C. elegans.

    Directory of Open Access Journals (Sweden)

    Ana Viñuela

    Full Text Available Organophosphorus pesticides (OPs were originally designed to affect the nervous system by inhibiting the enzyme acetylcholinesterase, an important regulator of the neurotransmitter acetylcholine. Over the past years evidence is mounting that these compounds affect many other processes. Little is known, however, about gene expression responses against OPs in the nematode Caenorhabditis elegans. This is surprising because C. elegans is extensively used as a model species in toxicity studies. To address this question we performed a microarray study in C. elegans which was exposed for 72 hrs to two widely used Ops, chlorpyrifos and diazinon, and a low dose mixture of these two compounds. Our analysis revealed transcriptional responses related to detoxification, stress, innate immunity, and transport and metabolism of lipids in all treatments. We found that for both compounds as well as in the mixture, these processes were regulated by different gene transcripts. Our results illustrate intense, and unexpected crosstalk between gene pathways in response to chlorpyrifos and diazinon in C. elegans.

  16. Inhibition, recovery and oxime-induced reactivation of muscle esterases following chlorpyrifos exposure in the earthworm Lumbricus terrestris

    International Nuclear Information System (INIS)

    Assessment of wildlife exposure to organophosphorus (OP) pesticides generally involves the measurement of cholinesterase (ChE) inhibition, and complementary biomarkers (or related endpoints) are rarely included. Herein, we investigated the time course inhibition and recovery of ChE and carboxylesterase (CE) activities in the earthworm Lumbricus terrestris exposed to chlorpyrifos, and the ability of oximes to reactivate the phosphorylated ChE activity. Results indicated that these esterase activities are a suitable multibiomarker scheme for monitoring OP exposure due to their high sensitivity to OP inhibition and slow recovery to full activity levels following pesticide exposure. Moreover, oximes reactivated the inhibited ChE activity of the earthworms exposed to 12 and 48 mg kg-1 chlorpyrifos during the first week following pesticide exposure. This methodology is useful for providing evidence for OP-mediated ChE inhibition in individuals with a short history of OP exposure (≤1 week); resulting a valuable approach for assessing multiple OP exposure episodes in the field. - Esterase inhibition combined with oxime reactivation methods is a suitable approach for monitoring organophosphate contamination

  17. Tricyclic sesquiterpene copaene prevents H2O2-induced neurotoxicity

    Directory of Open Access Journals (Sweden)

    Hasan Turkez

    2014-02-01

    Full Text Available Aim: Copaene (COP, a tricyclic sesquiterpene, is present in several essential oils of medicinal and aromatic plants and has antioxidant and anticarcinogenic features. But, very little information is known about the effects of COP on oxidative stress induced neurotoxicity. Method: We used hydrogen peroxide (H2O2 exposure for 6 h to model oxidative stress. Therefore, this experimental design allowed us to explore the neuroprotective potential of COP in H2O2-induced toxicity in rat cerebral cortex cell cultures for the first time. For this purpose, methyl thiazolyl tetrazolium (MTT and lactate dehydrogenase (LDH release assays were carried out to evaluate cytotoxicity. Total antioxidant capacity (TAC and total oxidative stress (TOS parameters were used to evaluate oxidative changes. In addition to determining of 8-hydroxy-2-deoxyguanosine (8-OH-dG levels, the single cell gel electrophoresis (SCGE or comet assay was also performed for measuring the resistance of neuronal DNA to H2O2-induced challenge. Result: The results of this study showed that survival and TAC levels of the cells decreased, while TOS, 8-OH-dG levels and the mean values of the total scores of cells showing DNA damage increased in the H2O2 alone treated cultures. But pre-treatment of COP suppressed the cytotoxicity, genotoxicity and oxidative stress which were increased by H2O2. Conclusion: It is proposed that COP as a natural product with an antioxidant capacity in mitigating oxidative injuries in the field of neurodegenerative diseases. [J Intercult Ethnopharmacol 2014; 3(1.000: 21-28

  18. 1,3-Dinitrobenzene neurotoxicity - Passage effect in immortalized astrocytes.

