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Sample records for chlorpyrifos exposure alters

  1. 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...

  2. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Repeated exposure to neurotoxic levels of chlorpyrifos alters hippocampal expression of neurotrophins and neuropeptides.

    Science.gov (United States)

    Lee, Young S; Lewis, John A; Ippolito, Danielle L; Hussainzada, Naissan; Lein, Pamela J; Jackson, David A; Stallings, Jonathan D

    2016-01-18

    Chlorpyrifos (CPF), an organophosphorus pesticide (OP), is one of the most widely used pesticides in the world. Subchronic exposures to CPF that do not cause cholinergic crisis are associated with problems in cognitive function (i.e., learning and memory deficits), but the biological mechanism(s) underlying this association remain speculative. To identify potential mechanisms of subchronic CPF neurotoxicity, adult male Long Evans (LE) rats were administered CPF at 3 or 10mg/kg/d (s.c.) for 21 days. We quantified mRNA and non-coding RNA (ncRNA) expression profiles by RNA-seq, microarray analysis and small ncRNA sequencing technology in the CA1 region of the hippocampus. Hippocampal slice immunohistochemistry was used to determine CPF-induced changes in protein expression and localization patterns. Neither dose of CPF caused overt clinical signs of cholinergic toxicity, although after 21 days of exposure, cholinesterase activity was decreased to 58% or 13% of control levels in the hippocampus of rats in the 3 or 10mg/kg/d groups, respectively. Differential gene expression in the CA1 region of the hippocampus was observed only in the 10mg/kg/d dose group relative to controls. Of the 1382 differentially expressed genes identified by RNA-seq and microarray analysis, 67 were common to both approaches. Differential expression of six of these genes (Bdnf, Cort, Crhbp, Nptx2, Npy and Pnoc) was verified in an independent CPF exposure study; immunohistochemistry demonstrated that CRHBP and NPY were elevated in the CA1 region of the hippocampus at 10mg/kg/d CPF. Gene ontology enrichment analysis suggested association of these genes with receptor-mediated cell survival signaling pathways. miR132/212 was also elevated in the CA1 hippocampal region, which may play a role in the disruption of neurotrophin-mediated cognitive processes after CPF administration. These findings identify potential mediators of CPF-induced neurobehavioral deficits following subchronic exposure to CPF at

  5. 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...

  6. Alterations in juvenile diploid and triploid African catfish skin gelatin yield and amino acid composition: Effects of chlorpyrifos and butachlor exposures.

    Science.gov (United States)

    Karami, Ali; Karbalaei, Samaneh; Zad Bagher, Fariba; Ismail, Amin; Simpson, Stuart L; Courtenay, Simon C

    2016-08-01

    Skin is a major by-product of the fisheries and aquaculture industries and is a valuable source of gelatin. This study examined the effect of triploidization on gelatin yield and proximate composition of the skin of African catfish (Clarias gariepinus). We further investigated the effects of two commonly used pesticides, chlorpyrifos (CPF) and butachlor (BUC), on the skin gelatin yield and amino acid composition in juvenile full-sibling diploid and triploid African catfish. In two separate experiments, diploid and triploid C. gariepinus were exposed for 21 days to graded CPF [mean measured: 10, 16, or 31 μg/L] or BUC concentrations [Mean measured: 22, 44, or 60 μg/L]. No differences in skin gelatin yield, amino acid or proximate compositions were observed between diploid and triploid control groups. None of the pesticide treatments affected the measured parameters in diploid fish. In triploids, however, gelatin yield was affected by CPF treatments while amino acid composition remained unchanged. Butachlor treatments did not alter any of the measured variables in triploid fish. To our knowledge, this study is the first to investigate changes in the skin gelatin yield and amino acid composition in any animal as a response to polyploidization and/or contaminant exposure. PMID:27182978

  7. Alterations in juvenile diploid and triploid African catfish skin gelatin yield and amino acid composition: Effects of chlorpyrifos and butachlor exposures.

    Science.gov (United States)

    Karami, Ali; Karbalaei, Samaneh; Zad Bagher, Fariba; Ismail, Amin; Simpson, Stuart L; Courtenay, Simon C

    2016-08-01

    Skin is a major by-product of the fisheries and aquaculture industries and is a valuable source of gelatin. This study examined the effect of triploidization on gelatin yield and proximate composition of the skin of African catfish (Clarias gariepinus). We further investigated the effects of two commonly used pesticides, chlorpyrifos (CPF) and butachlor (BUC), on the skin gelatin yield and amino acid composition in juvenile full-sibling diploid and triploid African catfish. In two separate experiments, diploid and triploid C. gariepinus were exposed for 21 days to graded CPF [mean measured: 10, 16, or 31 μg/L] or BUC concentrations [Mean measured: 22, 44, or 60 μg/L]. No differences in skin gelatin yield, amino acid or proximate compositions were observed between diploid and triploid control groups. None of the pesticide treatments affected the measured parameters in diploid fish. In triploids, however, gelatin yield was affected by CPF treatments while amino acid composition remained unchanged. Butachlor treatments did not alter any of the measured variables in triploid fish. To our knowledge, this study is the first to investigate changes in the skin gelatin yield and amino acid composition in any animal as a response to polyploidization and/or contaminant exposure.

  8. 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...

  9. 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...

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

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    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.

  11. 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...

  12. 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...

  13. 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

  14. In-residence, multiple route exposures to chlorpyrifos and diazinon estimated by indirect method models

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    Moschandreas, D. J.; Kim, Y.; Karuchit, S.; Ari, H.; Lebowitz, M. D.; O'Rourke, M. K.; Gordon, S.; Robertson, G.

    One of the objectives of the National Human Exposure Assessment Survey (NHEXAS) is to estimate exposures to several pollutants in multiple media and determine their distributions for the population of Arizona. This paper presents modeling methods used to estimate exposure distributions of chlorpyrifos and diazinon in the residential microenvironment using the database generated in Arizona (NHEXAS-AZ). A four-stage probability sampling design was used for sample selection. Exposures to pesticides were estimated using the indirect method of exposure calculation by combining measured concentrations of the two pesticides in multiple media with questionnaire information such as time subjects spent indoors, dietary and non-dietary items they consumed, and areas they touched. Most distributions of in-residence exposure to chlorpyrifos and diazinon were log-normal or nearly log-normal. Exposures to chlorpyrifos and diazinon vary by pesticide and route as well as by various demographic characteristics of the subjects. Comparisons of exposure to pesticides were investigated among subgroups of demographic categories, including gender, age, minority status, education, family income, household dwelling type, year the dwelling was built, pesticide use, and carpeted areas within dwellings. Residents with large carpeted areas within their dwellings have higher exposures to both pesticides for all routes than those in less carpet-covered areas. Depending on the route, several other determinants of exposure to pesticides were identified, but a clear pattern could not be established regarding the exposure differences between several subpopulation groups.

  15. 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...

  16. [Effects of single and co-exposure of Cu and chlorpyrifos on the toxicity of earthworm].

    Science.gov (United States)

    Xu, Dong-mei; Wang, Yan-hua; Wang, Nan; Rao, Gui-wei

    2015-01-01

    Combined pollution of heavy metal and pesticide had posed a serious threat to soil ecology and human living environment. As two common types of pollutants in soil environment, the environmental effects of combined pollution of Cu and chlorpyrifos are worth for attention. The acute lethal effects and avoiding behavior of single and co-exposure of Cu and chlorpyrifos on earthworms were analyzed by using the methods of standard OECD filter paper test and artificial soil test. Results showed that the LC(50,48 h) and LC(50,14 d) of the acute toxicity of Cu on earthworm in filter paper test and in artificial soil test were 2.23 microg x cm(-2) and 496.05 mg x kg(-1), respectively. The LC(50,48 h) and LC(50,14 d) of the acute toxicity of chlorpyrifos on earthworm in filter paper test and in artificial soil test were 5.94 microg x cm(-2) and 186.07 mg x kg(-1), respectively. In filter paper test and artificial soil test, the joint acute toxicity of Cu and chlorpyrifos showed an additive effect while the concentration was 1:1. The type of combined effects of co-exposure of Cu and chlorpyrifos was synergistic effect and antagonistic effect in filter paper test and artificial soil test, respectively, while the toxicity was 1:1. The results of avoidance behavior test showed that the joint effect of Cu and chlorpyrifos on the avoidance behavior of earthworms was antagonistic. PMID:25898676

  17. Cardiotoxicity in rabbits after a low-level exposure to diazinon, propoxur, and chlorpyrifos.

    Science.gov (United States)

    Zafiropoulos, A; Tsarouhas, K; Tsitsimpikou, C; Fragkiadaki, P; Germanakis, I; Tsardi, M; Maravgakis, G; Goutzourelas, N; Vasilaki, F; Kouretas, D; Hayes, Aw; Tsatsakis, Am

    2014-12-01

    Lethal cardiac complications leading to death and various arrhythmias have been reported after organophosphate and/or carbamate poisonings. The present study focuses on the long-term effects of repeated low-level exposure to diazinon, propoxur, and chlorpyrifos (CPF) on cardiac function in rabbits. The yearly based experimental scheme of exposure consisted of two oral administration periods, lasting 3 months and 1 month each, interrupted by an 8-month washout period (total duration 12 months). At the end of the experimental scheme, the rabbits underwent an echocardiographic evaluation under sedation, after which they were killed and the tissue and serum samples were collected. A mild localized cardiotoxic effect was established by echocardiography for the three pesticides tested. Severe histological alterations were identified, especially in the diazinon-treated animals in agreement with increased persistence of this pesticide established in the cardiac tissue. In addition, all pesticides tested increased the oxidative stress and oxidative modifications in the genomic DNA content of the cardiac tissues, each one following a distinct mechanism.

  18. 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...

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

    Energy Technology Data Exchange (ETDEWEB)

    Jager, Tjalling [Department of Theoretical Biology, Vrije Universiteit, de Boelelaan 1085, NL-1081 HV, Amsterdam (Netherlands)]. E-mail: tjalling@bio.vu.nl; Crommentuijn, Trudie [Ministry of Spatial Planning, Housing and the Environment (VROM), Rijnstraat 8, P.O. Box 30945, 2500 GX, The Hague (Netherlands); Gestel, Cornelis A.M. van [Department of Animal Ecology, Vrije Universiteit, de Boelelaan 1085, NL-1081 HV, Amsterdam (Netherlands); Kooijman, Sebastiaan A.L.M. [Department of Theoretical Biology, Vrije Universiteit, de Boelelaan 1085, NL-1081 HV, Amsterdam (Netherlands)

    2007-01-15

    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.

  20. 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.

  1. 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

  2. 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...

  3. 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

  4. 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

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

    Science.gov (United States)

    Jager, Tjalling; Crommentuijn, Trudie; van Gestel, Cornelis A M; Kooijman, Sebastiaan A L M

    2007-01-01

    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. PMID:16762466

  6. Changes in Behavior and Brain Acetylcholinesterase Activity in Mosquito Fish, Gambusia affinis in Response to the Sub-Lethal Exposure to Chlorpyrifos

    Directory of Open Access Journals (Sweden)

    R. Nageswara Rao

    2005-12-01

    Full Text Available Sub-lethal studies of chlorpyrifos, O,O-diethyl-O-(3,5,6-trichloro-2-pyridyl phosphorothioate on mosquito fish, Gambusia affinis were carried out in vivo, for 20 days to assess the locomotor behavior in relation to bioaccumulation and interaction with a targeted enzyme, acetylcholinesterase (AChE, EC: 3.1.1.7. Fish exposed to sub-lethal concentration of 60 Ag/L (1/5 of LC50 were under stress, and reduced their locomotor behavior like distance travelled per unit time (m/min and swimming speed (cm/sec with respect to the length of exposure. The alteration in locomotor behavior of fish may be due to an accumulation of acetylcholine (ACh, a neurotransmitter at synaptic junctions, due to the inhibition of AChE enzyme activity (40 to 55% in brain and also bioaccumulation of the toxicant in different parts of fish. The bioaccumulation values indicated that the accumulation of chlorpyrifos was maximum in viscera followed by head and body. The average bioconcentration values are 0.109, 0.009 and 0.004 Ag/g for viscera, head and body with depuration rates of 2.24, 1.69 and 0.39 ng/h respectively. It is evident from the results that the sub-lethal concentration [1/5 of LC50; equivalent to Lowest Observed Effect Concentration (LOEC] of chlorpyrifos can able to alter the locomotor behavior of G. affinis in relation to the length of exposure. The findings revealed that the locomotor activity of test organism could be considered as a suitable marker to evaluate the affect of toxicant even at LOEC levels.

  7. 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...

  8. 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...

  9. 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

  10. 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...

  11. 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...

  12. Acute high dose of chlorpyrifos alters performance of rats in the elevated plus-maze and the elevated T-maze.

    Science.gov (United States)

    López-Crespo, G A; Flores, P; Sánchez-Santed, F; Sánchez-Amate, M C

    2009-11-01

    Chlorpyrifos (CPF) is a broad spectrum organophosphate (OP) pesticide widely used in agriculture, industry and household. Several animal studies indicate emotional disturbances after CPF exposure, although the results are sometimes puzzling. Thus, both anxiolytic and anxiogenic effects of CPF have been reported in different animal models of anxiety [Sánchez-Amate MC, Flores P, Sánchez-Santed F. Effects of chlorpyrifos in the plus-maze model of anxiety. Behav Pharmacol 2001;12:285-92; Sánchez-Amate MC, Dávila E, Cañadas F, Flores P, Sánchez-Santed F. Chlorpyrifos shares stimulus properties with pentilenetetrazol as evaluated by and operant drug discrimination task. Neurotoxicology 2002;23:795-803; López-Crespo G, Carvajal F, Flores P, Sánchez-Santed F, Sánchez-Amate MC. Time-course of biochemical and behavioural effects of a single high dose of chlorpyrifos. Neurotoxicology 2007;28:541-7]. On the other hand, other behavioural effects of CPF are time-dependent [López-Crespo G, Carvajal F, Flores P, Sánchez-Santed F, Sánchez-Amate MC. Time-course of biochemical and behavioural effects of a single high dose of chlorpyrifos. Neurotoxicology 2007;28:541-7], raising the question that the effects of CPF could be task and post-administration time dependent. To test this hypothesis, three groups of rats were treated with a single high dose of CPF (250 mg/kg); one of the groups was tested on day 5 on the elevated plus-maze, to complete our previous study on day 2 [Sánchez-Amate MC, Flores P, Sánchez-Santed F. Effects of chlorpyrifos in the plus-maze model of anxiety. Behav Pharmacol 2001;12:285-92]. The remaining groups were tested on the elevated T-maze on days 2 and 5. CPF produced an increased open arm activity on the elevated plus-maze on day 5, an increased escape latency on the elevated T-maze on day 2 and an impaired inhibitory avoidance on day 5. Data are discussed taking together all studies carried out in our laboratory, confirming that CPF effects on

  13. Ameliorative effect of vitamin C and E on hematological alterations induced by chlorpyrifos alone and in conjunction with fluoride in Wistar rats

    Directory of Open Access Journals (Sweden)

    Naseer A. Baba

    2013-06-01

    Full Text Available Objective: Chlorpyrifos (CPF is a common organophosphorus pesticide used worldwide for the management of agricultural and household pests. Similarly excessive fluoride (F ingestion is an important public health problem all over the world due to high fluoride content in groundwater. The present study aimed to investigate the alterations in hematological parameters by CPF alone and in conjunction with fluoride and their amelioration by vitamin C and E. Methods: The study was carried out in two phases; in the first phase toxicity was induced by toxicants and in the second phase ameliorative efficacy of vitamins was tested. Results: In the first phase, repeated oral administration of fluoride in drinking water at the dose of 1 and 10 mg/l caused increased monocyte and total leukocyte count (TLC. On the other hand, orally administered CPF (1 mg/kg resulted in decrease of packed cell volume (PCV with increase in TLC; in addition, granulocytes and monocytes were significantly increased. CPF at 10 mg/kg significantly decreased PCV and total erythrocyte count (TEC, whereas increase in TLC was observed. Co-administration of fluoride in drinking water (10 mg/l and CPF via oral gavage (10 mg/kg for 28 days resulted in decrease of hemoglobin (Hb, PCV, TEC whereas increase in TLC. The differential leukocyte count (DLC showed a decrease in lymphocyte values but an increase in granulocytes and monocytes. Conclusion: Simultaneous administration of with vitamin C and E along with CPF and fluoride ameliorated various hematological parameters, except TLC, granulocytes and monocytes, induced by co-exposure of CPF and fluoride in Wistar rats. [J Exp Integr Med 2013; 3(3.000: 213-218

  14. Erythrocyte osmotic fragility and lipid peroxidation following chronic co-exposure of rats to chlorpyrifos and deltamethrin, and the beneficial effect of alpha-lipoic acid

    Directory of Open Access Journals (Sweden)

    Chidiebere Uchendu

    2014-01-01

    Full Text Available The present study aimed to evaluate the effect of chronic co-exposure to chlorpyrifos (CPF and deltamethrin (DLT on erythrocyte osmotic fragility, lipid peroxidation and the ameliorative effect of alpha-lipoic acid (ALA on erythrocyte fragility. Thirty-six male Wistar rats divided into six groups of six rats each were used for the study. Groups I (S/oil and II (ALA were given soya oil (2 ml/kg and ALA (60 mg/kg, respectively. Rats in group III (DLT and IV (CPF were exposed to DLT (6.25 mg/kg and CPF (4.75 mg/kg (1/20th of the previously determined LD50 of 125 mg/kg and 95 mg/kg, respectively, over a period of 48 h. Rats in group V (CPF + DLT were co-exposed to CPF (4.75 mg/kg and DLT (6.25 mg/kg, while those in group VI (ALA + CPF + DLT were pretreated with ALA (60 mg/kg and then co-exposed to CPF and DLT, 45 min later. The treatments were administered by gavage once daily for a period of 16 weeks. Blood collected at the end of the experimental period were analyzed for erythrocyte osmotic fragility and malondialdehyde (MDA concentration. The study showed that chronic co-exposure to CPF and DLT resulted in an increase in erythrocyte fragility and MDA concentration which were ameliorated by supplementation with alpha-lipoic acid. The study concluded that repeated co-exposure to CPF and DLT elevated erythrocyte fragility probably due to increased lipid peroxidation, and pretreatment with alpha-lipoic acid ameliorated these alterations.

  15. Ameliorative effect of vitamin E to mouse dams and their pups following exposure of mothers to chlorpyrifos during gestation and lactation periods.

    Science.gov (United States)

    Mansour, Sameeh Abdel-Kader; Gamet-Payrastre, Laurence

    2016-07-01

    Pesticides are omnipresent in environment, water, fruits, and vegetables and are considered as risk factors for human health. Consumers are mainly exposed to pesticides through diet, and the main question to be answered concerns the impact of such exposure on health. In this study, we developed a mouse model to mimic consumer exposure. During gestation and lactation periods, the experimental mouse dams (M) received one of the following treatments: (a) diet-free of pesticides; (b) diet enriched with chlorpyrifos (CPF; 44.0 μg kg(-1)); c) diet + oral vitamin E (vit. E; α-tocopherol; 200 mg/kg/mouse); and (d) diet enriched with CPF (44.0 μg/kg + oral vit. E (200 mg/kg/mouse). At weaning, pups (P) and dams were killed, and organs as well as blood samples were collected. Compared with control results, CPF induced alteration of measured parameters (e.g. organ weight, alkaline phosphatase, urea, malondialdehyde, superoxide dismutase, and cholinesterase) either in mouse dams or in their offspring. Also, CPF induced histological impairment in kidney, liver, and ovary. Administration of vit. E in conjunction with CPF clearly alleviated deviation of these parameters than those of control ones. In conclusion, a dietary exposure of mice during gestation and lactation to low dose of CPF led to significant changes in the mother but also in the weaned animals that have not been directly exposed to this pesticide. These biological and histological modifications could be reversed by an oral supplementation of vit. E. PMID:25234640

  16. Does the home environment and the sex of the child modify the adverse effects of prenatal exposure to chlorpyrifos on child working memory?

    OpenAIRE

    Horton, Megan K; Kahn, Linda G.; Perera, Frederica; Barr, Dana Boyd; Rauh, Virginia

    2012-01-01

    Prenatal exposure to chlorpyrifos (CPF), an organophosphorus insecticide, has long been associated with delayed neurocognitive development and most recently with decrements in working memory at age 7. In the current paper, we expanded the previous work on CPF to investigate how additional biological and social environmental factors might create or explain differential neurodevelopmental susceptibility, focusing on main and moderating effects of the quality of the home environment (HOME) and c...

  17. 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

  18. Inulin Supplementation Lowered the Metabolic Defects of Prolonged Exposure to Chlorpyrifos from Gestation to Young Adult Stage in Offspring Rats

    Science.gov (United States)

    Reygner, Julie; Lichtenberger, Lydia; Elmhiri, Ghada; Dou, Samir; Bahi-Jaber, Narges; Rhazi, Larbi; Depeint, Flore; Bach, Veronique

    2016-01-01

    Increasing evidence indicates that chlorpyrifos (CPF), an organophosphorus insecticide, is involved in metabolic disorders. We assess the hypothesis whether supplementation with prebiotics from gestation to adulthood, through a modulation of microbiota composition and fermentative activity, alleviates CPF induced metabolic disorders of 60 days old offspring. 5 groups of Wistar rats, from gestation until weaning, received two doses of CPF pesticide: 1 mg/kg/day (CPF1) or 3.5 mg/kg/day (CPF3.5) with free access to inulin (10g/L in drinking water). Then male pups received the same treatment as dams. Metabolic profile, leptin sensitivity, insulin receptor (IR) expression in liver, gut microbiota composition and short chain fatty acid composition (SCFAs) in the colon, were analyzed at postnatal day 60 in the offspring (PND 60). CPF3.5 increased offspring’s birth body weight (BW) but decreased BW at PND60. Inulin supplementation restored the BW at PND 60 to control levels. Hyperinsulinemia and decrease in insulin receptor β in liver were seen in CPF1 exposed rats. In contrast, hyperglycemia and decrease in insulin level were found in CPF3.5 rats. Inulin restored the levels of some metabolic parameters in CPF groups to ranges comparable with the controls. The total bacterial population, short chain fatty acid (SCFA) production and butyrate levels were enhanced in CPF groups receiving inulin. Our data indicate that developmental exposure to CPF interferes with metabolism with dose related effects evident at adulthood. By modulating microbiota population and fermentative activity, inulin corrected adult metabolic disorders of rats exposed to CPF during development. Prebiotics supply may be thus considered as a novel nutritional strategy to counteract insulin resistance and diabetes induced by a continuous pesticide exposure. PMID:27760213

  19. Exposures of aquatic organisms to the organophosphorus insecticide, chlorpyrifos resulting from use in the United States.

    Science.gov (United States)

    Williams, W Martin; Giddings, Jeffrey M; Purdy, John; Solomon, Keith R; Giesy, John P

    2014-01-01

    Concentrations of CPY in surface waters are an integral determinant of risk to aquatic organisms. CPY has been measured in surface waters of the U.S. in several environmental monitoring programs and these data were evaluated to characterize concentrations, in relation to major areas of use and changes to the label since 2001, particularly the removal of domestic uses. Frequencies of detection and 95th centile concentrations of CPY decreased more than fivefold between 1992 and 2010. Detections in 1992-2001 ranged from 10.2 to 53%, while 2002-2010 detections ranged from 7 to 11%. The 95th centile concentrations ranged from 0.007 to 0.056 j.lg L -I in 1992-2001 and 0.006-0.008 j.lg L -I in 2002-2010.The greatest frequency of detections occurred in samples from undeveloped and agricultural land-use classes. Samples from urban and mixed land-use classes had the smallest frequency of detections and 95th centile concentrations, consistent with the cessation of most homeowner uses in 2001. The active metabolite of CPY, CPYO, was not detected frequently or in large concentrations. In 10,375 analyses from several sampling programs conducted between 1999 and 2012, only 25 detections (0.24% of samples) of CPYO were reported and estimated concentrations were less than the LOQ.Although the monitoring data on CPY provide relevant insight in quantifying the range of concentrations in surface waters, few monitoring programs have sampled at a frequency sufficient to quantify the time-series pattern of exposure. Therefore,numerical simulations were used to characterize concentrations of CPY in water and sediment for three representative high exposure environments in the U.S. Thefate of CPY in the environment is dependent on a number of dissipation and degradation processes. In terms of surface waters, fate in soils is a major driver of the potential for runoff into surface waters and results from a number of dissipation studies in the laboratory were characterized. Aerobic

  20. 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...

  1. Decreased reelin expression and organophosphate pesticide exposure alters mouse behaviour and brain morphology

    Directory of Open Access Journals (Sweden)

    Cristina A. Ghiani

    2012-02-01

    Full Text Available Genetic and environmental factors are both likely to contribute to neurodevelopmental disorders, including ASDs (autism spectrum disorders. In this study, we examined the combinatorial effect of two factors thought to be involved in autism – reduction in the expression of the extracellular matrix protein reelin and prenatal exposure to an organophosphate pesticide, CPO (chlorpyrifos oxon. Mice with reduced reelin expression or prenatal exposure to CPO exhibited subtle changes in ultrasound vocalization, open field behaviour, social interaction and repetitive behaviour. Paradoxically, mice exposed to both variables often exhibited a mitigation of abnormal behaviours, rather than increased behavioural abnormalities as expected. We identified specific differences in males and females in response to both of these variables. In addition to behavioural abnormalities, we identified anatomical alterations in the olfactory bulb, piriform cortex, hippocampus and cerebellum. As with our behavioural studies, anatomical alterations appeared to be ameliorated in the presence of both variables. While these observations support an interaction between loss of reelin expression and CPO exposure, our results suggest a complexity to this interaction beyond an additive effect of individual phenotypes.

  2. Prenatal dexamethasone augments the neurobehavioral teratology of chlorpyrifos: significance for maternal stress and preterm labor.

    Science.gov (United States)

    Levin, Edward D; Cauley, Marty; Johnson, Joshua E; Cooper, Ellen M; Stapleton, Heather M; Ferguson, P Lee; Seidler, Frederic J; Slotkin, Theodore A

    2014-01-01

    Glucocorticoids are the consensus treatment given in preterm labor and are also elevated by maternal stress; organophosphate exposures are virtually ubiquitous, so human developmental coexposures to these two agents are common. This study explores how prenatal dexamethasone exposure modifies the neurobehavioral teratology of chlorpyrifos, one of the most widely used organophosphates. 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 (<10%) inhibition of brain cholinesterase activity. Dexamethasone did not alter brain chlorpyrifos concentrations, nor did either agent alone or in combination affect brain thyroxine levels. Assessments were carried out from adolescence through adulthood encompassing T-maze alternation, Figure 8 maze (locomotor activity, habituation), novelty-suppressed feeding and novel object recognition tests. For behaviors where chlorpyrifos or dexamethasone individually had small effects, the dual exposure produced larger, significant effects that reflected additivity (locomotor activity, novelty-suppressed feeding, novel object recognition). Where the individual effects were in opposite directions or were restricted to only one agent, we found enhancement of chlorpyrifos' effects by prenatal dexamethasone (habituation). Finally, for behaviors where controls displayed a normal sex difference in performance, the combined treatment either eliminated or reversed the difference (locomotor activity, novel object recognition). Combined exposure to dexamethasone and chlorpyrifos results in a worsened neurobehavioral outcome, providing a proof-of-principle that prenatal glucocorticoids can create a subpopulation with enhanced vulnerability to environmental toxicants.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Removal of carbofuran is not affected by co-application of chlorpyrifos in a coconut fiber/compost based biomixture after aging or pre-exposure.

    Science.gov (United States)

    Chin-Pampillo, Juan Salvador; Masís-Mora, Mario; Ruiz-Hidalgo, Karla; Carazo-Rojas, Elizabeth; Rodríguez-Rodríguez, Carlos E

    2016-08-01

    Biomixtures constitute the biologically active part of biopurification systems (BPS), which are used to treat pesticide-containing wastewater. The aim of this work was to determine whether co-application of chlorpyrifos (CLP) affects the removal of carbofuran (CFN) (both insecticide/nematicides) in a coconut fiber-compost-soil biomixture (FCS biomixture), after aging or previous exposure to CFN. Removal of CFN and two of its transformation products (3-hydroxycarbofuran and 3-ketocarbofuran) was enhanced in pre-exposed biomixtures in comparison to aged biomixtures. The co-application of CLP did not affect CFN removal, which suggests that CLP does not inhibit microbial populations in charge of CFN transformation. Contrary to the removal behavior, mineralization of radiolabeled (14)C-pesticides showed higher mineralization rates of CFN in aged biomixtures (with respect to freshly prepared or pre-exposed biomixtures). In the case of CLP, mineralization was favored in freshly prepared biomixtures, which could be ascribed to high sorption during aging and microbial inhibition by CFN in pre-exposure. Regardless of removal and mineralization results, toxicological assays revealed a steep decrease in the acute toxicity of the matrix on the microcrustacean Daphnia magna (over 97%) after 8days of treatment of individual pesticides or the mixture CFN/CLP. Results suggest that FCS biomixtures are suitable to be used in BPS for the treatment of wastewater in fields where both pesticides are employed. PMID:27521950

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

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    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.

  6. Biodegradation of chlorpyrifos by bacterial genus Pseudomonas.

    Science.gov (United States)

    Gilani, Razia Alam; Rafique, Mazhar; Rehman, Abdul; Munis, Muhammad Farooq Hussain; Rehman, Shafiq Ur; Chaudhary, Hassan Javed

    2016-02-01

    Chlorpyrifos is an organophosphorus pesticide commonly used in agriculture. It is noxious to a variety of organisms that include living soil biota along with beneficial arthropods, fish, birds, humans, animals, and plants. Exposure to chlorpyrifos may cause detrimental effects as delayed seedling emergence, fruit deformities, and abnormal cell division. Contamination of chlorpyrifos has been found about 24 km from the site of its application. There are many physico-chemical and biological approaches to remove organophosphorus pesticides from the ecosystem, among them most promising is biodegradation. The 3,5,6-trichloro-2-pyridinol (TCP) and diethylthiophosphate (DETP) as primary products are made when chlorpyrifos is degraded by soil microorganisms which further break into nontoxic metabolites as CO(2), H(2)O, and NH(3). Pseudomonas is a diversified genus possessing a series of catabolic pathways and enzymes involved in pesticide degradation. Pseudomonas putida MAS-1 is reported to be more efficient in chlorpyrifos degradation by a rate of 90% in 24 h among Pseudomonas genus. The current review analyzed the comparative potential of bacterial species in Pseudomonas genus for degradation of chlorpyrifos thus, expressing an ecofriendly approach for the treatment of environmental contaminants like pesticides. PMID:26837064

  7. Biodegradation of chlorpyrifos by bacterial genus Pseudomonas.

    Science.gov (United States)

    Gilani, Razia Alam; Rafique, Mazhar; Rehman, Abdul; Munis, Muhammad Farooq Hussain; Rehman, Shafiq Ur; Chaudhary, Hassan Javed

    2016-02-01

    Chlorpyrifos is an organophosphorus pesticide commonly used in agriculture. It is noxious to a variety of organisms that include living soil biota along with beneficial arthropods, fish, birds, humans, animals, and plants. Exposure to chlorpyrifos may cause detrimental effects as delayed seedling emergence, fruit deformities, and abnormal cell division. Contamination of chlorpyrifos has been found about 24 km from the site of its application. There are many physico-chemical and biological approaches to remove organophosphorus pesticides from the ecosystem, among them most promising is biodegradation. The 3,5,6-trichloro-2-pyridinol (TCP) and diethylthiophosphate (DETP) as primary products are made when chlorpyrifos is degraded by soil microorganisms which further break into nontoxic metabolites as CO(2), H(2)O, and NH(3). Pseudomonas is a diversified genus possessing a series of catabolic pathways and enzymes involved in pesticide degradation. Pseudomonas putida MAS-1 is reported to be more efficient in chlorpyrifos degradation by a rate of 90% in 24 h among Pseudomonas genus. The current review analyzed the comparative potential of bacterial species in Pseudomonas genus for degradation of chlorpyrifos thus, expressing an ecofriendly approach for the treatment of environmental contaminants like pesticides.

  8. Age-dependent pharmacokinetic and pharmacodynamic response in preweanling rats following oral exposure to the organophosphorus insecticide chlorpyrifos

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-03-01

    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 CPF-oxon and 3,5,6-trichloro-2-pyridinol (TCP), as well as B-esterase (cholinesterase; ChE) and A-esterase (PON-1) detoxification of CPF-oxon to TCP. The pharmacokinetics of CPF, TCP, and the extent of blood (plasma/RBC), and brain ChE inhibition in rats were determined on postnatal days (PND) -5, -12, and -17 following oral gavage administration of 1 and 10 mg CPF/kg of body weight. For all neonatal ages the blood TCP exceeded the CPF concentration, and within each age group there was no evidence of non-linear kinetics over the dose range evaluated. Younger animals demonstrated a greater sensitivity to ChE inhibition as evident by the dose- and age-dependent inhibition of plasma, RBC, and brain ChE. Of particular importance was the observation that even in rats as young as PND-5, the CYP450 metabolic capacity was adequate to metabolize CPF to both TCP and CPF-oxon based on the detection of TCP in blood and extensive ChE inhibition (biomarker of CPF-oxon) at all ages. In addition, the increase in the blood TCP concentration ({approx}3-fold) in PND-17 rats relative to the response in the younger animals, and the higher blood concentrations of CPF in neonatal rats (1.7 to 7.5-fold) relative to adults was consistent with an increase in CYP450 metabolic capacity with age. This is the first reported study that evaluated both the pharmacokinetics of the parent pesticide, the major metabolite and the extent of ChE inhibition dynamics in the same animals as a function of neonatal age. The results suggest that in the neonatal rat, CPF was rapidly absorbed and metabolized, and the extent of metabolism was age-dependent.

  9. Prenatal nicotine changes the response to postnatal chlorpyrifos: Interactions targeting serotonergic synaptic function and cognition.

    Science.gov (United States)

    Slotkin, Theodore A; Skavicus, Samantha; Levin, Edward D; Seidler, Frederic J

    2015-02-01

    Nicotine and chlorpyrifos are developmental neurotoxicants that target serotonin systems. We examined whether prenatal nicotine exposure alters the subsequent response to chlorpyrifos given postnatally. Pregnant rats received nicotine throughout gestation at 3mg/kg/day, a regimen designed to achieve plasma levels seen in smokers; chlorpyrifos was given to pups on postnatal days (PN) 1-4 at 1mg/kg, just above the detection threshold for brain cholinesterase inhibition. We assessed long-term effects from adolescence (PN30) through full adulthood (PN150), measuring the expression of serotonin receptors and serotonin turnover (index of presynaptic impulse activity) in cerebrocortical brain regions encompassing the projections that are known targets for nicotine and chlorpyrifos. Nicotine or chlorpyrifos individually increased the expression of serotonin receptors, with greater effects on males than on females and with distinct temporal and regional patterns indicative of adaptive synaptic changes rather than simply an extension of initial injury. This interpretation was confirmed by our finding an increase in serotonin turnover, connoting presynaptic serotonergic hyperactivity. Animals receiving the combined treatment showed a reduction in these adaptive effects on receptor binding and turnover relative to the individual agents, or even an effect in the opposite direction; further, normal sex differences in serotonin receptor concentrations were dissipated or reversed, an effect that was confirmed by behavioral evaluations in the Novel Objection Recognition Test. In addition to the known liabilities associated with maternal smoking during pregnancy, our results point to additional costs in the form of heightened vulnerability to neurotoxic chemicals encountered later in life. PMID:25592617

  10. Does Early-Life Exposure to Organophosphate Insecticides Lead to Prediabetes and Obesity?

    OpenAIRE

    Slotkin, Theodore A.

    2010-01-01

    Human exposures to organophosphate insecticides are ubiquitous. Although regarded as neurotoxicants, increasing evidence points toward lasting metabolic disruption from early-life organophosphate exposures. We gave neonatal rats chlorpyrifos, diazinon or parathion in doses devoid of any acute signs of toxicity, straddling the threshold for barely-detectable cholinesterase inhibition. Organophosphate exposure during a critical developmental window altered the trajectory of hepatic adenylyl cyc...

  11. Alterations in cognitive and psychological functioning after organic solvent exposure

    Energy Technology Data Exchange (ETDEWEB)

    Morrow, L.A.; Ryan, C.M.; Hodgson, M.J.; Robin, N. (Univ. of Pittsburgh School of Medicine, PA (USA))

    1990-05-01

    Exposure to organic solvents has been linked repeatedly to alterations in both personality and cognitive functioning. To assess the nature and extent of these changes more thoroughly, 32 workers with a history of exposure to mixtures of organic solvents and 32 age- and education-matched blue-collar workers with no history of exposure were assessed with a comprehensive battery of neuropsychological tests. Although both groups were comparable on measures of general intelligence, significant differences were found in virtually all other cognitive domains tested (Learning and Memory, Visuospatial, Attention and Mental Flexibility, Psychomotor Speed). In addition, Minnesota Multiphasic Personality Inventories of exposed workers indicated clinically significant levels of depression, anxiety, somatic concerns and disturbances in thinking. The reported psychological distress was unrelated to degree of cognitive deficit. Finally, several exposure-related variables were associated with poorer performance on tests of memory and visuospatial ability.

  12. 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...

  13. Gene Expression Profiling of Biological Pathway Alterations by Radiation Exposure

    Directory of Open Access Journals (Sweden)

    Kuei-Fang Lee

    2014-01-01

    Full Text Available Though damage caused by radiation has been the focus of rigorous research, the mechanisms through which radiation exerts harmful effects on cells are complex and not well-understood. In particular, the influence of low dose radiation exposure on the regulation of genes and pathways remains unclear. In an attempt to investigate the molecular alterations induced by varying doses of radiation, a genome-wide expression analysis was conducted. Peripheral blood mononuclear cells were collected from five participants and each sample was subjected to 0.5 Gy, 1 Gy, 2.5 Gy, and 5 Gy of cobalt 60 radiation, followed by array-based expression profiling. Gene set enrichment analysis indicated that the immune system and cancer development pathways appeared to be the major affected targets by radiation exposure. Therefore, 1 Gy radioactive exposure seemed to be a critical threshold dosage. In fact, after 1 Gy radiation exposure, expression levels of several genes including FADD, TNFRSF10B, TNFRSF8, TNFRSF10A, TNFSF10, TNFSF8, CASP1, and CASP4 that are associated with carcinogenesis and metabolic disorders showed significant alterations. Our results suggest that exposure to low-dose radiation may elicit changes in metabolic and immune pathways, potentially increasing the risk of immune dysfunctions and metabolic disorders.

  14. Effects of Single and Co-Exposure of Cu and Chlorpyrifos on the Toxicity of Earthworm%铜﹑毒死蜱单一与复合暴露对蚯蚓的毒性作用

    Institute of Scientific and Technical Information of China (English)

    徐冬梅; 王彦华; 王楠; 饶桂维

    2015-01-01

    Combined pollution of heavy metal and pesticide had posed a serious threat to soil ecology and human living environment. As two common types of pollutants in soil environment, the environmental effects of combined pollution of Cu and chlorpyrifos are worth for attention. The acute lethal effects and avoiding behavior of single and co-exposure of Cu and chlorpyrifos on earthworms were analyzed by using the methods of standard OECD filter paper test and artificial soil test. Results showed that the LC50,48 h and LC50,14 d of the acute toxicity of Cu on earthworm in filter paper test and in artificial soil test were 2. 23 μg•cm-2 and 496. 05 mg•kg-1 , respectively. The LC50,48 h and LC50,14 dof the acute toxicity of chlorpyrifos on earthworm in filter paper test and in artificial soil test were 5. 94 μg•cm-2 and 186. 07 mg•kg-1 , respectively. In filter paper test and artificial soil test, the joint acute toxicity of Cu and chlorpyrifos showed an additive effect while the concentration was 1:1. The type of combined effects of co-exposure of Cu and chlorpyrifos was synergistic effect and antagonistic effect in filter paper test and artificial soil test, respectively, while the toxicity was 1:1. The results of avoidance behavior test showed that the joint effect of Cu and chlorpyrifos on the avoidance behavior of earthworms was antagonistic.%土壤环境中重金属-农药复合污染已经对土壤生态和人类生存环境构成严重威胁.其中重金属铜和有机磷农药毒死蜱作为土壤环境中两类常见的污染物,其复合污染的环境效应值得关注.本文采用OECD标准滤纸接触法﹑人工土壤法研究了铜-毒死蜱单一及复合暴露对蚯蚓急性致死作用及回避行为的影响.结果表明,滤纸法和人工土壤法Cu对蚯蚓急性毒性的48 h-LC50和14 d-LC50分别为2.23μg•cm-2和496.05 mg•kg-1;而毒死蜱对蚯蚓急性毒性的48 h-LC50和14 d-LC50分别为5.94μg•cm-2和186.07 mg•kg-1.滤

  15. Gene Expression Profiling of Biological Pathway Alterations by Radiation Exposure

    OpenAIRE

    Lee, Kuei-Fang; Weng, Julia Tzu-Ya; Hsu, Paul Wei-Che; Chi, Yu-Hsiang; Chen, Ching-Kai; Liu, Ingrid Y.; CHEN, YI-CHENG; Wu, Lawrence Shih-Hsin

    2014-01-01

    Though damage caused by radiation has been the focus of rigorous research, the mechanisms through which radiation exerts harmful effects on cells are complex and not well-understood. In particular, the influence of low dose radiation exposure on the regulation of genes and pathways remains unclear. In an attempt to investigate the molecular alterations induced by varying doses of radiation, a genome-wide expression analysis was conducted. Peripheral blood mononuclear cells were collected from...

  16. Prenatal corticosteroid exposure alters early developmental seizures and behavior

    OpenAIRE

    Velíšek, Libor

    2011-01-01

    In humans, corticosteroids are often administered prenatally to improve lung development in preterm neonates. Studies in exposed children as well as in children, whose mothers experienced significant stress during pregnancy indicate behavioral problems and possible increased occurrence of epileptic spasms. This study investigated whether prenatal corticosteroid exposure alters early postnatal seizure susceptibility and behaviors. On gestational day 15, pregnant rats were injected i.p. with hy...

  17. 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...

  18. 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

  19. 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.

  20. 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.

  1. Cigarette smoke exposure-associated alterations to noncoding RNA

    Directory of Open Access Journals (Sweden)

    Matthew Alan Maccani

    2012-04-01

    Full Text Available Environmental exposures vary by timing, severity, and frequency and may have a number of deleterious effects throughout the life course. The period of in utero development, for example, is one of the most crucial stages of development during which adverse environmental exposures can both alter the growth and development of the fetus as well as lead to aberrant fetal programming, increasing disease risk. During fetal development and beyond, the plethora of exposures, including nutrients, drugs, stress, and trauma, influence health, development, and survival. Recent research in environmental epigenetics has investigated the roles of environmental exposures in influencing epigenetic modes of gene regulation during pregnancy and at various stages of life. Many relatively common environmental exposures, such as cigarette smoking, alcohol consumption, and drug use, may have consequences for the expression and function of noncoding RNA (ncRNA, important post-transcriptional regulators of gene expression. A number of ncRNA have been discovered, including microRNA (miRNA, Piwi-interacting RNA (piRNA, and long noncoding RNA (long ncRNA. The best-characterized species of ncRNA are miRNA, the mature forms of which are ~22 nucleotides in length and capable of post-transcriptionally regulating target mRNA utilizing mechanisms based largely on the degree of complementarity between miRNA and target mRNA. Because miRNA can still negatively regulate gene expression when imperfectly base-paired with a target mRNA, a single miRNA can have a large number of potential mRNA targets and can regulate many different biological processes critical for health and development. The following review analyzes the current literature detailing links between cigarette smoke exposure and aberrant expression and function of noncoding RNA, assesses how such alterations may have consequences throughout the life course, and proposes future directions for this intriguing field of

  2. 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.

  3. Alteration of gene expression by alcohol exposure at early neurulation

    Directory of Open Access Journals (Sweden)

    McClintick Jeanette N

    2011-02-01

    Full Text Available Abstract Background We have previously demonstrated that alcohol exposure at early neurulation induces growth retardation, neural tube abnormalities, and alteration of DNA methylation. To explore the global gene expression changes which may underline these developmental defects, microarray analyses were performed in a whole embryo mouse culture model that allows control over alcohol and embryonic variables. Result Alcohol caused teratogenesis in brain, heart, forelimb, and optic vesicle; a subset of the embryos also showed cranial neural tube defects. In microarray analysis (accession number GSM9545, adopting hypothesis-driven Gene Set Enrichment Analysis (GSEA informatics and intersection analysis of two independent experiments, we found that there was a collective reduction in expression of neural specification genes (neurogenin, Sox5, Bhlhe22, neural growth factor genes [Igf1, Efemp1, Klf10 (Tieg, and Edil3], and alteration of genes involved in cell growth, apoptosis, histone variants, eye and heart development. There was also a reduction of retinol binding protein 1 (Rbp1, and de novo expression of aldehyde dehydrogenase 1B1 (Aldh1B1. Remarkably, four key hematopoiesis genes (glycophorin A, adducin 2, beta-2 microglobulin, and ceruloplasmin were absent after alcohol treatment, and histone variant genes were reduced. The down-regulation of the neurospecification and the neurotrophic genes were further confirmed by quantitative RT-PCR. Furthermore, the gene expression profile demonstrated distinct subgroups which corresponded with two distinct alcohol-related neural tube phenotypes: an open (ALC-NTO and a closed neural tube (ALC-NTC. Further, the epidermal growth factor signaling pathway and histone variants were specifically altered in ALC-NTO, and a greater number of neurotrophic/growth factor genes were down-regulated in the ALC-NTO than in the ALC-NTC embryos. Conclusion This study revealed a set of genes vulnerable to alcohol exposure and

  4. 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

  5. 围生期毒死蜱暴露致子代8周雄鼠睾丸组织的氧化损伤%Perinatal Exposure to Chlorpyrifos Induced Testicular Oxidative Damage in 8 Week Offspring Male Rat

    Institute of Scientific and Technical Information of China (English)

    徐肖倩; 张敏; 王学梅; 方鑫; 李海玲; 戴红; 肖瑞

    2015-01-01

    Chlorpyrifos is one of the largest used and saled organophosphorus pesticides throughout the world. To explore the testicular oxidative damage of 8 week offspring male rat induced by perinatal exposure to chlorpyrifos, the healthy pregnant Wistar female rats were exposed to chlorpyrifos of 0, 0.75, 1.35 and 2.70 mg•kg-1 by gavage during GD 6—PND21 d. Until the offspring male rat reached the age of 8 week, histopathological changes of left testis were observed. We also detected the level of MDA and the activity of GST, GSH-Px, and T-SOD in right tes-tis. The results showed that although no statistical significance were observed in body weight, the organ coefficient of testis and epididymis compared with control group, both of them showed a downward trend and of MDA showed an upward trend when the dose increased (P>0.05). The decrease in the activity of T-SOD of all dose groups, the increase of the activity of GSH-Px of 1.35 mg•kg-1 and 2.70 mg•kg-1 dose groups and the increase in activity of GST of 2.70 mg•kg-1 dose group were statistically significant (P0.05);而MDA呈升高趋势(P>0.05)。各组T-SOD和1.35、2.70 mg•kg-1剂量组GSH-Px活力的下降及2.70 mg•kg-1剂量组GST活力的升高均有统计学意义(P<0.05)。睾丸组织病理学检查结果可见2.70 mg•kg-1剂量组睾丸组织有明显的损伤,管腔中精液量减少,生精细胞脱落增多。上述研究结果提示母鼠于围生期暴露于毒死蜱,可通过氧化损伤诱导子代雄性大鼠睾丸的毒性作用。

  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. 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...

  8. 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...

  9. 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.

  10. 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...

  11. 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.

  12. 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.

  13. 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

  14. Mere Exposure Alters Category Learning of Novel Objects

    OpenAIRE

    Folstein, Jonathan R.; Gauthier, Isabel; Palmeri, Thomas J.

    2010-01-01

    We investigated how mere exposure to complex objects with correlated or uncorrelated object features affects later category learning of new objects not seen during exposure. Correlations among pre-exposed object dimensions influenced later category learning. Unlike other published studies, the collection of pre-exposed objects provided no information regarding the categories to be learned, ruling out unsupervised or incidental category learning during pre-exposure. Instead, results are interp...

  15. Mere exposure alters category learning of novel objects

    OpenAIRE

    ThomasJPalmeri

    2010-01-01

    We investigated how mere exposure to complex objects with correlated or uncorrelated object features affects later category learning of new objects not seen during exposure. Correlations among pre-exposed object dimensions influenced later category learning. Unlike other published studies, the collection of pre-exposed objects provided no information regarding the categories to be learned, ruling out unsupervised or incidental category learning during pre-exposure. Instead, results are interp...

  16. 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...

  17. FINE PARTICLE EXPOSURE IS ASSOCIATED WITH ALTERED VENTRICULAR REPOLARIZATION

    Science.gov (United States)

    Exposure to fine airborne particulate matter (PM2.5) has previously been associated with cardiac events, especially in older people with cardiovascular disease and in diabetics. This study examined the cardiac effects of short-term exposures to ambient PM2.5 in a prospective pane...

  18. Sublethal toxicity of chlorpyrifos to salmonid olfaction after hypersaline acclimation.

    Science.gov (United States)

    Maryoung, Lindley A; Blunt, Brian; Tierney, Keith B; Schlenk, Daniel

    2015-04-01

    Salmonid habitats can be impacted by several environmental factors, such as salinization, which can also affect salmonid tolerance to anthropogenic stressors, such as pesticides. Previous studies have shown that hypersaline acclimation enhances the acute toxicity of certain organophosphate and carbamate pesticides to euryhaline fish; however, sublethal impacts have been far less studied. The current study aims to determine how hypersaline acclimation and exposure to the organophosphate chlorpyrifos (CPF) impact salmonid olfaction. Combined acclimation and exposure to CPF was shown to impact rainbow trout olfaction at the molecular, physiological, and behavioral levels. Concurrent exposure to hypersalinity and 0.5μg/L CPF upregulated four genes (chloride intracellular channel 4, G protein zgc:101761, calcium calmodulin dependent protein kinase II delta, and adrenergic alpha 2C receptor) that inhibit olfactory signal transduction. At the physiological level, hypersalinity and chlorpyrifos caused a decrease in sensory response to the amino acid l-serine and the bile salt taurocholic acid. Combined acclimation and exposure also negatively impacted behavior and reduced the avoidance of a predator cue (l-serine). Thus, acclimation to hypersaline conditions and exposure to environmentally relevant concentrations of chlorpyrifos caused an inhibition of olfactory signal transduction leading to a decreased response to odorants and impairment of olfactory mediated behaviors.

  19. 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.

  20. 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

  1. Radiation Exposure Alters Expression of Metabolic Enzyme Genes in Mice

    Science.gov (United States)

    Wotring, V. E.; Mangala, L. S.; Zhang, Y.; Wu, H.

    2011-01-01

    Most administered pharmaceuticals are metabolized by the liver. The health of the liver, especially the rate of its metabolic enzymes, determines the concentration of circulating drugs as well as the duration of their efficacy. Most pharmaceuticals are metabolized by the liver, and clinically-used medication doses are given with normal liver function in mind. A drug overdose can result in the case of a liver that is damaged and removing pharmaceuticals from the circulation at a rate slower than normal. Alternatively, if liver function is elevated and removing drugs from the system more quickly than usual, it would be as if too little drug had been given for effective treatment. Because of the importance of the liver in drug metabolism, we want to understand the effects of spaceflight on the enzymes of the liver and exposure to cosmic radiation is one aspect of spaceflight that can be modeled in ground experiments. Additionally, it has been previous noted that pre-exposure to small radiation doses seems to confer protection against later and larger radiation doses. This protective power of pre-exposure has been called a priming effect or radioadaptation. This study is an effort to examine the drug metabolizing effects of radioadaptation mechanisms that may be triggered by early exposure to low radiation doses.

  2. Alterations in the laryngeal mucosa after exposure to asbestos.

    OpenAIRE

    Kambic, V; Radsel, Z; Gale, N

    1989-01-01

    The laryngeal mucosa of 195 workers in an asbestos cement factory (Salonit Anhovo, Yugoslavia) and in a control group was examined. The factory manufactures asbestos cement products containing about 13% of asbestos (8% amosite, 12% crocidolite, and 80% chrysotile) of different provenance. Alterations in the laryngeal mucosa were more frequent in the factory workers than in the control group. The changes, mostly consistent with chronic laryngitis, were closely related to the degree of workplac...

  3. 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.

  4. Prenatal cadmium exposure alters postnatal immune cell development and function

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, Miranda L.; Holásková, Ida; Elliott, Meenal; Brundage, Kathleen M.; Schafer, Rosana; Barnett, John B., E-mail: jbarnett@hsc.wvu.edu

    2012-06-01

    Cadmium (Cd) is generally found in low concentrations in the environment due to its widespread and continual use, however, its concentration in some foods and cigarette smoke is high. Although evidence demonstrates that adult exposure to Cd causes changes in the immune system, there are limited reports of immunomodulatory effects of prenatal exposure to Cd. This study was designed to investigate the effects of prenatal exposure to Cd on the immune system of the offspring. Pregnant C57Bl/6 mice were exposed to an environmentally relevant dose of CdCl{sub 2} (10 ppm) and the effects on the immune system of the offspring were assessed at two time points following birth (2 and 7 weeks of age). Thymocyte and splenocyte phenotypes were analyzed by flow cytometry. Prenatal Cd exposure did not affect thymocyte populations at 2 and 7 weeks of age. In the spleen, the only significant effect on phenotype was a decrease in the number of macrophages in male offspring at both time points. Analysis of cytokine production by stimulated splenocytes demonstrated that prenatal Cd exposure decreased IL-2 and IL-4 production by cells from female offspring at 2 weeks of age. At 7 weeks of age, splenocyte IL-2 production was decreased in Cd-exposed males while IFN-γ production was decreased from both male and female Cd-exposed offspring. The ability of the Cd-exposed offspring to respond to immunization with a S. pneumoniae vaccine expressing T-dependent and T-independent streptococcal antigens showed marked increases in the levels of both T-dependent and T-independent serum antibody levels compared to control animals. CD4{sup +}FoxP3{sup +}CD25{sup +} (nTreg) cell percentages were increased in the spleen and thymus in all Cd-exposed offspring except in the female spleen where a decrease was seen. CD8{sup +}CD223{sup +} T cells were markedly decreased in the spleens in all offspring at 7 weeks of age. These findings suggest that even very low levels of Cd exposure during gestation can

  5. Sediment microbes and biofilms increase the bioavailability of chlorpyrifos in Chironomus riparius (Chironomidae, Diptera).

    Science.gov (United States)

    Widenfalk, Anneli; Lundqvist, Anna; Goedkoop, Willem

    2008-10-01

    In a microcosm study, the importance of different sources of organic matter (humic acids, sterile sediment, sediment, and a microbial extract) for the bioavailability of the hydrophobic pesticide chlorpyrifos to Chironomus riparius larvae was quantified. In the last two treatments biofilms were allowed to grow before (14)C-chlorpyrifos addition. Chlorpyrifos accumulation was quantified after 25 h of exposure and after 21 h of depuration. Larval accumulation was twice as high in the microbial extract treatment (447+/-79 microg/kg ww larvae) and 1.7 times higher in the sediment treatment (371+/-33 microg/kg). After depuration, chlorpyrifos accumulation in larval tissue showed even higher differences; 3.1 times higher tissue concentrations in the microbial extract treatment (218+/-21 microg/kg) and 2.2 times higher in the sediment treatment (156+/-35 microg/kg). In contrast, chlorpyrifos accumulation in the humic acid and sterile sediment did not differ from that in controls. These results show that living microbes and biofilms, by creating a microenvironment and providing food for larvae, markedly increase the bioavailability of chlorpyrifos to Chironomus riparius.

  6. 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.

  7. Organophosphorous pesticide exposure alters sperm chromatin structure in Mexican agricultural workers

    International Nuclear Information System (INIS)

    Our objective was to evaluate alterations in sperm chromatin structure in men occupationally exposed to a mixture of organophosphorus pesticides (OP) because these alterations have been proposed to compromise male fertility and offspring development. Chromatin susceptibility to in situ acid-induced denaturation structure was assessed by the sperm chromatin structure assay (SCSA). Urinary levels of alkylphosphates (DAP) were used to assess exposure. Diethylthiophosphate (DETP) was the most frequent OP metabolite found in urine samples indicating that compounds derived from thiophosphoric acid were mainly used. Chromatin structure was altered in most samples. About 75% of semen samples were classified as having poor fertility potential (>30% of Percentage of DNA Fragmentation Index [DFI%]), whereas individuals without OP occupational exposure showed average DFI% values of 9.9%. Most parameters of conventional semen analysis were within normality except for the presence of immature cells (IGC) in which 82% of the samples were above reference values. There were significant direct associations between urinary DETP concentrations and mean DFI and SD-DFI but marginally (P = 0.079) with DFI%, after adjustment for potential confounders, including IGC. This suggests that OP exposure alters sperm chromatin condensation, which could be reflected in an increased number of cells with greater susceptibility to DNA denaturation. This study showed that human sperm chromatin is a sensitive target to OP exposure and may contribute to adverse reproductive outcomes. Further studies on the relevance of protein phosphorylation as a possible mechanism by which OP alter sperm chromatin are required

  8. Alteration of rat fetal cerebral cortex development after prenatal exposure to polychlorinated biphenyls.

    Directory of Open Access Journals (Sweden)

    Elise Naveau

    Full Text Available Polychlorinated biphenyls (PCBs are environmental contaminants that persist in environment and human tissues. Perinatal exposure to these endocrine disruptors causes cognitive deficits and learning disabilities in children. These effects may involve their ability to interfere with thyroid hormone (TH action. We tested the hypothesis that developmental exposure to PCBs can concomitantly alter TH levels and TH-regulated events during cerebral cortex development: progenitor proliferation, cell cycle exit and neuron migration. Pregnant rats exposed to the commercial PCB mixture Aroclor 1254 ended gestation with reduced total and free serum thyroxine levels. Exposure to Aroclor 1254 increased cell cycle exit of the neuronal progenitors and delayed radial neuronal migration in the fetal cortex. Progenitor cell proliferation, cell death and differentiation rate were not altered by prenatal exposure to PCBs. Given that PCBs remain ubiquitous, though diminishing, contaminants in human systems, it is important that we further understand their deleterious effects in the brain.