    Science.gov (United States)

    Maurer, Laura L; Latham, Jackelyn D; Landis, Rory W; Song, Dong Hoon; Epstein, Tamir; Philbert, Martin A

    2016-03-01

    Age-related disturbances in astrocytic mitochondrial function are linked to loss of neuroprotection and decrements in neurological function. The immortalized rat neocortical astrocyte-derived cell line, DI-TNC1, provides a convenient model for the examination of cellular aging processes that are difficult to study in primary cell isolates from aged brain. Successive passages in culture may serve as a surrogate of aging in which time-dependent adaptation to culture conditions may result in altered responses to xenobiotic challenge. To investigate the hypothesis that astrocytic mitochondrial homeostatic function is decreased with time in culture, low passage DI-TNC1 astrocytes (LP; #2-8) and high passage DI-TNC1 astrocytes (HP; #17-28) were exposed to the mitochondrial neurotoxicant 1,3-dinitrobenzene (DNB). Cells were exposed in either monoculture or in co-culture with primary cortical neurons. Astrocyte mitochondrial membrane potential, morphology, ATP production and proliferation were monitored in monoculture, and the ability of DI-TNC1 cells to buffer K(+)-induced neuronal depolarization was examined in co-cultures. In HP DI-TNC1 cells, DNB exposure decreased proliferation, reduced mitochondrial membrane potential and significantly decreased mitochondrial form factor. Low passage DI-TNC1 cells effectively attenuated K(+)-induced neuronal depolarization in the presence of DNB whereas HP counterparts were unable to buffer K(+) in DNB challenge. Following DNB challenge, LP DI-TNC1 cells exhibited greater viability in co-culture than HP. The data provide compelling evidence that there is an abrupt phenotypic change in DI-TNC1 cells between passage #9-16 that significantly diminishes the ability of DI-TNC1 cells to compensate for neurotoxic challenge and provide neuroprotective spatial buffering. Whether or not these functional changes have an in vivo analog in aging brain remains to be determined. PMID:26769196

  19. Attenuation of arsenic neurotoxicity by curcumin in rats

    International Nuclear Information System (INIS)

    In view of continued exposure to arsenic and associated human health risk including neurotoxicity, neuroprotective efficacy of curcumin, a polyphenolic antioxidant, has been investigated in rats. A significant decrease in locomotor activity, grip strength (26%) and rota-rod performance (82%) was observed in rats treated with arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) as compared to controls. The arsenic treated rats also exhibited a decrease in the binding of striatal dopamine receptors (32%) and tyrosine hydroxylase (TH) immunoreactivity (19%) in striatum. Increased arsenic levels in corpus striatum (6.5 fold), frontal cortex (6.3 fold) and hippocampus (7.0 fold) associated with enhanced oxidative stress in these brain regions, as evident by an increase in lipid perioxidation, protein carbonyl and a decrease in the levels of glutathione and activity of superoxide dismutase, catalase and glutathione peroxidase with differential effects were observed in arsenic treated rats compared to controls. Simultaneous treatment with arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) and curcumin (100 mg/kg body weight, p.o., 28 days) caused an increase in locomotor activity and grip strength and improved the rota-rod performance in comparison to arsenic treated rats. Binding of striatal dopamine receptors and TH expression increased while arsenic levels and oxidative stress decreased in these brain regions in co-treated rats as compared to those treated with arsenic alone. No significant effect on any of these parameters was observed in rats treated with curcumin (100 mg/kg body weight, p.o., 28 days) alone compared to controls. A significant protection in behavioral, neurochemical and immunohistochemical parameters in rats simultaneously treated with arsenic and curcumin suggest the neuroprotective efficacy of curcumin.

  20. Translocation and neurotoxicity of CdTe quantum dots in RMEs motor neurons in nematode Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yunli; Wang, Xiong; Wu, Qiuli; Li, Yiping; Wang, Dayong, E-mail: dayongw@seu.edu.cn

    2015-02-11

    Graphical abstract: - Highlights: • We investigated in vivo neurotoxicity of CdTe QDs on RMEs motor neurons in C. elegans. • CdTe QDs in the range of μg/L caused neurotoxicity on RMEs motor neurons. • Bioavailability of CdTe QDs may be the primary inducer for CdTe QDs neurotoxicity. • Both oxidative stress and cell identity regulate the CdTe QDs neurotoxicity. • CdTe QDs were translocated and deposited into RMEs motor neurons. - Abstract: We employed Caenorhabditis elegans assay system to investigate in vivo neurotoxicity of CdTe quantum dots (QDs) on RMEs motor neurons, which are involved in controlling foraging behavior, and the underlying mechanism of such neurotoxicity. After prolonged exposure to 0.1–1 μg/L of CdTe QDs, abnormal foraging behavior and deficits in development of RMEs motor neurons were observed. The observed neurotoxicity from CdTe QDs on RMEs motor neurons might be not due to released Cd{sup 2+}. Overexpression of genes encoding Mn-SODs or unc-30 gene controlling cell identity of RMEs neurons prevented neurotoxic effects of CdTe QDs on RMEs motor neurons, suggesting the crucial roles of oxidative stress and cell identity in regulating CdTe QDs neurotoxicity. In nematodes, CdTe QDs could be translocated through intestinal barrier and be deposited in RMEs motor neurons. In contrast, CdTe@ZnS QDs could not be translocated into RMEs motor neurons and therefore, could only moderately accumulated in intestinal cells, suggesting that ZnS coating might reduce neurotoxicity of CdTe QDs on RMEs motor neurons. Therefore, the combinational effects of oxidative stress, cell identity, and bioavailability may contribute greatly to the mechanism of CdTe QDs neurotoxicity on RMEs motor neurons. Our results provide insights into understanding the potential risks of CdTe QDs on the development and function of nervous systems in animals.