  9. Alteration of rat fetal cerebral cortex development after prenatal exposure to polychlorinated biphenyls

    OpenAIRE

    Naveau, Elise; Pinson, Anneline; GERARD, Arlette; Nguyen, Laurent; Charlier, Corinne; Thomé, Jean-Pierre; Zoeller, Robert Thomas; Bourguignon, Jean-Pierre; Parent, Anne-Simone

    2014-01-01

    Polychlorinated biphenyls (PCBs) are environmental contaminants that persist in environment and human tissues. Perinatal exposure to these endocrine disruptors causes cognitive deficits and learning disabilities in children. These effects may involve their ability to interfere with thyroid hormone (TH) action. We tested the hypothesis that developmental exposure to PCBs can concomitantly alter TH levels and TH-regulated events during cerebral cortex development: progenitor proliferation, cell...

  10. Chronic alcohol exposure alters behavioral and synaptic plasticity of the rodent prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    Sven Kroener

    Full Text Available In the present study, we used a mouse model of chronic intermittent ethanol (CIE exposure to examine how CIE alters the plasticity of the medial prefrontal cortex (mPFC. In acute slices obtained either immediately or 1-week after the last episode of alcohol exposure, voltage-clamp recording of excitatory post-synaptic currents (EPSCs in mPFC layer V pyramidal neurons revealed that CIE exposure resulted in an increase in the NMDA/AMPA current ratio. This increase appeared to result from a selective increase in the NMDA component of the EPSC. Consistent with this, Western blot analysis of the postsynaptic density fraction showed that while there was no change in expression of the AMPA GluR1 subunit, NMDA NR1 and NRB subunits were significantly increased in CIE exposed mice when examined immediately after the last episode of alcohol exposure. Unexpectedly, this increase in NR1 and NR2B was no longer observed after 1-week of withdrawal in spite of a persistent increase in synaptic NMDA currents. Analysis of spines on the basal dendrites of layer V neurons revealed that while the total density of spines was not altered, there was a selective increase in the density of mushroom-type spines following CIE exposure. Examination of NMDA-receptor mediated spike-timing-dependent plasticity (STDP showed that CIE exposure was associated with altered expression of long-term potentiation (LTP. Lastly, behavioral studies using an attentional set-shifting task that depends upon the mPFC for optimal performance revealed deficits in cognitive flexibility in CIE exposed mice when tested up to 1-week after the last episode of alcohol exposure. Taken together, these observations are consistent with those in human alcoholics showing protracted deficits in executive function, and suggest these deficits may be associated with alterations in synaptic plasticity in the mPFC.

  11. ALTERATIONS IN BRAIN PROTEIN KINASE C ISOFORMS FOLLOWING DEVELOPMENTAL EXPOSURE TO POLYCHLORINATED BIPHENYL MIXTURE.

    Science.gov (United States)

    PCBs have been shown to alter several neurochemical end-points and are implicated in the etiology of some neurological diseases. Recent in vivo studies from our laboratory indicated that developmental exposure to a commercial PCB mixture, Aroclor 1254, caused perturbations in cal...

  12. Human Ozone (O3) Exposure Alters Serum Profile of Lipid Metabolites

    Science.gov (United States)

    HUMAN OZONE (O3) EXPOSURE ALTERS SERUM PROFILE OF LIPID METABOLITES Miller, D B.1; Kodavanti, U P.2 Karoly, E D.3; Cascio W.E2, Ghio, A J. 21. UNC-Chapel Hill, Chapel Hill, N.C., United States. 2. NHEERL, U.S. EPA, RTP, N.C., United States. 3. METABOLON INC., Durham, N.C., United...

  13. Adulthood stress responses in rats are variably altered as a factor of adolescent stress exposure.

    Science.gov (United States)

    Moore, Nicole L T; Altman, Daniel E; Gauchan, Sangeeta; Genovese, Raymond F

    2016-05-01

    Stress exposure during development may influence adulthood stress response severity. The present study investigates persisting effects of two adolescent stressors upon adulthood response to predator exposure (PE). Rats were exposed to underwater trauma (UWT) or PE during adolescence, then to PE after reaching adulthood. Rats were then exposed to predator odor (PO) to test responses to predator cues alone. Behavioral and neuroendocrine assessments were conducted to determine acute effects of each stress experience. Adolescent stress altered behavioral response to adulthood PE. Acoustic startle response was blunted. Bidirectional changes in plus maze exploration were revealed as a factor of adolescent stress type. Neuroendocrine response magnitude did not predict severity of adolescent or adult stress response, suggesting that different adolescent stress events may differentially alter developmental outcomes regardless of acute behavioral or neuroendocrine response. We report that exposure to two different stressors in adolescence may differentially affect stress response outcomes in adulthood. Acute response to an adolescent stressor may not be consistent across all stressors or all dependent measures, and may not predict alterations in developmental outcomes pertaining to adulthood stress exposure. Further studies are needed to characterize factors underlying long-term effects of a developmental stressor.

  14. Degradation of chlorpyrifos alone and in combination with chlorothalonil and their effects on soil microbial populations

    Institute of Scientific and Technical Information of China (English)

    CHU Xiaoqiang; FANG Hua; PAN Xuedong; WANG Xiao; SHAN Min; FENG Bo; YU Yunlong

    2008-01-01

    In practice, pesticides are usually applied simultaneously or one after another for crop protection, and this type of pesticide application often leads to a combined contamination of pesticide residues in the soil environment. A laboratory study was conducted to investigate the influence of chlorothalonil on chlorpyrifos degradation and its effects on soil bacterial, fungal, and actinomycete populations. Under the experimental conditions here, the half-lives of chlorpyrifos alone, and in combination with chlorothalonil, at the recommended and double dosages, were measured to be 3.24, 2.77, and 2.63 d, respectively. Chlorpyrifos degradation was not significantly altered by its combination with chlorothalonil. However, the inhibitory effect of chlorpyrifos on soil microorganisms was increased by its combination with chlorothalonil, and the increase was related to the levels of chlorothalonil added. Compared to those in the controls, the populations of bacteria, fungi, and actinomycetes were significantly reduced by 44.1%, 61.1%, and 72.8%, respectively, on the first day after treatment (DAT) by chlorpyrifos alone. With the addition of chlorothalonil, the inhibition was increased to 55.2%, 79.3%, and 85.8% at the recommended dosage, and 86.0%, 94.1%, and 90.8% at the double dosage, at one DAT, respectively. The results suggested that combined effects should be taken into account to assess the actual impacts of pesticide applications.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. [Photochemical degradation of chlorpyrifos in water].

    Science.gov (United States)

    Wu, Xiangwei; Hua, Rimao; Tang, Feng; Li, Xuede; Cao, Haiqun; Yue, Yongde

    2006-07-01

    In this paper, the effects of different light sources, temperature, pH, and water quality on the photochemical degradation of clilorpyrifos in water were examined under natural and simulated solar irradiation. The results showed that the photochemical degradation of chlorpyrifos in water followed the first order reaction, and its half-life was 0.62, 6.92, 19.74 and 22.50 h under high pressure mercury lamp (HPML), xenon lamp (XL), ultraviolet lamp (UV), and sunlight (SL) irradiation, respectively. Temperature had a significant effect on the degradation rate of chlorpyrifos, which was increased with increasing temperature and reached the maximum at 35 degrees C. The degradation rate of chlorpyrifos was stable both in acid and in neutral buffer solution, but enhanced in alkaline buffer solution. Water quality also had a significant effect, with a decreasing degradation rate of chlorpyrifos in the sequence of distilled water > tap water > river water > lake wate > paddy water.

  17. Developmental Exposure to Xenoestrogens at Low Doses Alters Femur Length and Tensile Strength in Adult Mice1

    OpenAIRE

    Pelch, Katherine E.; Carleton, Stephanie M.; Phillips, Charlotte L.; Nagel, Susan C.

    2011-01-01

    Developmental exposure to high doses of the synthetic xenoestrogen diethylstilbestrol (DES) has been reported to alter femur length and strength in adult mice. However, it is not known if developmental exposure to low, environmentally relevant doses of xenoestrogens alters adult bone geometry and strength. In this study we investigated the effects of developmental exposure to low doses of DES, bisphenol A (BPA), or ethinyl estradiol (EE2) on bone geometry and torsional strength. C57BL/6 mice ...

  18. 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.

  19. The Volitional Nature of Nicotine Exposure Alters Anandamide and Oleoylethanolamide Levels in the Ventral Tegmental Area

    Science.gov (United States)

    Buczynski, Matthew W; Polis, Ilham Y; Parsons, Loren H

    2013-01-01

    Cannabinoid-1 receptors (CB1) have an important role in nicotine reward and their function is disrupted by chronic nicotine exposure, suggesting nicotine-induced alterations in endocannabinoid (eCB) signaling. However, the effects of nicotine on brain eCB levels have not been rigorously evaluated. Volitional intake of nicotine produces physiological and behavioral effects distinct from forced drug administration, although the mechanisms underlying these effects are not known. This study compared the effects of volitional nicotine self-administration (SA) and forced nicotine exposure (yoked administration (YA)) on levels of eCBs and related neuroactive lipids in the ventral tegmental area (VTA) and other brain regions. Brain lipid levels were indexed both by in vivo microdialysis in the VTA and lipid extractions from brain tissues. Nicotine SA, but not YA, reduced baseline VTA dialysate oleoylethanolamide (OEA) levels relative to nicotine-naïve controls, and increased anandamide (AEA) release during nicotine intake. In contrast, all nicotine exposure paradigms increased VTA dialysate 2-arachidonoyl glycerol (2-AG) levels. Thus, nicotine differentially modulates brain lipid (2-AG, AEA, and OEA) signaling, and these modulations are influenced by the volitional nature of the drug exposure. Corresponding bulk tissue analysis failed to identify these lipid changes. Nicotine exposure had no effect on fatty acid amide hydrolase activity in the VTA, suggesting that changes in AEA and OEA signaling result from alterations in their nicotine-induced biosynthesis. Both CB1 (by AEA and 2-AG) and non-CB1 (by OEA) targets can alter the excitability and activity of the dopaminergic neurons in the VTA. Collectively, these findings implicate disrupted lipid signaling in the motivational effects of nicotine. PMID:23169348

  20. 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

  1. Maternal mobile phone exposure alters intrinsic electrophysiological properties of CA1 pyramidal neurons in rat offspring.

    Science.gov (United States)

    Razavinasab, Moazamehosadat; Moazzami, Kasra; Shabani, Mohammad

    2016-06-01

    Some studies have shown that exposure to electromagnetic field (EMF) may result in structural damage to neurons. In this study, we have elucidated the alteration in the hippocampal function of offspring Wistar rats (n = 8 rats in each group) that were chronically exposed to mobile phones during their gestational period by applying behavioral, histological, and electrophysiological tests. Rats in the EMF group were exposed to 900 MHz pulsed-EMF irradiation for 6 h/day. Whole cell recordings in hippocampal pyramidal cells in the mobile phone groups did show a decrease in neuronal excitability. Mobile phone exposure was mostly associated with a decrease in the number of action potentials fired in spontaneous activity and in response to current injection in both male and female groups. There was an increase in the amplitude of the afterhyperpolarization (AHP) in mobile phone rats compared with the control. The results of the passive avoidance and Morris water maze assessment of learning and memory performance showed that phone exposure significantly altered learning acquisition and memory retention in male and female rats compared with the control rats. Light microscopy study of brain sections of the control and mobile phone-exposed rats showed normal morphology.Our results suggest that exposure to mobile phones adversely affects the cognitive performance of both female and male offspring rats using behavioral and electrophysiological techniques. PMID:24604340

  2. Maternal mobile phone exposure alters intrinsic electrophysiological properties of CA1 pyramidal neurons in rat offspring.

    Science.gov (United States)

    Razavinasab, Moazamehosadat; Moazzami, Kasra; Shabani, Mohammad

    2016-06-01

    Some studies have shown that exposure to electromagnetic field (EMF) may result in structural damage to neurons. In this study, we have elucidated the alteration in the hippocampal function of offspring Wistar rats (n = 8 rats in each group) that were chronically exposed to mobile phones during their gestational period by applying behavioral, histological, and electrophysiological tests. Rats in the EMF group were exposed to 900 MHz pulsed-EMF irradiation for 6 h/day. Whole cell recordings in hippocampal pyramidal cells in the mobile phone groups did show a decrease in neuronal excitability. Mobile phone exposure was mostly associated with a decrease in the number of action potentials fired in spontaneous activity and in response to current injection in both male and female groups. There was an increase in the amplitude of the afterhyperpolarization (AHP) in mobile phone rats compared with the control. The results of the passive avoidance and Morris water maze assessment of learning and memory performance showed that phone exposure significantly altered learning acquisition and memory retention in male and female rats compared with the control rats. Light microscopy study of brain sections of the control and mobile phone-exposed rats showed normal morphology.Our results suggest that exposure to mobile phones adversely affects the cognitive performance of both female and male offspring rats using behavioral and electrophysiological techniques.

  3. Acetylcholinesterase inhibition in the threeridge mussel (Amblema plicata) by chlorpyrifos: implications for biomonitoring

    Science.gov (United States)

    Doran, W.J.; Cope, W.G.; Rada, R.G.; Sandheinrich, M.B.

    2001-01-01

    The effects of chlorpyrifos, an organophosphorus insecticide, were examined on the activity of the nervous system enzyme acetylcholinesterase (AChE) in the threeridge mussel Amblema plicata in a 24-day laboratory test. Thirty-six mussels in each of seven treatments (18 mussels per duplicate) were exposed to chlorpyrifos (0.1, 0.2, 0.3, 0.6, and 1.2 mg/L), a solvent (acetone), and a solvent-free (well water) control for 12, 24, or 96 h. The activity of AChE was measured in the anterior adductor muscle of eight mussels from each treatment after exposure. To assess potential latent effects, six mussels from each treatment were removed after 24 h of exposure and transferred to untreated water for a 21-day holding period; AChE activity was measured on three mussels from each treatment at 7 and 21 days of the holding period. The activity of AChE in chlorpyrifos-exposed mussels did not differ from controls after 12 or 24 h of exposure (t- test, P>0.05), but was significantly less than controls after 96 h (t- test, P=0.01). AChE activity did not vary among mussels at 24 h of exposure (i.e., Day 0 of holding period) and those at Day 7 and Day 21 of the holding period. Overall changes in AChE activity of mussels during the test were unrelated to individual chlorpyrifos concentrations and exposure times (repeated measure ANOVA; (P=0.06). A power analysis revealed that the sample size must be increased from 2 to 5 replicates (8 to 20 mussels per time interval and test concentration) to increase the probability of detecting significant differences in AChE activity. This calculated increase in sample size has potential implications for future biomonitoring studies with chlorpyrifos and unionid mussels.

  4. Altered Proteome of Burkholderia pseudomallei Colony Variants Induced by Exposure to Human Lung Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Anis Rageh Al-Maleki

    Full Text Available Burkholderia pseudomallei primary diagnostic cultures demonstrate colony morphology variation associated with expression of virulence and adaptation proteins. This study aims to examine the ability of B. pseudomallei colony variants (wild type [WT] and small colony variant [SCV] to survive and replicate intracellularly in A549 cells and to identify the alterations in the protein expression of these variants, post-exposure to the A549 cells. Intracellular survival and cytotoxicity assays were performed followed by proteomics analysis using two-dimensional gel electrophoresis. B. pseudomallei SCV survive longer than the WT. During post-exposure, among 259 and 260 protein spots of SCV and WT, respectively, 19 were differentially expressed. Among SCV post-exposure up-regulated proteins, glyceraldehyde 3-phosphate dehydrogenase, fructose-bisphosphate aldolase (CbbA and betaine aldehyde dehydrogenase were associated with adhesion and virulence. Among the down-regulated proteins, enolase (Eno is implicated in adhesion and virulence. Additionally, post-exposure expression profiles of both variants were compared with pre-exposure. In WT pre- vs post-exposure, 36 proteins were differentially expressed. Of the up-regulated proteins, translocator protein, Eno, nucleoside diphosphate kinase (Ndk, ferritin Dps-family DNA binding protein and peptidyl-prolyl cis-trans isomerase B were implicated in invasion and virulence. In SCV pre- vs post-exposure, 27 proteins were differentially expressed. Among the up-regulated proteins, flagellin, Eno, CbbA, Ndk and phenylacetate-coenzyme A ligase have similarly been implicated in adhesion, invasion. Protein profiles differences post-exposure provide insights into association between morphotypic and phenotypic characteristics of colony variants, strengthening the role of B. pseudomallei morphotypes in pathogenesis of melioidosis.

  5. Morning and Evening Blue-Enriched Light Exposure Alters Metabolic Function in Normal Weight Adults.

    Science.gov (United States)

    Cheung, Ivy N; Zee, Phyllis C; Shalman, Dov; Malkani, Roneil G; Kang, Joseph; Reid, Kathryn J

    2016-01-01

    Increasing evidence points to associations between light-dark exposure patterns, feeding behavior, and metabolism. This study aimed to determine the acute effects of 3 hours of morning versus evening blue-enriched light exposure compared to dim light on hunger, metabolic function, and physiological arousal. Nineteen healthy adults completed this 4-day inpatient protocol under dim light conditions (<20lux). Participants were randomized to 3 hours of blue-enriched light exposure on Day 3 starting either 0.5 hours after wake (n = 9; morning group) or 10.5 hours after wake (n = 10; evening group). All participants remained in dim light on Day 2 to serve as their baseline. Subjective hunger and sleepiness scales were collected hourly. Blood was sampled at 30-minute intervals for 4 hours in association with the light exposure period for glucose, insulin, cortisol, leptin, and ghrelin. Homeostatic model assessment of insulin resistance (HOMA-IR) and area under the curve (AUC) for insulin, glucose, HOMA-IR and cortisol were calculated. Comparisons relative to baseline were done using t-tests and repeated measures ANOVAs. In both the morning and evening groups, insulin total area, HOMA-IR, and HOMA-IR AUC were increased and subjective sleepiness was reduced with blue-enriched light compared to dim light. The evening group, but not the morning group, had significantly higher glucose peak value during blue-enriched light exposure compared to dim light. There were no other significant differences between the morning or the evening groups in response to blue-enriched light exposure. Blue-enriched light exposure acutely alters glucose metabolism and sleepiness, however the mechanisms behind this relationship and its impacts on hunger and appetite regulation remain unclear. These results provide further support for a role of environmental light exposure in the regulation of metabolism. PMID:27191727

  6. Genistein exposure inhibits growth and alters steroidogenesis in adult mouse antral follicles.

    Science.gov (United States)

    Patel, Shreya; Peretz, Jackye; Pan, Yuan-Xiang; Helferich, William G; Flaws, Jodi A

    2016-02-15

    Genistein is a naturally occurring isoflavone phytoestrogen commonly found in plant products such as soybeans, lentils, and chickpeas. Genistein, like other phytoestrogens, has the potential to mimic, enhance, or impair the estradiol biosynthesis pathway, thereby potentially altering ovarian follicle growth. Previous studies have inconsistently indicated that genistein exposure may alter granulosa cell proliferation and hormone production, but no studies have examined the effects of genistein on intact antral follicles. Thus, this study was designed to test the hypothesis that genistein exposure inhibits follicle growth and steroidogenesis in intact antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice were cultured with vehicle (dimethyl sulfoxide; DMSO) or genistein (6.0 and 36μM) for 18-96h. Every 24h, follicle diameters were measured to assess growth. At the end of each culture period, the media were pooled to measure hormone levels, and the cultured follicles were collected to measure expression of cell cycle regulators and steroidogenic enzymes. The results indicate that genistein (36μM) inhibits growth of mouse antral follicles. Additionally, genistein (6.0 and 36μM) increases progesterone, testosterone, and dehydroepiandrosterone (DHEA) levels, but decreases estrone and estradiol levels. The results also indicate that genistein alters the expression of steroidogenic enzymes at 24, 72 and 96h, and the expression of cell cycle regulators at 18h. These data indicate that genistein exposure inhibits antral follicle growth by inhibiting the cell cycle, alters sex steroid hormone levels, and dysregulates steroidogenic enzymes in cultured mouse antral follicles. PMID:26792615

  7. Fetal and neonatal exposure to the endocrine disruptor methoxychlor causes epigenetic alterations in adult ovarian genes.

    Science.gov (United States)

    Zama, Aparna Mahakali; Uzumcu, Mehmet

    2009-10-01

    Exposure to endocrine-disrupting chemicals during development could alter the epigenetic programming of the genome and result in adult-onset disease. Methoxychlor (MXC) and its metabolites possess estrogenic, antiestrogenic, and antiandrogenic activities. Previous studies showed that fetal/neonatal exposure to MXC caused adult ovarian dysfunction due to altered expression of key ovarian genes including estrogen receptor (ER)-beta, which was down-regulated, whereas ERalpha was unaffected. The objective of the current study was to evaluate changes in global and gene-specific methylation patterns in adult ovaries associated with the observed defects. Rats were exposed to MXC (20 microg/kgxd or 100 mg/kg.d) between embryonic d 19 and postnatal d 7. We performed DNA methylation analysis of the known promoters of ERalpha and ERbeta genes in postnatal d 50-60 ovaries using bisulfite sequencing and methylation-specific PCRs. Developmental exposure to MXC led to significant hypermethylation in the ERbeta promoter regions (P < 0.05), whereas the ERalpha promoter was unaffected. We assessed global DNA methylation changes using methylation-sensitive arbitrarily primed PCR and identified 10 genes that were hypermethylated in ovaries from exposed rats. To determine whether the MXC-induced methylation changes were associated with increased DNA methyltransferase (DNMT) levels, we measured the expression levels of Dnmt3a, Dnmt3b, and Dnmt3l using semiquantitative RT-PCR. Whereas Dnmt3a and Dnmt3l were unchanged, Dnmt3b expression was stimulated in ovaries of the 100 mg/kg MXC group (P < 0.05), suggesting that increased DNMT3B may cause DNA hypermethylation in the ovary. Overall, these data suggest that transient exposure to MXC during fetal and neonatal development affects adult ovarian function via altered methylation patterns.

  8. Early life exposure to allergen and ozone results in altered development in adolescent rhesus macaque lungs

    Energy Technology Data Exchange (ETDEWEB)

    Herring, M.J.; Putney, L.F.; St George, J.A. [California National Primate Research Center, Davis, CA (United States); Avdalovic, M.V. [Department of Internal Medicine, Division of Pulmonary and Critical Care, University of California, Davis, CA (United States); Schelegle, E.S.; Miller, L.A. [California National Primate Research Center, Davis, CA (United States); Hyde, D.M., E-mail: dmhyde@ucdavis.edu [California National Primate Research Center, Davis, CA (United States)

    2015-02-15

    In rhesus macaques, previous studies have shown that episodic exposure to allergen alone or combined with ozone inhalation during the first 6 months of life results in a condition with many of the hallmarks of asthma. This exposure regimen results in altered development of the distal airways and parenchyma (Avdalovic et al., 2012). We hypothesized that the observed alterations in the lung parenchyma would be permanent following a long-term recovery in filtered air (FA) housing. Forty-eight infant rhesus macaques (30 days old) sensitized to house dust mite (HDM) were treated with two week cycles of FA, house dust mite allergen (HDMA), ozone (O{sub 3}) or HDMA/ozone (HDMA + O{sub 3}) for five months. At the end of the five months, six animals from each group were necropsied. The other six animals in each group were allowed to recover in FA for 30 more months at which time they were necropsied. Design-based stereology was used to estimate volumes of lung components, number of alveoli, size of alveoli, distribution of alveolar volumes, interalveolar capillary density. After 30 months of recovery, monkeys exposed to HDMA, in either group, had significantly more alveoli than filtered air. These alveoli also had higher capillary densities as compared with FA controls. These results indicate that early life exposure to HDMA alone or HDMA + O{sub 3} alters the development process in the lung alveoli. - Highlights: • Abnormal lung development after postnatal exposure to ozone and allergen • This remodeling is shown as smaller, more numerous alveoli and narrower airways. • Allergen appears to have more of an effect than ozone during recovery. • These animals also have continued airway hyperresponsiveness (Moore et al. 2014)

  9. Early life exposure to allergen and ozone results in altered development in adolescent rhesus macaque lungs

    International Nuclear Information System (INIS)

    In rhesus macaques, previous studies have shown that episodic exposure to allergen alone or combined with ozone inhalation during the first 6 months of life results in a condition with many of the hallmarks of asthma. This exposure regimen results in altered development of the distal airways and parenchyma (Avdalovic et al., 2012). We hypothesized that the observed alterations in the lung parenchyma would be permanent following a long-term recovery in filtered air (FA) housing. Forty-eight infant rhesus macaques (30 days old) sensitized to house dust mite (HDM) were treated with two week cycles of FA, house dust mite allergen (HDMA), ozone (O3) or HDMA/ozone (HDMA + O3) for five months. At the end of the five months, six animals from each group were necropsied. The other six animals in each group were allowed to recover in FA for 30 more months at which time they were necropsied. Design-based stereology was used to estimate volumes of lung components, number of alveoli, size of alveoli, distribution of alveolar volumes, interalveolar capillary density. After 30 months of recovery, monkeys exposed to HDMA, in either group, had significantly more alveoli than filtered air. These alveoli also had higher capillary densities as compared with FA controls. These results indicate that early life exposure to HDMA alone or HDMA + O3 alters the development process in the lung alveoli. - Highlights: • Abnormal lung development after postnatal exposure to ozone and allergen • This remodeling is shown as smaller, more numerous alveoli and narrower airways. • Allergen appears to have more of an effect than ozone during recovery. • These animals also have continued airway hyperresponsiveness (Moore et al. 2014)

  10. 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.

  11. Growth Retardation and Altered Isotope Composition As Delayed Effects of PCB Exposure in Daphnia magna.

    Science.gov (United States)

    Ek, Caroline; Gerdes, Zandra; Garbaras, Andrius; Adolfsson-Erici, Margaretha; Gorokhova, Elena

    2016-08-01

    Trophic magnification factor (TMF) analysis employs stable isotope signatures to derive biomagnification potential for environmental contaminants. This approach relies on species δ(15)N values aligning with their trophic position (TP). This, however, may not always be true, because toxic exposure can alter growth and isotope allocation patterns. Here, effects of PCB exposure (mixture of PCB18, PCB40, PCB128, and PCB209) on δ(15)N and δ(13)C as well as processes driving these effects were explored using the cladoceran Daphnia magna. A two-part experiment assessed effects of toxic exposure during and after exposure; juvenile daphnids were exposed during 3 days (accumulation phase) and then allowed to depurate for 4 days (depuration phase). No effects on survival, growth, carbon and nitrogen content, and stable isotope composition were observed after the accumulation phase, whereas significant changes were detected in adults after the depuration phase. In particular, a significantly lower nitrogen content and a growth inhibition were observed, with a concomitant increase in δ(15)N (+0.1 ‰) and decrease in δ(13)C (-0.1 ‰). Although of low magnitude, these changes followed the predicted direction indicating that sublethal effects of contaminant exposure can lead to overestimation of TP and hence underestimated TMF. PMID:27367056

  12. In Vitro Exposure of Harbor Seal Immune Cells to Aroclor 1260 Alters Phocine Distemper Virus Replication.

    Science.gov (United States)

    Bogomolni, Andrea; Frasca, Salvatore; Levin, Milton; Matassa, Keith; Nielsen, Ole; Waring, Gordon; De Guise, Sylvain

    2016-01-01

    In the last 30 years, several large-scale marine mammal mortality events have occurred, often in close association with highly polluted regions, leading to suspicions that contaminant-induced immunosuppression contributed to these epizootics. Some of these recent events also identified morbillivirus as a cause of or contributor to death. The role of contaminant exposures regarding morbillivirus mortality is still unclear. The results of this study aimed to address the potential for a mixture of polychlorinated biphenyls (PCBs), specifically Aroclor 1260, to alter harbor seal T-lymphocyte proliferation and to assess if exposure resulted in increased likelihood of phocine distemper virus (PDV USA 2006) to infect susceptible seals in an in vitro system. Exposure of peripheral blood mononuclear cells to Aroclor 1260 did not significantly alter lymphocyte proliferation (1, 5, 10, and 20 ppm). However, using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), lymphocytes exposed to 20 ppm Aroclor 1260 exhibited a significant decrease in PDV replication at day 7 and a significant increase at day 11 compared with unexposed control cells. Similar and significant differences were apparent on exposure to Aroclor 1260 in monocytes and supernatant. The results here indicate that in harbor seals, Aroclor 1260 exposure results in a decrease in virus early during infection and an increase during late infection. The consequences of this contaminant-induced infection pattern in a highly susceptible host could result in a greater potential for systemic infection with greater viral load, which could explain the correlative findings seen in wild populations exposed to a range of persistent contaminants that suffer from morbillivirus epizootics. PMID:26142119

  13. 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

  14. Elevated bulk-silica exposures and evidence for multiple aqueous alteration episodes in Nili Fossae, Mars

    Science.gov (United States)

    Amador, Elena S.; Bandfield, Joshua L.

    2016-09-01

    The Nili Fossae region of Mars contains some of the most mineralogically diverse bedrock on the planet. Previous studies have established three main stratigraphic units in the region: a phyllosilicate-bearing basement rock, a variably altered olivine-rich basalt, and a capping rock. Here, we present evidence for the localized alteration of the northeast Nili Fossae capping unit, previously considered to be unaltered. Both near-infrared and thermal-infrared spectral datasets were analyzed, including the application of a method for determining the relative abundance of bulk-silica (SiO2) over surfaces using thermal emission imaging system (THEMIS) images. Elevated bulk-silica exposures are present on surfaces previously defined as unaltered capping rock. Given the lack of spectral evidence for phyllosilicate, hydrated silica, or quartz phases coincident with the newly detected exposures-the elevated bulk-silica may have formed under a number of aqueous scenarios, including as a product of the carbonation of the underlying olivine-rich basalt under moderate water: rock scenarios and temperatures. Regardless of formation mechanism, the detection of elevated bulk-silica exposures in the Nili Fossae capping unit extends the history of aqueous activity in the region to include all three of the main stratigraphic units.

  15. Nuclear and Mitochondrial DNA Alterations in Newborns with Prenatal Exposure to Cigarette Smoke

    Directory of Open Access Journals (Sweden)

    Francesca Pirini

    2015-01-01

    Full Text Available Newborns exposed to maternal cigarette smoke (CS in utero have an increased risk of developing chronic diseases, cancer, and acquiring decreased cognitive function in adulthood. Although the literature reports many deleterious effects associated with maternal cigarette smoking on the fetus, the molecular alterations and mechanisms of action are not yet clear. Smoking may act directly on nuclear DNA by inducing mutations or epigenetic modifications. Recent studies also indicate that smoking may act on mitochondrial DNA by inducing a change in the number of copies to make up for the damage caused by smoking on the respiratory chain and lack of energy. In addition, individual genetic susceptibility plays a significant role in determining the effects of smoking during development. Furthermore, prior exposure of paternal and maternal gametes to cigarette smoke may affect the health of the developing individual, not only the in utero exposure. This review examines the genetic and epigenetic alterations in nuclear and mitochondrial DNA associated with smoke exposure during the most sensitive periods of development (prior to conception, prenatal and early postnatal and assesses how such changes may have consequences for both fetal growth and development.

  16. Alterations in Cell Signaling Pathways in Breast Cancer Cells after Environmental Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Kulp, K; McCutcheon-Maloney, S M; Bennett, L M

    2003-02-01

    Recent human epidemiological studies suggest that up to 75% of human cancers can be attributed to environmental exposures. Understanding the biologic impact of being exposed to a lifetime of complex environmental mixtures that may not be fully characterized is currently a major challenge. Functional endpoints may be used to assess the gross health consequences of complex mixture exposures from groundwater contamination, superfund sites, biologic releases, or nutritional sources. Such endpoints include the stimulation of cell growth or the induction of a response in an animal model. An environmental exposure that upsets normal cell growth regulation may have important ramifications for cancer development. Stimulating cell growth may alter an individual's cancer risk by changing the expression of genes and proteins that have a role in growth regulatory pathways within cells. Modulating the regulation of these genes and their products may contribute to the initiation, promotion or progression of disease in response to environmental exposure. We are investigating diet-related compounds that induce cell proliferation in breast cancer cell lines. These compounds, PhIP, Flor-Essence{reg_sign} and Essiac{reg_sign}, may be part of an everyday diet. PhIP is a naturally occurring mutagen that is formed in well-cooked muscle meats. PhIP consistently causes dose-dependent breast tumor formation in rats and consumption of well-done meat has been linked to increased risk of breast cancer in women. Flor-Essence{reg_sign} and Essiac{reg_sign} herbal tonics are complementary and alternative medicines used by women who have been diagnosed with breast cancer as an alternative therapy for disease treatment and prevention. The long-term goal of this work is to identify those cellular pathways that are altered by a chemical or biologic environmental exposure and understand how those changes correlate with and or predict changes in human health risk. This project addressed this goal

  17. 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

  18. 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

  19. 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 ...

  20. Determination of 3,5,6-trichloro-2-pyridinol levels in the urine of termite control workers using chlorpyrifos.

    Directory of Open Access Journals (Sweden)

    Jitsunari,Fumihiko

    1989-10-01

    Full Text Available Chlorpyrifos, an organophosphorus insecticide, has been used to control termites since regulatory measures against the use of chlordanes were taken in September, 1986. We developed an improved gas chromatographic (GC method for the assay of 3,5,6-trichloro-2-pyridinol (TCP in the urine to use in the biological monitoring of exposure to chlorpyrifos. Urinary TCP was separated and determined accurately (C.V., 4% with high sensitivity (detection limit, 10 ng/ml and recovery (recovery greater than 90% using a wide bore capillary column (WBC column. The accuracy and precision of the present GC method are satisfactory. The time course of urinary excretion of TCP was followed in workers. The urinary TCP level was low in the off-season and high in the busy season. Variation in the urinary TCP level corresponded to the termite control season and the length of the working period. The urinary TCP level showed a change reciprocal to the variations in the plasma cholinesterase activity. From these results, it is surmised that the urinary TCP level represents the extent of exposure to chlorpyrifos. The decrease in the level of cholinesterase activity is suggested to be due to exposure to chlorpyrifos. Determination of the urinary TCP level by GC using a WBC column is useful in the biological monitoring of chlorpyrifos in termite control workers and potentially has practical application to health care.

  1. 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.

  2. Inhibition of acetylcholinesterase in guppies (Poecilia reticulata) by chlorpyrifos at sublethal concentrations: Methodological aspects

    Energy Technology Data Exchange (ETDEWEB)

    van der Wel, H.; Welling, W.

    1989-04-01

    Acetylcholinesterase activity is a potential biochemical indicator of toxic stress in fish and a sensitive parameter for testing water for the presence of organophosphates. A number of methodological aspects regarding the determination of the in vivo effect of chlorpyrifos on acetylcholinesterase in guppies have been investigated. It was found that with acetylthiocholine as a substrate, the contribution of pseudocholinesterase to the total cholinesterase activity can be neglected. Protection of acetylcholinesterase of guppies exposed to chlorpyrifos from additional, artifactual in vitro enzyme inhibition during homogenization is necessary. Very low concentrations of acetone in the exposure medium, resulting from dilution of the stock solution of chlorpyrifos in acetone, can result in large decreases in the oxygen content of this medium. This may affect the uptake rate of the toxic compound and, thereby, cholinesterase inhibition. Very low, sublethal concentrations of chlorpyrifos result in high inhibition levels of acetylcholinesterase (80-90%) in guppies within 2 weeks of continuous exposure. Recovery of the enzyme activity occurs after the exposed animals are kept in clean medium for 4 days, but the rate of recovery is considerably lower than the rate of inhibition.

  3. In vitro exposure of Ulva lactuca Linnaeus (Chlorophyta) to gasoline - Biochemical and morphological alterations.

    Science.gov (United States)

    Pilatti, Fernanda Kokowicz; Ramlov, Fernanda; Schmidt, Eder Carlos; Kreusch, Marianne; Pereira, Débora Tomazi; Costa, Christopher; de Oliveira, Eva Regina; Bauer, Cláudia M; Rocha, Miguel; Bouzon, Zenilda Laurita; Maraschin, Marcelo

    2016-08-01

    Refined fuels have considerable share of pollution of marine ecosystems. Gasoline is one of the most consumed fuel worldwide, but its effects on marine benthic primary producers are poorly investigated. In this study, Ulva lactuca was chosen as a biological model due to its cosmopolitan nature and tolerance to high levels and wide range of xenobiotics and our goal was to evaluate the effects of gasoline on ultrastructure and metabolism of that seaweed. The experimental design consisted of in vitro exposure of U. lactuca to four concentrations of gasoline (0.001%, 0.01%, 0.1%, and 1.0%, v/v) over 30 min, 1 h, 12 h, and 24 h, followed by cytochemical, SEM, and biochemical analysis. Increase in the number of cytoplasmic granules, loss of cell turgor, cytoplasmic shrinkage, and alterations in the mucilage were some of the ultrastructural alterations observed in thalli exposed to gasoline. Decrease in carotenoid and polyphenol contents, as well as increase of soluble sugars and starch contents were associated with the time of exposure to the xenobiotic. In combination, the results revealed important morphological and biochemical alterations in the phenotype of U. lactuca upon acute exposure to gasoline. This seaweed contain certain metabolites assigned as candidates to biomarkers of the environmental stress investigated and it is thought to be a promise species for usage in coastal ecosystems perturbation monitoring system. In addition, the findings suggest that U. lactuca is able to metabolize gasoline hydrocarbons and use them as energy source, acting as bioremediator of marine waters contaminated by petroleum derivatives. PMID:27192480

  4. Alterations in male rats following in utero exposure to betamethasone suggests changes in reproductive programming.

    Science.gov (United States)

    Borges, Cibele S; Dias, Ana Flávia M G; Rosa, Josiane Lima; Silva, Patricia V; Silva, Raquel F; Barros, Aline L; Sanabria, Marciana; Guerra, Marina T; Gregory, Mary; Cyr, Daniel G; De G Kempinas, Wilma

    2016-08-01

    Antenatal betamethasone is used for accelerating fetal lung maturation for women at risk of preterm birth. Altered sperm parameters were reported in adult rats after intrauterine exposure to betamethasone. In this study, male rat offspring were assessed for reproductive development after dam exposure to betamethasone (0.1mg/kg) or vehicle on Days 12, 13, 18 and 19 of pregnancy. The treatment resulted in reduction in the offspring body weight, delay in preputial separation, decreased seminal vesicle weight, testosterone levels and fertility, and increased testicular weight. In the testis, morphologically abnormal seminiferous tubules were observed, characterized by an irregular cell distribution with Sertoli cell that were displaced towards the tubular lumen. These cells expressed both Connexin 43 (Cx43) and Proliferative Nuclear Cell Antigen (PCNA). In conclusion, intrauterine betamethasone treatment appears to promote reproductive programming and impairment of rat sexual development and fertility due to, at least in part, unusual testicular disorders.

  5. Exposure to ozone reduces influenza disease severity and alters distribution of influenza viral antigens in murine lungs.

    OpenAIRE

    Wolcott, J A; Zee, Y. C.; Osebold, J W

    1982-01-01

    Exposure to ambient levels of ozone (0.5 ppm) was shown to alter the pathogenesis of respiratory infection after aerosol infection of mice with influenza A virus. A semiquantitative method for determination of the sites of virus replication by direct immunofluorescence indicated that exposure to ozone reduced the involvement of respiratory epithelium in the infectious process and resulted in a less widespread infection of the alveolar parenchyma. Furthermore, the ozone-mediated alteration in ...

  6. Developmental and lactational exposure to dieldrin alters mammary tumorigenesis in Her2/neu transgenic mice.

    Directory of Open Access Journals (Sweden)

    Heather L Cameron

    Full Text Available Breast cancer is the most common cancer in Western women and while its precise etiology is unknown, environmental factors are thought to play a role. The organochlorine pesticide dieldrin is a persistent environmental toxicant thought to increase the risk of breast cancer and reduce survival in the human population. The objective of this study was to define the effect of developmental exposure to environmentally relevant concentrations of dieldrin, on mammary tumor development in the offspring. Sexually mature FVB-MMTV/neu female mice were treated with vehicle (corn oil, or dieldrin (0.45, 2.25, and 4.5 microg/g body weight daily by gavage for 5 days prior to mating and then once weekly throughout gestation and lactation until weaning. Dieldrin concentrations were selected to produce serum levels representative of human background body burdens, occupational exposure, and overt toxicity. Treatment had no effect on litter size, birth weight or the number of pups surviving to weaning. The highest dose of dieldrin significantly increased the total tumor burden and the volume and number of tumors found in the thoracic mammary glands. Increased mRNA and protein expression of the neurotrophin BDNF and its receptor TrkB was increased in tumors from the offspring of dieldrin treated dams. This study indicates that developmental exposure to the environmental contaminant dieldrin causes increased tumor burden in genetically predisposed mice. Dieldrin exposure also altered the expression of BNDF and TrkB, novel modulators of cancer pathogenesis.

  7. MicroRNA Expression Profiling Altered by Variant Dosage of Radiation Exposure

    Directory of Open Access Journals (Sweden)

    Kuei-Fang Lee

    2014-01-01

    Full Text Available Various biological effects are associated with radiation exposure. Irradiated cells may elevate the risk for genetic instability, mutation, and cancer under low levels of radiation exposure, in addition to being able to extend the postradiation side effects in normal tissues. Radiation-induced bystander effect (RIBE is the focus of rigorous research as it may promote the development of cancer even at low radiation doses. Alterations in the DNA sequence could not explain these biological effects of radiation and it is thought that epigenetics factors may be involved. Indeed, some microRNAs (or miRNAs have been found to correlate radiation-induced damages and may be potential biomarkers for the various biological effects caused by different levels of radiation exposure. However, the regulatory role that miRNA plays in this aspect remains elusive. In this study, we profiled the expression changes in miRNA under fractionated radiation exposure in human peripheral blood mononuclear cells. By utilizing publicly available microRNA knowledge bases and performing cross validations with our previous gene expression profiling under the same radiation condition, we identified various miRNA-gene interactions specific to different doses of radiation treatment, providing new insights for the molecular underpinnings of radiation injury.

  8. Prenatal androgen exposure alters girls' responses to information indicating gender-appropriate behaviour.

    Science.gov (United States)

    Hines, Melissa; Pasterski, Vickie; Spencer, Debra; Neufeld, Sharon; Patalay, Praveetha; Hindmarsh, Peter C; Hughes, Ieuan A; Acerini, Carlo L

    2016-02-19

    Individual variability in human gender-related behaviour is influenced by many factors, including androgen exposure prenatally, as well as self-socialization and socialization by others postnatally. Many studies have looked at these types of influences in isolation, but little is known about how they work together. Here, we report that girls exposed to high concentrations of androgens prenatally, because they have the genetic condition congenital adrenal hyperplasia, show changes in processes related to self-socialization of gender-related behaviour. Specifically, they are less responsive than other girls to information that particular objects are for girls and they show reduced imitation of female models choosing particular objects. These findings suggest that prenatal androgen exposure may influence subsequent gender-related behaviours, including object (toy) choices, in part by changing processes involved in the self-socialization of gendered behaviour, rather than only by inducing permanent changes in the brain during early development. In addition, the findings suggest that some of the behavioural effects of prenatal androgen exposure might be subject to alteration by postnatal socialization processes. The findings also suggest a previously unknown influence of early androgen exposure on later processes involved in self-socialization of gender-related behaviour, and thus expand understanding of the developmental systems regulating human gender development. PMID:26833843

  9. Exposure of rainbow trout milt to mercury and cadmium alters sperm motility parameters and reproductive success

    International Nuclear Information System (INIS)

    In the current work, seminal plasma was used for the first time as an incubation medium for monitoring short-time exposure effects of sublethal concentrations of mercury and cadmium ions on rainbow trout sperm. Sperm motility parameters (CASA) and hatching rates were used as gamete quality markers. Additionally live/dead sperm viability test and comet assay of DNA fragmentation were performed. We demonstrated that computer-assisted sperm motility analysis (CASA) may serve as a predictor of reproductive success, when milt contaminated with heavy metals is used. Results presented in this study demonstrate that mercury ions altered sperm motility characteristics at 1-10 mg Hg2+/l and 10 mg Cd2+/l and hatching rates at 10 mg Hg2+/l and 10 mg Cd2+/l after 4 h of exposure. Although mercury ions affected sperm motility parameters immediately after dilution with milt as well as at 4 h of exposure, no differences in sperm motility parameters were found between intact and mercury-treated milt after 24 h of exposure. Our results suggest that rainbow trout seminal plasma has a protective role against the toxic effects of mercury ions of rainbow trout sperm motility.

  10. Altered quantities and in vivo activities of cholinesterase from Daphnia magna in sub-lethal exposure to organophosphorus insecticides.

    Science.gov (United States)

    Liu, Hongcui; Yuan, Bingqiang; Li, Shaonan

    2012-06-01

    For investigating relationship between activity of cholinesterase (ChE) and ambient concentration of anticholinesterases, Daphnia magna had been exposed for 21 day to sub-lethal concentrations, i.e. 1/6 EC(50), 1/36 EC(50), and 1/216 EC(50), of either triazophos or chlorpyrifos. Samples were taken at different points of time for measuring total activity and immunoreactive content of ChE and actual concentrations of the anticholinesterases. A type of antigen formerly developed by immunizing mice with purified ChE was utilized in this study to establish an indirect non-competitive ELISA for measuring immunoreactive content of ChE in Daphnia. Studies showed that for apparent activity, i.e. activity that was scaled with total protein, the insecticides caused 5.2-6.9 percent inhibition and 17.0-17.7 percent inductions during the 21 d exposure, whereas for inherent activity, i.e. activity that was scaled with immunoreactive protein, no induction was detected during the exposure. Accompanied by up to 65.9 percent and 68.0 percent promotion in terms of the immunoreactive content, up to 42.8 percent and 44.6 percent inhibition in terms of the inherent activity was indicated, respectively, for triazophos and chlopyrifos. Judged by measured concentrations, the inherent activity recovered faster than the rate of dissipation of the anticholinesterases. Result of the study suggested that the inherent activity was more sensitive than the apparent one in predicting sub-lethal and/or long-term stress of anticholinesterases. It also suggested that apart from promotion in terms of content of the ChE, the Daphnia developed capacities to block bio-concentration of anticholinesterases, and these capacities would make it liable to underestimate ambient concentration of anticholinesterases along with the time of exposure.

  11. Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure.

    Science.gov (United States)

    Manning, Elizabeth E; van den Buuse, Maarten

    2016-05-15

    Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal models have focussed on psychosis-related behaviours following methamphetamine, and less work has been done to assess endophenotypes relevant to other deficits observed in schizophrenia. Altered social behaviour is a feature of both the negative symptoms and cognitive deficits in schizophrenia, and significantly impacts patient functioning. We recently found that brain-derived neurotrophic factor (BDNF) heterozygous mice show disrupted sensitization to methamphetamine, supporting other work suggesting an important role of this neurotrophin in the pathophysiology of psychosis and the neuronal response to stimulant drugs. In the current study, we assessed social and cognitive behaviours in methamphetamine-treated BDNF heterozygous mice and wildtype littermate controls. Following chronic methamphetamine exposure male wildtype mice showed a 50% reduction in social novelty preference. Vehicle-treated male BDNF heterozygous mice showed a similar impairment in social novelty preference, with a trend for no further disruption by methamphetamine exposure. Female mice were unaffected in this task, and no groups showed any changes in sociability or short-term spatial memory. These findings suggest that chronic methamphetamine alters behaviour relevant to disruption of social cognition in schizophrenia, supporting other studies which demonstrate a close resemblance between persistent methamphetamine psychosis and schizophrenia. Together these findings suggest that dynamic regulation of BDNF signalling is necessary to mediate the effects of methamphetamine on behaviours relevant to schizophrenia.

  12. Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure.

    Science.gov (United States)

    Manning, Elizabeth E; van den Buuse, Maarten

    2016-05-15

    Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal models have focussed on psychosis-related behaviours following methamphetamine, and less work has been done to assess endophenotypes relevant to other deficits observed in schizophrenia. Altered social behaviour is a feature of both the negative symptoms and cognitive deficits in schizophrenia, and significantly impacts patient functioning. We recently found that brain-derived neurotrophic factor (BDNF) heterozygous mice show disrupted sensitization to methamphetamine, supporting other work suggesting an important role of this neurotrophin in the pathophysiology of psychosis and the neuronal response to stimulant drugs. In the current study, we assessed social and cognitive behaviours in methamphetamine-treated BDNF heterozygous mice and wildtype littermate controls. Following chronic methamphetamine exposure male wildtype mice showed a 50% reduction in social novelty preference. Vehicle-treated male BDNF heterozygous mice showed a similar impairment in social novelty preference, with a trend for no further disruption by methamphetamine exposure. Female mice were unaffected in this task, and no groups showed any changes in sociability or short-term spatial memory. These findings suggest that chronic methamphetamine alters behaviour relevant to disruption of social cognition in schizophrenia, supporting other studies which demonstrate a close resemblance between persistent methamphetamine psychosis and schizophrenia. Together these findings suggest that dynamic regulation of BDNF signalling is necessary to mediate the effects of methamphetamine on behaviours relevant to schizophrenia. PMID:26965573

  13. Alterations in the fat body and midgut of Culex quinquefasciatus larvae following exposure to different insecticides.

    Science.gov (United States)

    Alves, Stênio Nunes; Serrão, José Eduardo; Melo, Alan Lane

    2010-08-01

    This study describes morphological alterations in the fat body and midgut of Culex quinquefasciatus larvae following exposure to different insecticides. To this end, both third and fourth instars of C. quinquefasciatus larvae were exposed for 30 and 60 min to organophosphate (50 ppb), pyrethroids (20 and 30 ppb), and avermectin derivates (1.5 and 54 ppb). Following incubation, pH measurements of the larvae gut were recorded. The fat body and midgut were also analyzed by light and transmission electron microscopy. These studies demonstrate a decrease in the pH of the larvae anterior midgut following exposure to all of the tested insecticides. Histochemical tests revealed a strong reaction for neutral lipids in the control group and a marked decrease in the group exposed to cypermethrin. Furthermore, a weak reaction with acidic lipids in larvae exposed to deltamethrin, temephos, ivermectin and abamectin was also observed. Insecticide-exposed larvae also exhibited cytoplasm granule differences, relative to control larvae. Finally, we noted a small reduction in microvilli size in the apex of digestive cells, although vesicles were found to be present. The destructive changes in the larvae were very similar regardless of the type of insecticide analyzed. These data suggest that alterations in the fat body and midgut are a common response to cellular intoxication.

  14. Evaluation of biochemical alterations produced by combined exposure of fenvalerate and nitrate in Bubalus bubalis

    Directory of Open Access Journals (Sweden)

    Kamalpreet Kaur Gill

    2014-03-01

    Full Text Available Aim: Evaluation of combined effect of fenvalerate and nitrate on biochemical parameters in buffalo calves. Materials and Methods: Sixteen male buffalo calves were divided into four groups of four calves each. Group I receiving no treatment served as the control. Group II and III animals were orally administered with fenvalerate (1.0 mg/kg/day and sodium nitrate (20 mg/kg/day, respectively, for 21 consecutive days and were kept as positive control. Group IV animals were co-administered with fenvalerate and sodium nitrate at the above dose rates for 21 consecutive days. Biochemical parameters including Aspartate aminotransferase (AST, Alkaline phosphatase (ALP, Gamma-glutamyl transpeptidase (GGT, Lactate dehydrogenase (LDH, Glucose, Total protein, Albumin, Cholesterol, Blood urea nitrogen (BUN and Creatinine were determined on 0, 3, 7, 10, 14, 17 and 21 day of treatment. Estimation of these parameters was also done on 7th day of post-treatment period. Results: Co-administration of fenvalerate and sodium nitrate produced significant increase in the plasma levels of AST, ALP, GGT, LDH, glucose, BUN, cholesterol and creatinine while significant decrease in the plasma levels of total proteins was observed. No significant alteration was observed in albumin levels. Extent of organ damage as evidenced by biochemical alterations was more pronounced in calves exposed to combination of fenvalerate and sodium nitrate as compared to their individual exposures. Conclusion: Fenvalerate and sodium nitrate co-administration potentiates the toxicological injury produced, in comparison to their individual exposure.

  15. Alcohol Exposure Alters Mouse Lung Inflammation in Response to Inhaled Dust

    Directory of Open Access Journals (Sweden)

    Jill A. Poole

    2012-07-01

    Full Text Available Alcohol exposure is associated with increased lung infections and decreased mucociliary clearance. Occupational workers exposed to dusts from concentrated animal feeding operations (CAFOs are at risk for developing chronic inflammatory lung diseases. Agricultural worker co-exposure to alcohol and organic dust has been established, although little research has been conducted on the combination effects of alcohol and organic dusts on the lung. Previously, we have shown in a mouse model that exposure to hog dust extract (HDE collected from a CAFO results in the activation of protein kinase C (PKC, elevated lavage fluid cytokines/chemokines including interleukin-6 (IL-6, and the development of significant lung pathology. Because alcohol blocks airway epithelial cell release of IL-6 in vitro, we hypothesized that alcohol exposure would alter mouse lung inflammatory responses to HDE. To test this hypothesis, C57BL/6 mice were fed 20% alcohol or water ad libitum for 6 weeks and treated with 12.5% HDE by intranasal inhalation method daily during the final three weeks. Bronchoalveolar lavage fluid (BALF, tracheas and lungs were collected. HDE stimulated a 2–4 fold increase in lung and tracheal PKCε (epsilon activity in mice, but no such increase in PKCε activity was observed in dust-exposed mice fed alcohol. Similarly, alcohol-fed mice demonstrated significantly less IL-6 in lung lavage in response to dust than that observed in control mice instilled with HDE. TNFα levels were also inhibited in the alcohol and HDE-exposed mouse lung tissue as compared to the HDE only exposed group. HDE-induced lung inflammatory aggregates clearly present in the tissue from HDE only exposed animals were not visually detectable in the HDE/alcohol co-exposure group. Statistically significant weight reductions and 20% mortality were also observed in the mice co-exposed to HDE and alcohol. These data suggest that alcohol exposure depresses the ability

  16. Dissipation of chlorpyrifos on pakchoi inside and outside greenhouse

    Institute of Scientific and Technical Information of China (English)

    YU Yun-long; FANG Hua; WANG Xiao; YU Jing-quan; FAN De-fang

    2005-01-01

    The dissipation of chlorpyrifos on pakchoi inside and outside greenhouse was studied. The decline curve of chlorpyrifos on pakchoi could be described as first-order kinetic. The experimental data showed that both the hermetic environment of greenhouse and season affected dissipation rates of chlorpyrifos on pakchoi. Chlorpyrifos declined faster outside greenhouse than inside greenhouse.Chlorpyrifos residues at pre-harvest time were below the maximum residue limits (MRLs) fixed in China, whereas the values inside greenhouse were higher than those outside greenhouse by almost 50%. The recommended pre-harvest time established under conditions of open field might not always fit to greenhouse production.

  17. Leukocyte activity is altered in a ground based murine model of microgravity and proton radiation exposure.

    Directory of Open Access Journals (Sweden)

    Jenine K Sanzari

    Full Text Available Immune system adaptation during spaceflight is a concern in space medicine. Decreased circulating leukocytes observed during and after space flight infer suppressed immune responses and susceptibility to infection. The microgravity aspect of the space environment has been simulated on Earth to study adverse biological effects in astronauts. In this report, the hindlimb unloading (HU model was employed to investigate the combined effects of solar particle event-like proton radiation and simulated microgravity on immune cell parameters including lymphocyte subtype populations and activity. Lymphocytes are a type of white blood cell critical for adaptive immune responses and T lymphocytes are regulators of cell-mediated immunity, controlling the entire immune response. Mice were suspended prior to and after proton radiation exposure (2 Gy dose and total leukocyte numbers and splenic lymphocyte functionality were evaluated on days 4 or 21 after combined HU and radiation exposure. Total white blood cell (WBC, lymphocyte, neutrophil, and monocyte counts are reduced by approximately 65%, 70%, 55%, and 70%, respectively, compared to the non-treated control group at 4 days after combined exposure. Splenic lymphocyte subpopulations are altered at both time points investigated. At 21 days post-exposure to combined HU and proton radiation, T cell activation and proliferation were assessed in isolated lymphocytes. Cell surface expression of the Early Activation Marker, CD69, is decreased by 30% in the combined treatment group, compared to the non-treated control group and cell proliferation was suppressed by approximately 50%, compared to the non-treated control group. These findings reveal that the combined stressors (HU and proton radiation exposure result in decreased leukocyte numbers and function, which could contribute to immune system dysfunction in crew members. This investigation is one of the first to report on combined proton radiation and

  18. Prenatal cocaine exposure alters progenitor cell markers in the subventricular zone of the adult rat brain

    Science.gov (United States)

    Patel, Dhyanesh Arvind; Booze, Rosemarie M.; Mactutus, Charles F.

    2013-01-01

    Long-term consequences of early developmental exposure to drugs of abuse may have deleterious effects on the proliferative plasticity of the brain. The purpose of this study was to examine the long-term effects of prenatal exposure to cocaine, using the IV route of administration and doses that mimic the peak arterial levels of cocaine use in humans, on the proliferative cell types of the subventricular zones (SVZ) in the adult (180 days-old) rat brain. Employing immunocytochemistry, the expression of GFAP+ (type B cells) and nestin+(GFAP−) (Type C and A cells) staining was quantified in the subcallosal area of the SVZ. GFAP+ expression was significantly different between the prenatal cocaine treated group and the vehicle (saline) control group. The prenatal cocaine treated group possessed significantly lower GFAP+ expression relative to the vehicle control group, suggesting that prenatal cocaine exposure significantly reduced the expression of type B neural stem cells of the SVZ. In addition, there was a significant sex difference in nestin+ expression with females showing approximately 8–13% higher nestin+ expression compared to the males. More importantly, a significant prenatal treatment condition (prenatal cocaine, control) by sex interaction in nestin+ expression was confirmed, indicating different effects of cocaine based on sex of the animal. Specifically, prenatal cocaine exposure eliminated the basal difference between the sexes. Collectively, the present findings suggest that prenatal exposure to cocaine, when delivered via a protocol designed to capture prominent features of recreational usage, can selectively alter the major proliferative cell types in the subcallosal area of the SVZ in an adult rat brain, and does so differently for males and females. PMID:22119286

  19. Untargeted Metabolomics Reveals Predominant Alterations in Lipid Metabolism Following Light Exposure in Broccoli Sprouts.

    Science.gov (United States)

    Maldini, Mariateresa; Natella, Fausta; Baima, Simona; Morelli, Giorgio; Scaccini, Cristina; Langridge, James; Astarita, Giuseppe

    2015-01-01

    The consumption of vegetables belonging to the family Brassicaceae (e.g., broccoli and cauliflower) is linked to a reduced incidence of cancer and cardiovascular diseases. The molecular composition of such plants is strongly affected by growing conditions. Here we developed an unbiased metabolomics approach to investigate the effect of light and dark exposure on the metabolome of broccoli sprouts and we applied such an approach to provide a bird's-eye view of the overall metabolic response after light exposure. Broccoli seeds were germinated and grown hydroponically for five days in total darkness or with a light/dark photoperiod (16 h light/8 h dark cycle). We used an ultra-performance liquid-chromatography system coupled to an ion-mobility, time-of-flight mass spectrometer to profile the large array of metabolites present in the sprouts. Differences at the metabolite level between groups were analyzed using multivariate statistical analyses, including principal component analysis and correlation analysis. Altered metabolites were identified by searching publicly available and in-house databases. Metabolite pathway analyses were used to support the identification of subtle but significant changes among groups of related metabolites that may have gone unnoticed with conventional approaches. Besides the chlorophyll pathway, light exposure activated the biosynthesis and metabolism of sterol lipids, prenol lipids, and polyunsaturated lipids, which are essential for the photosynthetic machinery. Our results also revealed that light exposure increased the levels of polyketides, including flavonoids, and oxylipins, which play essential roles in the plant's developmental processes and defense mechanism against herbivores. This study highlights the significant contribution of light exposure to the ultimate metabolic phenotype, which might affect the cellular physiology and nutritional value of broccoli sprouts. Furthermore, this study highlights the potential of an

  20. Untargeted Metabolomics Reveals Predominant Alterations in Lipid Metabolism Following Light Exposure in Broccoli Sprouts

    Directory of Open Access Journals (Sweden)

    Mariateresa Maldini

    2015-06-01

    Full Text Available The consumption of vegetables belonging to the family Brassicaceae (e.g., broccoli and cauliflower is linked to a reduced incidence of cancer and cardiovascular diseases. The molecular composition of such plants is strongly affected by growing conditions. Here we developed an unbiased metabolomics approach to investigate the effect of light and dark exposure on the metabolome of broccoli sprouts and we applied such an approach to provide a bird’s-eye view of the overall metabolic response after light exposure. Broccoli seeds were germinated and grown hydroponically for five days in total darkness or with a light/dark photoperiod (16 h light/8 h dark cycle. We used an ultra-performance liquid-chromatography system coupled to an ion-mobility, time-of-flight mass spectrometer to profile the large array of metabolites present in the sprouts. Differences at the metabolite level between groups were analyzed using multivariate statistical analyses, including principal component analysis and correlation analysis. Altered metabolites were identified by searching publicly available and in-house databases. Metabolite pathway analyses were used to support the identification of subtle but significant changes among groups of related metabolites that may have gone unnoticed with conventional approaches. Besides the chlorophyll pathway, light exposure activated the biosynthesis and metabolism of sterol lipids, prenol lipids, and polyunsaturated lipids, which are essential for the photosynthetic machinery. Our results also revealed that light exposure increased the levels of polyketides, including flavonoids, and oxylipins, which play essential roles in the plant’s developmental processes and defense mechanism against herbivores. This study highlights the significant contribution of light exposure to the ultimate metabolic phenotype, which might affect the cellular physiology and nutritional value of broccoli sprouts. Furthermore, this study highlights the

  1. Exposure to low-dose rotenone precipitates synaptic plasticity alterations in PINK1 heterozygous knockout mice.

    Science.gov (United States)

    Martella, G; Madeo, G; Maltese, M; Vanni, V; Puglisi, F; Ferraro, E; Schirinzi, T; Valente, E M; Bonanni, L; Shen, J; Mandolesi, G; Mercuri, N B; Bonsi, P; Pisani, A

    2016-07-01

    Heterozygous mutations in the PINK1 gene are considered a susceptibility factor to develop early-onset Parkinson's disease (PD), as supported by dopamine hypometabolism in asymptomatic mutation carriers and subtle alterations of dopamine-dependent striatal synaptic plasticity in heterozygous PINK1 knockout (PINK1(+/-)) mice. The aim of the present study was to investigate whether exposure to low-dose rotenone of heterozygous PINK1(+/-) mice, compared to their wild-type PINK1(+/+) littermates, could impact on dopamine-dependent striatal synaptic plasticity, in the absence of apparent structural alterations. Mice were exposed to a range of concentrations of rotenone (0.01-1mg/kg). Chronic treatment with concentrations of rotenone up to 0.8mg/kg did not cause manifest neuronal loss or changes in ATP levels both in the striatum or substantia nigra of PINK1(+/-) and PINK1(+/+) mice. Moreover, rotenone (up to 0.8mg/kg) treatment did not induce mislocalization of the mitochondrial membrane protein Tom20 and release of cytochrome c in PINK1(+/-) striata. Accordingly, basic electrophysiological properties of nigral dopaminergic and striatal medium spiny neurons (MSNs) were normal. Despite the lack of gross alterations in neuronal viability in chronically-treated PINK1(+/-), a complete loss of both long-term depression (LTD) and long-term potentiation (LTP) was recorded in MSNs from PINK1(+/-) mice treated with a low rotenone (0.1mg/kg) concentration. Even lower concentrations (0.01mg/kg) blocked LTP induction in heterozygous PINK1(+/-) MSNs compared to PINK1(+/+) mice. Of interest, chronic pretreatment with the antioxidants alpha-tocopherol and Trolox, a water-soluble analog of vitamin E and powerful antioxidant, rescued synaptic plasticity impairment, confirming that, at the doses we utilized, rotenone did not induce irreversible alterations. In this model, chronic exposure to low-doses of rotenone was not sufficient to alter mitochondrial integrity and ATP production, but

  2. Sustained alterations in neuroimmune gene expression after daily, but not intermittent, alcohol exposure.

    Science.gov (United States)

    Gano, Anny; Doremus-Fitzwater, Tamara L; Deak, Terrence

    2016-09-01

    Acute ethanol intoxication is associated with Rapid Alterations in Neuroimmune Gene Expression (RANGE), including increased Interleukin (IL)-6 and Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα), and suppressed IL-1β and Tumor necrosis factor (TNF) α, yet little is known about adaptations in cytokines across the first few ethanol exposures. Thus, the present studies examined central cytokines during intoxication (3h post-ethanol) following 2, 4 or 6 intragastric ethanol challenges (4g/kg) delivered either daily or every-other-day (EOD). Subsequent analyses of blood ethanol concentrations (BECs) and corticosterone were performed to determine whether the schedule of ethanol delivery would alter the pharmacokinetics of, or general sensitivity to, subacute ethanol exposure. As expected, ethanol led to robust increases in IL-6 and IκBα gene expression in hippocampus, amygdala and bed nucleus of the stria terminalis (BNST), whereas IL-1β and TNFα were suppressed, thereby replicating our prior work. Ethanol-dependent increases in IL-6 and IκBα remained significant in all structures - even after 6 days of ethanol. When these doses were administered EOD, modest IL-6 increases in BNST were observed, with TNFα and IL-1β suppressed exclusively in the hippocampus. Analysis of BECs revealed a small but significant reduction in ethanol after 4 EOD exposures - an effect which was not observed when ethanol was delivered after 6 daily intubations. These findings suggest that ethanol-induced RANGE effects are not simply a function of ethanol load per se, and underscore the critical role that ethanol dosing interval plays in determining the neuroimmune consequences of alcohol. PMID:27208497

  3. Postnatal manganese exposure does not alter dopamine autoreceptor sensitivity in adult and adolescent male rats.

    Science.gov (United States)

    McDougall, Sanders A; Mohd-Yusof, Alena; Kaplan, Graham J; Abdulla, Zuhair I; Lee, Ryan J; Crawford, Cynthia A

    2013-04-15

    Administering manganese chloride (Mn) to rats on postnatal day (PD) 1-21 causes long-term reductions in dopamine transporter levels in the dorsal striatum, as well as a persistent increase in D1 and D2 receptor concentrations. Whether dopamine autoreceptors change in number or sensitivity is uncertain, although D2S receptors, which may be presynaptic in origin, are elevated in Mn-exposed rats. The purpose of this study was to determine if early Mn exposure causes long-term changes in dopamine autoreceptor sensitivity that persist into adolescence and adulthood. To this end, male rats were exposed to Mn on PD 1-21 and autoreceptor functioning was tested 7 or 70 days later by measuring (a) dopamine synthesis (i.e., DOPA accumulation) in the dorsal striatum after quinpirole or haloperidol treatment and (b) behavioral responsiveness after low-dose apomorphine treatment. Results showed that low doses (i.e., "autoreceptor" doses) of apomorphine (0.06 and 0.12 mg/kg) decreased the locomotor activity of adolescent and adult rats, while higher doses increased locomotion. The dopamine synthesis experiment also produced classic autoreceptor effects, because quinpirole decreased dorsal striatal DOPA accumulation; whereas, haloperidol increased DOPA levels in control rats, but not in rats given the nerve impulse inhibitor γ-butyrolactone. Importantly, early Mn exposure did not alter autoreceptor sensitivity when assessed in early adolescence or adulthood. The lack of Mn-induced effects was evident in both the dopamine synthesis and behavioral experiments. When considered together with past studies, it is clear that early Mn exposure alters the functioning of various dopaminergic presynaptic mechanisms, while dopamine autoreceptors remain unimpaired. PMID:23458069

  4. Variation characteristics of chlorpyrifos in nonsterile wetland plant hydroponic system.

    Science.gov (United States)

    Wang, Chuan; Zhou, Qiaohong; Zhang, Liping; Zhang, Yan; Xiao, Enrong; Wu, Zhenbin

    2013-01-01

    Six wetland plants were investigated for their effect on the degradation characteristics of chlorpyrifos in nonsterile hydroponic system at constant temperature of 28 degrees C. The results showed that the removal rates of chlorpyrifos in the water of plant systems were 1.26-5.56% higher than that in the control without plants. Scirpus validus and Typha angustifolia were better than other hygrophytes in elimination of chlorpyrifos. The removal rates of the two systems were up to 88%. Plants of acaulescent group had an advantage over caulescent group in removing chlorpyrifos. Phytoaccumulation of chlorpyrifos was observed, and the order of chlorpyrifos concentration in different plant tissues was root > stem > leaf. It was also found that chlorpyrifos and its metabolite TCP decreased rapidly at the initial step of the experiment.

  5. Neuroplastic alterations in the limbic system following cocaine or alcohol exposure.

    Science.gov (United States)

    Stuber, Garret D; Hopf, F Woodward; Tye, Kay M; Chen, Billy T; Bonci, Antonello

    2010-01-01

    Neuroplastic changes in the CNS are thought to be a fundamental component of learning and memory. While pioneering studies in the hippocampus and cerebellum have detailed many of the basic mechanisms that can lead to alterations in synaptic transmission based on previous activity, only more recently has synaptic plasticity been monitored after behavioral manipulation or drug exposure. In this chapter, we review evidence that drugs of abuse are powerful modulators of synaptic plasticity. Both the dopaminergic neurons of the ventral tegmental area as well medium spiny neurons in nucleus accumbens show enhanced excitatory synaptic strength following passive or active exposure to drugs such as cocaine and alcohol. In the VTA, both the enhancement of excitatory synaptic strength and the acquisition of drug-related behaviors depend on signaling through the N-methyl-D: -aspartate receptors (NMDARs) which are mechanistically thought to lead to increased synaptic insertion of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Synaptic insertion of AMPARs by drugs of abuse can be long lasting, depending on the route of administration, number of drug exposures, or whether the drugs are received passively or self-administered. PMID:21161748

  6. 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

  7. 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.

  8. Polychlorinated biphenyl exposure alters the expression profile of microRNAs associated with vascular diseases.

    Science.gov (United States)

    Wahlang, Banrida; Petriello, Michael C; Perkins, Jordan T; Shen, Shu; Hennig, Bernhard

    2016-09-01

    Exposure to persistent organic pollutants, including polychlorinated biphenyls (PCBs) is correlated with multiple vascular complications including endothelial cell dysfunction and atherosclerosis. PCB-induced activation of the vasculature subsequently leads to oxidative stress and induction of pro-inflammatory cytokines and adhesion proteins. Gene expression of these cytokines/proteins is known to be regulated by small, endogenous oligonucleotides known as microRNAs that interact with messenger RNA. MicroRNAs are an acknowledged component of the epigenome, but the role of environmentally-driven epigenetic changes such as toxicant-induced changes in microRNA profiles is currently understudied. The objective of this study was to determine the effects of PCB exposure on microRNA expression profile in primary human endothelial cells using the commercial PCB mixture Aroclor 1260. Samples were analyzed using Affymetrix GeneChip® miRNA 4.0 arrays for high throughput detection and selected microRNA gene expression was validated (RT-PCR). Microarray analysis identified 557 out of 6658 microRNAs that were changed with PCB exposure (p<0.05). In-silico analysis using MetaCore database identified 21 of these microRNAs to be associated with vascular diseases. Further validation showed that Aroclor 1260 increased miR-21, miR-31, miR-126, miR-221 and miR-222 expression levels. Upregulated miR-21 has been reported in cardiac injury while miR-126 and miR-31 modulate inflammation. Our results demonstrated evidence of altered microRNA expression with PCB exposure, thus providing novel insights into mechanisms of PCB toxicity. PMID:27288564

  9. Asthmatics exhibit altered oxylipin profiles compared to healthy individuals after subway air exposure.

    Directory of Open Access Journals (Sweden)

    Susanna L Lundström

    Full Text Available BACKGROUND: Asthma is a chronic inflammatory lung disease that causes significant morbidity and mortality worldwide. Air pollutants such as particulate matter (PM and oxidants are important factors in causing exacerbations in asthmatics, and the source and composition of pollutants greatly affects pathological implications. OBJECTIVES: This randomized crossover study investigated responses of the respiratory system to Stockholm subway air in asthmatics and healthy individuals. Eicosanoids and other oxylipins were quantified in the distal lung to provide a measure of shifts in lipid mediators in association with exposure to subway air relative to ambient air. METHODS: Sixty-four oxylipins representing the cyclooxygenase (COX, lipoxygenase (LOX and cytochrome P450 (CYP metabolic pathways were screened using liquid chromatography-tandem mass spectrometry (LC-MS/MS of bronchoalveolar lavage (BAL-fluid. Validations through immunocytochemistry staining of BAL-cells were performed for 15-LOX-1, COX-1, COX-2 and peroxisome proliferator-activated receptor gamma (PPARγ. Multivariate statistics were employed to interrogate acquired oxylipin and immunocytochemistry data in combination with patient clinical information. RESULTS: Asthmatics and healthy individuals exhibited divergent oxylipin profiles following exposure to ambient and subway air. Significant changes were observed in 8 metabolites of linoleic- and α-linolenic acid synthesized via the 15-LOX pathway, and of the COX product prostaglandin E(2 (PGE(2. Oxylipin levels were increased in healthy individuals following exposure to subway air, whereas asthmatics evidenced decreases or no change. CONCLUSIONS: Several of the altered oxylipins have known or suspected bronchoprotective or anti-inflammatory effects, suggesting a possible reduced anti-inflammatory response in asthmatics following exposure to subway air. These observations may have ramifications for sensitive subpopulations in urban areas.

  10. Early Phthalates Exposure in Pregnant Women Is Associated with Alteration of Thyroid Hormones.

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    Po-Chin Huang

    Full Text Available Previous studies revealed that phthalate exposure could alter thyroid hormones during the last trimester of pregnancy. However, thyroid hormones are crucial for fetal development during the first trimester. We aimed to clarify the effect of phthalate exposure on thyroid hormones during early pregnancy.We recruited 97 pregnant women who were offered an amniocentesis during the early trimester from an obstetrics clinic in southern Taiwan from 2013 to 2014. After signing an informed consent form, we collected amniotic fluid and urine samples from pregnant women to analyze 11 metabolites, including mono-ethyl phthalate (MEP, mono-(2-ethyl-5-carboxypentyl phthalate (MECPP, mono-(2-ethylhexyl phthalate (MEHP, mono-butyl phthalate (MnBP, of 9 phthalates using liquid chromatography/ tandem mass spectrometry. We collected blood samples from each subject to analyze serum thyroid hormones including thyroxine (T4, free T4, and thyroid-binding globulin (TBG.Three phthalate metabolites were discovered to be >80% in the urine samples of the pregnant women: MEP (88%, MnBP (81% and MECPP (86%. Median MnBP and MECPP levels in pregnant Taiwanese women were 21.5 and 17.6 μg/g-creatinine, respectively, that decreased after the 2011 Taiwan DEHP scandal. Results of principal component analysis suggested two major sources (DEHP and other phthalates of phthalates exposure in pregnant women. After adjusting for age, gestational age, TBG, urinary creatinine, and other phthalate metabolites, we found a significantly negative association between urinary MnBP levels and serum T4 (β = -5.41; p-value = 0.012; n = 97 in pregnant women using Bonferroni correction.We observed a potential change in the thyroid hormones of pregnant women during early pregnancy after DnBP exposure. Additional study is necessitated to clarify these associations.

  11. Early Phthalates Exposure in Pregnant Women Is Associated with Alteration of Thyroid Hormones

    Science.gov (United States)

    Tsai, Chih-Hsin; Liang, Wei-Yen; Li, Sih-Syuan; Huang, Han-Bin

    2016-01-01

    Introduction Previous studies revealed that phthalate exposure could alter thyroid hormones during the last trimester of pregnancy. However, thyroid hormones are crucial for fetal development during the first trimester. We aimed to clarify the effect of phthalate exposure on thyroid hormones during early pregnancy. Method We recruited 97 pregnant women who were offered an amniocentesis during the early trimester from an obstetrics clinic in southern Taiwan from 2013 to 2014. After signing an informed consent form, we collected amniotic fluid and urine samples from pregnant women to analyze 11 metabolites, including mono-ethyl phthalate (MEP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-(2-ethylhexyl) phthalate (MEHP), mono-butyl phthalate (MnBP), of 9 phthalates using liquid chromatography/ tandem mass spectrometry. We collected blood samples from each subject to analyze serum thyroid hormones including thyroxine (T4), free T4, and thyroid-binding globulin (TBG). Results Three phthalate metabolites were discovered to be >80% in the urine samples of the pregnant women: MEP (88%), MnBP (81%) and MECPP (86%). Median MnBP and MECPP levels in pregnant Taiwanese women were 21.5 and 17.6 μg/g-creatinine, respectively, that decreased after the 2011 Taiwan DEHP scandal. Results of principal component analysis suggested two major sources (DEHP and other phthalates) of phthalates exposure in pregnant women. After adjusting for age, gestational age, TBG, urinary creatinine, and other phthalate metabolites, we found a significantly negative association between urinary MnBP levels and serum T4 (β = –5.41; p-value = 0.012; n = 97) in pregnant women using Bonferroni correction. Conclusion We observed a potential change in the thyroid hormones of pregnant women during early pregnancy after DnBP exposure. Additional study is necessitated to clarify these associations. PMID:27455052

  12. Regional alterations of brain biogenic amines in young rats following chronic lead exposure

    Energy Technology Data Exchange (ETDEWEB)

    Dubas, T.C.; Stevenson, A.; Singhal, R.L.; Hrdina, P.D.

    1978-02-01

    An examination was made of neurochemical changes that occur in discrete brain regions of rats that have been chronically exposed to low levels of lead from birth, in order to provide further information on the involvement of brain biogenic amines in lead-induced neurotoxicity. Results indicate a relationship between exposure to lead and alterations in the brain levels of various putative neurotransmitters. However, changes in the functional activity of the neurotransmitter may not be adequately reflected in the change of its steady-state levels or may occur even in the absence of any changes in the actual concentrations. Lead may influence central neurotransmitter function by affecting one or several of the processes involved in the synthesis, release and/or disposition of biogenic amines.

  13. Triclosan exposure alters postembryonic development in a Pacific tree frog (Pseudacris regilla) Amphibian Metamorphosis Assay (TREEMA)

    International Nuclear Information System (INIS)

    The Amphibian Metamorphosis Assay (AMA), developed for Xenopus laevis, is designed to identify chemicals that disrupt thyroid hormone (TH)-mediated biological processes. We adapted the AMA for use on an ecologically-relevant North American species, the Pacific tree frog (Pseudacris regilla), and applied molecular endpoints to evaluate the effects of the antibacterial agent, triclosan (TCS). Premetamorphic (Gosner stage 26–28) tadpoles were immersed for 21 days in solvent control, 1.5 μg/L thyroxine (T4), 0.3, 3 and 30 μg/L (nominal) TCS, or combined T4/TCS treatments. Exposure effects were scored by morphometric (developmental stage, wet weight, and body, snout-vent and hindlimb lengths) and molecular (mRNA abundance using quantitative real time polymerase chain reaction) criteria. T4 treatment alone accelerated development concomitant with altered levels of TH receptors α and β, proliferating cell nuclear antigen, and gelatinase B mRNAs in the brain and tail. We observed TCS-induced perturbations in all of the molecular and morphological endpoints indicating that TCS exposure disrupts coordination of postembryonic tadpole development. Clear alterations in molecular endpoints were evident at day 2 whereas the earliest morphological effects appeared at day 4 and were most evident at day 21. Although TCS alone (3 and 30 μg/L) was protective against tadpole mortality, this protection was lost in the presence of T4. The Pacific tree frog is the most sensitive species examined to date displaying disruption of TH-mediated development by a common antimicrobial agent.

  14. Triclosan exposure alters postembryonic development in a Pacific tree frog (Pseudacris regilla) Amphibian Metamorphosis Assay (TREEMA)

    Energy Technology Data Exchange (ETDEWEB)

    Marlatt, Vicki L. [Nautilus Environmental, 8864 Commerce Court, Burnaby, B.C. V5A 4N7 (Canada); Veldhoen, Nik [Department of Biochemistry and Microbiology, University of Victoria, P.O. Box 3055 Stn CSC, Victoria, B.C. V8W 3P6 (Canada); Lo, Bonnie P. [Nautilus Environmental, 8864 Commerce Court, Burnaby, B.C. V5A 4N7 (Canada); Bakker, Dannika; Rehaume, Vicki; Vallee, Kurtis [Department of Biochemistry and Microbiology, University of Victoria, P.O. Box 3055 Stn CSC, Victoria, B.C. V8W 3P6 (Canada); Haberl, Maxine; Shang, Dayue; Aggelen, Graham C. van; Skirrow, Rachel C. [Pacific and Yukon Laboratory for Environmental Testing, Emergencies Operational Analytical Laboratories and Research Support Division, Environment Canada, 2645 Dollarton Highway, North Vancouver, B.C. V7H 1B1 (Canada); Elphick, James R. [Nautilus Environmental, 8864 Commerce Court, Burnaby, B.C. V5A 4N7 (Canada); Helbing, Caren C., E-mail: chelbing@uvic.ca [Department of Biochemistry and Microbiology, University of Victoria, P.O. Box 3055 Stn CSC, Victoria, B.C. V8W 3P6 (Canada)

    2013-01-15

    The Amphibian Metamorphosis Assay (AMA), developed for Xenopus laevis, is designed to identify chemicals that disrupt thyroid hormone (TH)-mediated biological processes. We adapted the AMA for use on an ecologically-relevant North American species, the Pacific tree frog (Pseudacris regilla), and applied molecular endpoints to evaluate the effects of the antibacterial agent, triclosan (TCS). Premetamorphic (Gosner stage 26-28) tadpoles were immersed for 21 days in solvent control, 1.5 {mu}g/L thyroxine (T{sub 4}), 0.3, 3 and 30 {mu}g/L (nominal) TCS, or combined T{sub 4}/TCS treatments. Exposure effects were scored by morphometric (developmental stage, wet weight, and body, snout-vent and hindlimb lengths) and molecular (mRNA abundance using quantitative real time polymerase chain reaction) criteria. T{sub 4} treatment alone accelerated development concomitant with altered levels of TH receptors {alpha} and {beta}, proliferating cell nuclear antigen, and gelatinase B mRNAs in the brain and tail. We observed TCS-induced perturbations in all of the molecular and morphological endpoints indicating that TCS exposure disrupts coordination of postembryonic tadpole development. Clear alterations in molecular endpoints were evident at day 2 whereas the earliest morphological effects appeared at day 4 and were most evident at day 21. Although TCS alone (3 and 30 {mu}g/L) was protective against tadpole mortality, this protection was lost in the presence of T{sub 4}. The Pacific tree frog is the most sensitive species examined to date displaying disruption of TH-mediated development by a common antimicrobial agent.

  15. Functional and inflammatory alterations in the lung following exposure of rats to nitrogen mustard

    International Nuclear Information System (INIS)

    Nitrogen mustard is a vesicant that causes damage to the respiratory tract. In these studies, we characterized the acute effects of nitrogen mustard on lung structure, inflammatory mediator expression, and pulmonary function, with the goal of identifying mediators potentially involved in toxicity. Treatment of rats (male Wistar, 200-225 g) with nitrogen mustard (mechlorethamine hydrochloride, i.t., 0.25 mg/kg) resulted in marked histological changes in the respiratory tract, including necrotizing bronchiolitis, thickening of alveolar septa, and inflammation which was evident within 24 h. This was associated with increases in bronchoalveolar lavage protein and cells, confirming injury to alveolar epithelial regions of the lung. Nitrogen mustard administration also resulted in increased expression of inducible nitric oxide synthase and cyclooxygenase-2, pro-inflammatory proteins implicated in lung injury, in alveolar macrophages and alveolar and bronchial epithelial cells. Expression of connective tissue growth factor and matrix metalloproteinase-9, mediators regulating extracellular matrix turnover was also increased, suggesting that pathways leading to chronic lung disease are initiated early in the pathogenic process. Following nitrogen mustard exposure, alterations in lung mechanics and function were also observed. These included decreases in baseline static compliance, end-tidal volume and airway resistance, and a pronounced loss of methacholine responsiveness in resistance, tissue damping and elastance. Taken together, these data demonstrate that nitrogen mustard induces rapid structural and inflammatory changes in the lung which are associated with altered lung functioning. Understanding the nature of the injury induced by nitrogen mustard and related analogs may aid in the development of efficacious therapies for treatment of pulmonary injury resulting from exposure to vesicants.

  16. Prenatal exposure to urban air nanoparticles in mice causes altered neuronal differentiation and depression-like responses.

    Directory of Open Access Journals (Sweden)

    David A Davis

    Full Text Available Emerging evidence suggests that excessive exposure to traffic-derived air pollution during pregnancy may increase the vulnerability to neurodevelopmental alterations that underlie a broad array of neuropsychiatric disorders. We present a mouse model for prenatal exposure to urban freeway nanoparticulate matter (nPM. In prior studies, we developed a model for adult rodent exposure to re-aerosolized urban nPM which caused inflammatory brain responses with altered neuronal glutamatergic functions. nPMs are collected continuously for one month from a local freeway and stored as an aqueous suspension, prior to re-aerosolization for exposure of mice under controlled dose and duration. This paradigm was used for a pilot study of prenatal nPM impact on neonatal neurons and adult behaviors. Adult C57BL/6J female mice were exposed to re-aerosolized nPM (350 µg/m(3 or control filtered ambient air for 10 weeks (3×5 hour exposures per week, encompassing gestation and oocyte maturation prior to mating. Prenatal nPM did not alter litter size, pup weight, or postnatal growth. Neonatal cerebral cortex neurons at 24 hours in vitro showed impaired differentiation, with 50% reduction of stage 3 neurons with long neurites and correspondingly more undifferentiated neurons at Stages 0 and 1. Neuron number after 24 hours of culture was not altered by prenatal nPM exposure. Addition of exogenous nPM (2 µg/ml to the cultures impaired pyramidal neuron Stage 3 differentiation by 60%. Adult males showed increased depression-like responses in the tail-suspension test, but not anxiety-related behaviors. These pilot data suggest that prenatal exposure to nPM can alter neuronal differentiation with gender-specific behavioral sequelae that may be relevant to human prenatal exposure to urban vehicular aerosols.

  17. RNA-Seq identifies key reproductive gene expression alterations in response to cadmium exposure.

    Science.gov (United States)

    Hu, Hanyang; Lu, Xing; Cen, Xiang; Chen, Xiaohua; Li, Feng; Zhong, Shan

    2014-01-01

    Cadmium is a common toxicant that is detrimental to many tissues. Although a number of transcriptional signatures have been revealed in different tissues after cadmium treatment, the genes involved in the cadmium caused male reproductive toxicity, and the underlying molecular mechanism remains unclear. Here we observed that the mice treated with different amount of cadmium in their rodent chow for six months exhibited reduced serum testosterone. We then performed RNA-seq to comprehensively investigate the mice testicular transcriptome to further elucidate the mechanism. Our results showed that hundreds of genes expression altered significantly in response to cadmium treatment. In particular, we found several transcriptional signatures closely related to the biological processes of regulation of hormone, gamete generation, and sexual reproduction, respectively. The expression of several testosterone synthetic key enzyme genes, such as Star, Cyp11a1, and Cyp17a1, were inhibited by the cadmium exposure. For better understanding of the cadmium-mediated transcriptional regulatory mechanism of the genes, we computationally analyzed the transcription factors binding sites and the mircoRNAs targets of the differentially expressed genes. Our findings suggest that the reproductive toxicity by cadmium exposure is implicated in multiple layers of deregulation of several biological processes and transcriptional regulation in mice. PMID:24982889

  18. RNA-Seq Identifies Key Reproductive Gene Expression Alterations in Response to Cadmium Exposure

    Directory of Open Access Journals (Sweden)

    Hanyang Hu

    2014-01-01

    Full Text Available Cadmium is a common toxicant that is detrimental to many tissues. Although a number of transcriptional signatures have been revealed in different tissues after cadmium treatment, the genes involved in the cadmium caused male reproductive toxicity, and the underlying molecular mechanism remains unclear. Here we observed that the mice treated with different amount of cadmium in their rodent chow for six months exhibited reduced serum testosterone. We then performed RNA-seq to comprehensively investigate the mice testicular transcriptome to further elucidate the mechanism. Our results showed that hundreds of genes expression altered significantly in response to cadmium treatment. In particular, we found several transcriptional signatures closely related to the biological processes of regulation of hormone, gamete generation, and sexual reproduction, respectively. The expression of several testosterone synthetic key enzyme genes, such as Star, Cyp11a1, and Cyp17a1, were inhibited by the cadmium exposure. For better understanding of the cadmium-mediated transcriptional regulatory mechanism of the genes, we computationally analyzed the transcription factors binding sites and the mircoRNAs targets of the differentially expressed genes. Our findings suggest that the reproductive toxicity by cadmium exposure is implicated in multiple layers of deregulation of several biological processes and transcriptional regulation in mice.

  19. Alteration of transcriptional networks in the entorhinal cortex after maternal immune activation and adolescent cannabinoid exposure.

    Science.gov (United States)

    Hollins, Sharon L; Zavitsanou, Katerina; Walker, Frederick Rohan; Cairns, Murray J

    2016-08-01

    Maternal immune activation (MIA) and adolescent cannabinoid exposure (ACE) have both been identified as major environmental risk factors for schizophrenia. We examined the effects of these two risk factors alone, and in combination, on gene expression during late adolescence. Pregnant rats were exposed to the viral infection mimic polyriboinosinic-polyribocytidylic acid (poly I:C) on gestational day (GD) 15. Adolescent offspring received daily injections of the cannabinoid HU210 for 14days starting on postnatal day (PND) 35. Gene expression was examined in the left entorhinal cortex (EC) using mRNA microarrays. We found prenatal treatment with poly I:C alone, or HU210 alone, produced relatively minor changes in gene expression. However, following combined treatments, offspring displayed significant changes in transcription. This dramatic and persistent alteration of transcriptional networks enriched with genes involved in neurotransmission, cellular signalling and schizophrenia, was associated with a corresponding perturbation in the expression of small non-coding microRNA (miRNA). These results suggest that a combination of environmental exposures during development leads to significant genomic remodeling that disrupts maturation of the EC and its associated circuitry with important implications as the potential antecedents of memory and learning deficits in schizophrenia and other neuropsychiatric disorders. PMID:26923065

  20. Levonorgestrel exposure to fathead minnows (Pimephales promelas) alters survival, growth, steroidogenic gene expression and hormone production.

    Science.gov (United States)

    Overturf, Matthew D; Overturf, Carmen L; Carty, Dennis R; Hala, David; Huggett, Duane B

    2014-03-01

    Human pharmaceuticals are commonly detected in the environment. Concern over these compounds in the environment center around the potential for pharmaceuticals to interfere with the endocrine system of aquatic organisms. The main focus of endocrine disruption research has centered on how estrogenic and androgenic compounds interact with the endocrine system to elicit reproductive effects. Other classes of compounds, such as progestins, have been overlooked. Recently, studies have investigated the potential for synthetic progestins to impair reproduction and growth in aquatic organisms. The present study utilizes the OECD 210 Early-life Stage (ELS) study to investigate the impacts levonorgestrel (LNG), a synthetic progestin, on fathead minnow (FHM) survival and growth. After 28 days post-hatch, survival of larval FHM was impacted at 462 ng/L, while growth was significantly reduced at 86.9 ng/L. Further analysis was conducted by measuring specific endocrine related mRNA transcript profiles in FHM larvae following the 28 day ELS exposure to LNG. Transcripts of 3β-HSD, 20β-HSD, CYP17, AR, ERα, and FSH were significantly down-regulated following 28d exposure to 16.3 ng/L LNG, while exposure to 86.9 ng/L significantly down-regulated 3β-HSD, 20β-HSD, CYP19A, and FSH. At 2,392 ng/L of LNG, a significant down-regulation occurred with CYP19A and ERβ transcripts, while mPRα and mPRβ profiles were significantly induced. No significant changes occurred in 11β-HSD, CYP11A, StAR, LHβ, and VTG mRNA expression following LNG exposure. An ex vivo steroidogenesis assay was conducted with sexually mature female FHM following a 7 day exposure 100 ng/L LNG with significant reductions observed in pregnenolone, 17α,20β-dihydroxy-4-pregnen-3-one (17,20-DHP), testosterone, and 11-ketotestosterone. Together these data suggest LNG can negatively impact FHM larval survival and growth, with significant alterations in endocrine related responses. PMID:24503577

  1. 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...

  2. Dietary exposure to the PCB mixture aroclor 1254 may compromise osmoregulation by altering central vasopressin release

    Energy Technology Data Exchange (ETDEWEB)

    Coburn, C.G. [Environmental Toxicology, Univ. of California at Riverside, CA (United States); Gillard, E.; Curras-Collazo, M. [Cell Biology and Neuroscience, Univ. of California at Riverside, CA (United States)

    2004-09-15

    Despite the importance of systemic osmoregulation, the potential deleterious effects of persistent organochlorines, such as polychlorinated biphenyls (PCBs), on body fluid regulation has not been thoroughly investigated. In an effort to ameliorate this deficit, the current study explores the toxic effects of PCBs on osmoregulation, and in particular, on the activity of the magnocellular neuroendocrine cell (MNC) system of the hypothalamus. MNCs of the supraoptic nucleus (SON) release oxytocin (OXY) and vasopressin (VP) from terminals in the neurohypophysis in response to dehydration. The latter is released to effect water conservation in response to dehydration via its action upon the kidney and through extra-renal actions. MNCs also secrete VP from their cell bodies and dendrites locally i.e., into the extracellular space of the SON. Although it has been shown that both intranuclear and systemic release rise in response to dehydration the physiological significance of intranuclear release has not been fully elucidated. We chose to use voluntary ingestion as the route of PCB exposure since it is more reflective of natural exposure compared to ip injection. One unexpected observation that resulted from pilot studies using ip injection of PCBs was the deleterious effects of the vehicle (corn oil) resulting in pooling of lipid within the abdominal cavity, mottling of the liver, fatty liver and general discoloration of all abdominal viscera at time of sacrifice. Therefore, all work described in this series of experiments have employed voluntary ingestion of the toxin. Work described in this paper suggests that PCBs in concentrations reflecting realistic lifetime exposure levels may negatively impact homeostatic mechanisms responsible for body water balance by altering somatodendritic (intranuclear) VP secretion in response to dehydration in vivo. The downstream consequences of such influence is currently under investigation, and preliminary evidence suggests that the

  3. Alteration of Pentylenetetrazol-induced kindling parameters by prenatal chronic Lead exposure in rats

    Directory of Open Access Journals (Sweden)

    Kebriyaei Zadeh A

    2001-08-01

    Full Text Available The effect of prenatal chronic lead exposure on pentylenetetrazol (PTZ-induced kindling parameters (seizure index, seizure latency and seizure stage in rats was studied. Adult female rats with a weight range of 140-180 g were selected and pretreated with lead acetate (0.05% w/v orally, 25 days prior to mating. The control group was given distilled water containing sodium acetate solution (0.05% w/v. After delivery, treatment was ceased, and after lactation, male neonates were separated from the females in both groups. After maturation of male rats, the PTZ-kindling was induced by daily interapritoneally injection of PTZ (30 mg/kg. Kindling parameters in the control and treated groups were determined. The results indicated that animals with prenatal lead exposure have full kindling state with 9-19 (16.87±1.54 injections, whereas this value for control group was 12-23 (18.62±1.48 injections. The seizure latency for the treated group was lower (P<0.05 than the control (2.29±0.44 min versus 3.65±0.45 min. The seizure severity (regarding to seizure index was statistically higher in the treated group (P<0.05. The seizure stages were also different in the treated and control groups (P<0.05. The seizure frequency of first and second stages of kindling in the control group was higher than that of treated one (P<0.05. Also the seizure frequency in the third and fourth kindling stages of case group was higher than controls (P<0.05. It is concluded that prenatal lead exposure alters seizure susceptibility in rat PTZ-Kindling model.

  4. Motor alterations associated with exposure to manganese in the environment in Mexico.

    Science.gov (United States)

    Rodríguez-Agudelo, Yaneth; Riojas-Rodríguez, Horacio; Ríos, Camilo; Rosas, Irma; Sabido Pedraza, Eva; Miranda, Javier; Siebe, Christina; Texcalac, José Luis; Santos-Burgoa, Carlos

    2006-09-15

    Overexposure to manganese (Mn) causes neurotoxicity (a Parkinson-like syndrome) or psychiatric damage ("manganese madness"). Several studies have shown alterations to motor and neural behavior associated with exposure to Mn in the workplace. However, there are few studies on the effects of environmental exposure of whole populations. We studied the risk of motor alterations in people living in a mining district in Mexico. We studied 288 individual people (168 women and 120 men) from eight communities at various distances from manganese extraction or processing facilities in the district of Molango. We measured manganese concentrations in airborne particles, water, soil and crops and evaluated the possible routes of Mn exposure. We also took samples of people's blood and determined their concentrations of Mn and lead (Pb). We used "Esquema de Diagnóstico Neuropsicológico" Ardila and Ostrosky-Solís's neuropsychological battery to evaluate motor functions. Concentrations of Mn in drinking water and maize grain were less than detection limits at most sampling sites. Manganese extractable by DTPA in soils ranged between 6 and 280 mg kg(-1) and means were largest close to Mn extraction or processing facilities. Air Mn concentration ranged between 0.003 and 5.86 microg/m(3); the mean value was 0.42 microg/m(3) and median was 0.10 microg/m(3), the average value (geometric mean) resulted to be 0.13 microg/m(3). Mean blood manganese concentration was 10.16 microg/l, and geometric mean 9.44 microg/l, ranged between 5.0 and 31.0 mcrog/l. We found no association between concentrations of Mn in blood and motor tests. There was a statistically significant association between Mn concentrations in air and motor tests that assessed the coordination of two movements (OR 3.69; 95% CI 0.9, 15.13) and position changes in hand movements (OR 3.09; CI 95% 1.07, 8.92). An association with tests evaluating conflictive reactions (task that explores verbal regulations of movements) was also

  5. Adult hippocampal neurogenesis and mRNA expression are altered by perinatal arsenic exposure in mice and restored by brief exposure to enrichment.

    Directory of Open Access Journals (Sweden)

    Christina R Tyler

    Full Text Available Arsenic is a common and pervasive environmental contaminant found in drinking water in varying concentrations depending on region. Exposure to arsenic induces behavioral and cognitive deficits in both human populations and in rodent models. The Environmental Protection Agency (EPA standard for the allotment of arsenic in drinking water is in the parts-per-billion range, yet our lab has shown that 50 ppb arsenic exposure during development can have far-reaching consequences into adulthood, including deficits in learning and memory, which have been linked to altered adult neurogenesis. Given that the morphological impact of developmental arsenic exposure on the hippocampus is unknown, we sought to evaluate proliferation and differentiation of adult neural progenitor cells in the dentate gyrus after 50 ppb arsenic exposure throughout the perinatal period of development in mice (equivalent to all three trimesters in humans using a BrdU pulse-chase assay. Proliferation of the neural progenitor population was decreased by 13% in arsenic-exposed mice, but was not significant. However, the number of differentiated cells was significantly decreased by 41% in arsenic-exposed mice compared to controls. Brief, daily exposure to environmental enrichment significantly increased proliferation and differentiation in both control and arsenic-exposed animals. Expression levels of 31% of neurogenesis-related genes including those involved in Alzheimer's disease, apoptosis, axonogenesis, growth, Notch signaling, and transcription factors were altered after arsenic exposure and restored after enrichment. Using a concentration previously considered safe by the EPA, perinatal arsenic exposure altered hippocampal morphology and gene expression, but did not inhibit the cellular neurogenic response to enrichment. It is possible that behavioral deficits observed during adulthood in animals exposed to arsenic during development derive from the lack of differentiated neural

  6. 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...

  7. Prenatal alcohol exposure alters methyl metabolism and programs serotonin transporter and glucocorticoid receptor expression in brain

    Science.gov (United States)

    Ngai, Ying Fai; Sulistyoningrum, Dian C.; O'Neill, Ryan; Innis, Sheila M.; Weinberg, Joanne

    2015-01-01

    Prenatal alcohol exposure (PAE) programs the fetal hypothalamic-pituitary-adrenal (HPA) axis, resulting in HPA dysregulation and hyperresponsiveness to stressors in adulthood. Molecular mechanisms mediating these alterations are not fully understood. Disturbances in one-carbon metabolism, a source of methyl donors for epigenetic processes, contributes to alcoholic liver disease. We assessed whether PAE affects one-carbon metabolism (including Mtr, Mat2a, Mthfr, and Cbs mRNA) and programming of HPA function genes (Nr3c1, Nr3c2, and Slc6a4) in offspring from ethanol-fed (E), pair-fed (PF), and ad libitum-fed control (C) dams. At gestation day 21, plasma total homocysteine and methionine concentrations were higher in E compared with C dams, and E fetuses had higher plasma methionine concentrations and lower whole brain Mtr and Mat2a mRNA compared with C fetuses. In adulthood (55 days), hippocampal Mtr and Cbs mRNA was lower in E compared with C males, whereas Mtr, Mat2a, Mthfr, and Cbs mRNA were higher in E compared with C females. We found lower Nr3c1 mRNA and lower nerve growth factor inducible protein A (NGFI-A) protein in the hippocampus of E compared with PF females, whereas hippocampal Slc6a4 mRNA was higher in E than C males. By contrast, hypothalamic Slc6a4 mRNA was lower in E males and females compared with C offspring. This was accompanied by higher hypothalamic Slc6a4 mean promoter methylation in E compared with PF females. These findings demonstrate that PAE is associated with alterations in one-carbon metabolism and has long-term and region-specific effects on gene expression in the brain. These findings advance our understanding of mechanisms of HPA dysregulation associated with PAE. PMID:26180184

  8. Individual variability in esterase activity and CYP1A levels in Chinook salmon (Oncorhynchus tshawytscha) exposed to esfenvalerate and chlorpyrifos

    Science.gov (United States)

    Wheelock, C.E.; Eder, K.J.; Werner, I.; Huang, H.; Jones, P.D.; Brammell, B.F.; Elskus, A.A.; Hammock, B.D.

    2005-01-01

    Acetylcholinesterase (AChE) activity has traditionally been monitored as a biomarker of organophosphate (OP) and/or carbamate exposure. However, AChE activity may not be the most sensitive endpoint for these agrochemicals, because OPs can cause adverse physiological effects at concentrations that do not affect AChE activity. Carboxylesterases are a related family of enzymes that have higher affinity than AChE for some OPs and carbamates and may be more sensitive indicators of environmental exposure to these pesticides. In this study, carboxylesterase and AChE activity, cytochrome P4501A (CYP1A) protein levels, and mortality were measured in individual juvenile Chinook salmon (Oncorhynchus tshawytscha) following exposure to an OP (chlorpyrifos) and a pyrethroid (esfenvalerate). As expected, high doses of chlorpyrifos and esfenvalerate were acutely toxic, with nominal concentrations (100 and 1 ??g/l, respectively) causing 100% mortality within 96 h. Exposure to chlorpyrifos at a high dose (7.3 ??g/l), but not a low dose (1.2 ??g/l), significantly inhibited AChE activity in both brain and muscle tissue (85% and 92% inhibition, respectively), while esfenvalerate exposure had no effect. In contrast, liver carboxylesterase activity was significantly inhibited at both the low and high chlorpyrifos dose exposure (56% and 79% inhibition, respectively), while esfenvalerate exposure still had little effect. The inhibition of carboxylesterase activity at levels of chlorpyrifos that did not affect AChE activity suggests that some salmon carboxylesterase isozymes may be more sensitive than AChE to inhibition by OPs. CYP1A protein levels were ???30% suppressed by chlorpyrifos exposure at the high dose, but esfenvalerate had no effect. Three teleost species, Chinook salmon, medaka (Oryzias latipes) and Sacramento splittail (Pogonichthys macrolepidotus), were examined for their ability to hydrolyze a series of pyrethroid surrogate substrates and in all cases hydrolysis activity was

  9. Morpho-toxicology of chlorpyrifos to prolactin cells of a freshwater catfish, Heteropneustes fossilis =Morpho-toxicology of chlorpyrifos to prolactin cells of a freshwater catfish, Heteropneustes fossilis

    Directory of Open Access Journals (Sweden)

    Diwakar Mishra

    2012-10-01

    Full Text Available In the present study, an organophosphorus compound Coroban (active ingredient chlorpyrifos – E.C. 20% was used. In short-term exposure the fish were subjected to 0.8 of 96h LC50 value of chlorpyrifos (1.76 mg L-1 for 96h. In long-term exposure the experiment was performed for 28 days by using 0.2 of 96h LC50 value of chlorpyrifos (0.44 mg L-1. Fish were killed on each time intervals from control and experimental (chlorpyrifos groups after 24, 48, 72, and 96h in short-term exposure and after 7, 14, 21, and 28 days in long-term experiment. Blood samples were collected and sera were analyzed for calcium. Pituitary glands were fixed for histological studies and stained with Herlant tetrachrome and Heidenhain’s azan techniques. Short-term exposure of chlorpyrifos caused decrease in the serum calcium levels. No change was noticed in the prolactin cells of chlorpyrifos treated fish. Long-term treatment with chlorpyrifos provoked hypocalcemia. The prolactin cells of treated fish exhibited slight degranulation after 21 days whereas the nuclear volume remained unchanged. After 28 days, the prolactin cells exhibited further degranulation and the nuclear volume recorded an increase. Cytolysis and vacuolization were also visible. No estudo presente, o composto organofosforo Coroban (ingrediente ativo clorpirifo – E.C. 20% foi usado. Na exposição a curto prazo os peixes foram submetido a 0,8 de valor LC50 de 96h de clorpirifo (1,76 mg L-1 durante 96h. Na exposição a longo prazo o experimento foi executado durante 28 dias usando 0,2 de valor LC50 de 96h de clorpirifos (0,44 mg L-1. Os peixes foram mortos a cada intervalo dos grupos controle e experimental (clorpirifos após 24, 48, 72, e 96h em exposição a curto prazo e após 7, 14, 21, e 28 dias no experimento a longo prazo. As amostras de sangue foram colhidas e o soro foi analisado para cálcio. As glândulas pituitárias foram fixadas para estudos histológicos e colorido por tetracromo de

  10. Exposure of soil microbial communities to chromium and arsenic alters their diversity and structure.

    Directory of Open Access Journals (Sweden)

    Cody S Sheik

    Full Text Available Extensive use of chromium (Cr and arsenic (As based preservatives from the leather tanning industry in Pakistan has had a deleterious effect on the soils surrounding production facilities. Bacteria have been shown to be an active component in the geochemical cycling of both Cr and As, but it is unknown how these compounds affect microbial community composition or the prevalence and form of metal resistance. Therefore, we sought to understand the effects that long-term exposure to As and Cr had on the diversity and structure of soil microbial communities. Soils from three spatially isolated tanning facilities in the Punjab province of Pakistan were analyzed. The structure, diversity and abundance of microbial 16S rRNA genes were highly influenced by the concentration and presence of hexavalent chromium (Cr (VI and arsenic. When compared to control soils, contaminated soils were dominated by Proteobacteria while Actinobacteria and Acidobacteria (which are generally abundant in pristine soils were minor components of the bacterial community. Shifts in community composition were significant and revealed that Cr (VI-containing soils were more similar to each other than to As contaminated soils lacking Cr (VI. Diversity of the arsenic resistance genes, arsB and ACR3 were also determined. Results showed that ACR3 becomes less diverse as arsenic concentrations increase with a single OTU dominating at the highest concentration. Chronic exposure to either Cr or As not only alters the composition of the soil bacterial community in general, but affects the arsenic resistant individuals in different ways.

  11. Sucrose exposure in early life alters adult motivation and weight gain.

    Directory of Open Access Journals (Sweden)

    Cristianne R M Frazier

    Full Text Available The cause of the current increase in obesity in westernized nations is poorly understood but is frequently attributed to a 'thrifty genotype,' an evolutionary predisposition to store calories in times of plenty to protect against future scarcity. In modern, industrialized environments that provide a ready, uninterrupted supply of energy-rich foods at low cost, this genetic predisposition is hypothesized to lead to obesity. Children are also exposed to this 'obesogenic' environment; however, whether such early dietary experience has developmental effects and contributes to adult vulnerability to obesity is unknown. Using mice, we tested the hypothesis that dietary experience during childhood and adolescence affects adult obesity risk. We gave mice unlimited or no access to sucrose for a short period post-weaning and measured sucrose-seeking, food consumption, and weight gain in adulthood. Unlimited access to sucrose early in life reduced sucrose-seeking when work was required to obtain it. When high-sugar/high-fat dietary options were made freely-available, however, the sucrose-exposed mice gained more weight than mice without early sucrose exposure. These results suggest that early, unlimited exposure to sucrose reduces motivation to acquire sucrose but promotes weight gain in adulthood when the cost of acquiring palatable, energy dense foods is low. This study demonstrates that early post-weaning experience can modify the expression of a 'thrifty genotype' and alter an adult animal's response to its environment, a finding consistent with evidence of pre- and peri-natal programming of adult obesity risk by maternal nutritional status. Our findings suggest the window for developmental effects of diet may extend into childhood, an observation with potentially important implications for both research and public policy in addressing the rising incidence of obesity.

  12. Exposure of soil microbial communities to chromium and arsenic alters their diversity and structure.

    Science.gov (United States)

    Sheik, Cody S; Mitchell, Tyler W; Rizvi, Fariha Z; Rehman, Yasir; Faisal, Muhammad; Hasnain, Shahida; McInerney, Michael J; Krumholz, Lee R

    2012-01-01

    Extensive use of chromium (Cr) and arsenic (As) based preservatives from the leather tanning industry in Pakistan has had a deleterious effect on the soils surrounding production facilities. Bacteria have been shown to be an active component in the geochemical cycling of both Cr and As, but it is unknown how these compounds affect microbial community composition or the prevalence and form of metal resistance. Therefore, we sought to understand the effects that long-term exposure to As and Cr had on the diversity and structure of soil microbial communities. Soils from three spatially isolated tanning facilities in the Punjab province of Pakistan were analyzed. The structure, diversity and abundance of microbial 16S rRNA genes were highly influenced by the concentration and presence of hexavalent chromium (Cr (VI)) and arsenic. When compared to control soils, contaminated soils were dominated by Proteobacteria while Actinobacteria and Acidobacteria (which are generally abundant in pristine soils) were minor components of the bacterial community. Shifts in community composition were significant and revealed that Cr (VI)-containing soils were more similar to each other than to As contaminated soils lacking Cr (VI). Diversity of the arsenic resistance genes, arsB and ACR3 were also determined. Results showed that ACR3 becomes less diverse as arsenic concentrations increase with a single OTU dominating at the highest concentration. Chronic exposure to either Cr or As not only alters the composition of the soil bacterial community in general, but affects the arsenic resistant individuals in different ways. PMID:22768219

  13. 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,...

  14. TIME-DEPENDENT EFFECTS ON GENE EXPRESSION IN RAT SEMINAL VESICLE DEVELOPMENTALLY ALTERED BY IN UTERO EXPOSURE TO TCDD

    Science.gov (United States)

    TIME-DEPENDENT EFFECTS ON GENE EXPRESSION IN RAT SEMINAL VESICLE DEVELOPMENTALLY ALTERED BY IN UTERO EXPOSURE TO TCDD. V M Richardson', J T Hamm2, and L S Birnbaum1. 'USEPA, ORD/NHEERL/ETD, Research Triangle Park, NC, USA, 'Curriculum in Toxicology, University of North Carolina, ...

  15. Prenatal exposure to gamma/neutron irradiation: Sensorimotor alterations and paradoxical effects on learning

    International Nuclear Information System (INIS)

    The effects of prenatal exposure on gamma/neutron radiations (0.5 Gy at about the 18th day of fetal life) were studied in a hybrid strain of mice (DBA/Cne males x C57BL/Cne females). During ontogeny, measurements of sensorimotor reflexes revealed in prenatally irradiated mice (1) a delay in sensorial development, (2) deficits in tests involving body motor control, and (3) a reduction of both motility and locomotor activity scores. In adulthood, the behaviour of prenatally irradiated and control mice was examined in the open field test and in reactivity to novelty. Moreover, their learning performance was compared in several situations. The results show that, in the open field test, only rearings were more frequent in irradiated mice. In the presence of a novel object, significant sex x treatment interactions were observed since ambulation and leaning against the novel object increased in irradiated females but decreased in irradiated males. Finally, when submitted to different learning tasks, irradiated mice were impaired in the radial maze, but paradoxically exhibited higher avoidance scores than control mice, possibly because of their low pain thresholds. Taken together, these observations indicate that late prenatal gamma/neutron irradiation induces long lasting alterations at the sensorimotor level which, in turn, can influence learning abilities of adult mice

  16. Prenatal exposure to gamma/neutron irradiation: Sensorimotor alterations and paradoxical effects on learning

    Energy Technology Data Exchange (ETDEWEB)

    Di Cicco, D.; Antal, S.; Ammassari-Teule, M. (Istituto di Psicobiologia e Psicofarmacologia del CNR, Rome (Italy))

    1991-01-01

    The effects of prenatal exposure on gamma/neutron radiations (0.5 Gy at about the 18th day of fetal life) were studied in a hybrid strain of mice (DBA/Cne males x C57BL/Cne females). During ontogeny, measurements of sensorimotor reflexes revealed in prenatally irradiated mice (1) a delay in sensorial development, (2) deficits in tests involving body motor control, and (3) a reduction of both motility and locomotor activity scores. In adulthood, the behaviour of prenatally irradiated and control mice was examined in the open field test and in reactivity to novelty. Moreover, their learning performance was compared in several situations. The results show that, in the open field test, only rearings were more frequent in irradiated mice. In the presence of a novel object, significant sex x treatment interactions were observed since ambulation and leaning against the novel object increased in irradiated females but decreased in irradiated males. Finally, when submitted to different learning tasks, irradiated mice were impaired in the radial maze, but paradoxically exhibited higher avoidance scores than control mice, possibly because of their low pain thresholds. Taken together, these observations indicate that late prenatal gamma/neutron irradiation induces long lasting alterations at the sensorimotor level which, in turn, can influence learning abilities of adult mice.