  1. Translocation and neurotoxicity of CdTe quantum dots in RMEs motor neurons in nematode Caenorhabditis elegans

    International Nuclear Information System (INIS)

    Graphical abstract: - Highlights: • We investigated in vivo neurotoxicity of CdTe QDs on RMEs motor neurons in C. elegans. • CdTe QDs in the range of μg/L caused neurotoxicity on RMEs motor neurons. • Bioavailability of CdTe QDs may be the primary inducer for CdTe QDs neurotoxicity. • Both oxidative stress and cell identity regulate the CdTe QDs neurotoxicity. • CdTe QDs were translocated and deposited into RMEs motor neurons. - Abstract: We employed Caenorhabditis elegans assay system to investigate in vivo neurotoxicity of CdTe quantum dots (QDs) on RMEs motor neurons, which are involved in controlling foraging behavior, and the underlying mechanism of such neurotoxicity. After prolonged exposure to 0.1–1 μg/L of CdTe QDs, abnormal foraging behavior and deficits in development of RMEs motor neurons were observed. The observed neurotoxicity from CdTe QDs on RMEs motor neurons might be not due to released Cd2+. Overexpression of genes encoding Mn-SODs or unc-30 gene controlling cell identity of RMEs neurons prevented neurotoxic effects of CdTe QDs on RMEs motor neurons, suggesting the crucial roles of oxidative stress and cell identity in regulating CdTe QDs neurotoxicity. In nematodes, CdTe QDs could be translocated through intestinal barrier and be deposited in RMEs motor neurons. In contrast, CdTe@ZnS QDs could not be translocated into RMEs motor neurons and therefore, could only moderately accumulated in intestinal cells, suggesting that ZnS coating might reduce neurotoxicity of CdTe QDs on RMEs motor neurons. Therefore, the combinational effects of oxidative stress, cell identity, and bioavailability may contribute greatly to the mechanism of CdTe QDs neurotoxicity on RMEs motor neurons. Our results provide insights into understanding the potential risks of CdTe QDs on the development and function of nervous systems in animals

  2. Cellular transport and secretion of the cyanobacterial neurotoxin BMAA into milk and egg : Implications for developmental neurotoxicity

    OpenAIRE

    Andersson, Marie

    2015-01-01

    The cyanobacterial amino acid β-N-methylamino-L-alanine (BMAA) is a neurotoxin implicated in the etiology of neurodegenerative diseases. Cyanobacteria are cosmopolitan organisms present in various environments. BMAA can cause long-term neurodegenerative alterations in rats exposed during the neonatal period, a period that corresponds to the last trimester and the first few years of life in humans. As BMAA has been reported to be bioaccumulated in the aquatic food chain and detected in mussels...

  3. THE DISTRIBUTION OF CHLORPYRIFOS FOLLOWING A CRACK AND CREVICE TYPE APPLICATION IN THE U.S. EPA INDOOR AIR QUALITY TEST HOUSE

    Science.gov (United States)

    A study was conducted in the U.S. EPA Indoor Air Quality Test House to determine the spatial and temporal distribution of chlorpyrifos following a professional crack and crevice application in the kitchen. Following the application, measurements were made in the kitchen, den a...

  4. THE DISTRIBUTION OF CHLORPYRIFOS FOLLOWING A CRACK AND CREVICE TYPE APPLICATION IN THE U.S. EPA INDOOR AIR QUALITY RESEARCH HOUSE

    Science.gov (United States)

    A study was conducted in the U.S. EPA Indoor Air Quality Research House to determine the spatial and temporal distribution of chlorpyrifos following a professional crack and crevice application in the kitchen. Following the application, measurements were made in the kitchen, de...