  17. Alteration of the enterohepatic recirculation of bile acids in rats after exposure to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Scanff, P.; Souidi, M.; Grison, S.; Griffiths, N.M.; Gourmelon, P. [Inst. de Radioprotection et de Surete Nucleaire, (IRSN), Direction de la RadioProtection de l' Homme, Service de Radiobiologie et d' Epidemiologie, Fontenay-aux-Roses, CEDEX (France)]. E-mail: pascale.scanff@irsn.fr

    2004-02-01

    The aim of this work was to study acute alterations of the enterohepatic recirculation (EHR) of bile acids 3 days after an 8-Gy radiation exposure in vivo in the rat by a washout technique. Using this technique in association with HPLC analysis, the EHR of the major individual bile acids was determined in control and irradiated animals. Ex vivo ileal taurocholate absorption was also studied in Ussing chambers. Major hepatic enzyme activities involved in bile acid synthesis were also measured. Measurements of bile acid intestinal content and intestinal absorption efficiency calculation from washout showed reduced intestinal absorption with significant differences from one bile acid to another: absorption of taurocholate and tauromuricholate was decreased, whereas absorption of the more hydrophobic taurochenodeoxycholate was increased, suggesting that intestinal passive diffusion was enhanced, whereas ileal active transport might be reduced. Basal hepatic secretion was increased only for taurocholate, in accordance with the marked increase of CYP8B1 activity in the liver. The results are clearly demonstrate that concomitantly with radiation-induced intestinal bile acid malabsorption, hepatic bile acid synthesis and secretion are also changed. A current working model for pathophysiological changes in enterohepatic recycling after irradiation is thus proposed. (author)

  18. Ethanol Exposure Alters Protein Expression in a Mouse Model of Fetal Alcohol Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Stephen Mason

    2012-01-01

    Full Text Available Alcohol exposure during development can result in variable growth retardation and facial dysmorphology known as fetal alcohol spectrum disorders. Although the mechanisms underlying the disorder are not fully understood, recent progress has been made that alcohol induces aberrant changes in gene expression and in the epigenome of embryos. To inform the gene and epigenetic changes in alcohol-induced teratology, we used whole-embryo culture to identify the alcohol-signature protein profile of neurulating C6 mice. Alcohol-treated and control cultures were homogenized, isoelectrically focused, and loaded for 2D gel electrophoresis. Stained gels were cross matched with analytical software. We identified 40 differentially expressed protein spots (P<0.01, and 9 spots were selected for LC/MS-MS identification. Misregulated proteins include serotransferrin, triosephosphate isomerase and ubiquitin-conjugating enzyme E2 N. Misregulation of serotransferrin and triosephosphate isomerase was confirmed with immunologic analysis. Alteration of proteins with roles in cellular function, cell cycle, and the ubiquitin-proteasome pathway was induced by alcohol. Several misregulated proteins interact with effectors of the NF-κB and Myc transcription factor cascades. Using a whole-embryo culture, we have identified misregulated proteins known to be involved in nervous system development and function.

  19. Long-term in vivo polychlorinated biphenyl 126 exposure induces oxidative stress and alters proteomic profile on islets of Langerhans

    Science.gov (United States)

    Loiola, Rodrigo Azevedo; Dos Anjos, Fabyana Maria; Shimada, Ana Lúcia; Cruz, Wesley Soares; Drewes, Carine Cristiane; Rodrigues, Stephen Fernandes; Cardozo, Karina Helena Morais; Carvalho, Valdemir Melechco; Pinto, Ernani; Farsky, Sandra Helena

    2016-06-01

    It has been recently proposed that exposure to polychlorinated biphenyls (PCBs) is a risk factor to type 2 diabetes mellitus (DM2). We investigated this hypothesis using long-term in vivo PCB126 exposure to rats addressing metabolic, cellular and proteomic parameters. Male Wistar rats were exposed to PCB126 (0.1, 1 or 10 μg/kg of body weight/day; for 15 days) or vehicle by intranasal instillation. Systemic alterations were quantified by body weight, insulin and glucose tolerance, and blood biochemical profile. Pancreatic toxicity was measured by inflammatory parameters, cell viability and cycle, free radical generation, and proteomic profile on islets of Langerhans. In vivo PCB126 exposure enhanced the body weight gain, impaired insulin sensitivity, reduced adipose tissue deposit, and elevated serum triglycerides, cholesterol, and insulin levels. Inflammatory parameters in the pancreas and cell morphology, viability and cycle were not altered in islets of Langerhans. Nevertheless, in vivo PCB126 exposure increased free radical generation and modified the expression of proteins related to oxidative stress on islets of Langerhans, which are indicative of early β-cell failure. Data herein obtained show that long-term in vivo PCB126 exposure through intranasal route induced alterations on islets of Langerhans related to early end points of DM2.

  20. 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...

  1. Alterations in catecholamine turnover in specific regions of the rat brain following acute exposure to nitrous oxide.

    Science.gov (United States)

    Karuri, A R; Kugel, G; Engelking, L R; Kumar, M S

    1998-04-01

    The effects of nitrous oxide (N2O) on steady-state concentrations and turnover rates of catecholamines in the olfactory bulb, hypothalamus, brain stem, hippocampus, striatum, thalamus, cerebral cortex, and spinal cord were determined in rats. Animals were exposed for 2 h to either 60% N2O or air. Immediately following exposure, all animals were injected intraperitoneally with alpha-methylparatyrosine (alphaMPT), a competitive inhibitor of tyrosine hydroxylase, and sacrificed at 0, 30, or 90 min postinjection. Brain catecholamine concentrations were determined using high-performance liquid chromatography coupled with electrochemical detection (HPLC-EC). Results indicate that N2O exposure significantly elevates steady-state concentrations of norepinephrine (NE) in the hypothalamus and striatum yet decreases amine levels in the brain stem region. Steady-state levels of dopamine (DA) were not significantly altered in any region of the CNS by N2O exposure. Acute exposure to N2O also resulted in significant decreases in the turnover rate of NE in the brain stem, yet it increased turnover of this amine in the olfactory bulb, hypothalamus, and striatum. Acute exposure to N2O resulted in a decreased turnover rate of DA in the hippocampus and striatum. In contrast, N2O appears to increase DA turnover in the olfactory bulb. These results indicate that acute exposure to N2O in rats causes region-specific alterations in steady-state levels and turnover rates of DA and NE within the central nervous system.

  2. Short-term exposure of arsenite disrupted thyroid endocrine system and altered gene transcription in the HPT axis in zebrafish

    International Nuclear Information System (INIS)

    Arsenic (As) pollution in aquatic environment may adversely impact fish health by disrupting their thyroid hormone homeostasis. In this study, we explored the effect of short-term exposure of arsenite (AsIII) on thyroid endocrine system in zebrafish. We measured As concentrations, As speciation, and thyroid hormone thyroxine levels in whole zebrafish, oxidative stress (H2O2) and damage (MDA) in the liver, and gene transcription in hypothalamic–pituitary–thyroid (HPT) axis in the brain and liver tissues of zebrafish after exposing to different AsIII concentrations for 48 h. Result indicated that exposure to AsIII increased inorganic As in zebrafish to 0.46–0.72 mg kg−1, induced oxidative stress with H2O2 being increased by 1.4–2.5 times and caused oxidative damage with MDA being augmented by 1.6 times. AsIII exposure increased thyroxine levels by 1.3–1.4 times and modulated gene transcription in HPT axis. Our study showed AsIII caused oxidative damage, affected thyroid endocrine system and altered gene transcription in HPT axis in zebrafish. - Highlights: • 48 h-LC50 value of arsenite (AsIII) was 42 mg L−1 for zebrafish. • AsIII exposure elevated oxidative stress and caused oxidative damage in zebrafish. • AsIII exposure increased the content of thyroid hormone thyroxine. • AsIII exposure altered gene transcription in the HPT axis in zebrafish. - Short-term exposure of arsenite caused oxidative stress, disrupted thyroid endocrine system and altered gene transcription in the HPT axis in Zebrafish

  3. Effects of sub-lethal neurite outgrowth inhibitory concentrations of chlorpyrifos oxon on cytoskeletal proteins and acetylcholinesterase in differentiating N2a cells

    Energy Technology Data Exchange (ETDEWEB)

    Flaskos, J., E-mail: flaskos@vet.auth.gr [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Nikolaidis, E. [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Harris, W. [School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom); Sachana, M. [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Hargreaves, A.J., E-mail: alan.hargreaves@ntu.ac.uk [School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom)

    2011-11-15

    Previous work in our laboratory has shown that sub-lethal concentrations (1-10 {mu}M) of chlorpyrifos (CPF), diazinon (DZ) and diazinon oxon (DZO) inhibit the outgrowth of axon-like neurites in differentiating mouse N2a neuroblastoma cells concomitant with altered levels and/or phosphorylation state of axonal cytoskeleton and growth-associated proteins. The aim of the present work was to determine whether chlorpyrifos oxon (CPO) was capable of inhibiting N2a cell differentiation in a similar manner. Using experimental conditions similar to our previous work, sub-lethal concentrations (1-10 {mu}M) of CPO were found to inhibit N2a cell differentiation. However, unlike previous studies with DZ and DZO, there was a high level of sustained inhibition of acetylcholinesterase (AChE) in CPO treated cells. Impairment of neurite outgrowth was also associated with reduced levels of growth associated protein-43 and neurofilament heavy chain (NFH), and the distribution of NFH in cells stained by indirect immunofluorescence was disrupted. However, in contrast to previous findings for DZO, the absolute level of phosphorylated NFH was unaffected by CPO exposure. Taken together, the findings suggest that sub-lethal concentrations of CPO inhibit axon outgrowth in differentiating N2a cells and that this effect involves reduced levels of two proteins that play key roles in axon outgrowth and maintenance. Although the inhibition of neurite outgrowth is unlikely to involve AChE inhibition directly, further work will help to determine whether the persistent inhibition of AChE by CPO can account for the different effects induced by CPO and DZO on the levels of total and phosphorylated NFH. -- Highlights: Black-Right-Pointing-Pointer Sub-lethal levels of chlorpyrifos oxon inhibit neurite outgrowth in N2a cells Black-Right-Pointing-Pointer Acetylcholinesterase exhibits sustained inhibition throughout exposure Black-Right-Pointing-Pointer The levels of neurofilament heavy chain and GAP-43

  4. Effects of sub-lethal neurite outgrowth inhibitory concentrations of chlorpyrifos oxon on cytoskeletal proteins and acetylcholinesterase in differentiating N2a cells

    International Nuclear Information System (INIS)

    Previous work in our laboratory has shown that sub-lethal concentrations (1–10 μM) of chlorpyrifos (CPF), diazinon (DZ) and diazinon oxon (DZO) inhibit the outgrowth of axon-like neurites in differentiating mouse N2a neuroblastoma cells concomitant with altered levels and/or phosphorylation state of axonal cytoskeleton and growth-associated proteins. The aim of the present work was to determine whether chlorpyrifos oxon (CPO) was capable of inhibiting N2a cell differentiation in a similar manner. Using experimental conditions similar to our previous work, sub-lethal concentrations (1–10 μM) of CPO were found to inhibit N2a cell differentiation. However, unlike previous studies with DZ and DZO, there was a high level of sustained inhibition of acetylcholinesterase (AChE) in CPO treated cells. Impairment of neurite outgrowth was also associated with reduced levels of growth associated protein-43 and neurofilament heavy chain (NFH), and the distribution of NFH in cells stained by indirect immunofluorescence was disrupted. However, in contrast to previous findings for DZO, the absolute level of phosphorylated NFH was unaffected by CPO exposure. Taken together, the findings suggest that sub-lethal concentrations of CPO inhibit axon outgrowth in differentiating N2a cells and that this effect involves reduced levels of two proteins that play key roles in axon outgrowth and maintenance. Although the inhibition of neurite outgrowth is unlikely to involve AChE inhibition directly, further work will help to determine whether the persistent inhibition of AChE by CPO can account for the different effects induced by CPO and DZO on the levels of total and phosphorylated NFH. -- Highlights: ► Sub-lethal levels of chlorpyrifos oxon inhibit neurite outgrowth in N2a cells ► Acetylcholinesterase exhibits sustained inhibition throughout exposure ► The levels of neurofilament heavy chain and GAP-43 protein are reduced ► Neurofilament heavy chain forms aggregates in cell

  5. Acute Exposure to Microcystin-Producing Cyanobacterium Microcystis aeruginosa Alters Adult Zebrafish (Danio rerio Swimming Performance Parameters

    Directory of Open Access Journals (Sweden)

    Luiza Wilges Kist

    2011-01-01

    Full Text Available Microcystins (MCs are toxins produced by cyanobacteria (blue-green algae, primarily Microcystis aeruginosa, forming water blooms worldwide. When an organism is exposed to environmental perturbations, alterations in normal behavioral patterns occur. Behavioral repertoire represents the consequence of a diversity of physiological and biochemical alterations. In this study, we assessed behavioral patterns and whole-body cortisol levels of adult zebrafish (Danio rerio exposed to cell culture of the microcystin-producing cyanobacterium M. aeruginosa (MC-LR, strain RST9501. MC-LR exposure (100 μg/L decreased by 63% the distance traveled and increased threefold the immobility time when compared to the control group. Interestingly, no significant alterations in the number of line crossings were found at the same MC-LR concentration and time of exposure. When animals were exposed to 50 and 100 μg/L, MC-LR promoted a significant increase (around 93% in the time spent in the bottom portion of the tank, suggesting an anxiogenic effect. The results also showed that none of the MC-LR concentrations tested promoted significant alterations in absolute turn angle, path efficiency, social behavior, or whole-body cortisol level. These findings indicate that behavior is susceptible to MC-LR exposure and provide evidence for a better understanding of the ecological consequences of toxic algal blooms.

  6. Acute Exposure to Microcystin-Producing Cyanobacterium Microcystis aeruginosa Alters Adult Zebrafish (Danio rerio) Swimming Performance Parameters.

    Science.gov (United States)

    Kist, Luiza Wilges; Piato, Angelo Luis; da Rosa, João Gabriel Santos; Koakoski, Gessi; Barcellos, Leonardo José Gil; Yunes, João Sarkis; Bonan, Carla Denise; Bogo, Maurício Reis

    2011-01-01

    Microcystins (MCs) are toxins produced by cyanobacteria (blue-green algae), primarily Microcystis aeruginosa, forming water blooms worldwide. When an organism is exposed to environmental perturbations, alterations in normal behavioral patterns occur. Behavioral repertoire represents the consequence of a diversity of physiological and biochemical alterations. In this study, we assessed behavioral patterns and whole-body cortisol levels of adult zebrafish (Danio rerio) exposed to cell culture of the microcystin-producing cyanobacterium M. aeruginosa (MC-LR, strain RST9501). MC-LR exposure (100 μg/L) decreased by 63% the distance traveled and increased threefold the immobility time when compared to the control group. Interestingly, no significant alterations in the number of line crossings were found at the same MC-LR concentration and time of exposure. When animals were exposed to 50 and 100 μg/L, MC-LR promoted a significant increase (around 93%) in the time spent in the bottom portion of the tank, suggesting an anxiogenic effect. The results also showed that none of the MC-LR concentrations tested promoted significant alterations in absolute turn angle, path efficiency, social behavior, or whole-body cortisol level. These findings indicate that behavior is susceptible to MC-LR exposure and provide evidence for a better understanding of the ecological consequences of toxic algal blooms. PMID:22253623

  7. Application of a mathematical model to describe the effects of chlorpyrifos on Caenorhabditis elegans development.

    Directory of Open Access Journals (Sweden)

    Windy A Boyd

    Full Text Available BACKGROUND: The nematode Caenorhabditis elegans is being assessed as an alternative model organism as part of an interagency effort to develop better means to test potentially toxic substances. As part of this effort, assays that use the COPAS Biosort flow sorting technology to record optical measurements (time of flight (TOF and extinction (EXT of individual nematodes under various chemical exposure conditions are being developed. A mathematical model has been created that uses Biosort data to quantitatively and qualitatively describe C. elegans growth, and link changes in growth rates to biological events. Chlorpyrifos, an organophosphate pesticide known to cause developmental delays and malformations in mammals, was used as a model toxicant to test the applicability of the growth model for in vivo toxicological testing. METHODOLOGY/PRINCIPAL FINDINGS: L1 larval nematodes were exposed to a range of sub-lethal chlorpyrifos concentrations (0-75 microM and measured every 12 h. In the absence of toxicant, C. elegans matured from L1s to gravid adults by 60 h. A mathematical model was used to estimate nematode size distributions at various times. Mathematical modeling of the distributions allowed the number of measured nematodes and log(EXT and log(TOF growth rates to be estimated. The model revealed three distinct growth phases. The points at which estimated growth rates changed (change points were constant across the ten chlorpyrifos concentrations. Concentration response curves with respect to several model-estimated quantities (numbers of measured nematodes, mean log(TOF and log(EXT, growth rates, and time to reach change points showed a significant decrease in C. elegans growth with increasing chlorpyrifos concentration. CONCLUSIONS: Effects of chlorpyrifos on C. elegans growth and development were mathematically modeled. Statistical tests confirmed a significant concentration effect on several model endpoints. This confirmed that chlorpyrifos

  8. 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...... 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...

  9. Honey Bee Gut Microbiome Is Altered by In-Hive Pesticide Exposures.

    Science.gov (United States)

    Kakumanu, Madhavi L; Reeves, Alison M; Anderson, Troy D; Rodrigues, Richard R; Williams, Mark A

    2016-01-01

    Honey bees (Apis mellifera) are the primary pollinators of major horticultural crops. Over the last few decades, a substantial decline in honey bees and their colonies have been reported. While a plethora of factors could contribute to the putative decline, pathogens, and pesticides are common concerns that draw attention. In addition to potential direct effects on honey bees, indirect pesticide effects could include alteration of essential gut microbial communities and symbionts that are important to honey bee health (e.g., immune system). The primary objective of this study was to determine the microbiome associated with honey bees exposed to commonly used in-hive pesticides: coumaphos, tau-fluvalinate, and chlorothalonil. Treatments were replicated at three independent locations near Blacksburg Virginia, and included a no-pesticide amended control at each location. The microbiome was characterized through pyrosequencing of V2-V3 regions of the bacterial 16S rRNA gene and fungal ITS region. Pesticide exposure significantly affected the structure of bacterial but not fungal communities. The bee bacteriome, similar to other studies, was dominated by sequences derived from Bacilli, Actinobacteria, α-, β-, γ-proteobacteria. The fungal community sequences were dominated by Ascomycetes and Basidiomycetes. The Multi-response permutation procedures (MRPP) and subsequent Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis indicated that chlorothalonil caused significant change to the structure and functional potential of the honey bee gut bacterial community relative to control. Putative genes for oxidative phosphorylation, for example, increased while sugar metabolism and peptidase potential declined in the microbiome of chlorothalonil exposed bees. The results of this field-based study suggest the potential for pesticide induced changes to the honey bee gut microbiome that warrant further investigation. PMID:27579024

  10. Honey Bee Gut Microbiome Is Altered by In-Hive Pesticide Exposures

    Science.gov (United States)

    Kakumanu, Madhavi L.; Reeves, Alison M.; Anderson, Troy D.; Rodrigues, Richard R.; Williams, Mark A.

    2016-01-01

    Honey bees (Apis mellifera) are the primary pollinators of major horticultural crops. Over the last few decades, a substantial decline in honey bees and their colonies have been reported. While a plethora of factors could contribute to the putative decline, pathogens, and pesticides are common concerns that draw attention. In addition to potential direct effects on honey bees, indirect pesticide effects could include alteration of essential gut microbial communities and symbionts that are important to honey bee health (e.g., immune system). The primary objective of this study was to determine the microbiome associated with honey bees exposed to commonly used in-hive pesticides: coumaphos, tau-fluvalinate, and chlorothalonil. Treatments were replicated at three independent locations near Blacksburg Virginia, and included a no-pesticide amended control at each location. The microbiome was characterized through pyrosequencing of V2–V3 regions of the bacterial 16S rRNA gene and fungal ITS region. Pesticide exposure significantly affected the structure of bacterial but not fungal communities. The bee bacteriome, similar to other studies, was dominated by sequences derived from Bacilli, Actinobacteria, α-, β-, γ-proteobacteria. The fungal community sequences were dominated by Ascomycetes and Basidiomycetes. The Multi-response permutation procedures (MRPP) and subsequent Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis indicated that chlorothalonil caused significant change to the structure and functional potential of the honey bee gut bacterial community relative to control. Putative genes for oxidative phosphorylation, for example, increased while sugar metabolism and peptidase potential declined in the microbiome of chlorothalonil exposed bees. The results of this field-based study suggest the potential for pesticide induced changes to the honey bee gut microbiome that warrant further investigation. PMID:27579024

  11. Exposure to Forced Swim Stress Alters Local Circuit Activity and Plasticity in the Dentate Gyrus of the Hippocampus

    Directory of Open Access Journals (Sweden)

    Mouna Maroun

    2008-02-01

    Full Text Available Studies have shown that, depending on its severity and context, stress can affect neural plasticity. Most related studies focused on synaptic plasticity and long-term potentiation (LTP of principle cells. However, evidence suggests that following high-frequency stimulation, which induces LTP in principal cells, modifications also take place at the level of complex interactions with interneurons within the dentate gyrus, that is, at the local circuit level. So far, the possible effects of stress on local circuit activity and plasticity were not studied. Therefore, we set out to examine the possible alterations in local circuit activity and plasticity following exposure to stress. Local circuit activity and plasticity were measured by using frequency dependant inhibition (FDI and commissural modulation protocols following exposure to a 15 minute-forced swim trial. Exposure to stress did not alter FDI. The application of theta-burst stimulation (TBS reduced FDI in both control and stressed rats, but this type of plasticity was greater in stressed rats. Commissural-induced inhibition was significantly higher in stressed rats both before and after applying theta-burst stimulation. These findings indicate that the exposure to acute stress affects aspects of local circuit activity and plasticity in the dentate gyrus. It is possible that these alterations underlie some of the behavioral consequences of the stress experience.

  12. Exposure to forced swim stress alters local circuit activity and plasticity in the dentate gyrus of the hippocampus.

    Science.gov (United States)

    Yarom, Orli; Maroun, Mouna; Richter-Levin, Gal

    2008-01-01

    Studies have shown that, depending on its severity and context, stress can affect neural plasticity. Most related studies focused on synaptic plasticity and long-term potentiation (LTP) of principle cells. However, evidence suggests that following high-frequency stimulation, which induces LTP in principal cells, modifications also take place at the level of complex interactions with interneurons within the dentate gyrus, that is, at the local circuit level. So far, the possible effects of stress on local circuit activity and plasticity were not studied. Therefore, we set out to examine the possible alterations in local circuit activity and plasticity following exposure to stress. Local circuit activity and plasticity were measured by using frequency dependant inhibition (FDI) and commissural modulation protocols following exposure to a 15 minute-forced swim trial. Exposure to stress did not alter FDI. The application of theta-burst stimulation (TBS) reduced FDI in both control and stressed rats, but this type of plasticity was greater in stressed rats. Commissural-induced inhibition was significantly higher in stressed rats both before and after applying theta-burst stimulation. These findings indicate that the exposure to acute stress affects aspects of local circuit activity and plasticity in the dentate gyrus. It is possible that these alterations underlie some of the behavioral consequences of the stress experience.

  13. Particulate and gas-phase products from the atmospheric degradation of chlorpyrifos and chlorpyrifos-oxon

    Science.gov (United States)

    Borrás, Esther; Ródenas, Milagros; Vázquez, Mónica; Vera, Teresa; Muñoz, Amalia

    2015-12-01

    The phosphorothioate structure is highly present in several pesticides. However, there is a lack of information about its degradation process in air and the secondary pollutants formed. Herein, the atmospheric reactions of chlorpyrifos, one of the most world-used insecticide, and its main degradation product - chlorpyrifos-oxon - are described. The photo-oxidation under the presence of NOx was studied in a large outdoor simulation chamber for both chlorpyrifos and chlorpyrifos-oxon, observing a rapid degradation (Half lifetime < 3.5 h for both compounds). Also, the photolysis reactions of both were studied. The formation of particulate matter (aerosol mass yield ranged 6-59%) and gaseous products were monitored. The chemical composition of minor products was studied, identifying 15 multi-oxygenated derivatives. The most abundant products were ring-retaining molecules such as 3,5,6-trichloropyridin-2-ol and ethyl 3,5,6-trichloropyridin-2-yl hydrogen phosphate. An atmospheric degradation mechanism has been amplified based on an oxidation started with OH-nucleophilic attack to Pdbnd S bond.

  14. 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)

  15. Long-term in vivo polychlorinated biphenyl 126 exposure induces oxidative stress and alters proteomic profile on islets of Langerhans

    OpenAIRE

    Loiola, Rodrigo Azevedo; dos Anjos, Fabyana Maria; Shimada, Ana Lúcia; Cruz, Wesley Soares; Drewes, Carine Cristiane; Rodrigues, Stephen Fernandes; Cardozo, Karina Helena Morais; Carvalho, Valdemir Melechco; Pinto, Ernani; Farsky, Sandra Helena

    2016-01-01

    It has been recently proposed that exposure to polychlorinated biphenyls (PCBs) is a risk factor to type 2 diabetes mellitus (DM2). We investigated this hypothesis using long-term in vivo PCB126 exposure to rats addressing metabolic, cellular and proteomic parameters. Male Wistar rats were exposed to PCB126 (0.1, 1 or 10 μg/kg of body weight/day; for 15 days) or vehicle by intranasal instillation. Systemic alterations were quantified by body weight, insulin and glucose tolerance, and blood bi...

  16. Sub-lethal Effects of Chlorpyrifos on Big Brown Bats (Eptesicus fuscus).

    Science.gov (United States)

    Eidels, Ronny R; Sparks, Daniel W; Whitaker, John O; Sprague, Charles A

    2016-10-01

    We determined dose-response curves for sublethal effects of the organophosphorus (OP) insecticide, chlorpyrifos, on bats. Big brown bats (Eptesicus fuscus, n = 64) were given a single dose of chlorpyrifos (nominal concentrations) of 0, 5, 10, 15, 20, 25, 30, or 60 µg/g body weight and examined at 12 or 24 h after dosing. A second experiment dosed 32 bats with 0 or 60 µg/g body weight and examined 1, 3, 7, or 14 days after dosing. Skin temperature and behavioral changes were recorded, and brain and plasma cholinesterase (ChE) activity were measured. The benchmark dose (BMD10) of chlorpyrifos that altered brain and plasma ChE activity at 24 h was 3.7 and 10.1 µg/g, respectively. The 95 % lower confidence limit for the BMD10 (i.e., BMDL10) was 1.6 and 7.7 µg/g. The best of five models (as determined by AIC) for impaired flight, impaired movement, or presence of tremors provided a BMD10 of 6.2, 12.9, and 7.8 µg/g body weight of chlorpyrifos, respectively. BMDL10 for impaired flight, impaired movement, or presence of tremors was 3.5, 6.6, and 5.3 µg/g body weight, respectively. In the wild, impaired ability to fly or crawl could be life-threatening. Brain and plasma ChE activity remained low for 3 days after dosing. Gradual recovery of enzyme activity was observed by 7 days in survivors. Brain and plasma ChE activity were still significantly lower than that of the control group at 14 days after dosing. PMID:27491870

  17. 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.

  18. 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

  19. Exposure to ozone reduces influenza disease severity and alters distribution of influenza viral antigens in murine lungs.

    Science.gov (United States)

    Wolcott, J A; Zee, Y C; Osebold, J W

    1982-09-01

    Exposure to ambient levels of ozone (0.5 ppm) was shown to alter the pathogenesis of respiratory infection after aerosol infection of mice with influenza A virus. A semiquantitative method for determination of the sites of virus replication by direct immunofluorescence indicated that exposure to ozone reduced the involvement of respiratory epithelium in the infectious process and resulted in a less widespread infection of the alveolar parenchyma. Furthermore, the ozone-mediated alteration in viral antigen distribution was consistent with significantly reduced influenza disease mortality and prolonged survival time, but only when the oxidant was present during the course of infection. Reduced disease severity in ozone-exposed animals appeared to be independent of peak pulmonary virus titers, pulmonary interferon titers, and pulmonary and serum-neutralizing antibody titers. These studies suggested that the distribution of influenza virus in the murine lung was a key factor in disease severity. PMID:6182839

  20. In vivo hydroquinone exposure alters circulating neutrophil activities and impairs LPS-induced lung inflammation in mice.

    Science.gov (United States)

    Ribeiro, André Luiz Teroso; Shimada, Ana Lúcia Borges; Hebeda, Cristina Bichels; de Oliveira, Tiago Franco; de Melo Loureiro, Ana Paula; Filho, Walter Dos Reis Pereira; Santos, Alcinéa Meigikos Dos Anjos; de Lima, Wothan Tavares; Farsky, Sandra Helena Poliselli

    2011-10-01

    Hydroquinone (HQ) is an environmental contaminant which causes immune toxicity. In this study, the effects of exposure to low doses of HQ on neutrophil mobilization into the LPS-inflamed lung were investigated. Male Swiss mice were exposed to aerosolized vehicle (control) or 12.5, 25 or 50ppm HQ (1h/day for 5 days). One hour later, oxidative burst, cell cycle, DNA fragmentation and adhesion molecules expressions in circulating neutrophils were determined by flow cytometry, and plasma malondialdehyde (MDA) levels were measured by HPLC. Also, 1h later the last exposures, inflammation was induced by LPS inhalation (0.1mg/ml/10min) and 3h later, the numbers of leukocytes in peripheral blood and in the bronchoalveolar lavage fluid (BALF) were determined using a Neubauer chamber and stained smears; adhesion molecules expressed on lung microvessel endothelial cells were quantified by immunohistochemistry; myeloperoxidase (MPO) activity was measured in the lung tissue by colorimetric assay; and cytokines in the BALF were determined by ELISA. In vivo HQ exposure augmented plasma MDA levels and oxidative activity of neutrophils, but did not cause alterations in cell cycle and DNA fragmentation. Under these conditions, the number of circulating leukocytes was not altered, but HQ exposure reduced LPS-induced neutrophil migration into the alveolar space, as these cells remained in the lung tissue. The impaired neutrophil migration into BALF may not be dependent on reduced cytokines secretions in the BALF and lung endothelial adhesion molecules expressions. However, HQ exposure increased the expression of β(2) and β(3) integrins and platelet-endothelial cell adhesion molecule-1 (PECAM-1) in neutrophils, which were not further enhanced by fMLP in vitro stimulation, indicating that HQ exposure activates circulating neutrophils, impairing further stimulatory responses. Therefore, it has been shown, for the first time, that neutrophils are target of lower levels of in vivo HQ

  1. Prenatal exposure to cannabinoids evokes long-lasting functional alterations by targeting CB1 receptors on developing cortical neurons.

    Science.gov (United States)

    de Salas-Quiroga, Adán; Díaz-Alonso, Javier; García-Rincón, Daniel; Remmers, Floortje; Vega, David; Gómez-Cañas, María; Lutz, Beat; Guzmán, Manuel; Galve-Roperh, Ismael

    2015-11-01

    The CB1 cannabinoid receptor, the main target of Δ(9)-tetrahydrocannabinol (THC), the most prominent psychoactive compound of marijuana, plays a crucial regulatory role in brain development as evidenced by the neurodevelopmental consequences of its manipulation in animal models. Likewise, recreational cannabis use during pregnancy affects brain structure and function of the progeny. However, the precise neurobiological substrates underlying the consequences of prenatal THC exposure remain unknown. As CB1 signaling is known to modulate long-range corticofugal connectivity, we analyzed the impact of THC exposure on cortical projection neuron development. THC administration to pregnant mice in a restricted time window interfered with subcerebral projection neuron generation, thereby altering corticospinal connectivity, and produced long-lasting alterations in the fine motor performance of the adult offspring. Consequences of THC exposure were reminiscent of those elicited by CB1 receptor genetic ablation, and CB1-null mice were resistant to THC-induced alterations. The identity of embryonic THC neuronal targets was determined by a Cre-mediated, lineage-specific, CB1 expression-rescue strategy in a CB1-null background. Early and selective CB1 reexpression in dorsal telencephalic glutamatergic neurons but not forebrain GABAergic neurons rescued the deficits in corticospinal motor neuron development of CB1-null mice and restored susceptibility to THC-induced motor alterations. In addition, THC administration induced an increase in seizure susceptibility that was mediated by its interference with CB1-dependent regulation of both glutamatergic and GABAergic neuron development. These findings demonstrate that prenatal exposure to THC has long-lasting deleterious consequences in the adult offspring solely mediated by its ability to disrupt the neurodevelopmental role of CB1 signaling.

  2. Sustained Exposure to the Widely Used Herbicide Atrazine: Altered Function and Loss of Neurons in Brain Monoamine Systems

    OpenAIRE

    Rodriguez, Veronica M.; Thiruchelvam, Mona; Cory-Slechta, Deborah A.

    2005-01-01

    The widespread use of atrazine (ATR) and its persistence in the environment have resulted in documented human exposure. Alterations in hypothalamic catecholamines have been suggested as the mechanistic basis of the toxicity of ATR to hormonal systems in females and the reproductive tract in males. Because multiple catecholamine systems are present in the brain, however, ATR could have far broader effects than are currently understood. Catecholaminergic systems such as the two major long-lengt...

  3. Postnatal manganese exposure alters dopamine transporter function in adult rats: Potential impact on nonassociative and associative processes.

    Science.gov (United States)

    McDougall, S A; Reichel, C M; Farley, C M; Flesher, M M; Der-Ghazarian, T; Cortez, A M; Wacan, J J; Martinez, C E; Varela, F A; Butt, A E; Crawford, C A

    2008-06-23

    In the present study, we examined whether exposing rats to a high-dose regimen of manganese chloride (Mn) during the postnatal period would depress presynaptic dopamine functioning and alter nonassociative and associative behaviors. To this end, rats were given oral supplements of Mn (750 microg/day) on postnatal days (PD) 1-21. On PD 90, dopamine transporter (DAT) immunoreactivity and [3H]dopamine uptake were assayed in the striatum and nucleus accumbens, while in vivo microdialysis was used to measure dopamine efflux in the same brain regions. The effects of postnatal Mn exposure on nigrostriatal functioning were evaluated by assessing rotorod performance and amphetamine-induced stereotypy in adulthood. In terms of associative processes, both cocaine-induced conditioned place preference (CPP) and sucrose-reinforced operant responding were examined. Results showed that postnatal Mn exposure caused persistent declines in DAT protein expression and [3H]dopamine uptake in the striatum and nucleus accumbens, as well as long-term reductions in striatal dopamine efflux. Rotorod performance did not differ according to exposure condition, however Mn-exposed rats did exhibit substantially more amphetamine-induced stereotypy than vehicle controls. Mn exposure did not alter performance on any aspect of the CPP task (preference, extinction, or reinstatement testing), nor did Mn affect progressive ratio responding (a measure of motivation). Interestingly, acquisition of a fixed ratio task was impaired in Mn-exposed rats, suggesting a deficit in procedural learning. In sum, these results indicate that postnatal Mn exposure causes persistent declines in various indices of presynaptic dopaminergic functioning. Mn-induced alterations in striatal functioning may have long-term impact on associative and nonassociative behavior. PMID:18485605

  4. Alteration of extracellular enzymes in pinto bean leaves upon exposure to air pollutants, ozone and sulfur dioxide

    Energy Technology Data Exchange (ETDEWEB)

    Peters, J.L.; Castillo, F.J.; Heath, R.L. (Univ. of California, Riverside (USA))

    1989-01-01

    Diamine oxidase and peroxidase, associated with the wall in pinto bean (Phaseolus vulgaris L. var Pinto) leaves, can be washed out by vacuum infiltration and assayed without grinding the leaf. The diamine oxidase activity is inhibited in vivo by exposure of the plants to ozone (dose of 0.6 microliters per liter {times} hour), whereas the peroxidase activity associated with the wall space is stimulated. This dose does not cause obvious necrosis or chlorosis of the leaf. These alterations are greater when the dose of ozone exposure is given as a triangular pulse (a slow rise to a peak of 0.24 microliters per liter followed by a slow fall) compared to that given as a constant square wave pulse of 0.15 microliters per liter for the same 4 hour period. Exposure of the plants to sulfur dioxide (at a concentration of 0.4 microliters per liter for 4 hours) does not result in any change in the diamine oxidase or peroxidase activities, yet the total sulfhydryl content of the leaf is increased, demonstrating the entry of sulfur dioxide. These two pollutants, with different chemical reactivities, affect the activities of the extracellular enzymes in different manners. In the case of ozone exposure, the inhibition of extracellular diamine oxidase could profoundly alter the movements of polyamines from cell to cell.

  5. Esterases activity in the axolotl Ambystoma mexicanum exposed to chlorpyrifos and its implication to motor activity.

    Science.gov (United States)

    Robles-Mendoza, Cecilia; Zúñiga-Lagunes, Sebastian R; Ponce de León-Hill, Claudia A; Hernández-Soto, Jesús; Vanegas-Pérez, Cecilia

    2011-10-01

    The axolotl Ambystoma mexicanum is a neotenic salamander considered a good biological model due to its ability to regenerate limbs, tail, brain and heart cells. Nevertheless, severe reduction of A. mexicanum wild populations in the lacustrine area of Xochimilco, the natural habitat of the axolotl, could be related to several environmental pressures as the presence of organophosphate pesticides (OPPs), intensively applied in agricultural activities in Xochimilco. Thus the aim of this study was to evaluate the effect of environmentally realistic chlorpyrifos (CPF) concentrations, a OPP commonly used in this zone, on esterases activity (acetylcholinesterase and carboxylesterase) and bioconcentration of CPF and to relate them with the motor activity of A. mexicanum juveniles. Axolotls were exposed 48 h to 0.05 and 0.1mg CPF/L, and the responses were evaluated at the end of the CPF exposure. Results suggest that CPF is bioconcentrated into axolotls and that the CPF internal concentrations are related with the observed inhibition activity of AChE (>50%) and CbE (≈ 50%). CPF concentration responsible of the inhibition of the 50% of AChE activity (IC50) was estimated in 0.04 mg CPF/L; however IC50 for CbE activity was not possible to calculate since inhibition levels were lower than 50%, results that suggest a higher resistance of CbE enzymatic activity to CPF. However, motor activity was a more sensitive endpoint to CPF poisoning since time that axolotls spent active and walking, frequency and speed of swimming, frequency of prey attack were reduced >90% of control groups. The motor activity alterations in the axolotl could be related with the registered esterases inhibition. Thus important alterations on axolotls were identified even at short time and low concentrations of CPF exposure. Also, it was possible to link biochemical responses as esterases activity with higher levels of biological organization as behavior. This study provides tools for the regulation of the

  6. Acute chlorine gas exposure produces transient inflammation and a progressive alteration in surfactant composition with accompanying mechanical dysfunction

    International Nuclear Information System (INIS)

    Acute Cl2 exposure following industrial accidents or military/terrorist activity causes pulmonary injury and severe acute respiratory distress. Prior studies suggest that antioxidant depletion is important in producing dysfunction, however a pathophysiologic mechanism has not been elucidated. We propose that acute Cl2 inhalation leads to oxidative modification of lung lining fluid, producing surfactant inactivation, inflammation and mechanical respiratory dysfunction at the organ level. C57BL/6J mice underwent whole-body exposure to an effective 60 ppm-hour Cl2 dose, and were euthanized 3, 24 and 48 h later. Whereas pulmonary architecture and endothelial barrier function were preserved, transient neutrophilia, peaking at 24 h, was noted. Increased expression of ARG1, CCL2, RETLNA, IL-1b, and PTGS2 genes was observed in bronchoalveolar lavage (BAL) cells with peak change in all genes at 24 h. Cl2 exposure had no effect on NOS2 mRNA or iNOS protein expression, nor on BAL NO3− or NO2−. Expression of the alternative macrophage activation markers, Relm-α and mannose receptor was increased in alveolar macrophages and pulmonary epithelium. Capillary surfactometry demonstrated impaired surfactant function, and altered BAL phospholipid and surfactant protein content following exposure. Organ level respiratory function was assessed by forced oscillation technique at 5 end expiratory pressures. Cl2 exposure had no significant effect on either airway or tissue resistance. Pulmonary elastance was elevated with time following exposure and demonstrated PEEP refractory derecruitment at 48 h, despite waning inflammation. These data support a role for surfactant inactivation as a physiologic mechanism underlying respiratory dysfunction following Cl2 inhalation. - Highlights: • Effect of 60 ppm*hr Cl2 gas on lung inflammation and mechanical function examined. • Pulmonary inflammation is transient and minor. • Alterations in surfactant homeostasis and pulmonary mechanics

  7. Maternal Dexamethasone Exposure Alters Synaptic Inputs to Gonadotropin-Releasing Hormone Neurons in the Early Postnatal Rat

    Science.gov (United States)

    Lim, Wei Ling; Idris, Marshita Mohd; Kevin, Felix Suresh; Soga, Tomoko; Parhar, Ishwar S.

    2016-01-01

    Maternal dexamethasone [(DEX); a glucocorticoid receptor agonist] exposure delays pubertal onset and alters reproductive behavior in the adult offspring. However, little is known whether maternal DEX exposure affects the offspring’s reproductive function by disrupting the gonadotropin-releasing hormone (GnRH) neuronal function in the brain. Therefore, this study determined the exposure of maternal DEX on the GnRH neuronal spine development and synaptic cluster inputs to GnRH neurons using transgenic rats expressing enhanced green fluorescent protein (EGFP) under the control of GnRH promoter. Pregnant females were administered with DEX (0.1 mg/kg) or vehicle (VEH, water) daily during gestation day 13–20. Confocal imaging was used to examine the spine density of EGFP–GnRH neurons by three-dimensional rendering and synaptic cluster inputs to EGFP–GnRH neurons by synapsin I immunohistochemistry on postnatal day 0 (P0) males. The spine morphology and number on GnRH neurons did not change between the P0 males following maternal DEX and VEH treatment. The number of synaptic clusters within the organum vasculosum of the lamina terminalis (OVLT) was decreased by maternal DEX exposure in P0 males. Furthermore, the number and levels of synaptic cluster inputs in close apposition with GnRH neurons was decreased following maternal DEX exposure in the OVLT region of P0 males. In addition, the postsynaptic marker molecule, postsynaptic density 95, was observed in GnRH neurons following both DEX and VEH treatment. These results suggest that maternal DEX exposure alters neural afferent inputs to GnRH neurons during early postnatal stage, which could lead to reproductive dysfunction during adulthood. PMID:27630615

  8. Early Exposure to Intermediate-Frequency Magnetic Fields Alters Brain Biomarkers without Histopathological Changes in Adult Mice

    Directory of Open Access Journals (Sweden)

    Tin-Tin Win-Shwe

    2015-04-01

    Full Text Available Recently we have reported that intermediate-frequency magnetic field (IF-MF exposure transiently altered the mRNA expression levels of memory function-related genes in the hippocampi of adult male mice. However, the effects of IF-MF exposure during brain development on neurological biomarkers have not yet been clarified. In the present study, we investigated the effect of IF-MF exposure during development on neurological and immunological markers in the mouse hippocampus in 3- and 7-week-old male mice. Pregnant C57BL/6J mice were exposed to IF-MF (21 kHz, 3.8 mT for one hour per day from organogenesis period day 7 to 17. At adolescence, some IF-MF-exposed mice were further divided into exposure, recovery, and sham-exposure groups. The adolescent-exposure groups were exposed again to IF-MF from postnatal day 27 to 48. The expression of mRNA in the hippocampi was examined using a real-time RT-PCR method, and microglia activation was examined by immunohistochemical analysis. The expression levels of NR1 and NR2B as well as transcription factors (CaMKIV, CREB1, inflammatory mediators (COX2, IL-1 b,TNF-α, and the oxidative stress marker heme-oxygenase (HO-1 were significantly increased in the IF-MF-exposed mice, compared with the control group, in the 7-week-old mice, but not in the 3-week-old mice. Microglia activation was not different between the control and other groups. This study provides the first evidence that early exposure to IF-MF reversibly affects the NMDA receptor, its related signaling pathways, and inflammatory mediators in the hippocampus of young adult mice; these changes are transient and recover after termination of exposure without histopathological changes.

  9. Identification of neural biomarkers of altered sexual differentiation following gestational exposure###

    Science.gov (United States)

    Sexual differentiation of the brain occurs during late gestation through the early postnatal period. The development of the phenotypical male brain is dependent on the aromatization of circulating testosterone to estradiol. Exposure to endocrine disrupting chemicals (EDCs) duri...

  10. IDENTIFICATION OF NEURAL BIOMARKERS OF ALTERED SEXUAL DIFFERENTIATION FOLLOWING GESTATIONAL EXPOSURE***

    Science.gov (United States)

    Sexual differentiation of the brain occurs during late gestation through the early postnatal period. The development of the phenotypical male brain is dependent on the aromatization of circulating testosterone to estradiol. Exposure to endocrine disrupting chemicals (EDCs) duri...

  11. Identification of neural biomarkers of altered sexual differentiation following gestational exposure

    Science.gov (United States)

    Sexual differentiation of the brain occurs during late gestation through the early postnatal period. The development of the phenotypical male brain is dependent on the aromatization of circulating testosterone to estradiol. Exposure to endocrine disrupting chemicals (EDCs) during...

  12. Developmental Exposure to PCBs Differentially Alters Sensitivity to Audiogenic and Kindling-Induced Seizures in Rats

    Science.gov (United States)

    Previously we reported an increased incidence of audiogenic seizures in offspring of pregnant rats exposed to an environmental mixture of polychlorinated biphenyls (PCBs). This study compares the proconvulsant properties of PCB exposure in audiogenic and electrical kindling seizu...

  13. Prenatal exposure to BPA alters the epigenome of the rat mammary gland and increases the propensity to neoplastic development.

    Directory of Open Access Journals (Sweden)

    Eugen Dhimolea

    Full Text Available Exposure to environmental estrogens (xenoestrogens may play a causal role in the increased breast cancer incidence which has been observed in Europe and the US over the last 50 years. The xenoestrogen bisphenol A (BPA leaches from plastic food/beverage containers and dental materials. Fetal exposure to BPA induces preneoplastic and neoplastic lesions in the adult rat mammary gland. Previous results suggest that BPA acts through the estrogen receptors which are detected exclusively in the mesenchyme during the exposure period by directly altering gene expression, leading to alterations of the reciprocal interactions between mesenchyme and epithelium. This initiates a long sequence of altered morphogenetic events leading to neoplastic transformation. Additionally, BPA induces epigenetic changes in some tissues. To explore this mechanism in the mammary gland, Wistar-Furth rats were exposed subcutaneously via osmotic pumps to vehicle or 250 µg BPA/kg BW/day, a dose that induced ductal carcinomas in situ. Females exposed from gestational day 9 to postnatal day (PND 1 were sacrificed at PND4, PND21 and at first estrus after PND50. Genomic DNA (gDNA was isolated from the mammary tissue and immuno-precipitated using anti-5-methylcytosine antibodies. Detection and quantification of gDNA methylation status using the Nimblegen ChIP array revealed 7412 differentially methylated gDNA segments (out of 58207 segments, with the majority of changes occurring at PND21. Transcriptomal analysis revealed that the majority of gene expression differences between BPA- and vehicle-treated animals were observed later (PND50. BPA exposure resulted in higher levels of pro-activation histone H3K4 trimethylation at the transcriptional initiation site of the alpha-lactalbumin gene at PND4, concomitantly enhancing mRNA expression of this gene. These results show that fetal BPA exposure triggers changes in the postnatal and adult mammary gland epigenome and alters gene

  14. Prenatal Exposure to BPA Alters the Epigenome of the Rat Mammary Gland and Increases the Propensity to Neoplastic Development

    Science.gov (United States)

    Dhimolea, Eugen; Wadia, Perinaaz R.; Murray, Tessa J.; Settles, Matthew L.; Treitman, Jo D.; Sonnenschein, Carlos; Shioda, Toshi; Soto, Ana M.

    2014-01-01

    Exposure to environmental estrogens (xenoestrogens) may play a causal role in the increased breast cancer incidence which has been observed in Europe and the US over the last 50 years. The xenoestrogen bisphenol A (BPA) leaches from plastic food/beverage containers and dental materials. Fetal exposure to BPA induces preneoplastic and neoplastic lesions in the adult rat mammary gland. Previous results suggest that BPA acts through the estrogen receptors which are detected exclusively in the mesenchyme during the exposure period by directly altering gene expression, leading to alterations of the reciprocal interactions between mesenchyme and epithelium. This initiates a long sequence of altered morphogenetic events leading to neoplastic transformation. Additionally, BPA induces epigenetic changes in some tissues. To explore this mechanism in the mammary gland, Wistar-Furth rats were exposed subcutaneously via osmotic pumps to vehicle or 250 µg BPA/kg BW/day, a dose that induced ductal carcinomas in situ. Females exposed from gestational day 9 to postnatal day (PND) 1 were sacrificed at PND4, PND21 and at first estrus after PND50. Genomic DNA (gDNA) was isolated from the mammary tissue and immuno-precipitated using anti-5-methylcytosine antibodies. Detection and quantification of gDNA methylation status using the Nimblegen ChIP array revealed 7412 differentially methylated gDNA segments (out of 58207 segments), with the majority of changes occurring at PND21. Transcriptomal analysis revealed that the majority of gene expression differences between BPA- and vehicle-treated animals were observed later (PND50). BPA exposure resulted in higher levels of pro-activation histone H3K4 trimethylation at the transcriptional initiation site of the alpha-lactalbumin gene at PND4, concomitantly enhancing mRNA expression of this gene. These results show that fetal BPA exposure triggers changes in the postnatal and adult mammary gland epigenome and alters gene expression patterns

  15. Functional Alterations in the Dorsal Raphe Nucleus Following Acute and Chronic Ethanol Exposure

    OpenAIRE

    Lowery-Gionta, Emily G; Marcinkiewcz, Catherine A.; Kash, Thomas L.

    2014-01-01

    Alcoholism is a pervasive disorder perpetuated in part to relieve negative mood states like anxiety experienced during alcohol withdrawal. Emerging evidence demonstrates a role for the serotonin-rich dorsal raphe (DR) in anxiety following ethanol withdrawal. The current study examined the effects of chronic ethanol vapor exposure on the DR using slice electrophysiology in male DBA2/J mice. We found that chronic ethanol exposure resulted in deficits in social approach indicative of increased a...

  16. Effects of phthalate exposure on asthma may be mediated through alterations in DNA methylation

    OpenAIRE

    Wang, I-Jen; Karmaus, Wilfried JJ; Chen, Su-Lien; Holloway, John W.; Ewart, Susan

    2015-01-01

    Background Phthalates may increase the asthma risk in children. Mechanisms underlying this association remain to be addressed. This study assesses the effect of phthalate exposures on epigenetic changes and the role of epigenetic changes for asthma. In the first step, urine and blood samples from 256 children of the Childhood Environment and Allergic diseases Study (CEAS) were analyzed. Urine 5OH-MEHP levels were quantified as an indicator of exposure, and asthma information was collected. DN...

  17. Paternal BPA exposure in early life alters Igf2 epigenetic status in sperm and induces pancreatic impairment in rat offspring.

    Science.gov (United States)

    Mao, Zhenxing; Xia, Wei; Chang, Huailong; Huo, Wenqian; Li, Yuanyuan; Xu, Shunqing

    2015-11-01

    Exposure to endocrine disruptors in utero appears to alter epigenetics in the male germ-line and subsequently promote adult-onset disease in subsequent generations. Fetal exposure to bisphenol A (BPA), a highly prevalent endocrine disruptor in environment, has been shown to alter epigenetic modification and result in glucose intolerance in adulthood. However, whether fetal exposure to BPA can induce epigenetic modification and phenotypic changes in their subsequent offspring are still unclear. The present study was designed to investigate whether exposure to BPA in early life induced glucose intolerance in the offspring through male germ line, and the underlying epigenetic molecular basis. F0 pregnant SD rats were received corn oil or 40 μg/kg/day of BPA during gestation and lactation. F1 male rats were maintained to generate F2 offspring by mating with untreated female rats. Both the F1 rats after weaning and the F2 offspring were not received any other treatments. Our results showed that male F2 offspring in the BPA group exhibited glucose intolerance and β-cell dysfunction. Decreased expression of Igf2 and associated hypermethylation of Igf2 were observed in islets of male F2 offspring. In addition, similar effects were observed in female F2 animals, but the effects were more pronounced in males. Moreover, abnormal expression and methylation of Igf2 was observed in sperm of adult F1 male rats, indicating that epigenetic modification in germ cells can be partly progressed to the next generation. Overall, our study suggests that BPA exposure during early life can result in generational transmission of glucose intolerance and β-cell dysfunction in the offspring through male germ line, which is associated with hypermethylation of Igf2 in islets. The changes of epigenetics in germ cells may contribute to this generational transmission. PMID:26276081

  18. Mechanisms of Imidacloprid-Induced Alteration of Hypothalamic-Pituitary-Adrenal (HPA Axis after Subchronic Exposure in Male Rats

    Directory of Open Access Journals (Sweden)

    Alya Annabi

    2015-11-01

    Full Text Available Imidacloprid (IMI is known to target the nicotinic acetylcholine receptors (nAChRs in insects, and potentially in mammals. However, IMI toxicity on mammalian tissues has not been adequately evaluated. The aim of the present study was to examine whether IMI induced functional impairment in hypthalamic-pituitary-adrenal (HPA axis tissues. An oral exposure of 40 mg IMI/kg for 28 days in male rats caused a significant increase in malondialdehyde (MDA level. The antioxidant catalase, superoxide dismutase, and glutathione S-transferase showed various alterations following administration, but a significantly depleted thiol (SH groups was only recorded in hypothalamic tissues. The increase in the relative weight of adrenal glands and the increased adrenal cholesterol and plasma adrenocorticotropic hormone (ACTH levels are indicative of general adaptation syndrome. The hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased, highlighting the alteration of cholinergic transmission. In conclusion, the findings obtained show that chronic exposure to IMI may alter biochemical processes of HPA axis.

  19. 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 (

  20. Sleep alterations following exposure to stress predict fear-associated memory impairments in a rodent model of PTSD.

    Science.gov (United States)

    Vanderheyden, William M; George, Sophie A; Urpa, Lea; Kehoe, Michaela; Liberzon, Israel; Poe, Gina R

    2015-08-01

    Sleep abnormalities, such as insomnia, nightmares, hyper-arousal, and difficulty initiating or maintaining sleep, are diagnostic criteria of posttraumatic stress disorder (PTSD). The vivid dream state, rapid eye movement (REM) sleep, has been implicated in processing emotional memories. We have hypothesized that REM sleep is maladaptive in those suffering from PTSD. However, the precise neurobiological mechanisms regulating sleep disturbances following trauma exposure are poorly understood. Using single prolonged stress (SPS), a well-validated rodent model of PTSD, we measured sleep alterations in response to stressor exposure and over a subsequent 7-day isolation period during which the PTSD-like phenotype develops. SPS resulted in acute increases in REM sleep and transition to REM sleep, and decreased waking in addition to alterations in sleep architecture. The severity of the PTSD-like phenotype was later assessed by measuring freezing levels on a fear-associated memory test. Interestingly, the change in REM sleep following SPS was significantly correlated with freezing behavior during extinction recall assessed more than a week later. Reductions in theta (4-10 Hz) and sigma (10-15 Hz) band power during transition to REM sleep also correlated with impaired fear-associated memory processing. These data reveal that changes in REM sleep, transition to REM sleep, waking, and theta and sigma power may serve as sleep biomarkers to identify individuals with increased susceptibility to PTSD following trauma exposure. PMID:26019008

  1. 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...

  2. 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...

  3. 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.

  4. Properties and uses of chlorpyrifos in the United States.

    Science.gov (United States)

    Solomon, Keith R; Williams, W Martin; Mackay, Donald; Purdy, John; Giddings, Jeffrey M; Giesy, John P

    2014-01-01

    Physical properties and use data provide the basis for estimating environmental exposures to chlorpyrifos (CPY) and for assessing its risks. The vapor pressure ofCPY is low, solubility in water is agricultural uses. In agricultural soils under field conditions,half-lives are shorter (2 to 120 d, N=58). The mean water-soil adsorption coefficient(Koc) of CPY is 8,216 mL g-1; negligible amounts enter plants via the roots,and it is not translocated in plants. Half-lives for hydrolysis in water are inversely dependent on pH, and range from 16 to 73 d. CPY is an inhibitor of acetylcholinesterase and is potentially toxic to most animals. Differences in susceptibility result from differences in rates of adsorption,distribution, metabolism, and excretion among species. CPY is an important tool in management of a large number of pests (mainly insects and mites) and is used on a wide range of crops in the U.S. Estimates of annual use in the U.S. from 2008 to 2012 range from 3.2 to 4.1 M kg y-1, which is about 50% less than the amount used prior to 2000. Applications to corn and soybeans accounts for 46-50%of CYP's annual use in the U.S.

  5. Developmental timing of sodium perchlorate exposure alters angiogenesis, thyroid follicle proliferation and sexual maturation in stickleback.

    Science.gov (United States)

    Furin, Christoff G; von Hippel, Frank A; Postlethwait, John H; Buck, C Loren; Cresko, William A; O'Hara, Todd M

    2015-08-01

    Perchlorate, a common aquatic contaminant, is well known to disrupt homeostasis of the hypothalamus-pituitary-thyroid axis. This study utilizes the threespine stickleback (Gasterosteus aculeatus) fish to determine if perchlorate exposure during certain windows of development has morphological effects on thyroid and gonads. Fish were moved from untreated water to perchlorate-contaminated water (30 and 100mg/L) starting at 0, 3, 7, 14, 21, 42, 154 and 305 days post fertilization until approximately one year old. A reciprocal treatment (fish in contaminated water switched to untreated water) was conducted on the same schedule. Perchlorate exposure increased angiogenesis and follicle proliferation in thyroid tissue, delayed gonadal maturity, and skewed sex ratios toward males; effects depended on concentration and timing of exposure. This study demonstrates that perchlorate exposure beginning during the first 42 days of development has profound effects on stickleback reproductive and thyroid tissues, and by implication can impact population dynamics. Long-term exposure studies that assess contaminant effects at various stages of development provide novel information to characterize risk to aquatic organisms, to facilitate management of resources, and to determine sensitive developmental windows for further study of underlying mechanisms. PMID:25865142

  6. Long-term exposure to incense smoke alters metabolism in Wistar albino rats.

    Science.gov (United States)

    Alokail, Majed S; Al-Daghri, Nasser M; Alarifi, Saud A; Draz, Hossam M; Hussain, Tajamul; Yakout, Sobhy M

    2011-03-01

    The burning of incense is an important source of indoor air pollution in Asia. We assessed the effect of long-term exposure to incense smoke on the body weight and levels of circulating glucose, triglycerides, total cholesterol, HDL-cholesterol, insulin, adiponectin and leptin in Wistar albino rats. Two groups of rats were used. First group (n = 12) was exposed daily to incense smoke for 4 months at the rate of 4 g day(-1) in the exposure chamber. Another group of rats (n = 12), was used as non-exposed control. Blood samples were collected from all animals after 4, 8, 12 and 16 weeks of exposure. Serum glucose, triglycerides, total cholesterol and HDL-cholesterol, LDL-cholesterol insulin, adiponectin and leptin were measured. Our results showed that incense smoke exposure was associated with decreased weight gain and the adverse metabolic changes of increased triglycerides and decreased HDL-cholesterol concentrations. Exposure to incense was also associated with a transient increase of leptin levels. Taken together, these data suggest that incense smoke influences metabolism adversely in rats. The effect of incense smoke on human health and the underlying mechanisms need to be studied further.