  5. Biodegradation of chlorpyrifos and its hydrolysis product 3,5,6-trichloro-2-pyridinol using a novel bacterium Ochrobactrum sp. JAS2: A proposal of its metabolic pathway.

    Science.gov (United States)

    Abraham, Jayanthi; Silambarasan, Sivagnanam

    2016-01-01

    Biodegradation of chlorpyrifos and its major metabolite 3,5,6-trichloro-2-pyridinol (TCP) were studied with a novel bacterial strain JAS2 isolated from paddy rhizosphere soil. The molecular characterization based on 16S rRNA gene sequence homology confirmed its identity as Ochrobactrum sp. JAS2. The JAS2 strain degraded 300mgl(-1) of chlorpyrifos within 12h of incubation in the aqueous medium and it produced the TCP metabolite. However, after 72h of incubation TCP was also completely degraded by the JAS2 strain. A tentative degradation pathway of chlorpyrifos by Ochrobactrum sp. JAS2 has been proposed on basis of GC-MS analysis. The complete degradation of chlorpyrifos occurred within 24h in the soil spiked with and without addition of nutrients inoculated with Ochrobactrum sp. JAS2. TCP was obtained in both the studies which was degraded completely by 96h in the soil spiked with nutrients and whereas 120h in absence of nutrients in the soil. The mpd gene which is responsible for organophosphorus hydrolase production was identified. The isolates Ochrobactrum sp. JAS2 also exhibited a time dependent increase in the amount of tricalcium phosphate solubilization in Pikovskaya's medium. Further screening of the strain JAS2 for auxiliary plant growth promoting activities revealed its remarkable capability of producing the indole acetic acid (IAA), hydrogen cyanide (HCN) and ammonia. PMID:26778429

  6. Beta-arrestin1 and 2 differently modulate metabotropic glutamate receptor 7 signaling in rat developmental sevoflurane-induced neuronal apoptosis.

    Science.gov (United States)

    Wang, W-Y; Wu, X-M; Jia, L-J; Zhang, H-H; Cai, F; Mao, H; Xu, W-C; Chen, L; Zhang, J; Hu, S-F

    2016-01-28

    Beta-arrestins (β-arrs) are initially known as negative regulators of G protein-coupled receptors (GPCRs). Recently, there is increasing evidence suggesting that β-arrs also serve as scaffolds and adapters that mediate distinct intracellular signal transduction initiated by GPCR activation. In the previous study, we have shown that metabotropic glutamate receptor 7 (mGluR7) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling may be involved in the developmental sevoflurane neurotoxicity. In the present study, we showed that activation of mGluR7 with a group III mGluRs orthosteric agonist LAP4 or an atypical mGluR7 allosteric agonist N,N'-bis(diphenylmethyl)-1,2-ethanediamine dihydrochloride (AMN082) significantly attenuated sevoflurane-induced neuronal apoptosis. Interestingly, this neuroprotective role of LAP4 could be partially reduced by β-arr1 small interfering RNA (siRNA) or β-arr2 siRNA transfection. In contrast, β-arr2 siRNA transfection alone abolished the effects of AMN082 on sevoflurane neurotoxicity. In addition, administration of LAP4 or AMN082 significantly enhanced Phospho-ERK1/2 in sevoflurane neurotoxicity, which could be abrogated by β-arr2 siRNA transfection, but not by β-arr1 siRNA transfection. Increased β-arr2-dependent Phospho-ERK1/2 signaling alleviated sevoflurane neurotoxicity by inhibiting bad phosphorylation. We also found that the neuroprotective role of AMN082 was completely reversed by ERK1/2 inhibitor 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene (U0126). Alternatively, treatment with U0126 partially suppressed the neuroprotective of LAP4, suggesting that other mechanisms may be implicated in this process. Further investigation indicated that, in the scenario of sevoflurane neurotoxicity, application of LAP4 (but not AMN082) increased the interaction of β-arrs with transcriptional factors CREB binding protein (CBP) and p300. LAP4 also enhanced the β-arr1-dependent H3 and H4 acetylation in

  7. A neurotoxic phospholipase A2 impairs yeast amphiphysin activity and reduces endocytosis.

    Directory of Open Access Journals (Sweden)