  7. Repeated exposure to amphetamine during adolescence alters inhibitory tone in the medial prefrontal cortex following drug re-exposure in adulthood.

    Science.gov (United States)

    Paul, Kush; Kang, Shuo; Cox, Charles L; Gulley, Joshua M

    2016-08-01

    Behavioral sensitization following repeated amphetamine (AMPH) exposure is associated with changes in GABA function in the medial prefrontal cortex (mPFC). In rats exposed to AMPH during adolescence compared to adulthood, there are unique patterns of sensitization that may reflect age-dependent differences in drug effects on prefrontal GABAergic function. In the current study, we used a sensitizing regimen of repeated AMPH exposure in adolescent and adult rats to determine if a post-withdrawal AMPH challenge would alter inhibitory transmission in the mPFC in a manner that depends on age of exposure. Male Sprague-Dawley rats were treated with saline or 3mg/kg AMPH (i.p.) during adolescence [postnatal day (P) 27-P45] or adulthood (P85- P103) and were sacrificed either at similar ages in adulthood (∼P133; experiment 1) or after similar withdrawal times (3-4 weeks; experiment 2). Spontaneous inhibitory postsynaptic currents (sIPSCs) were recorded in vitro from deep layer pyramidal cells in the mPFC using the whole-cell configuration. We found no effect of AMPH pre-exposure on baseline sIPSC frequency. Subsequent application of AMPH (25μM) produced a stable increase in sIPSC frequency in controls, suggesting that AMPH increases inhibitory tone in the mPFC. However, AMPH failed to increase sIPSCs in adolescent- or adult-exposed rats. In experiment 2, where withdrawal period was kept similar for both exposure groups, AMPH induced a suppression of sIPSC activity in adolescent-exposed rats. These results suggest that sensitizing treatment with AMPH during adolescence or adulthood dampens inhibitory influences on mPFC pyramidal cells, but potentially through different mechanisms. PMID:27085589

  8. Chronic Exposure to Arsenic in the Drinking Water Alters the Expression of Immune Response Genes in Mouse Lung

    Science.gov (United States)

    Kozul, Courtney D.; Hampton, Thomas H.; Davey, Jennifer C.; Gosse, Julie A.; Nomikos, Athena P.; Eisenhauer, Phillip L.; Weiss, Daniel J.; Thorpe, Jessica E.; Ihnat, Michael A.; Hamilton, Joshua W.

    2009-01-01

    Background Chronic exposure to drinking water arsenic is a significant worldwide environmental health concern. Exposure to As is associated with an increased risk of lung disease, which may make it a unique toxicant, because lung toxicity is usually associated with inhalation rather than ingestion. Objectives The goal of this study was to examine mRNA and protein expression changes in the lungs of mice exposed chronically to environmentally relevant concentrations of As in the food or drinking water, specifically examining the hypothesis that As may preferentially affect gene and protein expression related to immune function as part of its mechanism of toxicant action. Methods C57BL/6J mice fed a casein-based AIN-76A defined diet were exposed to 10 or 100 ppb As in drinking water or food for 5–6 weeks. Results Whole genome transcriptome profiling of animal lungs revealed significant alterations in the expression of many genes with functions in cell adhesion and migration, channels, receptors, differentiation and proliferation, and, most strikingly, aspects of the innate immune response. Confirmation of mRNA and protein expression changes in key genes of this response revealed that genes for interleukin 1β, interleukin 1 receptor, a number of toll-like receptors, and several cytokines and cytokine receptors were significantly altered in the lungs of As-exposed mice. Conclusions These findings indicate that chronic low-dose As exposure at the current U.S. drinking-water standard can elicit effects on the regulation of innate immunity, which may contribute to altered disease risk, particularly in lung. PMID:19654921

  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.

  10. 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

  11. The toxicity of chlorpyrifos on the early life stage of zebrafish: a survey on the endpoints at development, locomotor behavior, oxidative stress and immunotoxicity.

    Science.gov (United States)

    Jin, Yuanxiang; Liu, Zhenzhen; Peng, Tao; Fu, Zhengwei

    2015-04-01

    Chlorpyrifos (CPF) is one of the most toxic pesticides in aquatic ecosystem, but its toxicity mechanisms to fish are still not fully understood. This study examined the toxicity targets of CPF in early life stage of zebrafish on the endpoints at developmental toxicity, neurotoxicity, oxidative stress and immunotoxicity. Firstly, CPF exposure decreased the body length, inhibited the hatchability and heart rate, and resulted in a number of morphological abnormalities, primarily spinal deformities (SD) and pericardial edema (PE), in larval zebrafish. Secondly, the free swimming activities and the swimming behaviors of the larvae in response to the stimulation of light-to-dark photoperiod transition were significantly influenced by the exposure to 100 and 300 μg/L CPF. In addition, the activity of acetylcholinesterase (AChE) and the transcription of some genes related to neurotoxicity were also influenced by CPF exposure. Thirdly, CPF exposure induced oxidative stress in the larval zebrafish. The malondialdehyde (MDA) levels increased and the glutathione (GSH) contents decreased significantly in a concentration-dependent manner after the exposure to CPF for 96 hours post fertilization (hpf). CPF affected not only the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione S-transferase (GST), but also the transcriptional levels of their respective genes. Finally, the mRNA levels of the main cytokines including tumor necrosis factor α (Tnfα), interferon (Ifn), interleukin-1 beta (Il-1β), interleukin 6 (Il6), complement factor 4 (C4) in the larvae increased significantly after the exposure to 100 or 300 μg/L CPF for 96 hpf, suggesting that the innate immune system disturbed by CPF in larvae. Taken together, our results suggested that CPF had the potential to cause developmental toxicity, behavior alterations, oxidative stress and immunotoxicity in the larval zebrafish.

  12. Prenatal arsenic exposure alters gene expression in the adult liver to a proinflammatory state contributing to accelerated atherosclerosis.

    Directory of Open Access Journals (Sweden)

    J Christopher States

    Full Text Available The mechanisms by which environmental toxicants alter developmental processes predisposing individuals to adult onset chronic disease are not well-understood. Transplacental arsenic exposure promotes atherogenesis in apolipoprotein E-knockout (ApoE(-/- mice. Because the liver plays a central role in atherosclerosis, diabetes and metabolic syndrome, we hypothesized that accelerated atherosclerosis may be linked to altered hepatic development. This hypothesis was tested in ApoE(-/- mice exposed to 49 ppm arsenic in utero from gestational day (GD 8 to term. GD18 hepatic arsenic was 1.2 µg/g in dams and 350 ng/g in fetuses. The hepatic transcriptome was evaluated by microarray analysis to assess mRNA and microRNA abundance in control and exposed pups at postnatal day (PND 1 and PND70. Arsenic exposure altered postnatal developmental trajectory of mRNA and microRNA profiles. We identified an arsenic exposure related 51-gene signature at PND1 and PND70 with several hubs of interaction (Hspa8, IgM and Hnf4a. Gene ontology (GO annotation analyses indicated that pathways for gluconeogenesis and glycolysis were suppressed in exposed pups at PND1, and pathways for protein export, ribosome, antigen processing and presentation, and complement and coagulation cascades were induced by PND70. Promoter analysis of differentially-expressed transcripts identified enriched transcription factor binding sites and clustering to common regulatory sites. SREBP1 binding sites were identified in about 16% of PND70 differentially-expressed genes. Western blot analysis confirmed changes in the liver at PND70 that included increases of heat shock protein 70 (Hspa8 and active SREBP1. Plasma AST and ALT levels were increased at PND70. These results suggest that transplacental arsenic exposure alters developmental programming in fetal liver, leading to an enduring stress and proinflammatory response postnatally that may contribute to early onset of atherosclerosis. Genes

  13. Air pollution exposure during critical time periods in gestation and alterations in cord blood lymphocyte distribution: a cohort of livebirths

    Directory of Open Access Journals (Sweden)

    Herr Caroline EW

    2010-08-01

    Full Text Available Abstract Background Toxic exposures have been shown to influence maturation of the immune system during gestation. This study investigates the association between cord blood lymphocyte proportions and maternal exposure to air pollution during each gestational month. Methods Cord blood was analyzed using a FACSort flow cytometer to determine proportions of T lymphocytes (CD3+ cells and their subsets, CD4+ and CD8+, B lymphocytes (CD19+ and natural killer (NK cells. Ambient air concentrations of 12 polycyclic aromatic hydrocarbons (PAH and particulate matter 2.5 were measured using fixed site monitors. Arithmetic means of these pollutants, calculated for each gestational month, were used as exposure metrics. Data on covariates were obtained from medical records and questionnaires. Multivariable linear regression models were fitted to estimate associations between monthly PAH or PM2.5 and cord blood lymphocytes, adjusting for year of birth and district of residence and, in further models, gestational season and number of prior live births. Results The adjusted models show significant associations between PAHs or PM2.5 during early gestation and increases in CD3+ and CD4+ lymphocytes percentages and decreases in CD19+ and NK cell percentages in cord blood. In contrast, exposures during late gestation were associated with decreases in CD3+ and CD4+ fractions and increases in CD19+ and NK cell fractions. There was no significant association between alterations in lymphocyte distribution and air pollution exposure during the mid gestation. Conclusions PAHs and PM2.5 in ambient air may influence fetal immune development via shifts in cord blood lymphocytes distributions. Associations appear to differ by exposure in early versus late gestation.

  14. Exposure to N-Ethyl-N-Nitrosourea in Adult Mice Alters Structural and Functional Integrity of Neurogenic Sites

    Science.gov (United States)

    Capilla-Gonzalez, Vivian; Gil-Perotin, Sara; Ferragud, Antonio; Bonet-Ponce, Luis; Canales, Juan Jose; Garcia-Verdugo, Jose Manuel

    2012-01-01

    Background Previous studies have shown that prenatal exposure to the mutagen N-ethyl-N-nitrosourea (ENU), a N-nitroso compound (NOC) found in the environment, disrupts developmental neurogenesis and alters memory formation. Previously, we showed that postnatal ENU treatment induced lasting deficits in proliferation of neural progenitors in the subventricular zone (SVZ), the main neurogenic region in the adult mouse brain. The present study is aimed to examine, in mice exposed to ENU, both the structural features of adult neurogenic sites, incorporating the dentate gyrus (DG), and the behavioral performance in tasks sensitive to manipulations of adult neurogenesis. Methodology/Principal Findings 2-month old mice received 5 doses of ENU and were sacrificed 45 days after treatment. Then, an ultrastructural analysis of the SVZ and DG was performed to determine cellular composition in these regions, confirming a significant alteration. After bromodeoxyuridine injections, an S-phase exogenous marker, the immunohistochemical analysis revealed a deficit in proliferation and a decreased recruitment of newly generated cells in neurogenic areas of ENU-treated animals. Behavioral effects were also detected after ENU-exposure, observing impairment in odor discrimination task (habituation-dishabituation test) and a deficit in spatial memory (Barnes maze performance), two functions primarily related to the SVZ and the DG regions, respectively. Conclusions/Significance The results demonstrate that postnatal exposure to ENU produces severe disruption of adult neurogenesis in the SVZ and DG, as well as strong behavioral impairments. These findings highlight the potential risk of environmental NOC-exposure for the development of neural and behavioral deficits. PMID:22238669

  15. Neuroprotective Effect of Ginseng against Alteration of Calcium Binding Proteins Immunoreactivity in the Mice Hippocampus after Radiofrequency Exposure

    Directory of Open Access Journals (Sweden)

    Dhiraj Maskey

    2013-01-01

    Full Text Available Calcium binding proteins (CaBPs such as calbindin D28-k, parvalbumin, and calretinin are able to bind Ca2+ with high affinity. Changes in Ca2+ concentrations via CaBPs can disturb Ca2+ homeostasis. Brain damage can be induced by the prolonged electromagnetic field (EMF exposure with loss of interacellular Ca2+ balance. The present study investigated the radioprotective effect of ginseng in regard to CaBPs immunoreactivity (IR in the hippocampus through immunohistochemistry after one-month exposure at 1.6 SAR value by comparing sham control with exposed and ginseng-treated exposed groups separately. Loss of dendritic arborization was noted with the CaBPs in the Cornu Ammonis areas as well as a decrease of staining intensity of the granule cells in the dentate gyrus after exposure while no loss was observed in the ginseng-treated group. A significant difference in the relative mean density was noted between control and exposed groups but was nonsignificant in the ginseng-treated group. Decrease in CaBP IR with changes in the neuronal staining as observed in the exposed group would affect the hippocampal trisynaptic circuit by alteration of the Ca2+ concentration which could be prevented by ginseng. Hence, ginseng could contribute as a radioprotective agent against EMF exposure, contributing to the maintenance of Ca2+ homeostasis by preventing impairment of intracellular Ca2+ levels in the hippocampus.

  16. Bisphenol-A (BPA) Exposure Alters Endometrial Progesterone Receptor Expression in the Non-human Primate

    Science.gov (United States)

    Aldad, Tamir S.; Rahmani, Nora; Leranth, Csaba; Taylor, Hugh S.

    2011-01-01

    OBJECTIVE To evaluate the effect of BPA on endometrial PR expression in non-human primates and human cells. BPA is a xenoestrogen endocrine disruptor. Both BPA exposure and diminished progesterone action have been associated with pregnancy loss, endometriosis and endometrial hyperplasia/cancer. DESIGN Controlled trial in primates. SETTING University Animals African green monkeys INTERVENTIONS After oophorectomy, BPA (50μg/kg/day), estradiol, both or vehicle control were administered. . Estradiol and BPA were used in Ishikawa cells. MAIN OUTCOME MEASURES PR expression using IHC and qPCR. RESULTS PR expression was increased in estradiol treated primates compared to controls. Exposure to the combination of estradiol and BPA resulted in decreased PR expression compared to estradiol exposure alone (p<0.01). In Ishikawa cells treated with estradiol, PR expression increased 5.1 fold, however, when Ishikawa cells were simultaneously treated with estradiol and BPA, PR expression was decreased to 0.6 fold that of cells treated with estradiol alone (p<0.05). CONCLUSION BPA alone functions as a weak estrogen. However, when administered with estradiol, BPA diminishes estradiol induced PR expression. The estrogen-like effect of BPA reported in exposed humans may be mediated by PR blockade and a resultant decrease in the estrogen inhibition normally imparted by progesterone. Diminished PR expression may underlie previous reports linking BPA exposure to endometrial dysfunction in humans. PMID:21536273

  17. Exposure of fluid milk to LED light negatively affects consumer perception and alters underlying sensory properties.

    Science.gov (United States)

    Martin, Nicole; Carey, Nancy; Murphy, Steven; Kent, David; Bang, Jae; Stubbs, Tim; Wiedmann, Martin; Dando, Robin

    2016-06-01

    Fluid milk consumption per capita in the United States has been steadily declining since the 1940s. Many factors have contributed to this decline, including the increasing consumption of carbonated beverages and bottled water. To meet the challenge of stemming the decline in consumption of fluid milk, the dairy industry must take a systematic approach to identifying and correcting for factors that negatively affect consumers' perception of fluid milk quality. To that end, samples of fluid milk were evaluated to identify factors, with a particular focus on light-emitting diode (LED) light exposure, which negatively affect the perceived sensory quality of milk, and to quantify their relative effect on the consumer's experience. Fluid milk samples were sourced from 3 processing facilities with varying microbial postprocessing contamination patterns based on historical testing. The effect of fat content, light exposure, age, and microbiological content were assayed across 23 samples of fluid milk, via consumer, descriptive sensory, and instrumental analyses. Most notably, light exposure resulted in a broad negative reaction from consumers, more so than samples with microbiological contamination exceeding 20,000 cfu/mL on days approaching code. The predominant implication of the study is that a component of paramount importance in ensuring the success of the dairy industry would be to protect fluid milk from all sources of light exposure, from processing plant to consumer.

  18. GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE PERMANENTLY ALTERS REPRODUCTIVE COMPETENCE IN THE CD-1 MOUSE

    Science.gov (United States)

    While the adult mouse Leydig cell (LC) has been considered refractory to cytotoxic destruction by ethane dimethanesulfonate (EDS), the potential consequences of exposure during reproductive development in this species are unknown. Herein pregnant CD-1 mice were treated with 160 m...

  19. Exposure to hyperoxia in the neonatal period alters bone marrow function

    Science.gov (United States)

    Oxygen is often life saving in preterm infants, however, excessive exposure may lead to blood vessel and tissue injury in the lung and retina. Oxygen-treated neonates often exhibit bone marrow (BM) suppression requiring blood product transfusions. However, we do not know whether oxygen is directly t...

  20. Occupational exposure to diesel engine exhaust and alterations in lymphocyte subsets

    NARCIS (Netherlands)

    Lan, Qing; Vermeulen, Roel; Dai, Yufei; Ren, Dianzhi; Hu, Wei; Duan, Huawei; Niu, Yong; Xu, Jun; Fu, Wei; Meliefste, Kees; Zhou, Baosen; Yang, Jufang; Ye, Meng; Jia, Xiaowei; Meng, Tao; Bin, Ping; Kim, Christopher; Bassig, Bryan A; Hosgood, H Dean; Silverman, Debra; Zheng, Yuxin; Rothman, Nathaniel

    2015-01-01

    BACKGROUND: The International Agency for Research on Cancer recently classified diesel engine exhaust (DEE) as a Group I carcinogen based largely on its association with lung cancer. However, the exposure-response relationship is still a subject of debate and the underlying mechanism by which DEE ca

  1. Short GSM mobile phone exposure does not alter human auditory brainstem response

    Directory of Open Access Journals (Sweden)

    Thuróczy György

    2007-11-01

    Full Text Available Abstract Background There are about 1.6 billion GSM cellular phones in use throughout the world today. Numerous papers have reported various biological effects in humans exposed to electromagnetic fields emitted by mobile phones. The aim of the present study was to advance our understanding of potential adverse effects of the GSM mobile phones on the human hearing system. Methods Auditory Brainstem Response (ABR was recorded with three non-polarizing Ag-AgCl scalp electrodes in thirty young and healthy volunteers (age 18–26 years with normal hearing. ABR data were collected before, and immediately after a 10 minute exposure to 900 MHz pulsed electromagnetic field (EMF emitted by a commercial Nokia 6310 mobile phone. Fifteen subjects were exposed to genuine EMF and fifteen to sham EMF in a double blind and counterbalanced order. Possible effects of irradiation was analyzed by comparing the latency of ABR waves I, III and V before and after genuine/sham EMF exposure. Results Paired sample t-test was conducted for statistical analysis. Results revealed no significant differences in the latency of ABR waves I, III and V before and after 10 minutes of genuine/sham EMF exposure. Conclusion The present results suggest that, in our experimental conditions, a single 10 minute exposure of 900 MHz EMF emitted by a commercial mobile phone does not produce measurable immediate effects in the latency of auditory brainstem waves I, III and V.

  2. Temperature, hydric environment, and prior pathogen exposure alter the experimental severity of chytridiomycosis in boreal toads

    Science.gov (United States)

    Murphy, Peter J.; St-Hilaire, Sophie; Corn, Paul Stephen

    2011-01-01

    Prevalence of the pathogen Batrachochytrium dendrobatidis (Bd), implicated in amphibian population declines worldwide, is associated with habitat moisture and temperature, but few studies have varied these factors and measured the response to infection in amphibian hosts. We evaluated how varying humidity, contact with water, and temperature affected the manifestation of chytridiomycosis in boreal toads Anaxyrus (Bufo) boreas boreas and how prior exposure to Bd affects the likelihood of survival after re-exposure, such as may occur seasonally in long-lived species. Humidity did not affect survival or the degree of Bd infection, but a longer time in contact with water increased the likelihood of mortality. After exposure to ~106 Bd zoospores, all toads in continuous contact with water died within 30 d. Moreover, Bd-exposed toads that were disease-free after 64 d under dry conditions, developed lethal chytridiomycosis within 70 d of transfer to wet conditions. Toads in unheated aquaria (mean = 15°C) survived less than 48 d, while those in moderately heated aquaria (mean = 18°C) survived 115 d post-exposure and exhibited behavioral fever, selecting warmer sites across a temperature gradient. We also found benefits of prior Bd infection: previously exposed toads survived 3 times longer than Bd-naïve toads after re-exposure to 106 zoospores (89 vs. 30 d), but only when dry microenvironments were available. This study illustrates how the outcome of Bd infection in boreal toads is environmentally dependent: when continuously wet, high reinfection rates may overwhelm defenses, but periodic drying, moderate warming, and previous infection may allow infected toads to extend their survival.

  3. Acute chlorine gas exposure produces transient inflammation and a progressive alteration in surfactant composition with accompanying mechanical dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Massa, Christopher B.; Scott, Pamela; Abramova, Elena; Gardner, Carol; Laskin, Debra L.; Gow, Andrew J., E-mail: Gow@rci.rutgers.edu

    2014-07-01

    Acute Cl{sub 2} exposure following industrial accidents or military/terrorist activity causes pulmonary injury and severe acute respiratory distress. Prior studies suggest that antioxidant depletion is important in producing dysfunction, however a pathophysiologic mechanism has not been elucidated. We propose that acute Cl{sub 2} inhalation leads to oxidative modification of lung lining fluid, producing surfactant inactivation, inflammation and mechanical respiratory dysfunction at the organ level. C57BL/6J mice underwent whole-body exposure to an effective 60 ppm-hour Cl{sub 2} dose, and were euthanized 3, 24 and 48 h later. Whereas pulmonary architecture and endothelial barrier function were preserved, transient neutrophilia, peaking at 24 h, was noted. Increased expression of ARG1, CCL2, RETLNA, IL-1b, and PTGS2 genes was observed in bronchoalveolar lavage (BAL) cells with peak change in all genes at 24 h. Cl{sub 2} exposure had no effect on NOS2 mRNA or iNOS protein expression, nor on BAL NO{sub 3}{sup −} or NO{sub 2}{sup −}. Expression of the alternative macrophage activation markers, Relm-α and mannose receptor was increased in alveolar macrophages and pulmonary epithelium. Capillary surfactometry demonstrated impaired surfactant function, and altered BAL phospholipid and surfactant protein content following exposure. Organ level respiratory function was assessed by forced oscillation technique at 5 end expiratory pressures. Cl{sub 2} exposure had no significant effect on either airway or tissue resistance. Pulmonary elastance was elevated with time following exposure and demonstrated PEEP refractory derecruitment at 48 h, despite waning inflammation. These data support a role for surfactant inactivation as a physiologic mechanism underlying respiratory dysfunction following Cl{sub 2} inhalation. - Highlights: • Effect of 60 ppm*hr Cl{sub 2} gas on lung inflammation and mechanical function examined. • Pulmonary inflammation is transient and minor.

  4. Previous exposure of predatory fish to a pesticide alters palatability of larval amphibian prey.

    Science.gov (United States)

    Hanlon, Shane M; Parris, Matthew J

    2013-12-01

    Habitat preferences of organisms are reliant on a variety of factors. For amphibians specifically, preferences can depend on factors such as food availability, water quality, and the presence of potential predators. Because some amphibians breed in permanent bodies of water (e.g., ponds), the threat of predation (e.g., from fish) is constant. Thus, some amphibians are unpalatable to many predators, allowing them to coexist in the same habitats. However, the addition of anthropogenic stressors (i.e., pesticides) may alter the perceived palatability of prey items to predators. The authors tested the hypothesis that bluegill fish (Lepomis macrochirus), previously exposed to the pesticide carbaryl, would consume more unpalatable prey (Fowler's toad [Anaxyrus fowleri] tadpoles) than unexposed predators. Carbaryl is a pesticide that attacks the nervous system and is linked to taste sense in organisms. Moreover, the authors conducted an identical test using palatable prey (gray treefrog [Hyla versicolor] tadpoles) and predicted that no change in preference would be observed. In support of the primary hypothesis, bluegill exposed to the highest concentration of carbaryl consumed more A. fowleri tadpoles compared with those exposed to carbaryl at the lowest concentration or water control. Moreover, an effect of carbaryl on predation success on H. versicolor tadpoles was not observed. The present study shows that an anthropogenic stressor (carbaryl) can alter the perceived palatability of noxious prey to fish predators, potentially altering predator-prey relationships in natural settings. PMID:24383102

  5. Exposure to sublethal chromium and endosulfan alter the diel vertical migration (DVM) in freshwater zooplankton crustaceans.

    Science.gov (United States)

    Gutierrez, María Florencia; Gagneten, Ana María; Paggi, Juan Cesar

    2012-01-01

    Among zooplankton behaviors, diel migrations constitute one of the most effective predator avoidance strategy and confer metabolic and demographic advantages. We aim to examine whether sublethal concentrations of two widespread pollutants (a pesticide with endosulfan and chromium as potassium dichromate) alter the depth selection, vertical migration and grouping of five freshwater species: Argyrodiaptomus falcifer, Notodiaptomus conifer, Pseudosida variabilis, Ceriodaphnia dubia and Daphnia magna. In a series of experimental assays, performed with 150 cm length transparent tubes, we analyzed the ascents and descents movements through periods of 24 h. Among controls, the copepods showed a tendency to remain closest to the surface, however, N. conifer registered a downward movement of 18.14 cm between 06:00 and 12:00. The cladoceran P. variabilis occupied the deeper position (85 cm), C. dubia showed a tendency to hike to the surface at 06:00 (57.7 cm) descending to lower levels at 18:00. D. magna showed a constant movement of ascent between 00:00 and 18:00, making an average travel of 29.4 cm. When subjected to pollutants, these behaviors were altered. It is hypothesized that a reduction in swimming activity and disorientation would be the main cause of such alterations. The high sensitivity of this endpoint sugests it to be adecuate as a complement in future standard toxicity tests.

  6. Does prenatal exposure to vitamin D-fortified margarine and milk alter birth weight?

    DEFF Research Database (Denmark)

    Jensen, Camilla B; Berentzen, Tina L; Gamborg, Michael;

    2014-01-01

    The present study examined whether exposure to vitamin D from fortified margarine and milk during prenatal life influenced mean birth weight and the risk of high or low birth weight. The study was based on the Danish vitamin D fortification programme, which was a societal intervention...... with mandatory fortification of margarine during 1961-1985 and voluntary fortification of low-fat milk between 1972 and 1976. The influence of prenatal vitamin D exposure on birth weight was investigated among 51 883 Danish children, by comparing birth weight among individuals born during 2 years before or after...... the initiation and termination of vitamin D fortification programmes. In total, four sets of analyses were performed. Information on birth weight was available in the Copenhagen School Health Record Register for all school children in Copenhagen. The mean birth weight was lower among the exposed than non...

  7. Perinatal taurine exposure alters renal potassium excretion mechanisms in adult conscious rats

    OpenAIRE

    Roysommuti, Sanya; Malila, Pisamai; Lerdweeraphon, Wichaporn; Jirakulsomchok, Dusit; Wyss, J. Michael

    2010-01-01

    Perinatal taurine exposure has long-term effects on the arterial pressure and renal function. This study tests its influence on renal potassium excretion in young adult, conscious rats. Female Sprague-Dawley rats were fed normal rat chow and given water alone (C), 3% beta-alanine in water (taurine depletion, TD) or 3% taurine in water (taurine supplementation, TS), either from conception until delivery (fetal period; TDF or TSF) or from delivery until weaning (lactation period; TDL or TSL). I...

  8. Traffic pollution exposure is associated with altered brain connectivity in school children.

    Science.gov (United States)

    Pujol, Jesus; Martínez-Vilavella, Gerard; Macià, Dídac; Fenoll, Raquel; Alvarez-Pedrerol, Mar; Rivas, Ioar; Forns, Joan; Blanco-Hinojo, Laura; Capellades, Jaume; Querol, Xavier; Deus, Joan; Sunyer, Jordi

    2016-04-01

    Children are more vulnerable to the effects of environmental elements due to their active developmental processes. Exposure to urban air pollution has been associated with poorer cognitive performance, which is thought to be a result of direct interference with brain maturation. We aimed to assess the extent of such potential effects of urban pollution on child brain maturation using general indicators of vehicle exhaust measured in the school environment and a comprehensive imaging evaluation. A group of 263 children, aged 8 to 12 years, underwent MRI to quantify regional brain volumes, tissue composition, myelination, cortical thickness, neural tract architecture, membrane metabolites, functional connectivity in major neural networks and activation/deactivation dynamics during a sensory task. A combined measurement of elemental carbon and NO2 was used as a putative marker of vehicle exhaust. Air pollution exposure was associated with brain changes of a functional nature, with no evident effect on brain anatomy, structure or membrane metabolites. Specifically, a higher content of pollutants was associated with lower functional integration and segregation in key brain networks relevant to both inner mental processes (the default mode network) and stimulus-driven mental operations. Age and performance (motor response speed) both showed the opposite effect to that of pollution, thus indicating that higher exposure is associated with slower brain maturation. In conclusion, urban air pollution appears to adversely affect brain maturation in a critical age with changes specifically concerning the functional domain.

  9. Histopathologic alterations associated with global gene expression due to chronic dietary TCDD exposure in juvenile zebrafish.

    Directory of Open Access Journals (Sweden)

    Qing Liu

    Full Text Available The goal of this project was to investigate the effects and possible developmental disease implication of chronic dietary TCDD exposure on global gene expression anchored to histopathologic analysis in juvenile zebrafish by functional genomic, histopathologic and analytic chemistry methods. Specifically, juvenile zebrafish were fed Biodiet starter with TCDD added at 0, 0.1, 1, 10 and 100 ppb, and fish were sampled following 0, 7, 14, 28 and 42 d after initiation of the exposure. TCDD accumulated in a dose- and time-dependent manner and 100 ppb TCDD caused TCDD accumulation in female (15.49 ppb and male (18.04 ppb fish at 28 d post exposure. Dietary TCDD caused multiple lesions in liver, kidney, intestine and ovary of zebrafish and functional dysregulation such as depletion of glycogen in liver, retrobulbar edema, degeneration of nasal neurosensory epithelium, underdevelopment of intestine, and diminution in the fraction of ovarian follicles containing vitellogenic oocytes. Importantly, lesions in nasal epithelium and evidence of endocrine disruption based on alternatively spliced vasa transcripts are two novel and significant results of this study. Microarray gene expression analysis comparing vehicle control to dietary TCDD revealed dysregulated genes involved in pathways associated with cardiac necrosis/cell death, cardiac fibrosis, renal necrosis/cell death and liver necrosis/cell death. These baseline toxicological effects provide evidence for the potential mechanisms of developmental dysfunctions induced by TCDD and vasa as a biomarker for ovarian developmental disruption.

  10. Prenatal exposure to dexamethasone in the mouse alters cardiac growth patterns and increases pulse pressure in aged male offspring.

    Directory of Open Access Journals (Sweden)

    Lee O'Sullivan

    Full Text Available Exposure to synthetic glucocorticoids during development can result in later cardiovascular and renal disease in sheep and rats. Although prenatal glucocorticoid exposure is associated with impaired renal development, less is known about effects on the developing heart. This study aimed to examine the effects of a short-term exposure to dexamethasone (60 hours from embryonic day 12.5 on the developing mouse heart, and cardiovascular function in adult male offspring. Dexamethasone (DEX exposed fetuses were growth restricted compared to saline treated controls (SAL at E14.5, but there was no difference between groups at E17.5. Heart weights of the DEX fetuses also tended to be smaller at E14.5, but not different at E17.5. Cardiac AT1aR, Bax, and IGF-1 mRNA expression was significantly increased by DEX compared to SAL at E17.5. In 12-month-old offspring DEX exposure caused an increase in basal blood pressure of ~3 mmHg. In addition, DEX exposed mice had a widened pulse pressure compared to SAL. DEX exposed males at 12 months had an approximate 25% reduction in nephron number compared to SAL, but no difference in cardiomyocyte number. Exposure to DEX in utero appears to adversely impact on nephrogenesis and heart growth but is not associated with a cardiomyocyte deficit in male mice in adulthood, possibly due to compensatory growth of the myocardium following the initial insult. However, the widened pulse pressure may be indicative of altered vascular compliance.

  11. Alterations in cancer cell mechanical properties after fluid shear stress exposure: a micropipette aspiration study

    Directory of Open Access Journals (Sweden)

    Chivukula VK

    2015-01-01

    Full Text Available Venkat Keshav Chivukula,1 Benjamin L Krog,1,2 Jones T Nauseef,2 Michael D Henry,2 Sarah C Vigmostad1 1Department of Biomedical Engineering, 2Department of Molecular Physiology and Biophysics, Holden Comprehensive Cancer Center, University of Iowa, Seamans Center for the Engineering Arts and Sciences, Iowa City, IA, USA Abstract: Over 90% of cancer deaths result not from primary tumor development, but from metastatic tumors that arise after cancer cells circulate to distal sites via the circulatory system. While it is known that metastasis is an inefficient process, the effect of hemodynamic parameters such as fluid shear stress (FSS on the viability and efficacy of metastasis is not well understood. Recent work has shown that select cancer cells may be able to survive and possibly even adapt to FSS in vitro. The current research seeks to characterize the effect of FSS on the mechanical properties of suspended cancer cells in vitro. Nontransformed prostate epithelial cells (PrEC LH and transformed prostate cancer cells (PC-3 were used in this study. The Young's modulus was determined using micropipette aspiration. We examined cells in suspension but not exposed to FSS (unsheared and immediately after exposure to high (6,400 dyn/cm2 and low (510 dyn/cm2 FSS. The PrEC LH cells were ~140% stiffer than the PC-3 cells not exposed to FSS. Post-FSS exposure, there was an increase of ~77% in Young's modulus after exposure to high FSS and a ~47% increase in Young's modulus after exposure to low FSS for the PC-3 cells. There was no significant change in the Young's modulus of PrEC LH cells post-FSS exposure. Our findings indicate that cancer cells adapt to FSS, with an increased Young's modulus being one of the adaptive responses, and that this adaptation is specific only to PC-3 cells and is not seen in PrEC LH cells. Moreover, this adaptation appears to be graded in response to the magnitude of FSS experienced by the cancer cells. This is the first study

  12. Acute effects of tetracycline exposure in the freshwater fish Gambusia holbrooki: antioxidant effects, neurotoxicity and histological alterations.

    Science.gov (United States)

    Nunes, B; Antunes, S C; Gomes, R; Campos, J C; Braga, M R; Ramos, A S; Correia, A T

    2015-02-01

    A large body of evidence was compiled in the recent decades showing a noteworthy increase in the detection of pharmaceutical drugs in aquatic ecosystems. Due to its ubiquitous presence, chemical nature, and practical purpose, this type of contaminant can exert toxic effects in nontarget organisms. Exposure to pharmaceutical drugs can result in adaptive alterations, such as changes in tissues, or in key homeostatic mechanisms, such as antioxidant mechanisms, biochemical/physiological pathways, and cellular damage. These alterations can be monitored to determine the impact of these compounds on exposed aquatic organisms. Among pharmaceutical drugs in the environment, antibiotics are particularly important because they include a variety of substances widely used in medical and veterinary practice, livestock production, and aquaculture. This wide use constitutes a decisive factor contributing for their frequent detection in the aquatic environment. Tetracyclines are the individual antibiotic subclass with the second highest frequency of detection in environmental matrices. The characterization of the potential ecotoxicological effects of tetracycline is a much-required task; to attain this objective, the present study assessed the acute toxic effects of tetracycline in the freshwater fish species Gambusia holbrooki by the determination of histological changes in the gills and liver, changes in antioxidant defense [glutathione S-transferase (GST), catalase (CAT), and lipoperoxidative damage] as well as potential neurotoxicity (acetylcholinesterase activity). The obtained results suggest the existence of a cause-and-effect relationship between the exposure to tetracycline and histological alterations (more specifically in gills) and enzymatic activity (particularly the enzyme CAT in liver and GST in gills) indicating that this compound can exert a pro-oxidative activity. PMID:25475590

  13. Exposure to a glyphosate-based herbicide during pregnancy and lactation induces neurobehavioral alterations in rat offspring.

    Science.gov (United States)

    Gallegos, Cristina E; Bartos, Mariana; Bras, Cristina; Gumilar, Fernanda; Antonelli, Marta C; Minetti, Alejandra

    2016-03-01

    The impact of sub-lethal doses of herbicides on human health and the environment is a matter of controversy. Due to the fact that evidence particularly of the effects of glyphosate on the central nervous system of rat offspring by in utero exposure is scarce, the purpose of the present study was to assess the neurobehavioral effects of chronic exposure to a glyphosate-containing herbicide during pregnancy and lactation. To this end, pregnant Wistar rats were exposed through drinking water to 0.2% or 0.4% of a commercial formulation of glyphosate (corresponding to a concentration of 0.65 or 1.30g/L of glyphosate, respectively) during pregnancy and lactation and neurobehavioral alterations in offspring were analyzed. The postnatal day on which each pup acquired neonatal reflexes (righting, cliff aversion and negative geotaxis) and that on which eyes and auditory canals were fully opened were recorded for the assessment of sensorimotor development. Locomotor activity and anxiety levels were monitored via open field test and plus maze test, respectively, in 45- and 90-day-old offspring. Pups exposed to a glyphosate-based herbicide showed early onset of cliff aversion reflex and early auditory canal opening. A decrease in locomotor activity and in anxiety levels was also observed in the groups exposed to a glyphosate-containing herbicide. Findings from the present study reveal that early exposure to a glyphosate-based herbicide affects the central nervous system in rat offspring probably by altering mechanisms or neurotransmitter systems that regulate locomotor activity and anxiety.

  14. Embryonic caffeine exposure acts via A1 adenosine receptors to alter adult cardiac function and DNA methylation in mice.

    Directory of Open Access Journals (Sweden)

    Daniela L Buscariollo

    Full Text Available Evidence indicates that disruption of normal prenatal development influences an individual's risk of developing obesity and cardiovascular disease as an adult. Thus, understanding how in utero exposure to chemical agents leads to increased susceptibility to adult diseases is a critical health related issue. Our aim was to determine whether adenosine A1 receptors (A1ARs mediate the long-term effects of in utero caffeine exposure on cardiac function and whether these long-term effects are the result of changes in DNA methylation patterns in adult hearts. Pregnant A1AR knockout mice were treated with caffeine (20 mg/kg or vehicle (0.09% NaCl i.p. at embryonic day 8.5. This caffeine treatment results in serum levels equivalent to the consumption of 2-4 cups of coffee in humans. After dams gave birth, offspring were examined at 8-10 weeks of age. A1AR+/+ offspring treated in utero with caffeine were 10% heavier than vehicle controls. Using echocardiography, we observed altered cardiac function and morphology in adult mice exposed to caffeine in utero. Caffeine treatment decreased cardiac output by 11% and increased left ventricular wall thickness by 29% during diastole. Using DNA methylation arrays, we identified altered DNA methylation patterns in A1AR+/+ caffeine treated hearts, including 7719 differentially methylated regions (DMRs within the genome and an overall decrease in DNA methylation of 26%. Analysis of genes associated with DMRs revealed that many are associated with cardiac hypertrophy. These data demonstrate that A1ARs mediate in utero caffeine effects on cardiac function and growth and that caffeine exposure leads to changes in DNA methylation.

  15. 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.

  16. Early life exposure to environmental tobacco smoke alters immune response to asbestos via a shift in inflammatory phenotype resulting in increased disease development.

    Science.gov (United States)

    Brown, Traci Ann; Holian, Andrij; Pinkerton, Kent E; Lee, Joong Won; Cho, Yoon Hee

    2016-07-01

    Asbestos in combination with tobacco smoke exposure reportedly leads to more severe physiological consequences than asbestos alone; limited data also show an increased disease risk due to environmental tobacco smoke (ETS) exposure. Environmental influences during gestation and early lung development can result in physiological changes that alter risk for disease development throughout an individual's lifetime. Therefore, maternal lifestyle may impact the ability of offspring to subsequently respond to environmental insults and alter overall disease susceptibility. In this study, we examined the effects of exposure to ETS in utero and during early postnatal development on asbestos-related inflammation and disease in adulthood. ETS exposure in utero appeared to shift inflammation towards a Th2 phenotype, via suppression of Th1 inflammatory cytokine production. This effect was further pronounced in mice exposed to ETS in utero and during early postnatal development. In utero ETS exposure led to increased collagen deposition, a marker of fibrotic disease, when the offspring was later exposed to asbestos, which was further increased with additional ETS exposure during early postnatal development. These data suggest that ETS exposure in utero alters the immune responses and leads to greater disease development after asbestos exposure, which is further exacerbated when exposure to ETS continues during early postnatal development. PMID:27138493

  17. Transformation of Chlorpyrifos and Chlorpyrifos-Methyl in Prairie Pothole Porewaters

    Science.gov (United States)

    Anderson, R. M.; Chin, Y. P.

    2014-12-01

    The prairie pothole region (PPR) extends over approximately 700,000 km2 in the Great Plains region in United States and Canada and is a critical breeding ground for migratory waterfowl, as well as an important ecosystem for diverse invertebrates and aquatic plants (van der Valk, 2003). Consisting of up to 12 million permanent and temporary depressional wetlands, the PPR is negatively impacted by non-point source pesticide pollution due to extensive agricultural development in the region. Recent studies have shown that high (mM) levels of sulfate in the pothole lakes are capable of abiotically reducing dinitroaniline and chloroacetanilide pesticides (Zeng, 2011; Zeng, 2012). In this study the transformation of the organophosphorus pesticide chlorpyrifos (CP) and its analog chlorpyrifos-methyl (CPM) was studied using pore waters sampled from two pothole lakes. CP and CPM have been found to react in the laboratory with sulfur species via a SN2 mechanism, with degradation by sulfur compounds occurring faster than hydrolysis at high pH (Wu, 2006). To date the reaction of CP and CPM in natural environments with sulfur species has not been studied. Chlorpyrifos-methyl underwent rapid degradation in the presence of reduced sulfur species in pore water, while chlorpyrifos degradation occurred at significantly slower rates. Both CP and CPM degradation occurred at comparable rates to what has been previously observed in the laboratory (Wu, 2006). References van der Valk, Arnold G., and Roger L. Pederson. "The SWANCC decision and its implications for prairie potholes." Wetlands 23.3 (2003): 590-596. Wu, Tong, Qiu Gan, and Urs Jans. "Nucleophilic Substitution of Phosphorothionate Ester Pesticides with Bisulfide (HS-) and Polysulfides (Sn2-)." Environmental science & technology 40.17 (2006): 5428-5434. Zeng, Teng, et al. "Pesticide processing potential in prairie pothole porewaters."Environmental science & technology 45.16 (2011): 6814-6822. Zeng, Teng, Yu-Ping Chin, and William

  18. Internal Concentration and Time Are Important Modifiers of Toxicity: The Case of Chlorpyrifos on Caenorhabditis elegans.

    Science.gov (United States)

    Roh, Ji-Yeon; Lee, Hyun-Jeoung; Kwon, Jung-Hwan

    2016-09-01

    The internal concentration of chemicals in exposed organisms changes over time due to absorption, distribution, metabolism, and excretion processes since chemicals are taken up from the environment. Internal concentration and time are very important modifiers of toxicity when biomarkers are used to evaluate the potential hazards and risks of environmental pollutants. In this study, the responses of molecular biomarkers, and the fate of chemicals in the body, were comprehensively investigated to determine cause-and-effect relationships over time. Chlorpyrifos (CP) was selected as a model chemical, and Caenorhabditis elegans was exposed to CP for 4 h using the passive dosing method. Worms were then monitored in fresh medium during a 48-h recovery regime. The mRNA expression of genes related to CYP metabolism (cyp35a2 and cyp35a3) increased during the constant exposure phase. The body residue of CP decreased once it reached a peak level during the early stage of exposure, indicating that the initial uptake of CP rapidly induced biotransformation with the synthesis of new CYP metabolic proteins. The residual chlorpyrifos-oxon concentration, an acetylcholinesterase (AChE) inhibitor, continuously increased even after the recovery regime started. These delayed toxicokinetics seem to be important for the extension of AChE inhibition for up to 9 h after the start of the recovery regime. Comprehensive investigation into the molecular initiation events and changes in the internal concentrations of chemical species provide insight into response causality within the framework of an adverse outcome pathway.

  19. Developmental neurotoxic effects of two pesticides: Behavior and biomolecular studies on chlorpyrifos and carbaryl.

    Science.gov (United States)

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

    2015-11-01

    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 inhibit acetylcholinesterase (AChE) in the nervous system. The aim of the study was to investigate if the pesticides can induce neurotoxic effects, when exposure occurs during a period of rapid brain growth and maturation. The results from the present study show that both compounds can affect protein levels in the developing brain and induce persistent adult behavior and cognitive impairments, in mice neonatally exposed to a single oral dose of chlorpyrifos (0.1, 1.0 or 5mg/kg body weight) or carbaryl (0.5, 5.0 or 20.0mg/kg body weight) on postnatal day 10. The results also indicate that the developmental neurotoxic effects induced are not related to the classical mechanism of acute cholinergic hyperstimulation, as the AChE inhibition level (8-12%) remained below the threshold for causing systemic toxicity. The neurotoxic effects are more likely caused by a disturbed neurodevelopment, as similar behavioral neurotoxic effects have been reported in studies with pesticides such as organochlorines, organophosphates, pyrethroids and POPs, when exposed during a critical window of neonatal brain development.

  20. Short-term exposure of arsenite disrupted thyroid endocrine system and altered gene transcription in the HPT axis in zebrafish.

    Science.gov (United States)

    Sun, Hong-Jie; Li, Hong-Bo; Xiang, Ping; Zhang, Xiaowei; Ma, Lena Q

    2015-10-01

    Arsenic (As) pollution in aquatic environment may adversely impact fish health by disrupting their thyroid hormone homeostasis. In this study, we explored the effect of short-term exposure of arsenite (AsIII) on thyroid endocrine system in zebrafish. We measured As concentrations, As speciation, and thyroid hormone thyroxine levels in whole zebrafish, oxidative stress (H2O2) and damage (MDA) in the liver, and gene transcription in hypothalamic-pituitary-thyroid (HPT) axis in the brain and liver tissues of zebrafish after exposing to different AsIII concentrations for 48 h. Result indicated that exposure to AsIII increased inorganic As in zebrafish to 0.46-0.72 mg kg(-1), induced oxidative stress with H2O2 being increased by 1.4-2.5 times and caused oxidative damage with MDA being augmented by 1.6 times. AsIII exposure increased thyroxine levels by 1.3-1.4 times and modulated gene transcription in HPT axis. Our study showed AsIII caused oxidative damage, affected thyroid endocrine system and altered gene transcription in HPT axis in zebrafish.

  1. Chronic cigarette smoke exposure adversely alters 14C-arachidonic acid metabolism in rat lungs, aortas and platelets

    International Nuclear Information System (INIS)

    Male rats were exposed to freshly generated cigarette smoke once daily, 5 times a week for 10 weeks. Inhalation of smoke was verified by elevated carboxyhemoglobin in blood sampled immediately after smoke exposure and by increased lung aryl hydrocarbon hydroxylase activity 24 hours after the last smoke exposure. Aortic rings isolated from smoke-exposed rats synthesized less prostacyclin (PGI2) from 14C-arachidonic acid than rings from sham rats. Platelets from smoke-exposed rats synthesized more thromboxane (TXA2) from 14C-arachidonic acid than platelets from room controls but not those from sham rats. Lung microsomes from smoke-exposed rats synthesized more TXA2 and had a lower PGI2/TXA2 ratio than lung microsomes from room controls and shams. It is concluded that chronic cigarette smoke exposure alters arachidonic acid metabolism in aortas, platelets and lungs in a manner resulting in decreased PGI2 and increased TXA2, thereby creating a condition favoring platelet aggregation and a variety of cardiovascular diseases

  2. Genome-wide analysis of epigenomic alterations in fetal mouse forebrain after exposure to low doses of bisphenol A.

    Science.gov (United States)

    Yaoi, Takeshi; Itoh, Kyoko; Nakamura, Keiko; Ogi, Hiroshi; Fujiwara, Yasuhiro; Fushiki, Shinji

    2008-11-21

    Bisphenol A (BPA) is one of endocrine disrupting chemicals, being distributed widely in the environment. We have been studying the low dose effects of BPA on murine forebrain development. Here, we have investigated the genome-wide effect of maternal exposure to BPA on the epigenome in mouse forebrain at E12.5 and at E14.5. We scanned CpG methylation status in 2500 NotI loci, representing 48 (de)methylated unique loci. Methylation status in most of them was primarily developmental stage-dependent. Each of almost all cloned NotI loci was located in a CpG island (CGI) adjacent to 5' end of the transcriptional unit. The mRNA expression of two functionally related genes changed with development as well as the exposure to BPA. In both genes, changes at the transcriptional level correlated well with the changes in NotI methylation status. Taken together, epigenetic alterations in promoter-associated CGIs after exposure to BPA may underlie some effects on brain development. PMID:18804091

  3. Developmental exposure to bisphenol A (BPA) alters sexual differentiation in painted turtles (Chrysemys picta)

    Science.gov (United States)

    Jandegian, Caitlin M.; Deem, Sharon L.; Bhandari, Ramji K.; Holliday, Casey M.; Nicks, Diane; Rosenfeld, Cheryl S.; Selcer, Kyle; Tillitt, Donald E.; vom Saal, Fredrick S.; Velez, Vanessa; Yang, Ying; Holliday, Dawn K.

    2015-01-01

    Environmental chemicals can disrupt endocrine signaling and adversely impact sexual differentiation in wildlife. Bisphenol A (BPA) is an estrogenic chemical commonly found in a variety of habitats. In this study, we used painted turtles (Chrysemys picta), which have temperature-dependent sex determination (TSD), as an animal model for ontogenetic endocrine disruption by BPA. We hypothesized that BPA would override TSD and disrupt sexual development. We incubated farm-raised turtle eggs at the male-producing temperature (26 °C), randomly assigned individuals to treatment groups: control, vehicle control, 17β-estradiol (E2, 20 ng/g-egg) or 0.01, 1.0, 100 μg BPA/g-egg and harvested tissues at hatch. Typical female gonads were present in 89% of the E2-treated “males”, but in none of the control males (n = 35). Gonads of BPA-exposed turtles had varying amounts of ovarian-like cortical (OLC) tissue and disorganized testicular tubules in the medulla. Although the percentage of males with OLCs increased with BPA dose (BPA-low = 30%, BPA-medium = 33%, BPA-high = 39%), this difference was not significant (p = 0.85). In all three BPA treatments, SOX9 patterns revealed disorganized medullary testicular tubules and β-catenin expression in a thickened cortex. Liver vitellogenin, a female-specific liver protein commonly used as an exposure biomarker, was not induced by any of the treatments. Notably, these results suggest that developmental exposure to BPA disrupts sexual differentiation in painted turtles. Further examination is necessary to determine the underlying mechanisms of sex reversal in reptiles and how these translate to EDC exposure in wild populations.

  4. Metabolic and feeding behavior alterations provoked by prenatal exposure to aspartame.

    Science.gov (United States)

    von Poser Toigo, E; Huffell, A P; Mota, C S; Bertolini, D; Pettenuzzo, L F; Dalmaz, C

    2015-04-01

    The use of artificial sweeteners has increased together with the epidemic growth of obesity. In addition to their widespread use in sodas, artificial sweeteners are added to nearly 6000 other products sold in the US, including baby foods, frozen dinners and even yogurts. It has been suggested that the use of nonnutritive sweeteners can lead to body weight gain and an altered metabolic profile. However, very few studies have evaluated the effects of maternal consumption of artificial non-caloric sweeteners on body weight, feeding behavior or the metabolism of offspring in adult life. In this study, we found that animals exposed to aspartame during the prenatal period presented a higher consumption of sweet foods during adulthood and a greater susceptibility to alterations in metabolic parameters, such as increased glucose, LDL and triglycerides. These effects were observed in both males and females, although they were more pronounced in males. Despite the preliminary nature of this study, and the need for further confirmation of these effects, our data suggest that the consumption of sweeteners during gestation may have deleterious long-term effects and should be used with caution.

  5. Short-duration exposure to radiofrequency electromagnetic radiation alters the chlorophyll fluorescence of duckweeds (Lemna minor).

    Science.gov (United States)

    Senavirathna, Mudalige Don Hiranya Jayasanka; Takashi, Asaeda; Kimura, Yuichi

    2014-12-01

    Plants growing in natural environments are exposed to radiofrequency electromagnetic radiation (EMR) emitted by various communication network base stations. The environmental concentration of this radiation is increasing rapidly with the congested deployment of base stations. Although numerous scientific studies have been conducted to investigate the effects of EMR on the physiology of humans and animals, there have been few attempts to investigate the effects of EMR on plants. In this study, we attempted to evaluate the effects of EMR on photosynthesis by investigating the chlorophyll fluorescence (ChF) parameters of duckweed fronds. During the experiment, the fronds were tested with 2, 2.5, 3.5, 5.5 and 8 GHz EMR frequencies, which are not widely studied even though there is a potentially large concentration of these frequencies in the environment. The duckweed fronds were exposed to EMR for 30 min, 1 h and 24 h durations with electric field strength of 45-50 V/m for each frequency. The results indicated that exposure to EMR causes a change in the non-photochemical quenching of the duckweeds. The changes varied with the frequency of the EMR and were time-varying within a particular frequency. The temperature remained unchanged in the duckweed fronds upon exposure to EMR, which confirms that the effect is non-thermal.

  6. LOWER DOSE OF AMINOGLYCOSIDE OTOTOXIC EXPOSURE CAUSES PRESYNAPTIC ALTERATIONS ASSOICATED WITH HEARING LOSS

    Institute of Scientific and Technical Information of China (English)

    LIU Ke; WANG Xiaoyu; LI Sijun; TANG Siquan; XU Yice; WANG Xuefeng; SUN Jianhe; YANG Weiyan; YANG Shiming

    2014-01-01

    Objective To study presynaptic alternations of cochlear ribbons arising from aminoglycoside ototoxic stimuli in C57BL/6J mice. Methods Animals were injected with low dose gentamicin (100 mg/kg/day) for 14 days, From the 14th to 28th days, the mice were maintained free of gentamicin treatment. Immunohisto-chemistry labeling was employed to trace RIBEYE, a major presynaptic componment of ribbon synapses. RIBEYE/CtBP2 expression levels were assessed and compared with hearing threshold shifts. Auditory func-tion was assessed by auditory brainstem responses. The stereocilia of outer hair cells (OHCs) and IHCs was examined by scanning electron microscopy (SEM). Results Hearing thresholds were elevated with peak hearing loss observed on the 7th day after gentamicin exposure, followed by improvement after the 7th day. RIBEYE/CtBP2 expression directly correlated with observed hearing threshold shifts. Strikingly, we did not see any obvious changes in stereocilia in both OHCs and IHCs until the 28th day. Mild changes in stereocil-ia were only observed in OHCs on the 28th day. Conclusions These findings indicate that presynapse co-chlear ribbons, rather than stereocilia, may be sensitive to aminoglycoside ototoxic exposure in mice cochle-ae. A pattern of RIBEYE/CtBP2 expression changes seems to parallel hearing threshold shifts and suggests presynaptic response properties to lower dosage of aminoglycoside ototoxic stimuli.

  7. Exposure and Figure Out of Climate Induced Alterations in the Wetlands of Banglades

    Science.gov (United States)

    Siddiquee, S. A.; Rahman, M. Z.

    2015-12-01

    Unique geographic location and geo-morphological conditions of Bangladesh have made the wetlands of this country one of the most vulnerable to climate change. Wetland plays a crucial role in maintaining the ecological balance of ecosystems and cultural figures and which occupy around 50% of the area. Drought, excessive temperature, mountain snowfields and glaciers melting, riverbank erosion, salinity intrusion, flashflood, storm surges, higher water temperatures, precipitation anomalies, coastal cyclones, seasonal anomalies and extremes are main threats to the wetland ecosystem. Enhanced UV-B radiation and increased summer precipitation will significantly increase dissolved organic carbon concentrations altering major biogeochemical cycles and also will result into the expansion of range for many invasive aquatic weeds. Generally, rising temperature will lower water quality through a fall in oxygen concentrations, release of phosphorus from sediments, increased thermal stability, and altered mixing patterns. As a result biodiversity is getting degraded, many species of flora and fauna are getting threatened, and wetland-based ecosystem is getting degenerated. At the same time, the living conditions of local people are deteriorating as livelihoods, socioeconomic institutions, and extensive cultural values as well. For conserving and managing wetlands technology, legislation, educational knowledge, action plan strategy and restoration practices are required. In order to address the human needs in the changing climate community-based adaptation approaches and wetland restoration, practices had been taken in almost every type of wetlands in Bangladesh. Therefore, Bangladesh now needs a comprehensive strategy and integrated system combining political, economic, social, technological approaches and institutional supports to address sustainable wetland restoration, conservation and the newly added crisis, climate change.

  8. Lead Exposure Impairs Hippocampus Related Learning and Memory by Altering Synaptic Plasticity and Morphology During Juvenile Period.