    Mojca Mattiazzi

    Full Text Available BACKGROUND: Presynaptically neurotoxic phospholipases A(2 inhibit synaptic vesicle recycling through endocytosis. PRINCIPAL FINDINGS: Here we provide insight into the action of a presynaptically neurotoxic phospholipase A(2 ammodytoxin A (AtxA on clathrin-dependent endocytosis in budding yeast. AtxA caused changes in the dynamics of vesicle formation and scission from the plasma membrane in a phospholipase activity dependent manner. Our data, based on synthetic dosage lethality screen and the analysis of the dynamics of sites of endocytosis, indicate that AtxA impairs the activity of amphiphysin. CONCLUSIONS: We identified amphiphysin and endocytosis as the target of AtxA intracellular activity. We propose that AtxA reduces endocytosis following a mechanism of action which includes both a specific protein-protein interaction and enzymatic activity, and which is applicable to yeast and mammalian cells. Knowing how neurotoxic phospholipases A(2 work can open new ways to regulate endocytosis.

  8. From neurotoxic to chemosensory effects: new insights on acute solvent neurotoxicity exemplified by acute effects of 2-ethylhexanol.

    Science.gov (United States)

    van Thriel, Christoph; Kiesswetter, Ernst; Schäper, Michael; Blaszkewicz, Meinolf; Golka, Klaus; Juran, Stephanie; Kleinbeck, Stefan; Seeber, Andreas

    2007-03-01

    Historically, acute solvent neurotoxicity was strongly related to reversible narcotic states that could be detected by neurobehavioral tests (e.g., simple reaction time). Nowadays, the occupational exposure to chemicals is markedly reduced and the avoidance of chemosensory effects is more important for the regulation of solvents. Exemplarily, this study examines if the chemosensory perception of 2-ethylhexanol is capable to distract performance in demanding neurobehavioral tasks. In two experiments three time-weighted average concentrations of 2-ethylhexanol (C(TWA): 1.5, 10, and 20 ppm) were investigated. In experiment A (n=24) variable concentrations over time (4h) were used, experiment B (n=22) investigated constant concentrations. The experiments were conducted in a 29 m3 exposure laboratory. Cross-over designs with randomized sequences of exposures were used. Among the 46 male participants 19 subjects reported enhanced chemical sensitivity; the other 27 subjects did not show this personality feature. During the exposure periods neurobehavioral tests were presented twice (beginning; end), the intensity of chemosensory perceptions were rated thrice. The intensity of chemosensory perceptions showed a clear dose-dependency. Subjects' performance in the vigilance test was not affected by the different exposures. Moreover, the results of neurobehavioral tests measuring executive function were neither affected by the C(TWA) concentration nor by the exposure peaks. With increasing C(TWA), a subgroup of the chemically sensitive subjects showed deteriorated accuracy in a divided attention task. Especially the 20 ppm conditions were very annoying. Only during the constant 10 ppm condition the time courses of the annoyance and nasal irritation ratings indicated some adaptation. In general, with the applied neurobehavioral tests distractive effects of acute 2-ethylhexanol exposures up to 20 ppm could not be confirmed. In sensitive groups such distractive effects of

  9. Exosomes in developmental signalling.

    Science.gov (United States)

    McGough, Ian John; Vincent, Jean-Paul

    2016-07-15

    In order to achieve coordinated growth and patterning during development, cells must communicate with one another, sending and receiving signals that regulate their activities. Such developmental signals can be soluble, bound to the extracellular matrix, or tethered to the surface of adjacent cells. Cells can also signal by releasing exosomes - extracellular vesicles containing bioactive molecules such as RNA, DNA and enzymes. Recent work has suggested that exosomes can also carry signalling proteins, including ligands of the Notch receptor and secreted proteins of the Hedgehog and WNT families. Here, we describe the various types of exosomes and their biogenesis. We then survey the experimental strategies used so far to interfere with exosome formation and critically assess the role of exosomes in developmental signalling. PMID:27436038

  10. Severe fludarabine neurotoxicity after reduced intensity conditioning regimen to allogeneic hematopoietic stem cell transplantation: a case report

    OpenAIRE

    C. Annaloro; Costa, A.; N.S. Fracchiolla; G. Mometto; S. Artuso; G. Saporiti; Tagliaferri, E.; GRIFONI, F.; Onida, F.; Cortelezzi, A.

    2015-01-01

    Key Clinical Message We present a case of severe, irreversible neurotoxicity in a 55-year-old-patient with myelofibrosis undergoing hematopoietic stem cell transplantation following a reduced intensity conditioning including fludarabine. The patient developed progressive sensory-motor, visual and consciousness disturbances, eventually leading to death. MRI imaging pattern was unique and attributable to fludarabine neurotoxicity.

  11. Severe fludarabine neurotoxicity after reduced intensity conditioning regimen to allogeneic hematopoietic stem cell transplantation: a case report.

    Science.gov (United States)

    Annaloro, Claudio; Costa, Antonella; Fracchiolla, Nicola S; Mometto, Gabriella; Artuso, Silvia; Saporiti, Giorgia; Tagliaferri, Elena; Grifoni, Federica; Onida, Francesco; Cortelezzi, Agostino

    2015-07-01

    We present a case of severe, irreversible neurotoxicity in a 55-year-old-patient with myelofibrosis undergoing hematopoietic stem cell transplantation following a reduced intensity conditioning including fludarabine. The patient developed progressive sensory-motor, visual and consciousness disturbances, eventually leading to death. MRI imaging pattern was unique and attributable to fludarabine neurotoxicity. PMID:26273463

  12. Spinach or amaranth contains highest residue of metalaxyl, fluazifop-P-butyl, chlorpyrifos, and lambda-cyhalothrin on six leaf vegetables upon open field application.

    Science.gov (United States)

    Fan, Sufang; Zhang, Fengzu; Deng, Kailin; Yu, Chuanshan; Liu, Shaowen; Zhao, Pengyue; Pan, Canping

    2013-03-01

    To select representative leaf vegetables which may contain the highest residue, field experiments of metalaxyl, fluazifop-P-butyl, chlorpyrifos, and lambda-cyhalothrin on six crops including pakchoi, rape, crown daisy, amaranth, spinach, and lettuce were designed and conducted. In this study, a high-performance liquid chromatograph and electrospray ionization tandem mass spectrometer with multiple reaction monitoring was used to simultaneously determine metalaxyl and fluazifop-P-butyl residue in various samples, and a gas chromatograph with electron capture detector was used to detect chlorpyrifos and lambda-cyhalothrin. The limits of quantification (LOQ) of metalaxyl, fluazifop-P-butyl, chlorpyrifos, and lambda-cyhalothrin were in the range of 0.001-0.01 mg kg(-1) for all samples, and the average recoveries of all pesticides ranged from 67.6 to 119.1% at spiked levels of 0.01-0.1 mg kg(-1). In supervised field trials, the half-lives of metalaxyl, fluazifop-P-butyl, chlorpyrifos, and lambda-cyhalothrin were in the range of 1.11-3.79 days, 1.11-2.27 days, 1.13-5.17 days, and 1.77-6.24 days. It was also found that all pesticide residues in spinach and/or amaranth were higher than others after application. It is recommended that spinach or amaranth can be selected as a representative crop of leaf vegetables in studying systemic fungicide, insecticides, and herbicides with similarity as metalaxyl, fluazifop-P-butyl, chlorpyrifos, and lambda-cyhalothrin. PMID:23387923

  13. Anomalies and developmental defects

    International Nuclear Information System (INIS)

    Amonalies and developmental defects in trachea and bronchi (tracheal bronch us, diverticulum of trachea or bronchus, defects due to atresia of bronchial tre e, tracheobronchomegaly), lung vessels (aneurisms of pulmonary artery, agenesia, aplasia and hypoplasia of pulmonary artery,anomalies of pulmonary veins, varico sis of pulmonary veins), pulmonary tissue (lung sequestration, congenital lobar pulmonary emphysema, essential hemosiderosis), have beendescribed. The problems of the diagnosis of the above-mentioned diseases using roentgenograms are consid ered

  14. Comparative pharmacokinetics of chlorpyrifos versus its major metabolites following oral administration in the rat

    International Nuclear Information System (INIS)