    Science.gov (United States)

    Wang, Tao; Guan, Rui-Li; Liu, Ming-Chao; Shen, Xue-Feng; Chen, Jing Yuan; Zhao, Ming-Gao; Luo, Wen-Jing

    2016-08-01

    Lead (Pb) is an environmental neurotoxic metal. Pb exposure may cause neurobehavioral changes, such as learning and memory impairment, and adolescence violence among children. Previous animal models have largely focused on the effects of Pb exposure during early development (from gestation to lactation period) on neurobehavior. In this study, we exposed Sprague-Dawley rats during the juvenile stage (from juvenile period to adult period). We investigated the synaptic function and structural changes and the relationship of these changes to neurobehavioral deficits in adult rats. Our results showed that juvenile Pb exposure caused fear-conditioned memory impairment and anxiety-like behavior, but locomotion and pain behavior were indistinguishable from the controls. Electrophysiological studies showed that long-term potentiation induction was affected in Pb-exposed rats, and this was probably due to excitatory synaptic transmission impairment in Pb-exposed rats. We found that NMDA and AMPA receptor-mediated current was inhibited, whereas the GABA synaptic transmission was normal in Pb-exposed rats. NR2A and phosphorylated GluR1 expression decreased. Moreover, morphological studies showed that density of dendritic spines declined by about 20 % in the Pb-treated group. The spine showed an immature form in Pb-exposed rats, as indicated by spine size measurements. However, the length and arborization of dendrites were unchanged. Our results suggested that juvenile Pb exposure in rats is associated with alterations in the glutamate receptor, which caused synaptic functional and morphological changes in hippocampal CA1 pyramidal neurons, thereby leading to behavioral changes. PMID:26141123

  9. Hepatic and intestine alterations in mice after prolonged exposure to low oral doses of Microcystin-LR.

    Science.gov (United States)

    Sedan, Daniela; Laguens, Martín; Copparoni, Guido; Aranda, Jorge Oswaldo; Giannuzzi, Leda; Marra, Carlos Alberto; Andrinolo, Darío

    2015-09-15

    Oral intake of Microcystin-LR (MC-LR) is the principal route of exposure to this toxin, with prolonged exposure leading to liver damage of unspecific symptomatology. The aim of the present paper was therefore to investigate the liver and intestine damage generated by prolonged oral exposure to low MC-LR doses (50 and 100 μg MC-LR/kg body weight, administrated every 48 h during a month) in a murine model. We found alterations in TBARS, SOD activity and glutathione content in liver and intestine of mice exposed to both doses of MC-LR. Furthermore, the presence of MC-LR was detected in both organs. We also found hepatic steatosis (3.6 ± 0.6% and 15.3 ± 1.6%) and a decrease in intraepithelial lymphocytes (28.7 ± 5.0% and 44.2 ± 8.7%) in intestine of 50- and 100-μg MC-LR/kg treated animals, respectively. This result could have important implications for mucosal immunity, since intraepithelial lymphocytes are the principal effectors of this system. Our results indicate that prolonged oral exposure at 50 μg MC-LR/kg every 48 h generates significant damage not only in liver but also in intestine. This finding calls for a re-appraisal of the currently accepted NOAEL (No Observed Adverse Effect Level), 40 μg MC-LR/kg body weight, used to derive the guideline value for MC-LR in drinking water.

  10. Exposure to (12)C particles alters the normal dynamics of brain monoamine metabolism and behaviour in rats.

    Science.gov (United States)

    Belov, Oleg V; Belokopytova, Ksenia V; Bazyan, Ara S; Kudrin, Vladimir S; Narkevich, Viktor B; Ivanov, Aleksandr A; Severiukhin, Yury S; Timoshenko, Gennady N; Krasavin, Eugene A

    2016-09-01

    Planning of the deep-space exploration missions raises a number of questions on the radiation protection of astronauts. One of the medical concerns is associated with exposure of a crew to highly energetic particles of galactic cosmic rays. Among many other health disorders, irradiation with these particles has a substantial impact on the central nervous system (CNS). Although radiation damage to CNS has been addressed extensively during the last years, the mechanisms underlying observed impairments remain mostly unknown. The present study reveals neurochemical and behavioural alterations induced in rats by 1Gy of 500MeV/u (12)C particles with a relatively moderate linear energy transfer (10.6keV/μm). It is found that exposure to carbon ions leads to significant modification of the normal monoamine metabolism dynamics as well as the locomotor, exploratory, and anxiety-like behaviours during a two-month period. The obtained results indicate an abnormal redistribution of monoamines and their metabolites in different brain regions after exposure. The most pronounced impairments are detected in the prefrontal cortex, nucleus accumbens, and hypothalamus that illustrate the sensitivity of these brain regions to densely ionizing radiations. It is also shown that exposure to (12)C particles enhances the anxiety in animals and accelerates the age-related reduction in their exploratory capability. The observed monoamine metabolism pattern may indicate the presence of certain compensatory mechanisms being induced in response to irradiation and capable of partial restoration of monoaminergic systems' functions. Overall, these findings support a possibility of CNS damage by space-born particles of a relatively moderate linear energy transfer. PMID:27544862

  11. Exposure to the BPA-Substitute Bisphenol S Causes Unique Alterations of Germline Function

    Science.gov (United States)

    Chen, Yichang; Qiu, Zhiqun; Lee, Dong Yeon; Telesca, Donatello; Yang, Xia; Allard, Patrick

    2016-01-01

    Concerns about the safety of Bisphenol A, a chemical found in plastics, receipts, food packaging and more, have led to its replacement with substitutes now found in a multitude of consumer products. However, several popular BPA-free alternatives, such as Bisphenol S, share a high degree of structural similarity with BPA, suggesting that these substitutes may disrupt similar developmental and reproductive pathways. We compared the effects of BPA and BPS on germline and reproductive functions using the genetic model system Caenorhabditis elegans. We found that, similarly to BPA, BPS caused severe reproductive defects including germline apoptosis and embryonic lethality. However, meiotic recombination, targeted gene expression, whole transcriptome and ontology analyses as well as ToxCast data mining all indicate that these effects are partly achieved via mechanisms distinct from BPAs. These findings therefore raise new concerns about the safety of BPA alternatives and the risk associated with human exposure to mixtures. PMID:27472198

  12. Exposure to the BPA-Substitute Bisphenol S Causes Unique Alterations of Germline Function.

    Science.gov (United States)

    Chen, Yichang; Shu, Le; Qiu, Zhiqun; Lee, Dong Yeon; Settle, Sara J; Que Hee, Shane; Telesca, Donatello; Yang, Xia; Allard, Patrick

    2016-07-01

    Concerns about the safety of Bisphenol A, a chemical found in plastics, receipts, food packaging and more, have led to its replacement with substitutes now found in a multitude of consumer products. However, several popular BPA-free alternatives, such as Bisphenol S, share a high degree of structural similarity with BPA, suggesting that these substitutes may disrupt similar developmental and reproductive pathways. We compared the effects of BPA and BPS on germline and reproductive functions using the genetic model system Caenorhabditis elegans. We found that, similarly to BPA, BPS caused severe reproductive defects including germline apoptosis and embryonic lethality. However, meiotic recombination, targeted gene expression, whole transcriptome and ontology analyses as well as ToxCast data mining all indicate that these effects are partly achieved via mechanisms distinct from BPAs. These findings therefore raise new concerns about the safety of BPA alternatives and the risk associated with human exposure to mixtures. PMID:27472198

  13. Altered Microbiota Contributes to Reduced Diet-Induced Obesity upon Cold Exposure

    DEFF Research Database (Denmark)

    Ziętak, Marika; Kovatcheva-Datchary, Petia; Markiewicz, Lidia H;

    2016-01-01

    similar to that of germ-free mice. We observed a marked shift in the microbiome composition at the phylum and family levels within 1 day of acute cold exposure and after 4 weeks at 12°C. Gut microbiota was characterized by increased levels of Adlercreutzia, Mogibacteriaceae, Ruminococcaceae......, and Desulfovibrio and reduced levels of Bacilli, Erysipelotrichaceae, and the genus rc4-4. These genera have been associated with leanness and obesity, respectively. Germ-free mice fed a high-fat diet at room temperature gained less adiposity and improved glucose tolerance when transplanted with caecal microbiota...... of mice housed at 12°C compared to mice transplanted with microbiota from 29°C. Thus, a microbiota-liver-BAT axis may mediate protection against obesity at reduced temperature....

  14. Exposure to the BPA-Substitute Bisphenol S Causes Unique Alterations of Germline Function.

    Science.gov (United States)

    Chen, Yichang; Shu, Le; Qiu, Zhiqun; Lee, Dong Yeon; Settle, Sara J; Que Hee, Shane; Telesca, Donatello; Yang, Xia; Allard, Patrick

    2016-07-01

    Concerns about the safety of Bisphenol A, a chemical found in plastics, receipts, food packaging and more, have led to its replacement with substitutes now found in a multitude of consumer products. However, several popular BPA-free alternatives, such as Bisphenol S, share a high degree of structural similarity with BPA, suggesting that these substitutes may disrupt similar developmental and reproductive pathways. We compared the effects of BPA and BPS on germline and reproductive functions using the genetic model system Caenorhabditis elegans. We found that, similarly to BPA, BPS caused severe reproductive defects including germline apoptosis and embryonic lethality. However, meiotic recombination, targeted gene expression, whole transcriptome and ontology analyses as well as ToxCast data mining all indicate that these effects are partly achieved via mechanisms distinct from BPAs. These findings therefore raise new concerns about the safety of BPA alternatives and the risk associated with human exposure to mixtures.

  15. Chronic cocaine or ethanol exposure during adolescence alters novelty-related behaviors in adulthood.

    Science.gov (United States)

    Stansfield, Kirstie H; Kirstein, Cheryl L

    2007-04-01

    Adolescence is a time of high-risk behavior and increased exploration. This developmental period is marked by a greater probability to initiate drug use and is associated with an increased risk to develop addiction and adulthood dependency and drug use at this time is associated with an increased risk. Human adolescents are predisposed toward an increased likelihood of risk-taking behaviors [Zuckerman M. Sensation seeking and the endogenous deficit theory of drug abuse. NIDA Res Monogr 1986;74:59-70.], including drug use or initiation. In the present study, adolescent animals were exposed to twenty days of either saline (0.9% sodium chloride), cocaine (20 mg/kg) or ethanol (1 g/kg) i.p. followed by a fifteen-day washout period. All animals were tested as adults on several behavioral measures including locomotor activity induced by a novel environment, time spent in the center of an open field, novelty preference and novel object exploration. Animals exposed to cocaine during adolescence and tested as adults exhibited a greater locomotor response in a novel environment, spent less time in the center of the novel open field and spent less time with a novel object, results that are indicative of a stress or anxiogenic response to novelty or a novel situation. Adolescent animals chronically administered ethanol and tested as adults, unlike cocaine-exposed were not different from controls in a novel environment, indicated by locomotor activity or time spent with a novel object. However, ethanol-exposed animals approached the novel object more, suggesting that exposure to ethanol during development may result in less-inhibited behaviors during adulthood. The differences in adult behavioral responses after drug exposure during adolescence are likely due to differences in the mechanisms of action of the drugs and subsequent reward and/or stress responsivity. Future studies are needed to determine the neural substrates of these long lasting drug-induced changes. PMID

  16. Gestational exposure to low dose bisphenol A alters social behavior in juvenile mice.

    Directory of Open Access Journals (Sweden)

    Jennifer T Wolstenholme

    Full Text Available Bisphenol A (BPA is a man-made compound used to make polycarbonate plastics and epoxy resins; public health concerns have been fueled by findings that BPA exposure can reduce sex differences in brain and some behaviors. We asked if a low BPA dose, within the range measured in humans, ingested during pregnancy, would affect social behaviors in prepubertal mice. We noted sex differences in social interactions whereby females spent more time sitting side-by-side, while males engaged in more exploring and sitting alone. In addition BPA increased display of nose-to-nose contacts, play solicitations and approaches in both sexes. Interactions between sex and diet were found for self grooming, social interactions while sitting side-by-side and following the other mouse. In all these cases interactions were produced by differences between control and BPA females. We examined brains from embryos during late gestation to determine if gene expression differences might be correlated with some of the sexually dimorphic or BPA affected behaviors we observed. Because BPA treatments ended at birth we took the brains during embryogenesis to increase the probability of discovering BPA mediated effects. We also selected this embryonic age (E18.5 because it coincides with the onset of sexual differentiation of the brain. Interestingly, mRNA for the glutamate transporter, Slc1a1, was enhanced by exposure to BPA in female brains. Also we noted that BPA changed the expression of two of the three DNA methyltransferase genes, Dnmt1 and Dnmt3a. We propose that BPA affects DNA methylation of Sc1a1 during neural development. Sex differences in juvenile social interactions are affected by BPA and in particular this compound modifies behavior in females.

  17. Mainstream cigarette smoke exposure alters cytochrome P4502G1 expression in F344 rat olfactory mucosa

    International Nuclear Information System (INIS)

    Inhalation of mainstream cigarette smoke (MCS) by rats results in multifocal rhinitis, mucous hypersecretion, nasal epithelial hyperplasia and metaplasia, and focal olfactory mucosal atrophy. In humans, cigarette smoking causes long-term, dose-related alterations in olfactory function in both current and former smokers. An olfactory-specific cytochrome P450 has been identified in rabbits and rats. The presence of olfactory-specific P450s, as well as relatively high levels of other biotransformation enzymes, such as NADPH-cytochrome P450 reductase and UDP-glucuronosyl transferase, in the olfactory neuroepithelium suggest that these enzyme systems may play a role in olfaction. This hypothesis is strengthened by the observation that, in rats, the temporal gene activation of P4502G1 coincides with the postnatal increase in the sensitivity of olfactory response to odorants. The purpose of this investigation was to examine the effect of MCS exposure on P4502G1 protein expression

  18. Gene expression and pathologic alterations in juvenile rainbow trout due to chronic dietary TCDD exposure

    International Nuclear Information System (INIS)

    Highlights: •First report of the effects of dietary TCDD in juvenile trout smaller than 20 g. •TCDD uptake was estimated using published models and confirmed by GC. •First report of dietary TCDD-induced lesions in nasal epithelium in any species. •Several useful biomarkers are identified from microarray-based transcriptomics analysis. -- Abstract: The goal of this project was to use functional genomic methods to identify molecular biomarkers as indicators of the impact of TCDD exposure in rainbow trout. Specifically, we investigated the effects of chronic dietary TCDD exposure on whole juvenile rainbow trout global gene expression associated with histopathological analysis. Juvenile rainbow trout were fed Biodiet starter with TCDD added at 0, 0.1, 1, 10 and 100 ppb (ng TCDD/g food), and fish were sampled from each group at 7, 14, 28 and 42 days after initiation of feeding. 100 ppb TCDD caused 100% mortality at 39 days. Fish fed with 100 ppb TCDD food had TCDD accumulation of 47.37 ppb (ng TCDD/g fish) in whole fish at 28 days. Histological analysis from TCDD-treated trout sampled from 28 and 42 days revealed that obvious lesions were found in skin, oropharynx, liver, gas bladder, intestine, pancreas, nose and kidney. In addition, TCDD caused anemia in peripheral blood, decreases in abdominal fat, increases of remodeling of fin rays, edema in pericardium and retrobulbar hemorrhage in the 100 ppb TCDD-treated rainbow trout compared to the control group at 28 days. Dose- and time-dependent global gene expression analyses were performed using the cGRASP 16,000 (16K) cDNA microarray. TCDD-responsive whole body transcripts identified in the microarray experiments have putative functions involved in various biological processes including growth, cell proliferation, metabolic process, and immune system processes. Nine microarray-identified genes were selected for QPCR validation. CYP1A3 and CYP1A1 were common up-regulated genes and HBB1 was a common down

  19. Gene expression and pathologic alterations in juvenile rainbow trout due to chronic dietary TCDD exposure

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Qing [Department of Biological Sciences, University of Wisconsin-Milwaukee, Lapham Hall, 3209 N. Maryland Ave., Milwaukee, WI 53211 (United States); School of Freshwater Sciences, University of Wisconsin-Milwaukee, 600 E Greenfield Ave, Milwaukee, WI 53204 (United States); Rise, Matthew L. [Ocean Sciences Centre, Memorial University of Newfoundland, 1 Marine Lab Road, St. John' s, NL, A1C 5S7 (Canada); Spitsbergen, Jan M. [Department of Microbiology, Oregon State University, 220 Nash Hall, Corvallis, OR 97331 (United States); Hori, Tiago S. [Ocean Sciences Centre, Memorial University of Newfoundland, 1 Marine Lab Road, St. John' s, NL, A1C 5S7 (Canada); Mieritz, Mark; Geis, Steven [Wisconsin State Laboratory of Hygiene, 465 Henry Mall, Madison, WI 53706 (United States); McGraw, Joseph E. [School of Pharmacy, Concordia University Wisconsin, 12800 North Lake Shore Drive, Mequon, WI 53097 (United States); Goetz, Giles [School of Aquatic and Fishery Sciences, University of Washington, 1122 Northeast Boat Street, Seattle, WA 98195 (United States); Larson, Jeremy; Hutz, Reinhold J. [Department of Biological Sciences, University of Wisconsin-Milwaukee, Lapham Hall, 3209 N. Maryland Ave., Milwaukee, WI 53211 (United States); Carvan, Michael J., E-mail: carvanmj@uwm.edu [Department of Biological Sciences, University of Wisconsin-Milwaukee, Lapham Hall, 3209 N. Maryland Ave., Milwaukee, WI 53211 (United States); School of Freshwater Sciences, University of Wisconsin-Milwaukee, 600 E Greenfield Ave, Milwaukee, WI 53204 (United States)

    2013-09-15

    Highlights: •First report of the effects of dietary TCDD in juvenile trout smaller than 20 g. •TCDD uptake was estimated using published models and confirmed by GC. •First report of dietary TCDD-induced lesions in nasal epithelium in any species. •Several useful biomarkers are identified from microarray-based transcriptomics analysis. -- Abstract: The goal of this project was to use functional genomic methods to identify molecular biomarkers as indicators of the impact of TCDD exposure in rainbow trout. Specifically, we investigated the effects of chronic dietary TCDD exposure on whole juvenile rainbow trout global gene expression associated with histopathological analysis. Juvenile rainbow trout were fed Biodiet starter with TCDD added at 0, 0.1, 1, 10 and 100 ppb (ng TCDD/g food), and fish were sampled from each group at 7, 14, 28 and 42 days after initiation of feeding. 100 ppb TCDD caused 100% mortality at 39 days. Fish fed with 100 ppb TCDD food had TCDD accumulation of 47.37 ppb (ng TCDD/g fish) in whole fish at 28 days. Histological analysis from TCDD-treated trout sampled from 28 and 42 days revealed that obvious lesions were found in skin, oropharynx, liver, gas bladder, intestine, pancreas, nose and kidney. In addition, TCDD caused anemia in peripheral blood, decreases in abdominal fat, increases of remodeling of fin rays, edema in pericardium and retrobulbar hemorrhage in the 100 ppb TCDD-treated rainbow trout compared to the control group at 28 days. Dose- and time-dependent global gene expression analyses were performed using the cGRASP 16,000 (16K) cDNA microarray. TCDD-responsive whole body transcripts identified in the microarray experiments have putative functions involved in various biological processes including growth, cell proliferation, metabolic process, and immune system processes. Nine microarray-identified genes were selected for QPCR validation. CYP1A3 and CYP1A1 were common up-regulated genes and HBB1 was a common down

  20. Developmental Exposure to Aroclor 1254 Alters Migratory Behavior in Juvenile European Starlings (Sturnus vulgaris).

    Science.gov (United States)

    Flahr, Leanne M; Michel, Nicole L; Zahara, Alexander R D; Jones, Paul D; Morrissey, Christy A

    2015-05-19

    Birds exposed to endocrine disrupting chemicals during development could be susceptible to neurological and other physiological changes affecting migratory behaviors. We investigated the effects of ecologically relevant levels of Aroclor 1254, a polychlorinated biphenyl (PCB) mixture, on moult, fattening, migratory activity, and orientation in juvenile European starlings (Sturnus vulgaris). Birds were orally administered 0 (control), 0.35 (low), 0.70 (intermediate), or 1.05 (high) μg Aroclor 1254/g-body weight by gavage from 1 through 18 days posthatch and later exposed in captivity to a photoperiod shift simulating an autumn migration. Migratory activity and orientation were examined using Emlen funnel trials. Across treatments, we found significant increases in mass, fat, and moulting and decreasing plasma thyroid hormones over time. We observed a significant increase in activity as photoperiod was shifted from 13L:11D (light:dark) to 12L:12D, demonstrating that migratory condition was induced in captivity. At 12L:12D, control birds oriented to 155.95° (South-Southeast), while high-dosed birds did not. High-dosed birds showed a delayed orientation to 197.48° (South-Southwest) under 10L:14D, concomitant with apparent delays in moult. These findings demonstrate how subtle contaminant-induced alterations during development could lead to longer-scale effects, including changes in migratory activity and orientation, which could potentially result in deleterious effects on fitness and survival.

  1. Developmental exposure to Passiflora incarnata induces behavioural alterations in the male progeny.

    Science.gov (United States)

    Bacchi, André D; Ponte, Bianca; Vieira, Milene L; de Paula, Jaqueline C C; Mesquita, Suzana F P; Gerardin, Daniela C C; Moreira, Estefânia G

    2013-01-01

    Passiflora incarnata is marketed in many countries as a phytomedicine and is prescribed mainly as a sedative and anxiolytic. Even though the directions of most marketed phytomedicines recommend them to be used under medical supervision, reproductive and developmental studies are sparse and not mandatory for regulatory purposes. To evaluate the reproductive and developmental toxicity of P. incarnata, Wistar female rats were gavaged with 30 or 300 mg kg(-1) of this herb from gestational Day (GD) 0 to postnatal Day (PND) 21. P. incarnata treatment did not influence dams' bodyweight or food intake or their reproductive performance (post-implantation loss, litter size, litter weight). There was also no influence on the physical development of pups (bodyweight gain, day of vaginal opening or preputial separation) or their behaviour in the open-field at PND 22, 35 and 75. Sexual behaviour was disrupted in adult male pups exposed to 300 mg kg(-1) of P. incarnata; in this group, only 3 out of 11 pups were sexually competent. This behavioural disruption was not accompanied by alterations in plasma testosterone levels, reproductive-related organs and glands weights or sperm count. It is hypothesised that aromatase inhibition may be involved in the observed effect.

  2. Prenatal exposure to aflatoxin B1: developmental, behavioral, and reproductive alterations in male rats

    Science.gov (United States)

    Supriya, Ch.; Reddy, P. Sreenivasula

    2015-06-01

    Previous studies have shown that aflatoxin B1 (AfB1) inhibits androgen biosynthesis as a result of its ability to form a high-affinity complex with the steroidogenic acute regulatory protein. The results of the present study demonstrate the postnatal effects of in utero exposure to AfB1 in the rat. Pregnant Wistar rats were given 10, 20, or 50 μg AfB1/kg body weight daily from gestation day (GD) 12 to GD 19. At parturition, newborns were observed for clinical signs and survival. All animals were born alive and initially appeared to be active. Male pups from control and AfB1-exposed animals were weaned and maintained up to postnatal day (PD) 100. Litter size, birth weight, sex ratio, survival rate, and crown-rump length of the pups were significantly decreased in AfB1-exposed rats when compared to controls. Elapsed time (days) for testes to descend into the scrotal sac was significantly delayed in experimental pups when compared to control pups. Behavioral observations such as cliff avoidance, negative geotaxis, surface rightening activity, ascending wire mesh, open field behavior, and exploratory and locomotory activities were significantly impaired in experimental pups. Body weights and the indices of testis, cauda epididymis, prostate, seminal vesicles, and liver were significantly reduced on PD 100 in male rats exposed to AfB1 during embryonic development when compared with controls. Significant reduction in the testicular daily sperm production, epididymal sperm count, and number of viable, motile, and hypo-osmotic tail coiled sperm was observed in experimental rats. The levels of serum testosterone and activity levels of testicular hydroxysteroid dehydrogenases were significantly decreased in a dose-dependent manner with a significant increase in the serum follicle-stimulating hormone and luteinizing hormone in experimental rats. Deterioration in the testicular and cauda epididymal architecture was observed in experimental rats. The results of fertility

  3. Proteomics study revealed altered proteome of Dichogaster curgensis upon exposure to fly ash.

    Science.gov (United States)

    Markad, Vijaykumar L; Adav, Sunil S; Ghole, Vikram S; Sze, Siu Kwan; Kodam, Kisan M

    2016-10-01

    Fly ash is toxic and its escalating use as a soil amendment and disposal by dumping into environment is receiving alarming attention due to its impact on environment. Proteomics technology is being used for environmental studies since proteins respond rapidly when an organism is exposed to a toxicant, and hence soil engineers such as earthworms are used as model organisms to assess the toxic effects of soil toxicants. This study adopted proteomics technology and profiled proteome of earthworm Dichogaster curgensis that was exposed to fly ash, with main aim to elucidate fly ash effects on cellular and metabolic pathways. The functional classification of identified proteins revealed carbohydrate metabolism (14.36%), genetic information processing (15.02%), folding, sorting and degradation (10.83%), replication and repair (3.95%); environmental information processing (2.19%), signal transduction (9.61%), transport and catabolism (17.27%), energy metabolism (6.69%), etc. in the proteome. Proteomics data and functional assays revealed that the exposure of earthworm to fly ash induced protein synthesis, up-regulation of gluconeogenesis, disturbed energy metabolism, oxidative and cellular stress, and mis-folding of proteins. The regulation of ubiquitination, proteasome and modified alkaline comet assay in earthworm coelomocytes suggested DNA-protein cross link affecting chromatin remodeling and protein folding. PMID:27371791

  4. Altered Microbiota Contributes to Reduced Diet-Induced Obesity upon Cold Exposure.

    Science.gov (United States)

    Ziętak, Marika; Kovatcheva-Datchary, Petia; Markiewicz, Lidia H; Ståhlman, Marcus; Kozak, Leslie P; Bäckhed, Fredrik

    2016-06-14

    Maintenance of body temperature in cold-exposed animals requires induction of thermogenesis and management of fuel. Here, we demonstrated that reducing ambient temperature attenuated diet-induced obesity (DIO), which was associated with increased iBAT thermogenesis and a plasma bile acid profile similar to that of germ-free mice. We observed a marked shift in the microbiome composition at the phylum and family levels within 1 day of acute cold exposure and after 4 weeks at 12°C. Gut microbiota was characterized by increased levels of Adlercreutzia, Mogibacteriaceae, Ruminococcaceae, and Desulfovibrio and reduced levels of Bacilli, Erysipelotrichaceae, and the genus rc4-4. These genera have been associated with leanness and obesity, respectively. Germ-free mice fed a high-fat diet at room temperature gained less adiposity and improved glucose tolerance when transplanted with caecal microbiota of mice housed at 12°C compared to mice transplanted with microbiota from 29°C. Thus, a microbiota-liver-BAT axis may mediate protection against obesity at reduced temperature. PMID:27304513

  5. Biochemical and histological alterations in liver following sub chronic exposure of arsenic

    Directory of Open Access Journals (Sweden)

    Madhuri Mehta

    2015-07-01

    Full Text Available Objective: Contamination of groundwater with arsenic is of global concern. The present work was aimed to evaluate the biochemical and histological changes in liver of female rats induced by sodium arsenite at doses naturally found in groundwater of Punjab. Method: Twenty four female rats were divided into four groups of 6 animals each. Group I animals received distilled water and served as control; Group II-IV received arsenic at the dose of 10, 30 and 50 ppb (μg/L dissolved in distilled water ad libitum for 30 days. At the end of experiment, animals were sacrificed and liver was collected for biochemical and histological evaluation. Results: Biochemical analysis showed an increase in the activity of hepatic marker enzymes including transferases, phosphatases and lactate dehydrogenase (LDH. Also, the levels of antioxidant enzymes (catalase, reduced glutathione and glutathione-S-transferase decreased significantly (P<0.05 in treated animals when compared to control. A significant (P<0.05 dose dependent increase in the levels of lipid peroxidation and arsenic concentration in liver tissue was observed. Histological examination showed the presence of pyknotic bodies (necrosis and sinusoidal dilation in hepatocytes of treated groups. Conclusion: Sub chronic exposure of arsenic at these doses induces hepatotoxicity leading to oxidative stress.

  6. Long-term exposure to elevated CO2 and O3 alters aspen foliar chemistry across developmental stages.

    Science.gov (United States)

    Couture, J J; Holeski, L M; Lindroth, R L

    2014-03-01

    Anthropogenic activities are altering levels of greenhouse gases to the extent that multiple and diverse ecosystem processes are being affected. Two gases that substantially influence forest health are atmospheric carbon dioxide (CO2 ) and tropospheric ozone (O3 ). Plant chemistry will play an important role in regulating ecosystem processes in future environments, but little information exists about the longitudinal effects of elevated CO2 and O3 on phytochemistry, especially for long-lived species such as trees. To address this need, we analysed foliar chemical data from two genotypes of trembling aspen, Populus tremuloides, collected over 10 years of exposure to levels of CO2 and O3 predicted for the year 2050. Elevated CO2 and O3 altered both primary and secondary chemistry, and the magnitude and direction of the responses varied across developmental stages and between aspen genotypes. Our findings suggest that the effects of CO2 and O3 on phytochemical traits that influence forest processes will vary over tree developmental stages, highlighting the need to continue long-term, experimental atmospheric change research.

  7. Rotating wall vessel exposure alters protein secretion and global gene expression in Staphylococcus aureus

    Science.gov (United States)

    Rosado, Helena; O'Neill, Alex J.; Blake, Katy L.; Walther, Meik; Long, Paul F.; Hinds, Jason; Taylor, Peter W.

    2012-04-01

    Staphylococcus aureus is routinely recovered from air and surface samples taken aboard the International Space Station (ISS) and poses a health threat to crew. As bacteria respond to the low shear forces engendered by continuous rotation conditions in a Rotating Wall Vessel (RWV) and the reduced gravitational field of near-Earth flight by altering gene expression, we examined the effect of low-shear RWV growth on protein secretion and gene expression by three S. aureus isolates. When cultured under 1 g, the total amount of protein secreted by these strains varied up to fourfold; under continuous rotation conditions, protein secretion by all three strains was significantly reduced. Concentrations of individual proteins were differentially reduced and no evidence was found for increased lysis. These data suggest that growth under continuous rotation conditions reduces synthesis or secretion of proteins. A limited number of changes in gene expression under continuous rotation conditions were noted: in all isolates vraX, a gene encoding a polypeptide associated with cell wall stress, was down-regulated. A vraX deletion mutant of S. aureus SH1000 was constructed: no differences were found between SH1000 and ΔvraX with respect to colony phenotype, viability, protein export, antibiotic susceptibility, vancomycin kill kinetics, susceptibility to cold or heat and gene modulation. An ab initio protein-ligand docking simulation suggests a major binding site for β-lactam drugs such as imipenem. If such changes to the bacterial phenotype occur during spaceflight, they will compromise the capacity of staphylococci to cause systemic infection and to circumvent antibacterial chemotherapy.

  8. Prenatal Hyperandrogenization Induces Metabolic and Endocrine Alterations Which Depend on the Levels of Testosterone Exposure

    Science.gov (United States)

    Amalfi, Sabrina; Velez, Leandro Martín; Heber, María Florencia; Vighi, Susana; Ferreira, Silvana Rocío; Orozco, Adriana Vega; Pignataro, Omar; Motta, Alicia Beatriz

    2012-01-01

    Prenatal hyperandrogenism is able to induce polycystic ovary syndrome (PCOS) in rats. The aim of the present study was to establish if the levels of prenatal testosterone may determine the extent of metabolic and endocrine alterations during the adult life. Pregnant Sprague Dawley rats were prenatally injected with either 2 or 5 mg free testosterone (groups T2 and T5 respectively) from day 16 to day 19 day of gestation. Female offspring from T2 and T5 displayed different phenotype of PCOS during adult life. Offspring from T2 showed hyperandrogenism, ovarian cysts and ovulatory cycles whereas those from T5 displayed hyperandrogenism, ovarian cysts and anovulatory cycles. Both group showed increased circulating glucose levels after the intraperitoneal glucose tolerance test (IPGTT; an evaluation of insulin resistance). IPGTT was higher in T5 rats and directly correlated with body weight at prepubertal age. However, the decrease in the body weight at prepubertal age was compensated during adult life. Although both groups showed enhanced ovarian steroidogenesis, it appears that the molecular mechanisms involved were different. The higher dose of testosterone enhanced the expression of both the protein that regulates cholesterol availability (the steroidogenic acute regulatory protein (StAR)) and the protein expression of the transcriptional factor: peroxisome proliferator-activated receptor gamma (PPAR gamma). Prenatal hyperandrogenization induced an anti-oxidant response that prevented a possible pro-oxidant status. The higher dose of testosterone induced a pro-inflammatory state in ovarian tissue mediated by increased levels of prostaglandin E (PG) and the protein expression of cyclooxygenase 2 (COX2, the limiting enzyme of PGs synthesis). In summary, our data show that the levels of testosterone prenatally injected modulate the uterine environment and that this, in turn, would be responsible for the endocrine and metabolic abnormalities and the phenotype of PCOS

  9. Short-term withdrawal from developmental exposure to cocaine activates the glucocorticoid receptor and alters spine dynamics.

    Science.gov (United States)

    Caffino, Lucia; Giannotti, Giuseppe; Malpighi, Chiara; Racagni, Giorgio; Fumagalli, Fabio

    2015-10-01

    Although glucocorticoid receptors (GRs) contribute to the action of cocaine, their role following developmental exposure to the psychostimulant is still unknown. To address this issue, we exposed adolescent male rats to cocaine (20mg/kg/day) from post-natal day (PND) 28 to PND 42 and sacrificed them at PND 45 or 90. We studied the medial prefrontal cortex (mPFC), a brain region that is still developing during adolescence. In PND 45 rats we found enhanced GR transcription and translation as well as increased trafficking toward the nucleus of the receptor, with no alteration in plasma corticosterone levels. We also showed reduced expression of the GR co-chaperone FKBP51, that normally keeps the receptor in the cytoplasm, and increased expression of Src1, which cooperates in the activation of GR transcriptional activity, revealing that short withdrawal alters the finely tuned mechanisms regulating GR action. Since activation of GRs regulate dendritic spine morphology, we next investigated spine dynamics in cocaine-withdrawn rats. We found that PSD95, cofilin and F-actin, molecules regulating spine actin network, are reduced in the mPFC of PND 45 rats suggesting reduced spine density, confirmed by confocal imaging. Further, formation of filopodia, i.e. the inactive spines, is enhanced suggesting the formation of non-functional spines. Of note, no changes were found in molecules related to GR machinery or spine dynamics following long-term abstinence, i.e. in adult rats (PND 90). These findings demonstrate that short withdrawal promotes plastic changes in the developing brain via the dysregulation of the GR system and alterations in the spine network. PMID:26004981

  10. 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

  11. Repeated exposure of adult rats to transient oxidative stress induces various long-lasting alterations in cognitive and behavioral functions.

    Directory of Open Access Journals (Sweden)

    Yoshio Iguchi

    Full Text Available Exposure of neonates to oxidative stress may increase the risk of psychiatric disorders such as schizophrenia in adulthood. However, the effects of moderate oxidative stress on the adult brain are not completely understood. To address this issue, we systemically administrated 2-cyclohexen-1-one (CHX to adult rats to transiently reduce glutathione levels. Repeated administration of CHX did not affect the acquisition or motivation of an appetitive instrumental behavior (lever pressing rewarded by a food outcome under a progressive ratio schedule. In addition, response discrimination and reversal learning were not affected. However, acute CHX administration blunted the sensitivity of the instrumental performance to outcome devaluation, and this effect was prolonged in rats with a history of repeated CHX exposure, representing pro-depression-like phenotypes. On the other hand, repeated CHX administration reduced immobility in forced swimming tests and blunted acute cocaine-induced behaviors, implicating antidepressant-like effects. Multivariate analyses segregated a characteristic group of behavioral variables influenced by repeated CHX administration. Taken together, these findings suggest that repeated administration of CHX to adult rats did not cause a specific mental disorder, but it induced long-term alterations in behavioral and cognitive functions, possibly related to specific neural correlates.

  12. Age at First Exposure to Football Is Associated with Altered Corpus Callosum White Matter Microstructure in Former Professional Football Players.

    Science.gov (United States)

    Stamm, Julie M; Koerte, Inga K; Muehlmann, Marc; Pasternak, Ofer; Bourlas, Alexandra P; Baugh, Christine M; Giwerc, Michelle Y; Zhu, Anni; Coleman, Michael J; Bouix, Sylvain; Fritts, Nathan G; Martin, Brett M; Chaisson, Christine; McClean, Michael D; Lin, Alexander P; Cantu, Robert C; Tripodis, Yorghos; Stern, Robert A; Shenton, Martha E

    2015-11-15

    Youth football players may incur hundreds of repetitive head impacts (RHI) in one season. Our recent research suggests that exposure to RHI during a critical neurodevelopmental period prior to age 12 may lead to greater later-life mood, behavioral, and cognitive impairments. Here, we examine the relationship between age of first exposure (AFE) to RHI through tackle football and later-life corpus callosum (CC) microstructure using magnetic resonance diffusion tensor imaging (DTI). Forty retired National Football League (NFL) players, ages 40-65, were matched by age and divided into two groups based on their AFE to tackle football: before age 12 or at age 12 or older. Participants underwent DTI on a 3 Tesla Siemens (TIM-Verio) magnet. The whole CC and five subregions were defined and seeded using deterministic tractography. Dependent measures were fractional anisotropy (FA), trace, axial diffusivity, and radial diffusivity. Results showed that former NFL players in the AFE <12 group had significantly lower FA in anterior three CC regions and higher radial diffusivity in the most anterior CC region than those in the AFE ≥12 group. This is the first study to find a relationship between AFE to RHI and later-life CC microstructure. These results suggest that incurring RHI during critical periods of CC development may disrupt neurodevelopmental processes, including myelination, resulting in altered CC microstructure.

  13. Selenium exposure results in reduced reproduction in an invasive ant species and altered competitive behavior for a native ant species.

    Science.gov (United States)

    De La Riva, Deborah G; Trumble, John T

    2016-06-01

    Competitive ability and numerical dominance are important factors contributing to the ability of invasive ant species to establish and expand their ranges in new habitats. However, few studies have investigated the impact of environmental contamination on competitive behavior in ants as a potential factor influencing dynamics between invasive and native ant species. Here we investigated the widespread contaminant selenium to investigate its potential influence on invasion by the exotic Argentine ant, Linepithema humile, through effects on reproduction and competitive behavior. For the fecundity experiment, treatments were provided to Argentine ant colonies via to sugar water solutions containing one of three concentrations of selenium (0, 5 and 10 μg Se mL(-1)) that fall within the range found in soil and plants growing in contaminated areas. Competition experiments included both the Argentine ant and the native Dorymyrmex bicolor to determine the impact of selenium exposure (0 or 15 μg Se mL(-1)) on exploitation- and interference-competition between ant species. The results of the fecundity experiment revealed that selenium negatively impacted queen survival and brood production of Argentine ants. Viability of the developing brood was also affected in that offspring reached adulthood only in colonies that were not given selenium, whereas those in treated colonies died in their larval stages. Selenium exposure did not alter direct competitive behaviors for either species, but selenium exposure contributed to an increased bait discovery time for D. bicolor. Our results suggest that environmental toxins may not only pose problems for native ant species, but may also serve as a potential obstacle for establishment among exotic species.

  14. Exposure to a northern contaminant mixture (NCM alters hepatic energy and lipid metabolism exacerbating hepatic steatosis in obese JCR rats.

    Directory of Open Access Journals (Sweden)

    Ryan J Mailloux

    Full Text Available Non-alcoholic fatty liver disease (NAFLD, defined by the American Liver Society as the buildup of extra fat in liver cells that is not caused by alcohol, is the most common liver disease in North America. Obesity and type 2 diabetes are viewed as the major causes of NAFLD. Environmental contaminants have also been implicated in the development of NAFLD. Northern populations are exposed to a myriad of persistent organic pollutants including polychlorinated biphenyls, organochlorine pesticides, flame retardants, and toxic metals, while also affected by higher rates of obesity and alcohol abuse compared to the rest of Canada. In this study, we examined the impact of a mixture of 22 contaminants detected in Inuit blood on the development and progression of NAFLD in obese JCR rats with or without co-exposure to 10% ethanol. Hepatosteatosis was found in obese rat liver, which was worsened by exposure to 10% ethanol. NCM treatment increased the number of macrovesicular lipid droplets, total lipid contents, portion of mono- and polyunsaturated fatty acids in the liver. This was complemented by an increase in hepatic total cholesterol and cholesterol ester levels which was associated with changes in the expression of genes and proteins involved in lipid metabolism and transport. In addition, NCM treatment increased cytochrome P450 2E1 protein expression and decreased ubiquinone pool, and mitochondrial ATP synthase subunit ATP5A and Complex IV activity. Despite the changes in mitochondrial physiology, hepatic ATP levels were maintained high in NCM-treated versus control rats. This was due to a decrease in ATP utilization and an increase in creatine kinase activity. Collectively, our results suggest that NCM treatment decreases hepatic cholesterol export, possibly also increases cholesterol uptake from circulation, and promotes lipid accumulation and alters ATP homeostasis which exacerbates the existing hepatic steatosis in genetically obese JCR rats with

  15. Exposure to a northern contaminant mixture (NCM) alters hepatic energy and lipid metabolism exacerbating hepatic steatosis in obese JCR rats.

    Science.gov (United States)

    Mailloux, Ryan J; Florian, Maria; Chen, Qixuan; Yan, Jin; Petrov, Ivan; Coughlan, Melanie C; Laziyan, Mahemuti; Caldwell, Don; Lalande, Michelle; Patry, Dominique; Gagnon, Claude; Sarafin, Kurtis; Truong, Jocelyn; Chan, Hing Man; Ratnayake, Nimal; Li, Nanqin; Willmore, William G; Jin, Xiaolei

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD), defined by the American Liver Society as the buildup of extra fat in liver cells that is not caused by alcohol, is the most common liver disease in North America. Obesity and type 2 diabetes are viewed as the major causes of NAFLD. Environmental contaminants have also been implicated in the development of NAFLD. Northern populations are exposed to a myriad of persistent organic pollutants including polychlorinated biphenyls, organochlorine pesticides, flame retardants, and toxic metals, while also affected by higher rates of obesity and alcohol abuse compared to the rest of Canada. In this study, we examined the impact of a mixture of 22 contaminants detected in Inuit blood on the development and progression of NAFLD in obese JCR rats with or without co-exposure to 10% ethanol. Hepatosteatosis was found in obese rat liver, which was worsened by exposure to 10% ethanol. NCM treatment increased the number of macrovesicular lipid droplets, total lipid contents, portion of mono- and polyunsaturated fatty acids in the liver. This was complemented by an increase in hepatic total cholesterol and cholesterol ester levels which was associated with changes in the expression of genes and proteins involved in lipid metabolism and transport. In addition, NCM treatment increased cytochrome P450 2E1 protein expression and decreased ubiquinone pool, and mitochondrial ATP synthase subunit ATP5A and Complex IV activity. Despite the changes in mitochondrial physiology, hepatic ATP levels were maintained high in NCM-treated versus control rats. This was due to a decrease in ATP utilization and an increase in creatine kinase activity. Collectively, our results suggest that NCM treatment decreases hepatic cholesterol export, possibly also increases cholesterol uptake from circulation, and promotes lipid accumulation and alters ATP homeostasis which exacerbates the existing hepatic steatosis in genetically obese JCR rats with or without co-exposure

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

    Science.gov (United States)

    Giordano, Gennaro; Afsharinejad, Zhara; Guizzetti, Marina; Vitalone, Annabella; Kavanagh, Terrance J; Costa, Lucio G

    2007-03-01

    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.

  17. Gestational exposure to diethylstilbestrol alters cardiac structure/function, protein expression and DNA methylation in adult male mice progeny

    Energy Technology Data Exchange (ETDEWEB)

    Haddad, Rami, E-mail: rami.haddad@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec, Canada H3A 1A2 (Canada); Kasneci, Amanda, E-mail: amanda.kasneci@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Mepham, Kathryn, E-mail: katherine.mepham@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec, Canada H3A 1A2 (Canada); Sebag, Igal A., E-mail: igal.sebag@mcgill.ca [Division of Cardiology, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); and others

    2013-01-01

    Pregnant women, and thus their fetuses, are exposed to many endocrine disruptor compounds (EDCs). Fetal cardiomyocytes express sex hormone receptors making them potentially susceptible to re-programming by estrogenizing EDCs. Diethylstilbestrol (DES) is a proto-typical, non-steroidal estrogen. We hypothesized that changes in adult cardiac structure/function after gestational exposure to the test compound DES would be a proof in principle for the possibility of estrogenizing environmental EDCs to also alter the fetal heart. Vehicle (peanut oil) or DES (0.1, 1.0 and 10.0 μg/kg/da.) was orally delivered to pregnant C57bl/6n dams on gestation days 11.5–14.5. At 3 months, male progeny were left sedentary or were swim trained for 4 weeks. Echocardiography of isoflurane anesthetized mice revealed similar cardiac structure/function in all sedentary mice, but evidence of systolic dysfunction and increased diastolic relaxation after swim training at higher DES doses. The calcium homeostasis proteins, SERCA2a, phospholamban, phospho-serine 16 phospholamban and calsequestrin 2, are important for cardiac contraction and relaxation. Immunoblot analyses of ventricle homogenates showed increased expression of SERCA2a and calsequestrin 2 in DES mice and greater molecular remodeling of these proteins and phospho-serine 16 phospholamban in swim trained DES mice. DES increased cardiac DNA methyltransferase 3a expression and DNA methylation in the CpG island within the calsequestrin 2 promoter in heart. Thus, gestational DES epigenetically altered ventricular DNA, altered cardiac function and expression, and reduced the ability of adult progeny to cardiac remodel when physically challenged. We conclude that gestational exposure to estrogenizing EDCs may impact cardiac structure/function in adult males. -- Highlights: ► Gestational DES changes cardiac SERCA2a and CASQ2 expression. ► Echocardiography identified systolic dysfunction and increased diastolic relaxation. ► DES

  18. 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.

  19. 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.

  20. Influenza virus-induced alterations of cytochrome P-450 enzyme activities following exposure of mice to coal and diesel particulates.

    Science.gov (United States)

    Rabovsky, J; Judy, D J; Rodak, D J; Petersen, M

    1986-06-01

    We have investigated a relationship between two detoxication systems, metabolic detoxication through the cytochrome P-450 (P-450) pathway and resistance to infection through interferon (IFN), in mice infected with influenza virus following exposure to coal dust (CD) and diesel exhaust (DE) particulates. Mice were exposed by inhalation to filtered air (FA; control), CD, or DE for 1 month and then inoculated intranasally (IN) with influenza virus. During infection, 7-ethoxycoumarin deethylase (7ECdeEt'ase) and ethylmorphine demethylase (EMdeMe'ase) (monooxygenases), and NADPH cytochrome c reductase (NADPH c red'ase) were measured in liver microsomes. Temporal patterns of enzyme activities were observed with control animals. EMdeMe'ase and NADPH c red'ase exhibited peak values at Day 4 postinfection (27.6 and 482 nmole/min/mg protein, respectively), compared to initial activities (9.1 and 307 nmole/min/mg protein, respectively). 7ECdeEt'ase activity decreased between Days 1-3 postvirus infection and thereafter returned to the original value (1.7 nmole/min/mg protein). When the mice were first exposed to CD or DE particulates for 1 month prior to influenza infection, changes in enzyme temporal patterns were observed. The increased EMdeMe'ase activity at Day 4 was not observed in mice exposed to CD and was reduced in mice exposed to DE. Preexposure to either particulate resulted in the abolition of the increased Day 4 activity of NADPH c red'ase. The 7ECdeEt'ase postinfection temporal pattern was not affected by a preexposure to either particulate. Estimates of the enzyme activities after the 1-month exposure to FA, CD, or DE but before virus infection indicated no changes due to particulate exposure alone. Under these conditions of particulate exposure and virus infection, serum IFN levels in the mice used in this study peaked at Days 4-5 and were unaffected by the 1-month preexposure to CD or DE (Hahon et al., (1985). The data suggest the relationship that exists

  1. Low-dose BPA exposure alters the mesenchymal and epithelial transcriptomes of the mouse fetal mammary gland.

    Directory of Open Access Journals (Sweden)

    Perinaaz R Wadia

    Full Text Available Exposure of rodent fetuses to low doses of the endocrine disruptor bisphenol A (BPA causes subtle morphological changes in the prenatal mammary gland and results in pre-cancerous and cancerous lesions during adulthood. To examine whether the BPA-induced morphological alterations of the fetal mouse mammary glands are a associated with changes in mRNA expression reflecting estrogenic actions and/or b dependent on the estrogen receptor α (ERα, we compared the transcriptomal effects of BPA and the steroidal estrogen ethinylestradiol (EE2 on fetal mammary tissues of wild type and ERα knock-out mice. Mammary glands from fetuses of dams exposed to vehicle, 250 ng BPA/kg BW/d or 10 ng EE2/kg BW/d from embryonic day (E 8 were harvested at E19. Transcriptomal analyses on the ductal epithelium and periductal stroma revealed altered expression of genes involved in the focal adhesion and adipogenesis pathways in the BPA-exposed stroma while genes regulating the apoptosis pathway changed their expression in the BPA-exposed epithelium. These changes in gene expression correlated with previously reported histological changes in matrix organization, adipogenesis, and lumen formation resulting in enhanced maturation of the fat-pad and delayed lumen formation in the epithelium of BPA-exposed fetal mammary glands. Overall similarities in the transcriptomal effects of BPA and EE2 were more pronounced in the epithelium, than in the stroma. In addition, the effects of BPA and EE2 on the expression of various genes involved in mammary stromal-epithelial interactions were suppressed in the absence of ERα. These observations support a model whereby BPA and EE2 act directly on the stroma, which expresses ERα, ERβ and GPR30 in fetal mammary glands, and that the stroma, in turn, affects gene expression in the epithelium, where ERα and ERβ are below the level of detection at this stage of development.

  2. Low-Dose BPA Exposure Alters the Mesenchymal and Epithelial Transcriptomes of the Mouse Fetal Mammary Gland

    Science.gov (United States)

    Wadia, Perinaaz R.; Cabaton, Nicolas J.; Borrero, Michael D.; Rubin, Beverly S.; Sonnenschein, Carlos; Shioda, Toshi; Soto, Ana M.

    2013-01-01

    Exposure of rodent fetuses to low doses of the endocrine disruptor bisphenol A (BPA) causes subtle morphological changes in the prenatal mammary gland and results in pre-cancerous and cancerous lesions during adulthood. To examine whether the BPA-induced morphological alterations of the fetal mouse mammary glands are a) associated with changes in mRNA expression reflecting estrogenic actions and/or b) dependent on the estrogen receptor α (ERα), we compared the transcriptomal effects of BPA and the steroidal estrogen ethinylestradiol (EE2) on fetal mammary tissues of wild type and ERα knock-out mice. Mammary glands from fetuses of dams exposed to vehicle, 250 ng BPA/kg BW/d or 10 ng EE2/kg BW/d from embryonic day (E) 8 were harvested at E19. Transcriptomal analyses on the ductal epithelium and periductal stroma revealed altered expression of genes involved in the focal adhesion and adipogenesis pathways in the BPA-exposed stroma while genes regulating the apoptosis pathway changed their expression in the BPA-exposed epithelium. These changes in gene expression correlated with previously reported histological changes in matrix organization, adipogenesis, and lumen formation resulting in enhanced maturation of the fat-pad and delayed lumen formation in the epithelium of BPA-exposed fetal mammary glands. Overall similarities in the transcriptomal effects of BPA and EE2 were more pronounced in the epithelium, than in the stroma. In addition, the effects of BPA and EE2 on the expression of various genes involved in mammary stromal-epithelial interactions were suppressed in the absence of ERα. These observations support a model whereby BPA and EE2 act directly on the stroma, which expresses ERα, ERβ and GPR30 in fetal mammary glands, and that the stroma, in turn, affects gene expression in the epithelium, where ERα and ERβ are below the level of detection at this stage of development. PMID:23704952

  3. 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)

  4. Paternal alcohol exposure in mice alters brain NGF and BDNF and increases ethanol-elicited preference in male offspring.

    Science.gov (United States)

    Ceccanti, Mauro; Coccurello, Roberto; Carito, Valentina; Ciafrè, Stefania; Ferraguti, Giampiero; Giacovazzo, Giacomo; Mancinelli, Rosanna; Tirassa, Paola; Chaldakov, George N; Pascale, Esterina; Ceccanti, Marco; Codazzo, Claudia; Fiore, Marco

    2016-07-01

    Ethanol (EtOH) exposure during pregnancy induces cognitive and physiological deficits in the offspring. However, the role of paternal alcohol exposure (PAE) on offspring EtOH sensitivity and neurotrophins has not received much attention. The present study examined whether PAE may disrupt nerve growth factor (NGF) and/or brain-derived neurotrophic factor (BDNF) and affect EtOH preference/rewarding properties in the male offspring. CD1 sire mice were chronically addicted for EtOH or administered with sucrose. Their male offsprings when adult were assessed for EtOH preference by a conditioned place preference paradigm. NGF and BDNF, their receptors (p75(NTR) , TrkA and TrkB), dopamine active transporter (DAT), dopamine receptors D1 and D2, pro-NGF and pro-BDNF were also evaluated in brain areas. PAE affected NGF levels in frontal cortex, striatum, olfactory lobes, hippocampus and hypothalamus. BDNF alterations in frontal cortex, striatum and olfactory lobes were found. PAE induced a higher susceptibility to the EtOH rewarding effects mostly evident at the lower concentration (0.5 g/kg) that was ineffective in non-PAE offsprings. Moreover, higher ethanol concentrations (1.5 g/kg) produced an aversive response in PAE animals and a significant preference in non-PAE offspring. PAE affected also TrkA in the hippocampus and p75(NTR) in the frontal cortex. DAT was affected in the olfactory lobes in PAE animals treated with 0.5 g/kg of ethanol while no differences were found on D1/D2 receptors and for pro-NGF or pro-BDNF. In conclusion, this study shows that: PAE affects NGF and BDNF expression in the mouse brain; PAE may induce ethanol intake preference in the male offspring. PMID:25940002

  5. Vinpocetine and Vitamin E Modulates Some Biochemical Alterations Induced by Exposure to Ionizing Radiation and Chloropyrifos in Rats

    International Nuclear Information System (INIS)

    Acapi-Cav is a well balanced and well tolerated formula containing vinpocetine and vitamin E. The objective of this study was to investigate the effect of vinpocetine and vitamin E on the oxidative stress, electrolytes and monoamines level in rats exposed to ionizing radiation (gamma rays), chloropyrifos (CPF) as well as rats exposed to a combination of gamma rays and CPF. Irradiation was performed by whole body exposure of rats to 8 Gy delivered at 1 Gy every 4 days. CPF was administered to rats by oral gavages at a dose of 3.6 mg/kg body weight ( 1/10 LD50 ) daily for 30 days. Vinpocetine and vitamin E were administered to rats by oral gavages at a dose of 20 mg/kg body weight daily during 7 days before starting the experiment and continued during the period of exposure to gamma rays and/or CPF. The results revealed significant increase of malondialdehyde (MDA) level associated with a significant decrease of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in the blood of rats exposed to gamma rays and/or CPF indicating oxidative stress. The levels of serum electrolytes (sodium Na+, potassium K+, calcium Ca++ and magnesium Mg) showed significant decrease. Serum dopamine (DA) level was decreased and norepinephrine (NE) was increased while epinephrine (EPI) showed non-significant change. The level of serum monoamine oxidase (MAO) showed significant increase. The administration of vinpocetine and vitamin E to rats exposed to gamma rays and/or CPF significantly reduced the amount of MDA which associated with an increase in the level of antioxidants and significant improvement was recorded for electrolytes level. The results demonstrated that vinpocetine and vitamin E significantly attenuated the increase of MAO and induced significant amelioration in the level of monoamines. It could be concluded that vinpocetine and vitamin E might protect the body from oxidative damage and electrolytes and monoamines alterations in rats exposed to gamma rays and

  6. Altered Gene Expressions and Cytogenetic Repair Efficiency in Cells with Suppressed Expression of XPA after Proton Exposure

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Gridley, Daila S.; Mehta, Satish K.; Pierson, Duane L.; Wu, Honglu

    2009-01-01

    Cellular responses to damages from ionizing radiation (IR) exposure are influenced not only by the genes involved in DNA double strand break (DSB) repair, but also by non- DSB repair genes. We demonstrated previously that suppressed expression of several non-DSB repair genes, such as XPA, elevated IR-induced cytogenetic damages. In the present study, we exposed human fibroblasts that were treated with control or XPA targeting siRNA to 250 MeV protons (0 to 4 Gy), and analyzed chromosome aberrations and expressions of genes involved in DNA repair. As expected, after proton irradiation, cells with suppressed expression of XPA showed a significantly elevated frequency of chromosome aberrations compared with control siRNA treated (CS) cells. Protons caused more severe DNA damages in XPA knock-down cells, as 36% cells contained multiple aberrations compared to 25% in CS cells after 4Gy proton irradiation. Comparison of gene expressions using the real-time PCR array technique revealed that expressions of p53 and its regulated genes in irradiated XPA suppressed cells were altered similarly as in CS cells, suggesting that the impairment of IR induced DNA repair in XPA suppressed cells is p53-independent. Except for XPA, which was more than 2 fold down regulated in XPA suppressed cells, several other DNA damage sensing and repair genes (GTSE1, RBBP8, RAD51, UNG and XRCC2) were shown a more than 1.5 fold difference between XPA knock-down cells and CS cells after proton exposure. The possible involvement of these genes in the impairment of DNA repair in XPA suppressed cells will be further investigated.