    Chlorpyrifos (CPF) is a commonly used diethylphosphorothionate organophosphorus (OP) insecticide. Diethylphosphate (DEP), diethylthiophosphate (DETP) and 3,5,6-trichloro-2-pyridinol (TCPy) are products of both in vivo metabolism and environmental degradation of CPF and are routinely measured in urine as biomarkers of exposure. Hence, urinary biomonitoring of TCPy, DEP and DETP may be reflective of an individual's contact with both the parent pesticide and exposure to these metabolites in the environment. In the current study, simultaneous dosing of 13C- or 2H-isotopically labeled CPF (13C-labeled CPF, 5 13C on the TCPy ring; or 2H-labeled CPF, diethyl-D10 (deuterium labeled) on the side chain) were exploited to directly compare the pharmacokinetics and metabolism of CPF with TCPy, and DETP. The key objective in the current study was to quantitatively evaluate the pharmacokinetics of the individual metabolites relative to their formation following a dose of CPF. Individual metabolites were co-administered (oral gavage) with the parent compound at equal molar doses (14 μmol/kg; ∼5 mg/kg CPF). Major differences in the pharmacokinetics between CPF and metabolite doses were observed within the first 3 h of exposure, due to the required metabolism of CPF to initially form TCPy and DETP. Nonetheless, once a substantial amount of CPF has been metabolized (≥3 h post-dosing) pharmacokinetics for both treatment groups and metabolites were very comparable. Urinary excretion rates for orally administered TCPy and DETP relative to 13C-CPF or 2H-CPF derived 13C-TCPy and 2H-DETP were consistent with blood pharmacokinetics, and the urinary clearance of metabolite dosed groups were comparable with the results for the 13C- and 2H-CPF groups. Since the pharmacokinetics of the individual metabolites were not modified by co-exposure to CPF; it suggests that environmental exposure to low dose mixtures of pesticides and metabolites will not impact their pharmacokinetics.

  15. Neurotoxicity during induction treatment of childhood acute lymphoblastic leukaemia: Two case reports

    Directory of Open Access Journals (Sweden)

    Kostić Gordana

    2009-01-01

    Full Text Available Introduction. During chemotherapy of acute lymphoblastic leukaemia (ALL, children sometimes exhibit neurological disturbances. Chemiotherapeutic regimens include methotrexate, administered either intravenously or via intrathecal route. Although multiple drugs are used in addition to methotrexate, the acute neurotoxicity reported in patients is usually attributed to methotrexate. The acute neurotoxicity usually results in stroke-like symptoms such as aphasia, weakness, sensory deficits, ataxia and seizures. Outline of Cases. From 2002 until January 2008, 32 children with ALL were diagnosed and treated at the Children's Hospital in Niš. The patients' age ranged from 1.5 to 16 years. They were treated in accordance with the protocol ALL IC-BFM 2002 (ALL Intercontinental Berlin Frankfurt M'nster 2002. Two of the patients (6.25% exhibited neurotoxicity. After the occurrence of neurological symptoms, the patients were ophthalmologically and neurologically examined. In addition, the magnetic resonance (MR imaging, computerized tomography and electroencephalography were applied. The paper presents two patients, aged 9 and 15 years respectively, who exhibited acute neurotoxicity - methotrexate encephalopathy during ALL treatment. Both patients had tonic-clonic seizures and neurological symptoms in the course of the induction therapy. Neurotoxicity occurred 7 days after the third, and 3 days after the fourth intrathecal methotrexate therapy. MR images confirmed multi-focal morphological changes of brain density in one of the patients, while the other patient had normal CT reading. Even though the development significantly differed, the changes were reversible in both patients. Conclusion. The neurotoxicity in patients with ALL can be combined with significant structural changes of the brain, but also morphological changes can be absent. Several questions concerning aetiology and treatment of neurological events are raised.

  16. The investigation of correlation between Iminoral concentration and neurotoxic levels after kidney transplantation

    Directory of Open Access Journals (Sweden)

    Zahra Tolou-Ghamari

    2015-01-01

    Full Text Available Background: Neurotoxicity side effects related to cyclosporine kinetics could lead to dysfunction of kidney graft and patient outcome after transplantation. The aim of this study was evidence-based pharmacotherapy of kidney transplant recipients and to investigate neurotoxic levels of Iminoral. Materials and Methods: The results of 2239 cyclosporine trough levels obtained from 743 patients were studied. Seventy-five adult kidney recipients who received Iminoral were studied for neurotoxicity symptoms. Demographic, clinical, hematology and biochemical data were recorded in d-base and analyzed using SPSS application for windows. Results: The mean value related to cyclosporine C 0 was 246.3 μg/l. In the 48% the signs of neurotoxicity such as tremor and headache were noted, but only in 9% the levels of cyclosporine C 0 were >400 μg/l. Further studies on 75 patients showed that the incidence of neurotoxic side effects were as follows: Tremor in 35, headache in 24 and anxiety in 34 recipients of kidney. The prescribed drug regimens from the day of transplant in most patients were based on mycophenolic acid or cellcept, pulse therapy using methylprednisolone (daily from kidney transplant up to 3 days after transplant, cyclosporine or Iminoral plus other drugs related to each individual. Administrations of ganciclovir, thymoglobulin, clotrimazol and prednisolone were also distinguished with immunosuppressant-based therapy simultaneously. Conclusion: Evidence-based study related to pharmacotherapy of Iminoral showed that clinical presentation related to neurotoxic side effects such as tremor, headache and anxiety might be due to many factors such as polypharmacy. Planning immunosuppression to individual patients based on programmed therapeutic Iminoral monitoring, avoiding polypharmacy in terms of removal or drug minimization and focusing on first week after transplant seem to be a realistic option.

  17. Investigation of treatment related neurotoxicity following childhood cancer by proton magnetic resonance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Davidson, A

    1999-05-01

    Children who survive treatment for cancer may suffer late effects, and neurotoxicity is a particular problem following central nervous system (CNS) directed therapy. Conventionally, this is assessed by neuropsychological assessments and neuroimaging. Cognitive deficits cannot be detected until several years after therapy, and although neuroimaging abnormalities are frequent they do not appear to be predictive of late problems. Thus, this study evaluated the role of localised proton magnetic resonance spectroscopy ({sup 1}H-MRS), a non-invasive method of quantifying metabolites in-vivo, which has the potential to be a sensitive, and quantifiable, means of detecting neurotoxicity and predicting clinical outcome.

  18. Role of genetic polymorphism of human plasma paraoxonase/arylesterase in hydrolysis of the insecticide metabolites chlorpyrifos oxon and paraoxon.

    OpenAIRE

    Furlong, C E; Richter, R J; Seidel, S L; Motulsky, A G

    1988-01-01

    Plasma paraoxonase is a polymorphic enzyme that hydrolyzes paraoxon, the neurotoxic, active metabolite of the insecticide parathion. This enzyme is specified by at least two alleles with frequencies of about .7 and .3 among Caucasoid populations. A specific assay was developed that measured the activity of human plasma paraoxonase without interference from serum albumin which contributes significantly to the hydrolytic breakdown of paraoxon at the high pH values used in many previous assays. ...

  19. Determination of half life of the pesticides chlorpyrifos (14C) in an agricultural soil of the VI region by means of the using isotopic techniques

    International Nuclear Information System (INIS)

    Chlorpyrifos is an organophosphorus insecticide widely used in Chilean agriculture in the control of plagues of insects in soil and several crops. From an environmental point of view, to know the behavior and fate of Chlorpyrifos under different moisture regimes in soil is important because it contributes to optimize its use, assuring that collateral effects do not take place inside or outside the application area and in addition it specifies the optimal conditions of application to obtain better results in the treatment with the land insecticide. In this work it was studied the half life of Chlorpyrifos (14C) in an agricultural soil of VI Region, by means of the use of Isotopic techniques, under two moisture regimes of 50 and 75% of the Field Capacity. The ground samples were fortified with doses of 10 mg/Kg and incubated to 20oC and in absence of light. The dissipation of Chlorpyrifos in soil was determined during 110 days of test, through the quantification of remaining 14CO2 by liquid scintillation counting. Results show temporary differences in the half life for different moisture regimes, with T1/2 of 21 and 28 days for the soil to 75 and 50% of the Field Capacity, respectively. It was studied the factors related to soil and plaguicide that could affect speed of degradation, either accelerating or inhibiting the process of dissipation of Chlorpyrifos, under the described moisture regimes. The results indicated that the fast degradation of the insecticide organophosphorus in the soil to 75% of the CC is product of biotic and abiotic processes. Between the abiotic processes the neutral hydrolysis constituted the principal route of dissipation, mainly due to the moisture content and pH presented in soil (pH 7,2). Nevertheless, factors as the high content of organic matter of the soil, low water solubility, high coefficient of adsorption and bond p=S of the Chlorpyrifos, they suggest the sorption process would inhibit hydrolysis, slowing down the determined times

  20. Exposure to Organophosphates Reduces the Expression of Neurotrophic Factors in Neonatal Rat Brain Regions: Similarities and Differences in the Effects of Chlorpyrifos and Diazinon on the Fibroblast Growth Factor Superfamily

    OpenAIRE

    Slotkin, Theodore A.; Seidler, Frederic J; Fumagalli, Fabio

    2007-01-01

    Background The fibroblast growth factor (FGF) superfamily of neurotrophic factors plays critical roles in neural cell development, brain assembly, and recovery from neuronal injury. Objectives We administered two organophosphate pesticides, chlorpyrifos and diazinon, to neonatal rats on postnatal days 1–4, using doses below the threshold for systemic toxicity or growth impairment, and spanning the threshold for barely detectable cholinesterase inhibition: 1 mg/kg/day chlorpyrifos and 1 or 2 m...