  7. Acute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II Diabetes

    Science.gov (United States)

    Abstract for Society of Toxicology, March 22-25, 2015, San Diego, CAAcute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II DiabetesS.J. Snow1,3, D. Miller2, V. Bass2, M. Schladweiler3, A. Ledbetter3, J. Richards3, C...

  8. 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.

  9. Prenatal drug exposure to illicit drugs alters working memory-related brain activity and underlying network properties in adolescence.

    Science.gov (United States)

    Schweitzer, Julie B; Riggins, Tracy; Liang, Xia; Gallen, Courtney; Kurup, Pradeep K; Ross, Thomas J; Black, Maureen M; Nair, Prasanna; Salmeron, Betty Jo

    2015-01-01

    The persistence of effects of prenatal drug exposure (PDE) on brain functioning during adolescence is poorly understood. We explored neural activation to a visuospatial working memory (VSWM) versus a control task using functional magnetic resonance imaging (fMRI) in adolescents with PDE and a community comparison group (CC) of non-exposed adolescents. We applied graph theory metrics to resting state data using a network of nodes derived from the VSWM task activation map to further explore connectivity underlying WM functioning. Participants (ages 12-15 years) included 47 adolescents (27 PDE and 20 CC). All analyses controlled for potentially confounding differences in birth characteristics and postnatal environment. Significant group by task differences in brain activation emerged in the left middle frontal gyrus (BA 6) with the CC group, but not the PDE group, activating this region during VSWM. The PDE group deactivated the culmen, whereas the CC group activated it during the VSWM task. The CC group demonstrated a significant relation between reaction time and culmen activation, not present in the PDE group. The network analysis underlying VSWM performance showed that PDE group had lower global efficiency than the CC group and a trend level reduction in local efficiency. The network node corresponding to the BA 6 group by task interaction showed reduced nodal efficiency and fewer direct connections to other nodes in the network. These results suggest that adolescence reveals altered neural functioning related to response planning that may reflect less efficient network functioning in youth with PDE.

  10. DNA content alterations in Tetrahymena pyriformis macronucleus after exposure to food preservatives sodium nitrate and sodium benzoate.

    Science.gov (United States)

    Loutsidou, Ariadni C; Hatzi, Vasiliki I; Chasapis, C T; Terzoudi, Georgia I; Spiliopoulou, Chara A; Stefanidou, Maria E

    2012-12-01

    The toxicity, in terms of changes in the DNA content, of two food preservatives, sodium nitrate and sodium benzoate was studied on the protozoan Tetrahymena pyriformis using DNA image analysis technology. For this purpose, selected doses of both food additives were administered for 2 h to protozoa cultures and DNA image analysis of T. pyriformis nuclei was performed. The analysis was based on the measurement of the Mean Optical Density which represents the cellular DNA content. The results have shown that after exposure of the protozoan cultures to doses equivalent to ADI, a statistically significant increase in the macronuclear DNA content compared to the unexposed control samples was observed. The observed increase in the macronuclear DNA content is indicative of the stimulation of the mitotic process and the observed increase in MOD, accompanied by a stimulation of the protozoan proliferation activity is in consistence with this assumption. Since alterations at the DNA level such as DNA content and uncontrolled mitogenic stimulation have been linked with chemical carcinogenesis, the results of the present study add information on the toxicogenomic profile of the selected chemicals and may potentially lead to reconsideration of the excessive use of nitrates aiming to protect public health.

  11. 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

  12. 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 ...

  13. Histological alterations under metal exposure in gills of European perch (Perca fluviatilis L. from Topolnitsa Reservoir (Bulgaria

    Directory of Open Access Journals (Sweden)

    Georgieva Еlenka

    2015-01-01

    Full Text Available Topolnitsa Reservoir is located in a region of Bulgaria rich in copper mines where intensive mining has been ongoing for several decades. General data on the ecological status of the reservoir and the effects of metal on fish is relatively scarce. The first aim of the study was to measure the concentrations of six metals (As, Cd, Cu, Ni, Pb and Zn in water samples and in the gills of European perch (Perca fluviatilis L.. The second objective was to examine gill structure and determine the severity of histological alteration as a result of metal exposure. Surface water and fish gill samples were collected in spring, summer and autumn in 2012 and metal and histological analyses were performed. Metal concentrations in the water samples varied, but only Cu concentrations were determined in all three seasons and they were higher than the maximum permissible levels. The gill metal concentrations were significantly higher (P<0.05 than in the water. Examination of gill structure revealed the presence of proliferative and degenerative changes, as well as changes in the blood vessels. Histological lesions were similar in their severity in all three seasons. This study provides the first information about metal effects on the morphology of European perch gills from Topolnitsa Reservoir. It can be concluded that the metal contamination of the Topolnitsa Reservoir and fish is chronic and that it can negatively affect the structure and function of fish gills. As metals display a tendency to accumulate in fish gills, their effects are expected to become more severe with time, as they affect gill functions.

  14. 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,...

  15. 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...

  16. Long-term alterations in vulnerability to addiction to drugs of abuse and in brain gene expression after early life ethanol exposure.

    Science.gov (United States)

    Barbier, Estelle; Pierrefiche, Olivier; Vaudry, David; Vaudry, Hubert; Daoust, Martine; Naassila, Mickaël

    2008-12-01

    Exposure to ethanol early in life can have long-lasting implications on brain function and drug of abuse response later in life. The present study investigated in rats, the long-term consequences of pre- and postnatal (early life) ethanol exposure on drug consumption/reward and the molecular targets potentially associated with these behavioral alterations. Since a relationship has been demonstrated between heightened drugs intake and susceptibility to drugs-induced locomotor activity/sensitization, anxiolysis, we tested these behavioral responses, depending on the drug, in control and early life ethanol-exposed animals. Our results show that progeny exposed to early life ethanol displayed increased consumption of ethanol solutions and increased sensitivity to cocaine rewarding effects assessed in the conditioned place preference test. Offspring exposed to ethanol were more sensitive to the anxiolytic effect of ethanol and the increased sensitivity could, at least in part, explain the alteration in the consumption of ethanol for its anxiolytic effects. In addition, the sensitivity to hypothermic effects of ethanol and ethanol metabolism were not altered by early life ethanol exposure. The sensitization to cocaine (20 mg/kg) and to amphetamine (1.2 mg/kg) was increased after early life ethanol exposure and, could partly explain, an increase in the rewarding properties of psychostimulants. Gene expression analysis revealed that expression of a large number of genes was altered in brain regions involved in the reinforcing effects of drugs of abuse. Dopaminergic receptors and transporter binding sites were also down-regulated in the striatum of ethanol-exposed offspring. Such long-term neurochemical alterations in transmitter systems and in the behavioral responses to ethanol and other drugs of abuse may confer an increased liability for addiction in exposed offspring. PMID:18713641

  17. Urinary biomarker concentrations of captan, chlormequat, chlorpyrifos and cypermethrin in UK adults and children living near agricultural land.

    Science.gov (United States)

    Galea, Karen S; MacCalman, Laura; Jones, Kate; Cocker, John; Teedon, Paul; Cherrie, John W; van Tongeren, Martie

    2015-01-01

    There is limited information on the exposure to pesticides experienced by UK residents living near agricultural land. This study aimed to investigate their pesticide exposure in relation to spray events. Farmers treating crops with captan, chlormequat, chlorpyrifos or cypermethrin provided spray event information. Adults and children residing ≤100 m from sprayed fields provided first-morning void urine samples during and outwith the spray season. Selected samples (1-2 days after a spray event and at other times (background samples)) were analysed and creatinine adjusted. Generalised Linear Mixed Models were used to investigate if urinary biomarkers of these pesticides were elevated after spray events. The final data set for statistical analysis contained 1518 urine samples from 140 participants, consisting of 523 spray event and 995 background samples which were analysed for pesticide urinary biomarkers. For captan and cypermethrin, the proportion of values below the limit of detection was greater than 80%, with no difference between spray event and background samples. For chlormequat and chlorpyrifos, the geometric mean urinary biomarker concentrations following spray events were 15.4 μg/g creatinine and 2.5 μg/g creatinine, respectively, compared with 16.5 μg/g creatinine and 3.0 μg/g creatinine for background samples within the spraying season. Outwith the spraying season, concentrations for chlorpyrifos were the same as those within spraying season backgrounds, but for chlormequat, lower concentrations were observed outwith the spraying season (12.3 μg/g creatinine). Overall, we observed no evidence indicative of additional urinary pesticide biomarker excretion as a result of spray events, suggesting that sources other than local spraying are responsible for the relatively low urinary pesticide biomarkers detected in the study population.

  18. [Thermodynamics adsorption and its influencing factors of chlorpyrifos and triazophos on the bentonite and humus].

    Science.gov (United States)

    Zhu, Li-Jun; Zhang, Wei; Zhang, Jin-Chi; Zai, De-Xin; Zhao, Rong

    2010-11-01

    The adsorption of chlorpyrifos and triazophos on bentonite and humus was investigated by using the equilibrium oscillometry. The adsorption capacity of chlorpyrifos and triazophos on humus was great higher than bentonite at the same concentration. Equilibrium data of Langmuir, Freundlich isotherms showed significant relationship to the adsorption of chlorpyrifos and triazophos on humus (chlorpyrifos: R2 0.996 4, 0.996 3; triazophos: R2 0.998 9, 0.992 4). Langmuir isotherm was the best for chlorpyrifos and triazophos on bentonite (chlorpyrifos: R2 = 0.995 7, triazophos: R2 = 0.998 9). The pH value, adsorption equilibrium time and temperature were the main factors affecting adsorption of chlorpyrifos and triazophos on bentonite and humus. The adsorption equilibrium time on mixed adsorbent was 12h for chlorpyrifos and 6h for triazophos respectively. The mass ratio of humus and bentonite was 12% and 14% respectively, the adsorption of chlorpyrifos and triazophos was the stronglest and tended to saturation. At different temperatures by calculating the thermodynamic parameters deltaG, deltaH and deltaS, confirmed that the adsorption reaction was a spontaneous exothermic process theoretically. The adsorption was the best when the pH value was 6.0 and the temperature was 15 degrees C.

  19. 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

  20. [Biodegradation mechanism of DDT and chlorpyrifos using molecular simulation].

    Science.gov (United States)

    Lin, Yu-Zhen; Zeng, Guang-Ming; Zhang, Yu; Chen, Ming; Jiang, Min; Zhang, Jia-Chao; Lu, Lun-Hui; Liu, Li-Feng

    2012-03-01

    In order to explore the microscopic degradation mechanism of organic pesticides degrading enzymes, we used molecular docking method to investigate the binding modes of DDT to laccase and chlorpyrifos to organophosphorus hydrolase, and obtained the corresponding complex structures. According to the principle of minimum scoring, the results showed that the MolDock scores were -103.134 and -111.626, re-rank scores were -72.858 and -80.261, respectively. And we used LPC/CSU server search the interactions between organic pesticides and their degrading enzymes. Our results showed that hydrophobic interaction was the strongest contacts in DDT-laccase complex, and both hydrogen bonds and hydrophobic interactions were the strongest contacts when chlorpyrifos-organophosphorus hydrolase complex. The amino acid residues Tyr224 in laccase and Arg254 in organophosphorus hydrolase were detected to play significant roles in catalytic processes.

  1. Chlorpyrifos Detection by Piezoelectric Biosensor Based on Acetylcholinesterase Immobilization

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Acetylcholinesterase (AChE) was immobilized on multilayer films assembled by poly diallyldimethylammonium chloride (PDDA) and ι-carrageenan (IC) on silver-coated crystal electrode surfaces to detect the chlorpyrifos belonging to the organophosphates pesticide.Mass sensitive quartz crystal microbalance (QCM) was used to study the effect of AChE concentration and pH of phosphate buffer solution on immobilized acetylcholinesterase.The optimized conditions were as follows: pH was 6.0 which was near isoelectric ...

  2. 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)

  3. Prenatal exposure to moderate levels of ethanol alters social behavior in adult rats: Relationship to structural plasticity and immediate early gene expression in frontal cortex

    OpenAIRE

    Derek A Hamilton; Akers, Katherine G.; Rice, James P.; Johnson, Travis E.; Candelaria-Cook, Felicha T.; Maes, Levi I.; Rosenberg, Martina; Valenzuela, C. Fernando; Savage, Daniel D.

    2009-01-01

    The goals of the present study were to characterize the effects of prenatal exposure to moderate levels of ethanol on adult social behavior, and to evaluate fetal-ethanol-related effects on dendritic morphology, structural plasticity and activity-related immediate early gene (IEG) expression in the agranular insular (AID) and prelimbic (Cg3) regions of frontal cortex. Baseline fetal-ethanol-related alterations in social behavior were limited to reductions in social investigation in males. Rep...

  4. Contamination of fresh water fish “Schizothorax niger” with chlorpyrifos from “Dal Lake” basins, India

    Directory of Open Access Journals (Sweden)

    Banday Muddasir

    2012-12-01

    Full Text Available Dal Lake a Sub-Himalyan urban Lake is one of the most beautiful lakes of India and second largest in Jammu & Kashmir. Intensive farming practiced in the surrounding area of Dal Lake and its floating gardensleads to an enhanced vulnerability of crops to pests and indiscriminate use of pesticides. Possible transfer of these hazardous molecules from vegetable fields to the aquatic environment of the Lake, poses a potential threat to the aquatic species and human health as well. In the present investigation conducted from 2008 to 2010, 135 samples of fish including 81 samples of schizothorax niger ( Algaad / Kasheer Gaad and 54 samples of Cyprinus carpii (Punjab Gaad were collected from three basins of Dal Lake namely Hazratbal, Nigeen and Cheshmashahi basin. The samples were analyzed for seven commonly used pesticides viz. Butachlor, γHCH,Chlorpyrifos, Hexaconazole, Endosulfan 1, Endosulfan 2 and Dichlorvas. Detection and quantification of pesticide residues was performed by GC-MS/MS (Thermofinnigan Polaris Q type equipped with Ni ECD. It was found that 73 samples (54.07% out of 135 were contaminated with chlorpyrifos an organophosphate pesticide with mean concentration of (0.0009 ± 0.0010ng/kg with concentration ranging from undetected to 0.003ng/kg. The highest concentration was found in Hazratbal basin in 2009 (0.002 ± 0.001ng/kg. The results also reveal that level of pesticide was higher in pesticide use season than non use season except in 2009 when levels were same. With respect to basins the results show that mean concentration of chlorpyrifos level was higher in pesticide application season than non application season except in Nigeen basin in 2008 and 2009 where levels were same (0.001±0.001ng/kg and in Hazratbal basin in 2010 where levels were same (0.001±0.001ng/kg. The results indicate a sub acute exposure of chlorpyrifos in a locally consumed Schizothorax niger and not in Cyprinus carpii. These findings suggest that low dose

  5. Altered mRNA editing and expression of ionotropic glutamate receptors after kainic acid exposure in cyclooxygenase-2 deficient mice.

    Directory of Open Access Journals (Sweden)

    Luca Caracciolo

    Full Text Available Kainic acid (KA binds to the AMPA/KA receptors and induces seizures that result in inflammation, oxidative damage and neuronal death. We previously showed that cyclooxygenase-2 deficient (COX-2(-/- mice are more vulnerable to KA-induced excitotoxicity. Here, we investigated whether the increased susceptibility of COX-2(-/- mice to KA is associated with altered mRNA expression and editing of glutamate receptors. The expression of AMPA GluR2, GluR3 and KA GluR6 was increased in vehicle-injected COX-2(-/- mice compared to wild type (WT mice in hippocampus and cortex, whereas gene expression of NMDA receptors was decreased. KA treatment decreased the expression of AMPA, KA and NMDA receptors in the hippocampus, with a significant effect in COX-2(-/- mice. Furthermore, we analyzed RNA editing levels and found that the level of GluR3 R/G editing site was selectively increased in the hippocampus and decreased in the cortex in COX-2(-/- compared with WT mice. After KA, GluR4 R/G editing site, flip form, was increased in the hippocampus of COX-2(-/- mice. Treatment of WT mice with the COX-2 inhibitor celecoxib for two weeks decreased the expression of AMPA/KA and NMDAR subunits after KA, as observed in COX-2(-/- mice. After KA exposure, COX-2(-/- mice showed increased mRNA expression of markers of inflammation and oxidative stress, such as cytokines (TNF-α, IL-1β and IL-6, inducible nitric oxide synthase (iNOS, microglia (CD11b and astrocyte (GFAP. Thus, COX-2 gene deletion can exacerbate the inflammatory response to KA. We suggest that COX-2 plays a role in attenuating glutamate excitotoxicity by modulating RNA editing of AMPA/KA and mRNA expression of all ionotropic glutamate receptor subunits and, in turn, neuronal excitability. These changes may contribute to the increased vulnerability of COX-2(-/- mice to KA. The overstimulation of glutamate receptors as a consequence of COX-2 gene deletion suggests a functional coupling between COX-2 and the

  6. Lead Exposure during Synaptogenesis Alters Vesicular Proteins and Impairs Vesicular Release: Potential Role of NMDA Receptor–Dependent BDNF Signaling

    OpenAIRE

    Neal, April P.; Stansfield, Kirstie H.; Worley, Paul F.; Thompson, Richard E.; Guilarte, Tomás R.

    2010-01-01

    Lead (Pb2+) exposure is known to affect presynaptic neurotransmitter release in both in vivo and cell culture models. However, the precise mechanism by which Pb2+ impairs neurotransmitter release remains unknown. In the current study, we show that Pb2+ exposure during synaptogenesis in cultured hippocampal neurons produces the loss of synaptophysin (Syn) and synaptobrevin (Syb), two proteins involved in vesicular release. Pb2+ exposure also increased the number of presynaptic contact sites. H...

  7. Multi-generational effects of polybrominated diphenylethers exposure: embryonic exposure of male American kestrels (Falco sparverius) to DE-71 alters reproductive success and behaviors.

    Science.gov (United States)

    Marteinson, Sarah C; Bird, David M; Shutt, J Laird; Letcher, Robert J; Ritchie, Ian J; Fernie, Kim J

    2010-08-01

    Polybrominated diphenylethers (PBDEs) are additive flame-retardants that are environmentally persistent and bioaccumulative compounds of particular concern to species at high trophic levels, including predatory birds. The developmental effects of in ovo exposure to male birds at environmentally relevant levels of the PBDE technical mixture, DE-71, on reproductive success and behaviors using captive American kestrels (Falco sparverius) were determined. Males were exposed in ovo by direct maternal transfer to DE-71 and unintentionally to low concentrations of hexabromocyclododecane (HBCD) at three mean +/- standard error DE-71 concentrations of 288.60 +/- 33.35 ng/g wet weight (low-exposure), 1130.59 +/- 95.34 ng/g wet weight (high-exposure), or background levels of 3.01 +/- 0.46 ng/g wet weight (control). One year following exposure, males were paired with unexposed females. Reproductive success was lower in the high exposure pairs: 43% failed to lay eggs while all other pairs laid complete clutches; they also laid smaller clutches and produced smaller eggs with reduced fertility, parameters that were negatively correlated with paternal in ovo concentrations of all PBDEs, as well as individual congeners and HBCD. Throughout courtship, there were fewer copulations by all in ovo exposed males, fewer mate-calls made by high-exposure males, and decreasing trends in pair-bonding and nest-box behaviors across treatments that continued during brood rearing. The reductions in clutch size and fertility were associated with the reduced frequencies of male courtship behaviors, and were associated with increasing concentrations of the PBDE congeners BDE-47, -99, -100, -53, -138, and HBCD. The results of the present study confirm effects noted in the F(0) generation and demonstrate that exposure to DE-71 affects multiple generations of this predatory avian species at environmentally relevant levels of exposure. PMID:20821627

  8. Effects of cerium dioxide nanoparticles in Oncorhynchus mykiss liver after an acute exposure: assessment of oxidative stress, genotoxicity and histological alterations

    Directory of Open Access Journals (Sweden)

    Ana Cristina Nunes

    2015-12-01

    Full Text Available At present cerium oxide nanoparticles (CeO2 NP have numerous applications ranging from industry to the household, leading to its wide distribution namely in the aquatic environment. The hereby study aimed to assess the toxic effects of CeO2 NPs in Oncorhynchus mykiss liver following an acute exposure (96h to three different concentrations (0.25, 2.5 and 25 mg/L in terms of the genotoxicity (comet assay, oxidative stress response (Catalase CAT; Glutathione S-Transferases GSTs; Thiobarbituric Acid Reactive Substances TBARS and histopathology. CeO2 NP exposure resulted in genotoxic damage in all exposure treatments, inhibition of CAT in the highest concentration and histopathological changes in all exposure concentrations with predominance of progressive and circulatory alterations. However TBARS and GSTs showed no significant differences comparatively to the control (unexposed group. The results suggest that CeO2 NP are able to cause genotoxicity, biochemical impairment and histological alterations in the liver of rainbow trout.

  9. In utero and lactational exposure to PCB 118 and PCB 153 alter ovarian follicular dynamics and GnRH-induced luteinizing hormone secretion in female lambs

    DEFF Research Database (Denmark)

    Kraugerud, Marianne; Aleksandersen, Mona; Nyengaard, Jens Randel;

    2012-01-01

    The effects of in utero and lactational exposure to two structurally different polychlorinated biphenyl (PCB) congeners on follicular dynamics and the pituitary-gonadal axis in female lambs were investigated. Pregnant ewes received corn oil, PCB 118, or PCB 153, and offspring was maintained until...... dynamics in lambs and modulate the responsiveness of the pituitary gland to GnRH.The effects of in utero and lactational exposure to two structurally different polychlorinated biphenyl (PCB) congeners on follicular dynamics and the pituitary-gonadal axis in female lambs were investigated. Pregnant ewes...... exposure group. We conclude that PCB 153 and PCB 118 alter follicular dynamics in lambs and modulate the responsiveness of the pituitary gland to GnRH....

  10. Exposure to cypermethrin and mancozeb alters the expression profile of THBS1, SPP1, FEZ1 and GPNMB in human peripheral blood mononuclear cells.

    Science.gov (United States)

    Mandarapu, Rajesh; Prakhya, Balakrishna Murthy

    2016-07-01

    The complex immune system displays a coordinated transcriptional response to xenobiotic exposure by altering expression of designated transcription factors that, in turn, trigger immune responses. Despite the identification of several transcription factors that contribute to regulatory response, very little is known about the specific role of factors that are triggered due to exposure to obnoxious pesticides. Here, for the first time, alterations in human peripheral blood lymphocyte expression of transcriptional factors - thrombospondin-1 (THBS-1), secretory phospho-protein-1 (SPP-1), glycoprotein non-metastatic-β (GPNMB) and fasciculation and elongation factor ζ-1 (FEZ-1), due to in vitro exposure to the crop protection chemicals cypermethrin and mancozeb are reported. Results revealed significant changes in expression profiles due to mancozeb exposure, supporting its immune dysfunction potential; in contrast, cypermethrin exposure did not cause significant changes. Based on these effects on gene expression across the doses tested, it was likely key components of immune mechanisms such as proliferation, cell adhesion, apoptosis and cell activation in human PBMC were affected. Although these data are from in vitro experiments, the results point out the potential role for changes in these factors in the etiology of defective T-cell immune function seen in humans occupationally exposed to crop protection chemicals like mancozeb. These studies suggest the involvement of transcription factors in regulation of pesticide-induced immune dysfunction; these studies also represent a novel approach for identifying potential immune-related dysfunctions due to exposure to pesticides. Further studies are needed to better understand the functional significance of these in vitro findings. PMID:26796295

  11. Combined Inhaled Diesel Exhaust Particles and Allergen Exposure Alter Methylation of T Helper Genes and IgE Production In Vivo

    Science.gov (United States)

    Liu, Jinming; Ballaney, Manisha; Al-alem, Umaima; Quan, Chunli; Jin, Ximei; Perera, Frederica; Chen, Lung-Chi; Miller, Rachel L.

    2008-01-01

    Changes in methylation of CpG sites at the interleukin (IL)-4 and interferon (IFN)-γ promoters are associated with T helper (Th) 2 polarization in vitro. No previous studies have examined whether air pollution or allergen exposure alters methylation of these two genes in vivo. We hypothesized that diesel exhaust particles (DEP) would induce hypermethylation of the IFN-γ promoter and hypomethylation of IL-4 in CD4+ T cells among mice sensitized to the fungus allergen Aspergillus fumigatus.We also hypothesized that DEP-induced methylation changes would affect immunoglobulin (Ig) E regulation. BALB/c mice were exposed to a 3-week course of inhaled DEP exposure while undergoing intranasal sensitization to A. fumigatus. Purified DNA from splenic CD4+ cells underwent bisulfite treatment, PCR amplification, and pyrosequencing. Sera IgE levels were compared with methylation levels at several CpG sites in the IL-4 and IFN-γ promoter. Total IgE production was increased following intranasal sensitization A. fumigatus. IgE production was augmented further following combined exposure to A. fumigatus and DEP exposure. Inhaled DEP exposure and intranasal A. fumigatus induced hypermethylation at CpG−45, CpG−53, CpG−205 sites of the IFN-γ promoter and hypomethylation at CpG−408 of the IL-4 promoter. Altered methylation of promoters of both genes was correlated significantly with changes in IgE levels. This study is the first to demonstrate that inhaled environmental exposures influence methylation of Th genes in vivo, supporting a new paradigm in asthma pathogenesis. PMID:18042818

  12. 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

  13. Amygdala kindling in immature rats: proconvulsant effect of the organophosphate insecticide-chlorpyrifos.

    Science.gov (United States)

    Wurpel, J N; Hirt, P C; Bidanset, J H

    1993-01-01

    Administration of the organophosphate insecticide, chlorpyrifos to immature rats exerted a proconvulsant effect on seizures induced by kindling. Chlorpyrifos was administered to 16 or 17 day old rats in a dose range of 0.3 to 10 mg/kg, subcutaneously. Amygdala kindling was performed by stimulating the rats every 15 minutes to a total of 20 stimulations. Kindling occurred more rapidly in the chlorpyrifos treated rats than vehicle treated rats, the proconvulsant effect was dose-dependent. The proconvulsant effect of chlorpyrifos was more pronounced in the early stages of kindling, indicating a possible increase in local excitability of the amygdala in the presence of chlorpyrifos. Chlorpyrifos also reduced the after discharge threshold in the amygdala in a dose-dependent manner and increased the duration of after discharges elicited by electrical stimulus, indicating an increase in excitability of the amygdala. The effects of chlorpyrifos on kindling were additive with xylene: the proconvulsant effect in the early stages of kindling was greatly enhanced by xylene. Xylene, administered alone as a 0.2% solution, reduced the after discharge threshold of the amygdala, increased the after discharge duration and increased the rate of kindling. These experiments demonstrate a proconvulsant effect of chlorpyrifos in amygdala kindling and this proconvulsant action is additive with xylene.

  14. 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.

  15. 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

  16. Novel molecular events associated with altered steroidogenesis induced by exposure to atrazine in the intact and castrate male rat

    Science.gov (United States)

    Toxicology is increasingly focused on molecular events comprising adverse outcome pathways. Atrazine activates the hypothalamic-pituitary adrenal axis, but relationships to gonadal alterations are unknown. We characterized hormone profiles and adrenal (intact and castrate) and te...

  17. Enhanced Negative Emotion and Alcohol Craving, and Altered Physiological Responses Following Stress and Cue Exposure in Alcohol Dependent Individuals

    OpenAIRE

    Sinha, Rajita; Fox, Helen C.; Hong, Kwangik A.; Bergquist, Keri; Bhagwagar, Zubin; Siedlarz, Kristen M.

    2008-01-01

    Chronic alcohol abuse is associated with changes in stress and reward pathways that could alter vulnerability to emotional stress and alcohol craving. This study examines whether chronic alcohol abuse is associated with altered stress and alcohol craving responses. Treatment-engaged, 28-day abstinent alcohol-dependent individuals (ADs; 6F/22M), and social drinkers (SDs; 10F/18M) were exposed to a brief guided imagery of a personalized stressful, alcohol-related and neutral-relaxing situation,...

  18. 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

  19. Vitamin E Mitigates Chronic Chlorpyrifos-Induced Oxidative Changes in Pituitary Glands and Testes in Wistar Rats

    Directory of Open Access Journals (Sweden)

    M. Shittu

    2012-01-01

    Full Text Available Problem statement: The sperm counts of men have declined by about 50% in the last few decades. The contribution of environmental contaminants to this decline cannot be overemphasized. Pesticide is one of the most pervasive environmental chemical contaminants that have been of increased use due to the compelling need to feed the ever-growing world human and animal population and protect their health. Chlorpyrifos (CPF, a widely used Organophosphate (OP insecticide has been reported to alter male reproductive hormones and semen characteristics. Apart from acetyl cholinesterase inhibition, the induction of oxidative stress is one of the molecular mechanisms implicated in CPF poisoning. Approach: The present study was aimed at evaluating the effect of vitamin E in mitigating oxidative damage to the pituitary gland and the testis, induced by chronic CPF administration in Wistar rats. Methodology: Twenty adult male Wistar rats divided into 4 groups of 5 rats in each group were used for this study. Group I received soya oil (2 mL kg-1, while Group II was administered vitamin E (75 mg kg-1; Group III was administered CPF only (10.6 mg kg-1~1/8th LD50, while group IV was pretreated with vitamin E (75 mg kg-1 and exposed to CPF (10.6 mg kg-1 30 min later. The regimens were administered orally by gavages once daily for a period of 15 weeks. At the end of the treatment period, the rats were sacrificed and the pituitary glands and testicular tissues were assayed for the concentrations of Malonaldehyde (MDA and the activities of Superoxide Dismutase (SOD and Catalane (CAT. Results: The result showed that the increase in concentrations of pituitary and testicular MDA and a decrease in the activities of SOD and CAT recorded in the group exposed to CPF were ameliorated by pretreatment with vitamin E. Conclusion: This indicates that vitamin E mitigates reproductive toxicity induced by chronic CPF exposure due to its protective antioxidant activity on pituitary

  20. 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

  1. GESTATIONAL PFOA EXPOSURE OF MICE IS ASSOCIATED WITH ALTERED MAMMARY GLAND DEVELOPMENT IN DAMS AND FEMALE OFFSPRING

    Science.gov (United States)

    Perfluorooctanoic acid (PFOA), with diverse and widespread commercial and industrial applications, has been detected in human and wildlife sera. Previous mouse studies linked prenatal PFOA exposure to decreased neonatal body weights (BWs) and survival in a dose-dependent manner. ...

  2. 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

  3. Postnatal exposure to trichloroethylene alters glutathione redox homeostasis, methylation potential, and neurotrophin expression in the mouse hippocampus

    OpenAIRE

    Blossom, Sarah J.; Melnyk, Stepan; Cooney, Craig A.; Gilbert, Kathleen M.; James, S. Jill

    2012-01-01

    Previous studies have shown that continuous exposure throughout gestation until the juvenile period to environmentally-relevant doses of trichloroethylene (TCE) in the drinking water of MRL+/+ mice promoted adverse behavior associated with glutathione depletion in the cerebellum indicating increased sensitivity to oxidative stress. The purpose of this study was to extend our findings and further characterize the impact of TCE exposure on redox homeostasis and biomarkers of oxidative stress in...

  4. Histomorphological and Histochemical Alterations Following Short-term Inhalation Exposure to Sulfur Mustard on Visceral Organs of Mice

    Institute of Scientific and Technical Information of China (English)

    S. C. PANT; R. VIJAYARAGHAVAN

    1999-01-01

    Toxic effects of inhaled sulfur mustard (SM) on the histology of visceral organs was investigated by exposing mice to 84.6mg/m3 for 1 h duration, using controlled single exposure conditions. A progressive fall in body weight from third day onwards was noticed. Light microscopic examination of the pulmonary tissue of these animals at 6 h post exposure revealed that the tracheobronchial epithelium remained intact, but was infiltrated by inflammatorv cells. By 24 h post exposure, the mucosecretory cells were destroyed. The inflammatory reaction was maximum at 48 h. Bv 7th day post exposure there was swelling and vacuolation of lung parenchymal cells and thrombi formation. In addition SM caused congestion and hemorrhage at alveolar level. SM also caused granulovacuolar degeneration with perinuclear clumping of the cytoplasm of hepatocytes and renal parenchymal cells. Renal lesions were characterized by congestion and hemorrhage. Among visceral tissues, maximum atrophy was observed in spleen. Distribution of lesions increased with post exposure period. The maximum lesions were observed at 7th day post-exposure.

  5. Long-term signal of population disturbance after pulse exposure to an insecticide: rapid recovery of abundance, persistent alteration of structure.

    Science.gov (United States)

    Liess, Matthias; Pieters, Barry Johan; Duquesne, Sabine

    2006-05-01

    Little is known about the effect of pulse exposure to toxicants on populations when density regulation is present. Yet, for a more realistic risk assessment, it is necessary to include effect and recovery at the population level. Here, we investigate the long-term and delayed effects as well as the subsequent recovery of populations of Daphnia magna. A 24-h pulse of the pyrethroid fenvalerate reduced the abundance at a concentration of 1.0 microg/L and higher. However, abundance recovered and reached control levels after one to two generation times (GTs) following reproduction of surviving individuals (GT = 8 d, from birth until first reproduction). At high concentrations above the acute median lethal concentration (3.2 micorg/L), abundance initially decreased even more strongly but was then elevated compared to control values for an extended period of time. Population structure (size distribution) was affected at lower concentrations than abundance (> 0.8 microg/L). In addition, the alteration of population structure lasted for a long time, so that control levels were approached only after approximately six or seven GTs. Our results show that pulse exposure to toxicants may lead to a long-term alteration of population structure even at sublethal concentrations. Possible mechanisms that sustain the effects of toxicants may be delayed life-history effects on the individual level and elevated competition because of altered population structure on the population level. PMID:16704065

  6. Exposure to the Contraceptive Progestin, Gestodene, Alters Reproductive Behavior, Arrests Egg Deposition, and Masculinizes Development in the Fathead Minnow (Pimephales promelas).

    Science.gov (United States)

    Frankel, Tyler E; Meyer, Michael T; Kolpin, Dana W; Gillis, Amanda B; Alvarez, David A; Orlando, Edward F

    2016-06-01

    Endogenous progestogens and pharmaceutical progestins enter the environment through wastewater treatment plant effluent and agricultural field runoff. Lab studies demonstrate strong, negative exposure effects of these chemicals on aquatic vertebrate reproduction. Behavior can be a sensitive, early indicator of exposure to environmental contaminants associated with altered reproduction yet is rarely examined in ecotoxicology studies. Gestodene is a human contraceptive progestin and a potent activator of fish androgen receptors. Our objective was to test the effects of gestodene on reproductive behavior and associated egg deposition in the fathead minnow. After only 1 day, males exposed to ng/L of gestodene were more aggressive and less interested in courtship and mating, and exposed females displayed less female courtship behavior. Interestingly, 25% of the gestodene tanks contained a female that drove the male out of the breeding tile and displayed male-typical courtship behaviors toward the other female. Gestodene decreased or arrested egg deposition with no observed gonadal histopathology. Together, these results suggest that effects on egg deposition are primarily due to altered reproductive behavior. The mechanisms by which gestodene disrupts behavior are unknown. Nonetheless, the rapid and profound alterations of the reproductive biology of gestodene-exposed fish suggest that wild populations could be similarly affected. PMID:27129041

  7. 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.

  8. Secondhand tobacco smoke exposure differentially alters nucleus tractus solitarius neurons at two different ages in developing non-human primates

    International Nuclear Information System (INIS)

    Exposing children to secondhand tobacco smoke (SHS) is associated with increased risk for asthma, bronchiolitis and SIDS. The role for changes in the developing CNS contributing to these problems has not been fully explored. We used rhesus macaques to test the hypothesis that SHS exposure during development triggers neuroplastic changes in the nucleus tractus solitarius (NTS), where lung sensory information related to changes in airway and lung function is first integrated. Pregnant monkeys were exposed to filtered air (FA) or SHS for 6 h/day, 5 days/week starting at 50-day gestational age. Mother/infant pairs continued the exposures postnatally to age 3 or 13 months, which may be equivalent to approximately 1 or 4 years of human age, respectively. Whole-cell recordings were made of second-order NTS neurons in transverse brainstem slices. To target the consequences of SHS exposure based on neuronal subgroups, we classified NTS neurons into two phenotypes, rapid-onset spiking (RS) and delayed-onset spiking (DS), and then evaluated intrinsic and synaptic excitabilities in FA-exposed animals. RS neurons showed greater cell excitability especially at age of 3 months while DS neurons received greater amplitudes of excitatory postsynaptic currents (EPSCs). Developmental neuroplasticity such as increases in intrinsic and synaptic excitabilities were detected especially in DS neurons. In 3 month olds, SHS exposure effects were limited to excitatory changes in RS neurons, specifically increases in evoked EPSC amplitudes and increased spiking responses accompanied by shortened action potential width. By 13 months, the continued SHS exposure inhibited DS neuronal activity; decreases in evoked EPSC amplitudes and blunted spiking responses accompanied by prolonged action potential width. The influence of SHS exposure on age-related and phenotype specific changes may be associated with age-specific respiratory problems, for which SHS exposure can increase the risk, such as SIDS

  9. BPA exposure during in vitro oocyte maturation results in dose-dependent alterations to embryo development rates, apoptosis rate, sex ratio and gene expression.

    Science.gov (United States)

    Ferris, Jacqueline; Mahboubi, Kiana; MacLusky, Neil; King, W Allan; Favetta, Laura A

    2016-01-01

    Alterations in the oocyte's environment can negatively affect embryo development. Oocyte quality, which can determine embryonic viability, is easily perturbed, thus factors affecting normal oocyte maturation are a concern. Bisphenol A (BPA) is an endocrine disrupting chemical that elicits a variety of reproductive effects. BPA has previously been found to disrupt meiosis, however the embryonic effects in mammals are not well documented. Here, bovine oocytes were matured in vitro with and without BPA treatment. Resulting embryos exhibited decreased embryonic development rates, increased apoptosis, and a skewed sex ratio. Gene expression in blastocysts was not altered, whereas treatment with 15ng/mL BPA resulted in increased expression of several of the genes studies, however this increase was largely due to a vehicle effect. BPA exposure during oocyte maturation in vitro can therefore, in a dose-dependent way, decrease oocyte and embryo quality and developmental potential and affect gene expression of developmentally important transcripts. PMID:26686065

  10. Alterations along the Hypothalamic-Pituitary-Thyroid Axis of the Zebrafish (Danio rerio after Exposure to Propylthiouracil

    Directory of Open Access Journals (Sweden)

    Florian Schmidt

    2011-01-01

    Full Text Available In the past, various approaches have been developed to detect adverse effects of pollutants on the thyroid of vertebrates, most of these with special emphasis on the South African clawed frog, Xenopus laevis. Although fish are primarily affected by thyroid-disrupting chemicals, studies into alterations of the thyroid of fish are scarce. Therefore, effects of the reference compound propylthiouracil on histopathology of the thyroid axis were analyzed in a modified early life-stage test with zebrafish (Danio rerio exposed to propylthiouracil. The test substance induced dose-dependent alterations of thyroidal tissue concomitant with increases in the number of surrounding blood vessels. Despite this massive proliferation of the thyroid, zebrafish were not able to maintain thyroxin concentrations. The pituitary was affected displaying significant alterations in thyroid-stimulating hormone cell counts. Quantitative evaluation of pituitary surface areas revealed a dose-dependent increase of adenohypophyseal tissue. Distinct histopathological effects may contribute to a more easy identification and interpretation of alterations induced by thyroid-disrupting chemicals.

  11. Developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters DNA methyltransferase (dnmt) expression in zebrafish (Danio rerio)

    International Nuclear Information System (INIS)

    DNA methylation is one of the most important epigenetic modifications involved in the regulation of gene expression. The DNA methylation reaction is catalyzed by DNA methyltransferases (DNMTs). Recent studies have demonstrated that toxicants can affect normal development by altering DNA methylation patterns, but the mechanisms of action are poorly understood. Hence, we tested the hypothesis that developmental exposure to TCDD affects dnmt gene expression patterns. Zebrafish embryos were exposed to 5 nM TCDD for 1 h from 4 to 5 h post-fertilization (hpf) and sampled at 12, 24, 48, 72, and 96 hpf to determine dnmt gene expression and DNA methylation patterns. We performed a detailed analysis of zebrafish dnmt gene expression during development and in adult tissues. Our results demonstrate that dnmt3b genes are highly expressed in early stages of development, and dnmt3a genes are more abundant in later stages. TCDD exposure upregulated dnmt1 and dnmt3b2 expression, whereas dnmt3a1, 3b1, and 3b4 are downregulated following exposure. We did not observe any TCDD-induced differences in global methylation or hydroxymethylation levels, but the promoter methylation of aryl hydrocarbon receptor (AHR) target genes was altered. In TCDD-exposed embryos, AHR repressor a (ahrra) and c-fos promoters were differentially methylated. To characterize the TCDD effects on DNMTs, we cloned the dnmt promoters with xenobiotic response elements and conducted AHR transactivation assays using a luciferase reporter system. Our results suggest that ahr2 can regulate dnmt3a1, dnmt3a2, and dnmt3b2 expression. Overall, we demonstrate that developmental exposure to TCDD alters dnmt expression and DNA methylation patterns. - Highlights: • TCDD altered the dnmt expression in a gene and developmental time-specific manner. • TCDD hypermethylated ahrra and hypomethylated c-fos proximal promoter regions. • Functional analysis suggests that ahr2 can regulate dnmt3a1, 3a2, and 3b2 expression. • Dnmt

  12. Developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters DNA methyltransferase (dnmt) expression in zebrafish (Danio rerio)

    Energy Technology Data Exchange (ETDEWEB)

    Aluru, Neelakanteswar, E-mail: naluru@whoi.edu [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Kuo, Elaine [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Stanford University, 450 Serra Mall, Stanford, CA 94305 (United States); Helfrich, Lily W. [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Northwestern University, 633 Clark St, Evanston, IL 60208 (United States); Karchner, Sibel I. [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Linney, Elwood A. [Department of Molecular Genetics and Microbiology, Duke University Medical Center, Box 3020, Durham, NC 27710 (United States); Pais, June E. [New England Biolabs, 240 County Road, Ipswich, MA 01938 (United States); Franks, Diana G. [Biology Department and Woods Hole Center for Oceans and Human Health, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States)

    2015-04-15

    DNA methylation is one of the most important epigenetic modifications involved in the regulation of gene expression. The DNA methylation reaction is catalyzed by DNA methyltransferases (DNMTs). Recent studies have demonstrated that toxicants can affect normal development by altering DNA methylation patterns, but the mechanisms of action are poorly understood. Hence, we tested the hypothesis that developmental exposure to TCDD affects dnmt gene expression patterns. Zebrafish embryos were exposed to 5 nM TCDD for 1 h from 4 to 5 h post-fertilization (hpf) and sampled at 12, 24, 48, 72, and 96 hpf to determine dnmt gene expression and DNA methylation patterns. We performed a detailed analysis of zebrafish dnmt gene expression during development and in adult tissues. Our results demonstrate that dnmt3b genes are highly expressed in early stages of development, and dnmt3a genes are more abundant in later stages. TCDD exposure upregulated dnmt1 and dnmt3b2 expression, whereas dnmt3a1, 3b1, and 3b4 are downregulated following exposure. We did not observe any TCDD-induced differences in global methylation or hydroxymethylation levels, but the promoter methylation of aryl hydrocarbon receptor (AHR) target genes was altered. In TCDD-exposed embryos, AHR repressor a (ahrra) and c-fos promoters were differentially methylated. To characterize the TCDD effects on DNMTs, we cloned the dnmt promoters with xenobiotic response elements and conducted AHR transactivation assays using a luciferase reporter system. Our results suggest that ahr2 can regulate dnmt3a1, dnmt3a2, and dnmt3b2 expression. Overall, we demonstrate that developmental exposure to TCDD alters dnmt expression and DNA methylation patterns. - Highlights: • TCDD altered the dnmt expression in a gene and developmental time-specific manner. • TCDD hypermethylated ahrra and hypomethylated c-fos proximal promoter regions. • Functional analysis suggests that ahr2 can regulate dnmt3a1, 3a2, and 3b2 expression. • Dnmt

  13. Chronic Exposure to Arsenic in Drinking Water Causes Alterations in Locomotor Activity and Decreases Striatal mRNA for the D2 Dopamine Receptor in CD1 Male Mice

    OpenAIRE

    Moreno Ávila, Claudia Leticia; Limón-Pacheco, Jorge H.; Giordano., Magda; Rodríguez, Verónica M.

    2016-01-01

    Arsenic exposure has been associated with sensory, motor, memory, and learning alterations in humans and alterations in locomotor activity, behavioral tasks, and neurotransmitters systems in rodents. In this study, CD1 mice were exposed to 0.5 or 5.0 mg As/L of drinking water for 6 months. Locomotor activity, aggression, interspecific behavior and physical appearance, monoamines levels, and expression of the messenger for dopamine receptors D1 and D2 were assessed. Arsenic exposure produced h...

  14. 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

  15. 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.

  16. Acute developmental exposure to polybrominated diphenyl ether 47 (PBDE 47) alters dopamine concentration within the brains of male mice.

    Science.gov (United States)

    Polybrominated diphenyl ethers (PBDEs) are commonly used as commercial flame retardants in a variety of products including plastics and textiles. Previous studies in our laboratory and in the literature have shown that exposure to a specific PBDE congener, PBDE 47, during a criti...

  17. Moderate (2%, v/v) Ethanol Feeding Alters Hepatic Wound Healing after Acute Carbon Tetrachloride Exposure in Mice.

    Science.gov (United States)

    Deshpande, Krutika T; Liu, Shinlan; McCracken, Jennifer M; Jiang, Lu; Gaw, Ta Ehpaw; Kaydo, Lindsey N; Richard, Zachary C; O'Neil, Maura F; Pritchard, Michele T

    2016-01-06

    Wound healing consists of three overlapping phases: inflammation, proliferation, and matrix synthesis and remodeling. Prolonged alcohol abuse can cause liver fibrosis due to deregulated matrix remodeling. Previous studies demonstrated that moderate ethanol feeding enhances liver fibrogenic markers and frank fibrosis independent of differences in CCl₄-induced liver injury. Our objective was to determine whether or not other phases of the hepatic wound healing response were affected by moderate ethanol after CCl₄ exposure. Mice were fed moderate ethanol (2% v/v) for two days and then were exposed to CCl₄ and euthanized 24-96 h later. Liver injury was not different between pair- and ethanol-fed mice; however, removal of necrotic tissue was delayed after CCl₄-induced liver injury in ethanol-fed mice. Inflammation, measured by TNFα mRNA and protein and hepatic Ly6c transcript accumulation, was reduced and associated with enhanced hepatocyte apoptosis after ethanol feeding. Hepatocytes entered the cell cycle equivalently in pair- and ethanol-fed mice after CCl₄ exposure, but hepatocyte proliferation was prolonged in livers from ethanol-fed mice. CCl₄-induced hepatic stellate cell activation was increased and matrix remodeling was prolonged in ethanol-fed mice compared to controls. Taken together, moderate ethanol affected each phase of the wound healing response to CCl₄. These data highlight previously unknown effects of moderate ethanol exposure on hepatic wound healing after acute hepatotoxicant exposure.

  18. Modulation of estrogenic exposure effects via alterations in salinity and dissolved oxygen in male fathead minnows, Pimephales promelas

    Science.gov (United States)

    Laboratory exposure data indicate that estrogens and estrogen mimics can cause endocrine disruption in male fathead minnows (Pimephales promelas). In the wild, conditions are not static as is often the case in the laboratory. Changes in water quality parameters, such as salinity influx due to road s...

  19. Gestational exposure to cadmium alters crucial offspring rat brain enzyme activities: the role of cadmium-free lactation.

    Science.gov (United States)

    Liapi, Charis; Stolakis, Vasileios; Zarros, Apostolos; Zissis, Konstantinos M; Botis, John; Al-Humadi, Hussam; Tsakiris, Stylianos

    2013-11-01

    The present study aimed to shed more light on the effects of gestational (in utero) exposure to cadmium (Cd) on crucial brain enzyme activities of Wistar rat offspring, as well as to assess the potential protective/restorative role that a Cd-free lactation might have on these effects. In contrast to earlier findings of ours regarding the pattern of effects that adult-onset exposure to Cd has on brain AChE, Na(+),K(+)- and Mg(2+)-ATPase activities, as well as in contrast to similar experimental approaches implementing the sacrificing mode of anaesthesia, in utero exposure to Cd-chloride results in increased AChE and Na(+),K(+)-ATPase activities in the newborn rat brain homogenates that were ameliorated through a Cd-free lactation (as assessed in the brain of 21-day-old offspring). Mg(2+)-ATPase activity was not found to be significantly modified under the examined experimental conditions. These findings could provide the basis for a further evaluation of the herein discussed neurotoxic effects of in utero exposure to Cd, in a brain region-specific manner.

  20. Genetics and preliminary mechanism of chlorpyrifos resistance in Phenacoccus solenopsis Tinsley (Homoptera: Pseudococcidae).

    Science.gov (United States)

    Afzal, Muhammad Babar Shahzad; Ijaz, Mamuna; Farooq, Zahra; Shad, Sarfraz Ali; Abbas, Naeem

    2015-03-01

    Cotton mealybug, Phenacoccus solenopsis Tinsley, is a serious pest of cotton and other crops and infestation by this pest results in yield losses that affect the economy of Pakistan. Various groups of insecticides have been used to control this pest but resistance development is a major factor that inhibits its control in the field. Chlorpyrifos is a common insecticide used against many pests including P. solenopsis. The present experiment was designed to assess the genetics and mechanism of chlorpyrifos resistance and to develop a better resistance management strategy and assess the genetics and mechanism of chlorpyrifos resistance. Before selection, the field strain showed 3.1-fold resistance compared to the susceptible strain (CSS). After 8 rounds of selection with chlorpyrifos, a selected population developed a 191.0-fold resistance compared to the CSS. The LC50 values of F1 (CRR ♀ × CSS ♂) and F1(†) (CRR ♂ × CSS ♀) strains were not significantly different and dominance (DLC) values were 0.42 and 0.55. Reciprocal crosses between chlorpyrifos susceptible and resistant strains indicated that resistance was autosomal and incompletely recessive. The monogenic model of fit test and calculation of number of genes segregating in the chlorpyrifos resistant strain demonstrated that resistance is controlled by multiple genes. A value of 0.59 was calculated for realized heritability for chlorpyrifos resistance. Synergism bioassays with piperonyl butoxide and S, S, S-butyl phosphorotrithioate showed that chlorpyrifos resistance was associated with microsomal oxidases and esterases. It was concluded that chlorpyrifos resistance in P. solenopsis was autosomally inherited, incompletely recessive and polygenic. These findings would be helpful to improve the management of P. solenopsis.

  1. Effects of chlorpyrifos on the growth and reproduction of earthworms,Eisenia foetida%毒死蜱对蚯蚓生长和繁殖的影响

    Institute of Scientific and Technical Information of China (English)

    程燕; 姜锦林; 卜元卿; 周军英; 单正军

    2015-01-01

    为探明毒死蜱对蚯蚓的影响,以赤子爱胜蚓Eisenia foetida为受试生物,以人工土壤为试验基质,采用接触暴露法,研究了毒死蜱对赤子爱胜蚓的急性毒性以及对蚯蚓生长和繁殖的影响。结果表明:在有效试验条件下,毒死蜱对蚯蚓的14 d-LC50值为88.75 mg/kg(每千克干土中含毒死蜱有效成分毫克数,其余同);暴露28 d后,10、25、50、80及100 mg/kg处理组蚯蚓的平均体重与对照相比依次下降了9.8%、15.7%、17.5%、23.9%和27.0%,体重下降与药剂处理浓度之间高度相关,且除10 mg/kg处理组外均与对照差异显著( P ﹤0.01,r =0.984);毒死蜱10、25、50、80及100 mg/kg处理组对蚯蚓繁殖的抑制率分别为32.26%、80.97%、89.03%、89.68%和97.42%,繁殖抑制率与药剂浓度之间存在一定的相关性( P﹥0.01,r=0.788);毒死蜱影响蚯蚓生长和繁殖的28 d最低可观测效应浓度( LOEC)值为25 mg/kg。%In order to explore the effects of chlorpyrifos on earthworms, the acute toxicity of chlorpyrifos to Eisenia foetida and the effects of chlorpyrifos on the growth and reproduction of earthworms were investigated by exposing E. foetida to chlorpyrifos in artificial soil. The results indicated that the 14 d-LC50 value of chlorpyrifos to E. foetida was 88. 75 mg a. i. /kg dry soil;After exposure to chlorpyrifos at 10,25,50,80 and 100 mg a. i. /kg dry soil for 28 d,the weight of E. foetida reduced significantly except the treatment of 10 mg a. i. /kg dry soil;the body weight reducing rates were 9. 8%,15. 7%,17. 5%,23. 9% and 27. 0%,respectively,demonstrating a high correlation between the body weight reducing rate and the concentration( P﹤0 . 01 ,r=0 . 984 ). The reproduction inhibition rates of chlorpyrifos E. foetida at 10,25,50,80 and 100 mg/kg dry soil were 32. 26%,80. 97%,89. 03%,89. 68% and 97. 42%,respectively,indicating a certain correlation (P﹥0

  2. Dioxin exposure reduces the steroidogenic capacity of mouse antral follicles mainly at the level of HSD17B1 without altering atresia

    Energy Technology Data Exchange (ETDEWEB)

    Karman, Bethany N., E-mail: bklement@illinois.edu; Basavarajappa, Mallikarjuna S., E-mail: mbshivapur@gmail.com; Hannon, Patrick, E-mail: phannon2@illinois.edu; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2012-10-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent ovarian toxicant. Previously, we demonstrated that in vitro TCDD (1 nM) exposure decreases production/secretion of the sex steroid hormones progesterone (P4), androstenedione (A4), testosterone (T), and 17β-estradiol (E2) in mouse antral follicles. The purpose of this study was to determine the mechanism by which TCDD inhibits steroidogenesis. Specifically, we examined the effects of TCDD on the steroidogenic enzymes, atresia, and the aryl hydrocarbon receptor (AHR) protein. TCDD exposure for 48 h increased levels of A4, without changing HSD3B1 protein, HSD17B1 protein, estrone (E1), T or E2 levels. Further, TCDD did not alter atresia ratings compared to vehicle at 48 h. TCDD, however, did down regulate the AHR protein at 48 h. TCDD exposure for 96 h decreased transcript levels for Cyp11a1, Cyp17a1, Hsd17b1, and Cyp19a1, but increased Hsd3b1 transcript. TCDD exposure particularly lowered both Hsd17b1 transcript and HSD17B1 protein. However, TCDD exposure did not affect levels of E1 in the media nor atresia ratings at 96 h. TCDD, however, decreased levels of the proapoptotic factor Bax. Collectively, these data suggest that TCDD exposure causes a major block in the steroidogenic enzyme conversion of A4 to T and E1 to E2 and that it regulates apoptotic pathways, favoring survival over death in antral follicles. Finally, the down‐regulation of the AHR protein in TCDD exposed follicles persisted at 96 h, indicating that the activation and proteasomal degradation of this receptor likely plays a central role in the impaired steroidogenic capacity and altered apoptotic pathway of exposed antral follicles. -- Highlights: ► TCDD disrupts steroidogenic enzymes in mouse antral follicles. ► TCDD particularly affects the HSD17B1 enzyme in mouse antral follicles. ► TCDD does not affect atresia ratings in mouse antral follicles. ► TCDD decreases levels of the proapoptitic factor Bax in mouse antral follicles.

  3. 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

  4. 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...

  5. Perinatal exposure to benzyl butyl phthalate induces alterations in neuronal development/maturation protein expression, estrogen responses, and fear conditioning in rodents.

    Science.gov (United States)

    DeBartolo, Danielle; Jayatilaka, Sahani; Yan Siu, Nga; Rose, Melissa; Ramos, Raddy L; Betz, Adrienne J

    2016-02-01

    Phthalate exposure has recently been associated with behavioral actions that are linked to its endocrine-disrupting properties. The purpose of this study was to investigate the molecular, anatomical, and behavioral effects of indirect perinatal benzyl butyl phthalate (BBP) exposure in offspring of BBP-treated pregnant dams. In two separate experiments, we administered BBP (10.0 μg/ml) on food pellets to pregnant dams and examined the offspring. The first experiment revealed reproductive anatomical abnormalities linked to BBP's endocrine-disrupting properties, whereas histological analysis revealed preserved hippocampal neuronal migration. The second experiment demonstrated learning and memory impairments accompanied by molecular abnormalities in multiple brain regions. Offspring from BBP-treated dams had altered levels of several proteins important for neuronal circuitry formation, tissue development, and maturation. We suggest that BBP administration disrupts normal learning and that these effects could be related to alterations in brain development and result in a phenotype similar to that observed in neurodevelopmental disorders. PMID:26376073

  6. Perfluorooctanoic acid exposure alters polyunsaturated fatty acid composition, induces oxidative stress and activates the AKT/AMPK pathway in mouse epididymis.

    Science.gov (United States)

    Lu, Yin; Pan, Yitao; Sheng, Nan; Zhao, Allan Z; Dai, Jiayin

    2016-09-01

    Perfluorooctanoic acid (PFOA) is a degradation-resistant compound with a carbon-fluorine bond. Although PFOA emissions have been reduced since 2000, it remains persistent in the environment. Several studies on laboratory animals indicate that PFOA exposure can impact male fertility. Here, adult male mice received either PFOA (1.25, 5 or 20 mg/kg/d) or an equal volume of water for 28 d consecutively. PFOA accumulated in the epididymis in a dose-dependent manner and resulted in reduced epididymis weight, lower levels of triglycerides (TG), cholesterol (CHO), and free fatty acids (FFA), and activated AKT/AMPK signaling in the epididymis. Altered polyunsaturated fatty acid (PUFA) compositions, such as a higher arachidonic acid:linoleic acid (AA:LA) ratio, concomitant with excessive oxidative stress, as demonstrated by increased malonaldehyde (MDA) and decreased glutathione peroxidase (GSH-Px) in the epididymis, were observed in epididymis tissue following treatment with PFOA. These results indicate that the epididymis is a potential target of PFOA. Oxidative stress and PUFA alteration might help explain the sperm injury and male reproductive dysfunction induced by PFOA exposure. PMID:27262104

  7. Alterations in the infrared spectral signature of avian feathers reflect potential chemical exposure: a pilot study comparing two sites in Pakistan.

    Science.gov (United States)

    Llabjani, Valon; Malik, Riffat N; Trevisan, Júlio; Hoti, Valmira; Ukpebor, Justina; Shinwari, Zabta K; Moeckel, Claudia; Jones, Kevin C; Shore, Richard F; Martin, Francis L

    2012-11-01

    Chemical contamination of ecosystems is a global issue with evidence that pollutants impact on living organisms in a harmful fashion. Developing sensor approaches that would allow the derivation of biomarkers or signatures of effect in target sentinel organisms and monitor environmental chemical contamination in a high throughput manner is of utmost importance. As biomolecules absorb infrared (IR), signature vibrational spectra related to structure and function can be derived. In light of this, we tested the notion that IR spectra of bird feathers might reflect environmental chemical contaminant exposure patterns. Feathers were collected from monospecific heronries of cattle egret based in two independent locations (Trimu vs. Mailsi) in the Punjab province of Pakistan; these sites were found to differ in their chemical contamination patterns. Feather samples were chemically analyzed for polychlorinated biphenyls, polybrominated diphenyl ethers, organochlorines and heavy metals. Attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy was employed to derive a spectral signature of individual feathers. Resultant IR spectra were then subjected to canonical correspondence analysis (CAA) to determine whether feather spectral signatures correlate to chemical exposure. Additionally, we explored if principal component analysis (PCA) and linear discriminant analysis (LDA) could be applied to distinguish site-specific differences; linear discriminant function (LDF) was also applied to classify sites. The sampled feathers varied in their chemical exposure patterns depending on whether they were sourced from one site associated with heavy metal exposure or the other which suggested high organic pollutant exposures. CCA of chemical and spectral data showed a correlation between spectral signatures and chemical exposure. PCA-LDA readily distinguished feathers from the two different sites. Discriminating alterations were identified and these were associated with

  8. Epigenetic Changes Induced by Air Toxics: Formaldehyde Exposure Alters miRNA Expression Profiles in Human Lung Cells

    OpenAIRE

    Rager, Julia E.; Smeester, Lisa; Jaspers, Ilona; Sexton, Kenneth G.; Fry, Rebecca C.

    2010-01-01

    Background Exposure to formaldehyde, a known air toxic, is associated with cancer and lung disease. Despite the adverse health effects of formaldehyde, the mechanisms underlying formaldehyde-induced disease remain largely unknown. Research has uncovered microRNAs (miRNAs) as key posttranscriptional regulators of gene expression that may influence cellular disease state. Although studies have compared different miRNA expression patterns between diseased and healthy tissue, this is the first st...

  9. Neonatal Exposure to Parathion Alters Lipid Metabolism in Adulthood: Interactions with Dietary Fat Intake and Implications for Neurodevelopmental Deficits

    OpenAIRE

    Lassiter, T. Leon; Ryde, Ian T.; Levin, Edward D.; Seidler, Frederic J; Slotkin, Theodore A.

    2010-01-01

    Organophosphates are developmental neurotoxicants but recent evidence also points to metabolic dysfunction. We determined whether neonatal parathion exposure in rats has long-term effects on regulation of adipokines and lipid peroxidation. We also assessed the interaction of these effects with increased fat intake. Rats were given parathion on postnatal days 1–4 using doses (0.1 or 0.2 mg/kg/day) that straddle the threshold for barely detectable cholinesterase inhibition and the first signs o...

  10. Mechanisms of Imidacloprid-Induced Alteration of Hypothalamic-Pituitary-Adrenal (HPA) Axis after Subchronic Exposure in Male Rats

    OpenAIRE

    Alya Annabi; Ines El-Bini Dhouib; Houssem Dkhili; Yassine Bdiri; Ines Rejeb; Najoua Gharbi; Saloua El-Fazâa; Mohamed Montassar Lasram

    2015-01-01

    Imidacloprid (IMI) is known to target the nicotinic acetylcholine receptors (nAChRs) in insects, and potentially in mammals. However, IMI toxicity on mammalian tissues has not been adequately evaluated. The aim of the present study was to examine whether IMI induced functional impairment in hypthalamic-pituitary-adrenal (HPA) axis tissues. An oral exposure of 40 mg IMI/kg for 28 days in male rats caused a significant increase in malondialdehyde (MDA) level. The antioxidant catalase, superoxid...

  11. Perinatal exposure to a noncoplanar polychlorinated biphenyl alters tonotopy, receptive fields, and plasticity in rat primary auditory cortex

    OpenAIRE

    Kenet, T; Froemke, R. C.; Schreiner, C. E.; Pessah, I N; Merzenich, M. M.

    2007-01-01

    Noncoplanar polychlorinated biphenyls (PCBs) are widely dispersed in human environment and tissues. Here, an exemplar noncoplanar PCB was fed to rat dams during gestation and throughout three subsequent nursing weeks. Although the hearing sensitivity and brainstem auditory responses of pups were normal, exposure resulted in the abnormal development of the primary auditory cortex (A1). A1 was irregularly shaped and marked by internal nonresponsive zones, its topographic organization was grossl...

  12. Adolescent opiate exposure in the female rat induces subtle alterations in maternal care and transgenerational effects on play behavior.

    Directory of Open Access Journals (Sweden)

    Nicole L. Johnson

    2011-06-01

    Full Text Available The non-medical use of prescription opiates, such as Vicodin® and MSContin®, has increased dramatically over the past decade. Of particular concern is the rising popularity of these drugs in adolescent female populations. Use during this critical developmental period could have significant long-term consequences for both the female user as well as potential effects on her future offspring. To address this issue, we have begun modeling adolescent opiate exposure in female rats and have observed significant transgenerational effects despite the fact that all drugs are withdrawn several weeks prior to pregnancy. The purpose of the current set of studies was to determine whether adolescent morphine exposure modifies postpartum care. In addition, we also examined juvenile play behavior in both male and female offspring. The choice of the social play paradigm was based on previous findings demonstrating effects of both postpartum care and opioid activity on play behavior. The findings revealed subtle modifications in the maternal behavior of adolescent morphine-exposed females, primarily related to the amount of time females’ spend nursing and in non-nursing contact with their young. In addition, male offspring of adolescent morphine-exposed mothers (MOR-F1 demonstrate decreased rough and tumble play behaviors, with no significant differences in general social behaviors (i.e. social grooming and social exploration. Moreover, there was a tendency toward increased rough and tumble play in MOR-F1 females, demonstrating the sex-specific nature of these effects. Given the importance of the postpartum environment on neurodevelopment, it is possible that modifications in maternal-offspring interactions, related to a history of adolescent opiate exposure, plays a role in the observed transgenerational effects. Overall, these studies indicate that the long-term consequences of adolescent opiate exposure can impact both the female and her future offspring.

  13. Neurological effects of inorganic arsenic exposure: altered cysteine/glutamate transport, NMDA expression and spatial memory impairment.

    Directory of Open Access Journals (Sweden)

    Lucio A Ramos-Chávez

    2015-02-01

    Full Text Available Inorganic arsenic (iAs is an important natural pollutant. Millions of individuals worldwide drink water with high levels of iAs. Chronic exposure to iAs has been associated with lower IQ and learning disabilities as well as memory impairment. iAs is methylated in tissues such as the brain generating mono and dimethylated species. iAs methylation requires cellular glutathione (GSH, which is the main antioxidant in the central nervous system. In humans, As species cross the placenta and are found in cord blood. A CD1 mouse model was used to investigate effects of gestational iAs exposure which can lead to oxidative damage, disrupted cysteine/glutamate transport and its putative impact in learning and memory. On postnatal days (PNDs 1, 15 and 90, the expression of membrane transporters related to GSH synthesis and glutamate transport and toxicity, such as xCT, EAAC1, GLAST and GLT1, as well as LAT1, were analyzed. Also, the expression of the glutamate receptor N-methyl-D-aspartate (NMDAR subunits NR2A and B as well as the presence of As species in cortex and hippocampus were investigated. On PND 90, an object location task was performed to associate exposure with memory impairment. Gestational exposure to iAs affected the expression of cysteine/glutamate transporters in cortex and hippocampus and induced a negative modulation of NMDAR NR2B subunit in the hippocampus. Behavioral tasks showed significant spatial memory impairment in males while the effect was marginal in females.

  14. Early-life stress exposure associated with altered prefrontal resting-state fMRI connectivity in young children

    Directory of Open Access Journals (Sweden)

    Özlem Ece Demir-Lira

    2016-06-01

    Full Text Available Early-life stress (ELS exposure is associated with adverse outcomes across the lifespan. We examined the relation of ELS exposure to resting-state fMRI in children ages 4–7 years. ELS in the first years of life, but not concurrent, was associated with higher regional homogeneity of resting-state fMRI in the left lateral frontal cortex. Resting-state fMRI functional connectivity analyses showed that the region of left lateral frontal cortex demonstrating heightened regional homogeneity associated with ELS was negatively correlated with right temporal/parahippocampal areas. Moreover, higher regional homogeneity in the left lateral frontal cortex and its negative coupling with the right middle temporal/parahippocampal areas were associated with poorer performance on a reversal-learning task performed outside the scanner. Association of ELS exposure with regional homogeneity was independent of other early adversities. These findings suggest that ELS may influence the development of cognitive control in the lateral prefrontal cortex and its interactions with temporal cortex.

  15. Alterations in cell migration and cell viability of wounded human skin fibroblasts following visible red light exposure

    Science.gov (United States)

    Prabhu, Vijendra; Rao, Bola Sadashiva S.; Mahato, Krishna Kishore

    2014-02-01

    The present study intended to examine the effect of visible red light on structural and cellular parameters on wounded skin fibroblast cells. To achieve the stated objective, uniform scratch was created on confluent monolayered human skin fibroblast cells, and were exposed to single dose of He-Ne laser (15 mm spot, 6.6808 mWcm-2) at 1, 2, 3, 4, 5, 6 and 7 Jcm-2 in the presence and absence of 10% fetal bovine serum (FBS). Beam profile measurements of the expanded laser beam were conducted to ensure the beam uniformity. The influence of laser dose on the change in temperature was recorded using sensitive temperature probe. Additionally, following laser exposure cell migration and cell survival were documented at different time intervals on wounded human skin fibroblast cells grown in vitro. Beam profile measurements indicated more or less uniform power distribution over the whole beam area. Temperature monitoring of sham irradiated control and laser treatment groups displayed negligible temperature change indicating the absence of thermal effect at the tested laser doses. In the absence of 10% FBS, single exposure of different laser doses failed to produce any significant effects on cell migration or cell survival. However, in the presence of serum single exposure of 5 J/cm2 on wounded skin fibroblasts significantly enhanced the cell migration (PLLLT acts by improving cell migration and cell proliferation to produce measurable changes in wounded fibroblast cells.

  16. Prenatal and Lactational Exposure to Bisphenol A in Mice Alters Expression of Genes Involved in Cortical Barrel Development without Morphological Changes

    International Nuclear Information System (INIS)

    It has been reported that premature infants in neonatal intensive care units are exposed to a high rate of bisphenol A (BPA), an endocrine disrupting chemical. Our previous studies demonstrated that corticothalamic projection was disrupted by prenatal exposure to BPA, which persisted even in adult mice. We therefore analyzed whether prenatal and lactational exposure to low doses of BPA affected the formation of the cortical barrel, the barreloid of the thalamus, and the barrelette of the brainstem in terms of the histology and the expression of genes involved in the barrel development. Pregnant mice were injected subcutaneously with 20 µg/kg of BPA daily from embryonic day 0 (E0) to postnatal 3 weeks (P3W), while the control mice received a vehicle alone. The barrel, barreloid and barrelette of the adult mice were examined by cytochrome C oxidase (COX) staining. There were no significant differences in the total and septal areas and the patterning of the posterior medial barrel subfield (PMBSF), barreloid and barrelette, between the BPA-exposure and control groups in the adult mice. The developmental study at postnatal day 1 (PD1), PD4 and PD8 revealed that the cortical barrel vaguely appeared at PD4 and completely formed at PD8 in both groups. The expression pattern of some genes was spatiotemporally altered depending on the sex and the treatment. These results suggest that the trigeminal projection and the thalamic relay to the cortical barrel were spared after prenatal and lactational exposure to low doses of BPA, although prenatal exposure to BPA was previously shown to disrupt the corticothalamic projection

  17. Prenatal and Lactational Exposure to Bisphenol A in Mice Alters Expression of Genes Involved in Cortical Barrel Development without Morphological Changes.

    Science.gov (United States)

    Han, Longzhe; Itoh, Kyoko; Yaoi, Takeshi; Moriwaki, Sanzo; Kato, Shingo; Nakamura, Keiko; Fushiki, Shinji

    2011-02-26

    It has been reported that premature infants in neonatal intensive care units are exposed to a high rate of bisphenol A (BPA), an endocrine disrupting chemical. Our previous studies demonstrated that corticothalamic projection was disrupted by prenatal exposure to BPA, which persisted even in adult mice. We therefore analyzed whether prenatal and lactational exposure to low doses of BPA affected the formation of the cortical barrel, the barreloid of the thalamus, and the barrelette of the brainstem in terms of the histology and the expression of genes involved in the barrel development. Pregnant mice were injected subcutaneously with 20 µg/kg of BPA daily from embryonic day 0 (E0) to postnatal 3 weeks (P3W), while the control mice received a vehicle alone. The barrel, barreloid and barrelette of the adult mice were examined by cytochrome C oxidase (COX) staining. There were no significant differences in the total and septal areas and the patterning of the posterior medial barrel subfield (PMBSF), barreloid and barrelette, between the BPA-exposure and control groups in the adult mice. The developmental study at postnatal day 1 (PD1), PD4 and PD8 revealed that the cortical barrel vaguely appeared at PD4 and completely formed at PD8 in both groups. The expression pattern of some genes was spatiotemporally altered depending on the sex and the treatment. These results suggest that the trigeminal projection and the thalamic relay to the cortical barrel were spared after prenatal and lactational exposure to low doses of BPA, although prenatal exposure to BPA was previously shown to disrupt the corticothalamic projection. PMID:21448315

  18. Neonatal exposure to benzo[a]pyrene induces oxidative stress causing altered hippocampal cytomorphometry and behavior during early adolescence period of male Wistar rats.

    Science.gov (United States)

    Patel, Bhupesh; Das, Saroj Kumar; Das, Swagatika; Das, Lipsa; Patri, Manorama

    2016-05-01

    Environmental neurotoxicants like benzo[a]pyrene (B[a]P) have been well documented regarding their potential to induce oxidative stress. However, neonatal exposure to B[a]P and its subsequent effect on anti-oxidant defence system and hippocampal cytomorphometry leading to behavioral changes have not been fully elucidated. We investigated the effect of acute exposure of B[a]P on five days old male Wistar pups administered with single dose of B[a]P (0.2 μg/kg BW) through intracisternal mode. Control group was administered with vehicle i.e., DMSO and a separate group of rats without any treatment was taken as naive group. Behavioral analysis showed anxiolytic-like behavior with significant increase in time spent in open arm in elevated plus maze. Further, significant reduction in fall off time during rotarod test showing B[a]P induced locomotor hyperactivity and impaired motor co-ordination in adolescent rats. B[a]P induced behavioral changes were further associated with altered anti-oxidant defence system involving significant reduction in the total ATPase, Na(+) K(+) ATPase, Mg(2+) ATPase, GR and GPx activity with a significant elevation in the activity of catalase and GST as compared to naive and control groups. Cytomorphometry of hippocampus showed that the number of neurons and glia in B[a]P treated group were significantly reduced as compared to naive and control. Subsequent observation showed that the area and perimeter of hippocampus, hippocampal neurons and neuronal nucleus were significantly reduced in B[a]P treated group as compared to naive and control. The findings of the present study suggest that the alteration in hippocampal cytomorphometry and neuronal population associated with impaired antioxidant signaling and mood in B[a]P treated group could be an outcome of neuromorphological alteration leading to pyknotic cell death or impaired differential migration of neurons during early postnatal brain development. PMID:26946409

  19. Postnatal Manganese Exposure Alters Dopamine Transporter Function in Adult Rats: Potential Impact on Nonassociative and Associative Processes

    OpenAIRE

    McDougall, S. A.; Reichel, C. M.; Farley, C M; Flesher, M. M.; Der-Ghazarian, T.; Cortez, A. M.; Wacan, J. J.; Martinez, C. E.; VARELA, F. A.; Butt, A E; Crawford, C. A.

    2008-01-01

    In the present study, we examined whether exposing rats to a high-dose regimen of manganese chloride (Mn) during the postnatal period would depress presynaptic dopamine functioning and alter nonassociative and associative behaviors. To this end, rats were given oral supplements of Mn (750 μg/day) on postnatal days (PD) 1–21. On PD 90, dopamine transporter (DAT) immunoreactivity and [3H]dopamine uptake were assayed in the striatum and nucleus accumbens, while in vivo microdialysis was used to ...

  20. The Alterations of Serum Cortisol Level and Blood Cell Count in Male Rats after a Short Term Exposure to Burned Radioactive Lantern Mantle Powder

    Directory of Open Access Journals (Sweden)

    Rezaeian Mohsen

    2010-03-01

    Full Text Available Background: Most lantern mantles contain low levels of radioactive thorium. Although radioactive lantern mantles present a minimal radiation health hazard, it is generally believed when inhaled or ingested, it can be dangerous. The purpose of this study was to assess the effect of short term exposure to radioactive lantern mantle on serum cortisol level and blood count.Materials and Methods: This experimental study was conducted in 2007-2009 in the school of medicine of Rafsanjan University of Medical Sciences. Twenty eight rats were divided randomly into two groups of 14 animals each. The first group was exposed to 600 mg burned radioactive lantern mantle powder (activity of 800Bq for 24 hours and inhaled radon released from mantles. The second group was exposed to non-radioactive lantern mantle powder at the same interval. Paired t-test was used to evaluate the difference in the means of cortisol and blood cell count in both groups. P<0.05 was considered as the significance level.Results: Short term exposure of animals to radioactive lantern mantle powder led to a statistically significant decreased cortisol level, while no statistically significant decrease was found in animals that were exposed to non-radioactive mantle powder. Furthermore, a significant reduction was shown in post-exposure counts of WBC in the case group.Conclusions: Despite alteration of serum cortisol level, this study could not show stimulatory effects in some blood counts

  1. Exposure to the synthetic FXR agonist GW4064 causes alterations in gene expression and sublethal hepatotoxicity in eleutheroembryo medaka (Oryzias latipes)

    International Nuclear Information System (INIS)

    The small freshwater teleost, medaka (Oryzias latipes), has a history of usage in studies of chronic toxicity of liver and biliary system. Recent progress with this model has focused on defining the medaka hepatobiliary system. Here we investigate critical liver function and toxicity by examining the in vivo role and function of the farnesoid X receptor alpha (FXRα, NR1H4), a member of the nuclear receptor superfamily that plays an essential role in the regulation of bile acid homeostasis. Quantitative mRNA analysis of medaka FXRα demonstrates differential expression of two FXRα isoforms designated Fxrα1 and Fxrα2, in both free swimming medaka embryos with remaining yolk (eleutheroembryos, EEs) and adults. Activation of medaka Fxrα in vivo with GW4064 (a strong FXRα agonist) resulted in modification of gene expression for defined FXRα gene targets including the bile salt export protein, small heterodimer partner, and cytochrome P450 7A1. Histological examination of medaka liver subsequent to GW4064 exposure demonstrated significant lipid accumulation, cellular and organelle alterations in both hepatocytes and biliary epithelial cells of the liver. This report of hepatobiliary injury following GW4064 exposure extends previous investigations of the intrahepatic biliary system in medaka, reveals sensitivity to toxicant exposure, and illustrates the need for added resolution in detection and interpretation of toxic responses in this vertebrate.

  2. Prenatal alcohol exposure alters synaptic activity of adult hippocampal dentate granule cells under conditions of enriched environment.

    Science.gov (United States)

    Kajimoto, Kenta; Valenzuela, C Fernando; Allan, Andrea M; Ge, Shaoyu; Gu, Yan; Cunningham, Lee Anna

    2016-08-01

    Prenatal alcohol exposure (PAE) results in fetal alcohol spectrum disorder (FASD), which is characterized by a wide range of cognitive and behavioral deficits that may be linked to impaired hippocampal function and adult neurogenesis. Preclinical studies in mouse models of FASD indicate that PAE markedly attenuates enrichment-mediated increases in the number of adult-generated hippocampal dentate granule cells (aDGCs), but whether synaptic activity is also affected has not been studied. Here, we utilized retroviral birth-dating coupled with whole cell patch electrophysiological recordings to assess the effects of PAE on enrichment-mediated changes in excitatory and inhibitory synaptic activity as a function of DGC age. We found that exposure to an enriched environment (EE) had no effect on baseline synaptic activity of 4- or 8-week-old aDGCs from control mice, but significantly enhanced the excitatory/inhibitory ratio of synaptic activity in 8-week-old aDGCs from PAE mice. In contrast, exposure to EE significantly enhanced the excitatory/inhibitory ratio of synaptic activity in older pre-existing DGCs situated in the outer dentate granule cell layer (i.e., those generated during embryonic development; dDGCs) in control mice, an effect that was blunted in PAE mice. These findings indicate distinct electrophysiological responses of hippocampal DGCs to behavioral challenge based on cellular ontogenetic age, and suggest that PAE disrupts EE-mediated changes in overall hippocampal network activity. These findings may have implications for future therapeutic targeting of hippocampal dentate circuitry in clinical FASD. © 2016 Wiley Periodicals, Inc. PMID:27009742

  3. Alterations of the In Vivo Torque-Velocity Relationship of Human Skeletal Muscle Following 30 Days Exposure to Simulated Microgravity

    Science.gov (United States)

    Dudley, Gary A.; Duvoisin, Marc R.; Convertino, Victor A.; Buchanan, Paul

    1989-01-01

    The purpose of this study was to examine the effect of 30 d of 6 deg headdown bedrest (BR) on the in vivo strength of skeletal muscle. Peak angle specific (0.78 rad below horizontal) torque of the knee extensor (KE) and flexor (KF) muscle groups of both limbs was assessed during unilateral efforts at four speeds (0.52, 1.74, 2.97 and 4.19 rad/s) during concentric and at three speeds (0.52, 1.74 and 2.97 rad/s) during eccentric actions. The average decrease (P less than 0.05) of peak angle specific torque directly post-BR for the KE across speeds of concentric and eccentric actions was about 19% (n = 7). Recovery for 30 d following BR markedly improved strength to about 92% (P greater than 0.05) of 'normal'. Strength of the KF was not altered (P greater than 0.05) by BR (about a 6% decrease independent of speed and type of muscle action). Changes of strength were not affected by the type or speed of muscle action. The results indicate that strength of ex-tensor more than of flexor muscle groups of the lower limb is decreased by 30 d of bedrest and that this response does not alter the nature of the in vivo torque-velocity relation.

  4. Detrimental psychophysiological effects of early maternal deprivation in adolescent and adult rodents: altered responses to cannabinoid exposure.

    Science.gov (United States)

    Marco, Eva M; Adriani, Walter; Llorente, Ricardo; Laviola, Giovanni; Viveros, María-Paz

    2009-04-01

    Environmental rearing conditions during the neonatal period are critical for the establishment of neurobiological factors controlling behavior and stress responsiveness. Early maternal deprivation (MD), consisting of a single 24-h maternal deprivation episode during early neonatal life, has been proposed as an animal model for certain psychopathologies including anxiety, depression and schizophrenic-related disorders. Despite first onset of mental disorders usually occur during adolescence, characterization of MD has been mostly developed in adult animals. We review here a series of experiments that were conducted on rats and mice, in which we analyzed the psychoimmunoendocrine outcomes of MD at both adolescence and adulthood. As a whole our results indicate that MD might promote a depressive-like trait that may be present from adolescence to maturity. Maternally deprived adolescent animals also displayed altered locomotor responses, a reduced interest for social investigation and seemed prone for impulsive behavior. Therefore, MD in rodents is further confirmed as a suitable animal model for the study of neuropsychiatric disorders that might become evident during adolescence. Given the increasing consumption of cannabis derivatives among the juvenile population and the reported comorbidity of neuropsychiatric symptoms with cannabis abuse, we also discuss our results indicating altered responses of maternally deprived adolescent animals to cannabinoid compounds.

  5. Influenza virus-induced alterations of cytochrome P-450 enzyme activities following exposure of mice to coal and diesel particulates

    Energy Technology Data Exchange (ETDEWEB)

    Rabovsky, J.; Judy, D.J.; Rodak, D.J.; Petersen, M.

    1986-06-01

    We have investigated a relationship between two detoxication systems, metabolic detoxication through the cytochrome P-450 (P-450) pathway and resistance to infection through interferon (IFN), in mice infected with influenza virus following exposure to coal dust (CD) and diesel exhaust (DE) particulates. Mice were exposed by inhalation to filtered air (FA; control), CD, or DE for 1 month and then inoculated intranasally (IN) with influenza virus. During infection, 7-ethoxycoumarin deethylase (7ECdeEt'ase) and ethylmorphine demethylase (EMdeMe'ase) (monooxygenases), and NADPH cytochrome c reductase (NADPH c red'ase) were measured in liver microsomes. Temporal patterns of enzyme activities were observed with control animals. EMdeMe'ase and NADPH c red'ase exhibited peak values at Day 4 postinfection (27.6 and 482 nmole/min/mg protein, respectively), compared to initial activities (9.1 and 307 nmole/min/mg protein, respectively). 7ECdeEt'ase activity decreased between Days 1-3 postvirus infection and thereafter returned to the original value (1.7 nmole/min/mg protein). When the mice were first exposed to CD or DE particulates for 1 month prior to influenza infection, changes in enzyme temporal patterns were observed. The increased EMdeMe'ase activity at Day 4 was not observed in mice exposed to CD and was reduced in mice exposed to DE. Preexposure to either particulate resulted in the abolition of the increased Day 4 activity of NADPH c red'ase. The 7ECdeEt'ase postinfection temporal pattern was not affected by a preexposure to either particulate. Estimates of the enzyme activities after the 1-month exposure to FA, CD, or DE but before virus infection indicated no changes due to particulate exposure alone. Under conditions of particulate exposure and virus infection, serum IFN levels peaked at Days 4-5 and were unaffected by the 1-month preexposure to CD or DE.

  6. 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 ...

  7. 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...

  8. AGE-RELATED EFFECTS OF CHLORPYRIFOS ON ACETYLCHOLINE RELEASE IN RAT BRAIN. (R825811)

    Science.gov (United States)

    Chlorpyrifos (CPF) is an organophosphorus insecticide that elicits toxicity through inhibition of acetylcholinesterase (AChE). Young animals are markedly more sensitive than adults to the acute toxicity of CPF. We evaluated acetylcholine (ACh) release and its muscarinic recept...

  9. Hepatotoxic Alterations Induced by Subchronic Exposure of Rats to Formulated Fenvalerate (20% EC) by Nose Only Inhalation

    Institute of Scientific and Technical Information of China (English)

    U. MANI; A. K. PRASAD; V. SURESHKUMAR; P. KUMAR; KEWAL LAL; B. K. MAJI; K. K. DUTTA

    2004-01-01

    Fenvalerate (20% EC) is a synthetic pyrethroid, which is commonly used in India by farmers for the protection of many food and vegetable crops against a wide variety of insects. However, its inhalation toxicity data is very limited in the literature due to the fact that the exposure levels associated with these effects were usually not reported. Hence, inhalation exposure was carried out to investigate the hepatotoxic effects. Method Adult male rats were exposed to fen for 4 h/day, 5 days a week for 90 days by using Flow Past Nose Only Inhalation Chamber. Sham treated control rats were exposed to compressed air in the inhalation chamber for the same period. Results The results indicated hepatomegaly, increased activities of serum clinical enzymes (indicative of liver damage/dysfunction) along with pronounced histopathological damage of liver. Conclusion The hepatotoxic potential of formulated Fen (20% EC) in rats exposed by nose only inhalation is being reported for the first time and warrant adequate safety measures for human beings exposed to this insecticide, particularly by inhalation route.

  10. Prenatal exposure to alcohol and 3,4-methylenedioxymethamphetamine (ecstasy) alters adult hippocampal neurogenesis and causes enduring memory deficits.

    Science.gov (United States)

    Canales, Juan J; Ferrer-Donato, Agueda

    2014-01-01

    Recreational drug use among pregnant women is a source of concern due to potential harmful effects of drug exposure on prenatal and infant development. The simultaneous abuse of ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] and alcohol is prevalent among young adults, including young expectant mothers. Here, we used a rat model to study the potential risks associated with exposure to alcohol and MDMA during pregnancy. Pregnant rats received alcohol, MDMA, or both alcohol and MDMA by gavage at E13 through E15 twice daily. Female offspring treated prenatally with the combination of alcohol and MDMA, but not those exposed to either drug separately, showed at 3 months of age decreased exploratory activity and impaired working memory function. Prenatal treatment with the combination of alcohol and MDMA decreased proliferation of neuronal precursors in the adult dentate gyrus of the hippocampus, as measured by 5-bromo-2-deoxyuridine labelling, and adult neurogenesis, assessed by quantifying doublecortin expression. These results provide the first evidence that the simultaneous abuse of alcohol and ecstasy during pregnancy, even for short periods of time, may cause significant abnormalities in neurocognitive development.

  11. Exposure of Brassica juncea (L) to arsenic species in hydroponic medium: comparative analysis in accumulation and biochemical and transcriptional alterations.

    Science.gov (United States)

    Ahmad, Mohd Anwar; Gupta, Meetu

    2013-11-01

    Arsenic (As) contamination in the environment has attracted considerable attention worldwide. The objective of the present study was to see the comparative effect of As species As(III) and As(V) on accumulation, biochemical responses, and gene expression analysis in Brassica juncea var. Pusa Jaganath (PJn). Hydroponically grown 14-day-old seedlings of B. juncea were treated with different concentrations of As(III) and As(V). Accumulation of total As increased with increasing concentration of both As species and exposure time, mainly in roots. Reduction in seed germination, root-shoot length, chlorophyll, and protein content were observed with increasing concentration and exposure time of both As species, being more in As(III)-treated leaves. PJn variety showed that antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX)) and stress-related parameters (cysteine, proline, and malondialdehyde (MDA)) were stimulated and allows plant to tolerate both As species. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis in leaves showed significant changes in protein profile with more stringent effect with As(III) stress. Semiquantitative RT-PCR analysis showed regulation in expression of phytochelatin synthase (PCS), metallothionine-2 (MT-2), glutathione reductase (GR), and glutathione synthetase (GS) genes under both As(III) and As(V) stresses. Results suggested that accumulation and inhibition on physiological parameters differ according to the As species, while molecular and biochemical parameters showed a combinatorial type of tolerance mechanism against As(III) and As(V) stresses.

  12. Mercury exposure associated with altered plasma thyroid hormones in the declining western pond turtle (Emys marmorata) from California mountain streams

    Science.gov (United States)

    Meyer, Erik; Eagles-Smith, Collin A.; Sparling, Donald; Blumenshine, Steve

    2014-01-01

    Mercury (Hg) is a global threat to wildlife health that can impair many physiological processes. Mercury has well-documented endocrine activity; however, little work on the effects of Hg on the thyroid hormones triiodothyronine (T3) and thyroxine (T4) in aquatic wildlife exists despite the fact that it is a sensitive endpoint of contaminant exposure. An emerging body of evidence points to the toxicological susceptibility of aquatic reptiles to Hg exposure. We examined the endocrine disrupting potential of Hg in the western pond turtle (Emys marmorata), a long-lived reptile that is in decline throughout California and the Pacific Northwest. We measured total Hg (THg) concentrations in red blood cells (RBCs) and plasma T3 and T4 of turtles from several locations in California that have been impacted by historic gold mining. Across all turtles from all sites, the geometric mean and standard error THg concentration was 0.805 ± 0.025 μg/g dry weight. Sampling region and mass were the strongest determinants of RBC THg. Relationships between RBC THg and T3 and T4 were consistent with Hg-induced disruption of T4 deiodination, a mechanism of toxicity that may cause excess T4 levels and depressed concentrations of biologically active T3.

  13. Potential Association of Lead Exposure During Early Development of Mice With Alteration of Hippocampus Nitric Oxide Levels and Learning Memory

    Institute of Scientific and Technical Information of China (English)

    LI SUN; ZHENG-YAN ZHAO; JIAN HU; XIE-LAI ZHOU

    2005-01-01

    Objective Chronic lead (Pb) exposure during development is known to produce learning deficits. Nitric oxide participates in the synaptic mechanisms involved in certain forms of learning and memory. This study was designed to clarify whether Pb-induced impairment in learning and memory was associated with the changes of nitric oxide levels in mice brains.Methods Sixty Balb/c mice aged 10 days were chosen. A model of lead exposure was established by drinking 0.025%, 0.05%,0.075% lead acetate, respectively for 8 weeks. The controls were orally given distilled water. The ability to learn and memorize was examined by open field test, T-water maze test. In parallel with the behavioral data, NO level of hippocampus tissue was detected by biochemical assay. Results Compared with control groups, (1) the weight of 0.075% group was significantly reduced (P<0.05); (2) The number of times in mice attaining the required standards in T-water maze test was lower in 0.075%group (P<0.01). No significant difference was found between experimental and control groups in open field test (P>0.05); (3)NO level of mouse hippocampus tissue was decreased in 0.075% group (P<0.01). Conclusions The findings suggest that decreased hippocampus NO level may contribute to the Pb-induced deficits in learning and memory processes.

  14. How safe is the use of chlorpyrifos: Revelations through its effect on layer birds

    Science.gov (United States)

    Singh, P. P.; Kumar, Ashok; Chauhan, R. S.; Pankaj, P. K.

    2016-01-01

    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. PMID:27536038

  15. 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.

  16. 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.

  17. 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

  18. Protracted abstinence from chronic ethanol exposure alters the structure of neurons and expression of oligodendrocytes and myelin in the medial prefrontal cortex.

    Science.gov (United States)

    Navarro, A I; Mandyam, C D

    2015-05-01

    In rodents, chronic intermittent ethanol vapor exposure (CIE) produces alcohol dependence, alters the structure and activity of pyramidal neurons and decreases the number of oligodendroglial progenitors in the medial prefrontal cortex (mPFC). In this study, adult Wistar rats were exposed to seven weeks of CIE and were withdrawn from CIE for 21 days (protracted abstinence; PA). Tissue enriched in the mPFC was processed for Western blot analysis and Golgi-Cox staining to investigate the long-lasting effects of CIE on the structure of mPFC neurons and the levels of myelin-associated proteins. PA increased dendritic arborization within apical dendrites of pyramidal neurons. These changes occurred concurrently with hypophosphorylation of the N-methyl-d-aspartate (NMDA) receptor 2B (NR2B) at Tyr-1472. PA increased myelin basic protein (MBP) levels which occurred concurrently with hypophosphorylation of the premyelinating oligodendrocyte bHLH transcription factor Olig2 in the mPFC. Given that PA is associated with increased sensitivity to stress and hypothalamic-pituitary-adrenal (HPA) axis dysregulation, and stress alters oligodendrocyte expression as a function of glucocorticoid receptor (GR) activation, the levels of total GR and phosphorylated GR were also evaluated. PA produced hypophosphorylation of the GR at Ser-232 without affecting expression of total protein. These findings demonstrate persistent and compensatory effects of ethanol in the mPFC long after cessation of CIE, including enhanced myelin production and impaired GR function. Collectively, these results suggest a novel relationship between oligodendrocytes and GR in the mPFC, in which stress may alter frontal cortex function in alcohol dependent subjects by promoting hypermyelination, thereby altering the cellular composition and white matter structure in the mPFC.

  19. 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.

  20. 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...

  1. 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)...

  2. 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 ...

  3. 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

  4. 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...

  5. Risk of prenatal depression and stress treatment: alteration on serotonin system of offspring through exposure to Fluoxetine

    Science.gov (United States)

    Pei, Siran; Liu, Li; Zhong, Zhaomin; Wang, Han; Lin, Shuo; Shang, Jing

    2016-01-01

    Fluoxetine is widely used to treat depression, including depression in pregnant and postpartum women. Studies suggest that fluoxetine may have adverse effects on offspring, presumably through its action on various serotonin receptors (HTRs). However, definitive evidence and the underlying mechanisms are largely unavailable. As initial steps towards establishing a human cellular and animal model, we analyzed the expression patterns of several HTRs through the differentiation of human induced pluripotent stem (hiPS) cells into neuronal cells, and analyzed expression pattern in zebrafish embryos. Treatment of zebrafish embryos with fluoxetine significantly blocked the expression of multiple HTRs. Furthermore, fluoxetine gave rise to a change in neuropsychology. Embryos treated with fluoxetine continued to exhibit abnormal behavior upto 12 days post fertilization due to changes in HTRs. These findings support a possible long-term risk of serotonin pathway alteration, possibly resulting from the “placental drug transfer”. PMID:27703173

  6. Alterations of organ histopathology and metallolhionein mRNA expression in silver barb, Puntius gonionotus during subchronic cadmium exposure

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Common silver barb, Puntius gonionotus exposed to the nominal concentration of 0.06 mg/L Cd for 60 d, were assessed for histopathological alterations (gills, liver and kidney), metal accumulation, and metallothionein (MT) mRNA expression. Fish exhibited pathological symptoms such as hypertrophy and hyperplasia of primary and secondary gill lamellae, vacuolization in hepatocytes, and prominent tubular and glomerular damage in the kidney. In addition, kidney accumulated the highest content of cadmium, more than gills and liver. Expression of MT mRNA was increased in both liver and kidney of treated fish. Hepatic MT levels remained high after fish were removed to Cd-free water. In contrast, MT expression in kidney was peaked after 28 d of treatment and drastically dropped when fish were removed to Cd-free water. The high concentrations of Cd in hepatic tissues indicated an accumulation site or permanent damage on this tissue.

  7. Study on Immunochemical Assays for the Organophosphorus Insecticide Chlorpyrifos

    Institute of Scientific and Technical Information of China (English)

    WU Gang; HUANG Ya-li; ZHU Guo-nian; WU Hui-ming; LI Cong

    2004-01-01

    The anti-chlorpyrifos polyclonal antibodies were obtained by using the artificial immune antigen to immune in New Zealand′s white rabbits. The enzyme-tagged antibodies were prepared by coupling horseradish peroxidase (HRP) to the purified antibody with the modified sodium periodate method. The indirect competitive enzyme linked immuno-sorbent assays (ELISA) and the HRP-taggedantibodydirect ELISA (E-Ab) were established, respectively.The limit of detection (LOD) for the indirect ELISA and E-Ab were 0.0033 and 0.0042 μg mL-1, respectively. The linear detection ranged well from 0.005 to 2.0 μg mL-1.

  8. Sex Specific Estrogen Receptor beta (ERβ) mRNA Expression in the Rat Hypothalamus and Amygdala is Altered by Neonatal Bisphenol A (BPA) Exposure

    Science.gov (United States)

    Cao, Jinyan; Joyner, Linwood; Mickens, Jillian A.; Leyrer, Stephanie M; Patisaul, Heather B

    2014-01-01

    Perinatal life is a critical window for sexually dimorphic brain organization, and profoundly influenced by steroid hormones. Exposure to endocrine disrupting compounds (EDCs) may disrupt this process, resulting in compromised reproductive physiology and behavior. To test the hypothesis that neonatal BPA exposure can alter sex specific postnatal ERβ expression in brain regions fundamental to sociosexual behavior we mapped ERβ mRNA levels in the principal nucleus of the bed nucleus of the stria terminalis (BNSTp), paraventricular nucleus (PVN), anterior portion of the medial amygdaloid nucleus (MeA), super optic nucleus (SON), suprachiasmic nucleus (SCN) and lateral habenula (LHb) across postnatal days (PNDs) 0 to 19. Next, rat pups of both sexes were subcutaneously injected over the first three days of life with 10 μg estradiol benzoate (EB), 50 μg/kg BPA (LBPA), or 50 mg/kg BPA (HBPA) and ERβ levels quantified in each region of interest (ROI) on PNDs 4 and 10. EB exposure decreased ERβ signal in most female ROIs, and in the male PVN. In the BNSTp, ERβ expression decreased in LBPA males and HBPA females on PND 10, thereby reversing the sex difference in expression. In the PVN, ERβ mRNA levels were elevated in LBPA females, also resulting in a reversal of sexually dimorphic expression. In the MeA, BPA decreased ERβ expression on PND 4. Collectively, these data demonstrate that region and sex specific ERβ expression is vulnerable to neonatal BPA exposure in regions of the developing rat brain critical to sociosexual behavior. PMID:24352099

  9. Embryonic co-exposure to methoxychlor and Clophen A50 alters sexual behavior in adult male quail.

    Science.gov (United States)

    Halldin, Krister; Axelsson, Jeanette; Brunström, Björn

    2005-04-01

    Embryonic exposure to estrogens and estrogenic pollutants is known to demasculinize sexual behavior in adult male Japanese quail. In the present study, we administered the insecticide methoxychlor to quail eggs at a dose of 150 microg/g egg and then studied sexual behavior and other reproductive variables in adult males. In a second experiment we administered the same dose of methoxychlor together with 10 microg/g egg of the commercial polychlorinated biphenyl (PCB) mixture Clophen A50 (CA50) and also CA50 alone. Neither methoxychlor nor CA50 had any significant effects by themselves, but when they were administered together a significant reduction in male sexual behavior was observed. It seems likely that induction of biotransformation enzymes in the embryos by CA50 resulted in increased conversion of methoxychlor to the more estrogenic metabolite 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE).

  10. Altered calcium handling and increased contraction force in human embryonic stem cell derived cardiomyocytes following short term dexamethasone exposure.

    Science.gov (United States)

    Kosmidis, Georgios; Bellin, Milena; Ribeiro, Marcelo C; van Meer, Berend; Ward-van Oostwaard, Dorien; Passier, Robert; Tertoolen, Leon G J; Mummery, Christine L; Casini, Simona

    2015-11-27

    One limitation in using human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) for disease modeling and cardiac safety pharmacology is their immature functional phenotype compared with adult cardiomyocytes. Here, we report that treatment of human embryonic stem cell derived cardiomyocytes (hESC-CMs) with dexamethasone, a synthetic glucocorticoid, activated glucocorticoid signaling which in turn improved their calcium handling properties and contractility. L-type calcium current and action potential properties were not affected by dexamethasone but significantly faster calcium decay, increased forces of contraction and sarcomeric lengths, were observed in hESC-CMs after dexamethasone exposure. Activating the glucocorticoid pathway can thus contribute to mediating hPSC-CMs maturation.

  11. 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

  12. 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.

  13. Bisphenol A exposure during adulthood alters expression of aromatase and 5α-reductase isozymes in rat prostate.

    Directory of Open Access Journals (Sweden)

    Beatriz Castro

    Full Text Available The high incidence of prostate cancer (PCa and benign prostatic hypertrophy (BPH in elderly men is a cause of increasing public health concern. In recent years, various environmental endocrine disruptors, such as bisphenol A (BPA, have been shown to disrupt sexual organs, including the prostate gland. However, the mechanisms underlying these effects remain unclear. Because androgens and estrogens are important factors in prostate physiopathology, our objective was to examine in rat ventral prostate the effects of adult exposure to BPA on 5α-Reductase isozymes (5α-R types 1, 2, and 3 and aromatase, key enzymes in the biosynthesis of dihydrotestosterone and estradiol, respectively. Adult rats were subcutaneously injected for four days with BPA (25, 50, 300, or 600 µg/Kg/d dissolved in vehicle. Quantitative RT-PCR, western blot and immunohistochemical analyses showed lower mRNA and protein levels of 5α-R1 and 5α-R2 in BPA-treated groups versus controls but higher mRNA levels of 5α-R3, recently proposed as a biomarker of malignancy. However, BPA treatment augmented mRNA and protein levels of aromatase, whose increase has been described in prostate diseases. BPA-treated rats also evidenced a higher plasma estradiol/testosterone ratio, which is associated with prostate disease. Our results may offer new insights into the role of BPA in the development of prostate disease and may be of great value for studying the prostate disease risk associated with exposure to BPA in adulthood.

  14. ACSL6 is associated with the number of cigarettes smoked and its expression is altered by chronic nicotine exposure.

    Directory of Open Access Journals (Sweden)

    Jingchun Chen

    Full Text Available Individuals with schizophrenia tend to be heavy smokers and are at high risk for tobacco dependence. However, the nature of the comorbidity is not entirely clear. We previously reported evidence for association of schizophrenia with SNPs and SNP haplotypes in a region of chromosome 5q containing the SPEC2, PDZ-GEF2 and ACSL6 genes. In this current study, analysis of the control subjects of the Molecular Genetics of Schizophrenia (MGS sample showed similar pattern of association with number of cigarettes smoked per day (numCIG for the same region. To further test if this locus is associated with tobacco smoking as measured by numCIG and FTND, we conducted replication and meta-analysis in 12 independent samples (n>16,000 for two markers in ACSL6 reported in our previous schizophrenia study. In the meta-analysis of the replication samples, we found that rs667437 and rs477084 were significantly associated with numCIG (p = 0.00038 and 0.00136 respectively but not with FTND scores. We then used in vitro and in vivo techniques to test if nicotine exposure influences the expression of ACSL6 in brain. Primary cortical culture studies showed that chronic (5-day exposure to nicotine stimulated ACSL6 mRNA expression. Fourteen days of nicotine administration via osmotic mini pump also increased ACSL6 protein levels in the prefrontal cortex and hippocampus of mice. These increases were suppressed by injection of the nicotinic receptor antagonist mecamylamine, suggesting that elevated expression of ACSL6 requires nicotinic receptor activation. These findings suggest that variations in the ACSL6 gene may contribute to the quantity of cigarettes smoked. The independent associations of this locus with schizophrenia and with numCIG in non-schizophrenic subjects suggest that this locus may be a common liability to both conditions.

  15. Epigenetic modulation upon exposure of lung fibroblasts to TiO2 and ZnO nanoparticles: alterations in DNA methylation

    Directory of Open Access Journals (Sweden)

    Patil NA

    2016-09-01

    Full Text Available Nayana A Patil,1,2 WN Gade,2 Deepti D Deobagkar1 1Department of Zoology, Molecular Biology Research Laboratory, Centre of Advanced Studies, 2Department of Biotechnology, Proteomic Research Laboratory, Savitribai Phule Pune University, Pune, India Abstract: Titanium dioxide (TiO2 and zinc oxide (ZnO nanoparticles (NPs are promising candidates for numerous applications in consumer products. This will lead to increased human exposure, thus posing a threat to human health. Both these types of NPs have been studied for their cell toxicity, immunotoxicity, and genotoxicity. However, effects of these NPs on epigenetic modulations have not been studied. Epigenetics is an important link in the genotype and phenotype modulation and misregulation can often lead to lifestyle diseases. In this study, we have evaluated the DNA methylation-based epigenetic changes upon exposure to various concentrations of NPs. The investigation was designed to evaluate global DNA methylation, estimating the corresponding methyltransferase activity and expression of Dnmt gene using lung fibroblast (MRC5 cell line as lungs are the primary route of entry and target of occupational exposure to TiO2 and ZnO NPs. Enzyme-linked immunosorbent assay-based immunochemical assay revealed dose-related decrease in global DNA methylation and DNA methyltransferase activity. We also found direct correlation between the concentration of NPs, global methylation levels, and expression levels of Dnmt1, 3A, and 3B genes upon exposure. This is the first study to investigate effect of exposure to TiO2 and ZnO on DNA methylation levels in MRC5 cells. Epigenetic processes are known to play an important role in reprogramming and adaptation ability of an organism and can have long-term consequences. We suggest that changes in DNA methylation can serve as good biomarkers for early exposure to NPs since they occur at concentrations well below the sublethal levels. Our results demonstrate a clear

  16. Development and recovery of histopathological alterations in the gonads of zebrafish (Danio rerio) after single and combined exposure to endocrine disruptors (17α-ethinylestradiol and fadrozole).

    Science.gov (United States)

    Luzio, Ana; Monteiro, Sandra M; Rocha, Eduardo; Fontaínhas-Fernandes, António A; Coimbra, Ana M

    2016-06-01

    Exposure of wildlife to endocrine disrupting chemicals (EDCs) is not necessarily continuous. Due to seasonal changes and variable industrial and agricultural activities it often occurs intermittently. Thus, it is possible that aquatic organisms may be more affected by periodic peak exposure than by chronic exposure. Therefore, an experimental scenario including an exposure from 2h to 90 days post-fertilization (dpf) and a subsequent recovery period until 150 dpf was chosen to assess the potential reversibility of the effects of sex steroids on sexual and gonad development of zebrafish (Danio rerio). The aim of this study was to investigate the persistence of the endocrine effects of an estrogen (EE2-17α-ethinylestradiol, 4ng/L), an inhibitor of estrogen synthesis (Fad-fadrozole, 50μg/L) or their binary mixture (Mix-EE2+ Fad, 4ng/L+50μg/L). Afterwards, a semi-quantitative histological assessment was used to investigate histopathological changes on gonad differentiation and development. The data showed that fadrozole, alone or in combination with EE2, permanently disrupts the sexual development, inducing masculinization and causing severe pathological alterations in testis, such as intersex associated to the enlargement of sperm ducts, interstitial changes, asynchronous development and detachment of basal membrane. After exposures to both EDCs and their mixture, the gonad histopathology revealed interstitial proteinaceous fluid deposits and, in ovaries, there were atretic oocytes, and presumably degenerative mineralization. On the other hand, the gonadal changes induced by EE2 alone seem to be partially reversible when the exposure regime changed to a recovery period. In addition, EE2 enhanced zebrafish growth in both genders, with male fish presenting signs of early obesity such as the presence of adipocytes in testis. Moreover, sex ratio was slightly skewed toward females, at 90 and 105 dpf, in zebrafish exposed to EE2. The data further indicate that long

  17. Altered formalin-induced pain and Fos induction in the periaqueductal grey of preadolescent rats following neonatal LPS exposure.

    Directory of Open Access Journals (Sweden)

    Ihssane Zouikr

    Full Text Available Animal and human studies have demonstrated that early pain experiences can produce alterations in the nociceptive systems later in life including increased sensitivity to mechanical, thermal, and chemical stimuli. However, less is known about the impact of neonatal immune challenge on future responses to noxious stimuli and the reactivity of neural substrates involved in analgesia. Here we demonstrate that rats exposed to Lipopolysaccharide (LPS; 0.05 mg/kg IP, Salmonella enteritidis during postnatal day (PND 3 and 5 displayed enhanced formalin-induced flinching but not licking following formalin injection at PND 22. This LPS-induced hyperalgesia was accompanied by distinct recruitment of supra-spinal regions involved in analgesia as indicated by significantly attenuated Fos-protein induction in the rostral dorsal periaqueductal grey (DPAG as well as rostral and caudal axes of the ventrolateral PAG (VLPAG. Formalin injections were associated with increased Fos-protein labelling in lateral habenula (LHb as compared to medial habenula (MHb, however the intensity of this labelling did not differ as a result of neonatal immune challenge. These data highlight the importance of neonatal immune priming in programming inflammatory pain sensitivity later in development and highlight the PAG as a possible mediator of this process.

  18. Prenatal exposure to di-n-butyl phthalate (DBP) differentially alters androgen cascade in undeformed versus hypospadiac male rat offspring.

    Science.gov (United States)

    Jiang, Jun-Tao; Zhong, Chen; Zhu, Yi-Ping; Xu, Dong-Liang; Wood, Kristofer; Sun, Wen-Lan; Li, En-Hui; Liu, Zhi-Hong; Zhao, Wei; Ruan, Yuan; Xia, Shu-Jie

    2016-06-01

    This study was to compare the alterations of androgen cascades in di-n-butyl phthalate (DBP)-exposed male offspring without hypospadias (undeformed) versus those with hypospadias. To induce hypospadias in male offspring, pregnant rats received DBP via oral gavage at a dose of 750mg/kg BW/day during gestational days 14-18. The mRNA expression levels of genes downstream of the androgen signaling pathway, such as androgen receptor (AR) and Srd5a2, in testes of undeformed rat pups were similar to those in controls; in hypospadiac rat pups these levels were significantly lower than those of control pups. In contrast, both undeformed and hypospadiac rats had decreased serum testosterone levels, reduced mRNA expression of key enzymes in the androgen synthetic pathway in the testes, and ablated genes of developmental pathways, such as Shh, Bmp4, Fgf8, Fgf10 and Fgfr2, in the genital tubercle (GT) as compared to those in DBP-unexposed controls, albeit hypospadiac rats had a more severe decrement than those of undeformed rats. Although other possibilities cannot be excluded, our findings suggest that the relatively normal levels of testosterone-AR-Srd5a2 may contribute to the resistance to DBP toxicity in undeformed rats. In conclusion, our results showed a potential correlation between decreased testosterone levels, reduced mRNA expression of AR and Srd5a2 and the occurrence of hypospadias in male rat offspring prenatally exposed to DBP. PMID:26948521

  19. Cyto-architectural Alterations in the Corpuscles of Stannius of Stinging Catfish Heteropneustes fossilis after Exposure to a Botanical Pesticide (Nerium indicum

    Directory of Open Access Journals (Sweden)

    ManiRam Prasad

    2014-03-01

    Full Text Available Background: This investigation describes the cyto-architectural alterations observed in the corpuscles of Stannius of stinging catfish Heteropneustes fossilis after treatment with a botanical pesticide Nerium indicum. Methods: Heteropneustes fossilis were subjected to 11.27 and 2.81 mg/L of Nerium indicum leaf extract over short- and long-term exposure periods, respectively. Blood was collected for calcium analysis and corpuscles of Stannius (CS gland were fixed on 24, 48, 72 and 96 h in the short-term experiment and after 7, 14, 21, and 28 days in the long-term experiment. Results: Serum calcium levels decreased from 48 h to 96 h. CS remains unaffected till 72 h. After the 96-hour treatment, increased granulation was observed in AF- positive cells. Nuclear volume of these cells exhibited no change throughout the short-term treatment. Slight increases in nuclear volume of AF-negative cells were recorded after 96 h. Nerium indicum caused decreases in serum calcium levels of H. fossilis from day 14 to 28. CS exhibited no alterations up to 14 days of exposure. AF-positive cells of CS depicted increased granulation after 21 days of treatment. Nuclear volume of these cells exhibited a slight decrease from day 21 to 28. Heavy accumulation of AF-positive granules was observed and few degenerating cells were noticed. Nuclear volume of AF-negative cells increased after 21 and 28 days of treatment. Vacuolization and degeneration occurred in certain places. Conclusion: It is inferred from the present study that the botanical pesticide Nerium indicum induced severe changes in the corpuscles of Stannius of catfish.

  20. Effect of atrazine and chlorpyrifos on common carp's liver%毒死蜱和阿特拉津对鲤肝脏的影响

    Institute of Scientific and Technical Information of China (English)

    韩英; 郝其睿; 魏菁; 赵荣伟; 牟振波; 徐革锋; 刘洋

    2015-01-01

    探讨阿特拉津(Atrazine,ATR)、毒死蜱(Chlorpyrifos,CPF)及其混合物对鲤(Cyprinus carpio L.)肝脏和血液相关指标的影响。将实验鲤分别暴露于不同浓度的阿特拉津、毒死蜱及其混合物中,并分别于175、350和525 d采集其肝组织、血液等样品。结果表明,阿特拉津和毒死蜱在鲤肝组织中均有残留,残留量随暴露时间及浓度的增加而降低;与对照组比较,各染毒组碱性磷酸酶、谷丙转氨酶及血糖水平显著升高,总蛋白、白蛋白水平下降,抗氧化能力下降,且毒死蜱与阿特拉津混合后毒性作用更强,说明两者的毒性有叠加作用;染毒后,肝脏ER-α和VTG-II基因表达水平升高。结果显示,鲤肝脏对阿特拉津和毒死蜱有较强的代谢能力,阿特拉津和毒死蜱在鲤肝脏无富集作用;阿特拉津和毒死蜱使鲤肝功能受损,抗氧化能力降低;ER-α和VTG-II基因的高调表达显示出阿特拉津和毒死蜱对鲤亦有环境雌激素作用。%In this study our purpose is to discuss the effects of atrazine and chlorpyrifos and their mixture to related index of common carp's liver and blood. Exposeed experimental carps respectively in atrazine, chlorpyrifos and their mixture of different concentrations, and collected samples of common carp's liver and blood at 175, 350 and 525 d. Results showed that both atrazine and chlorpyrifos had re-sidual in common carp's liver and the residual quantity reduced with the exposure time and the concen-tration increasing. Compared to the control group, the alkaline phosphatase, glutamic-pyruvic transami-nase and blood glucose levels of each infected group had significant rise, while the total protein and al-bumin levels declined. Moreover, the toxicity of the mixture of atrazine and chlorpyrifos was stronger than that prior to the blending, which illustrated the toxicity of the two have superposition. After infected, the expression

  1. Long-term exposure to paraquat alters behavioral parameters and dopamine levels in adult zebrafish (Danio rerio).

    Science.gov (United States)

    Bortolotto, Josiane W; Cognato, Giana P; Christoff, Raissa R; Roesler, Laura N; Leite, Carlos E; Kist, Luiza W; Bogo, Mauricio R; Vianna, Monica R; Bonan, Carla D

    2014-04-01

    Chronic exposure to paraquat (Pq), a toxic herbicide, can result in Parkinsonian symptoms. This study evaluated the effect of the systemic administration of Pq on locomotion, learning and memory, social interaction, tyrosine hydroxylase (TH) expression, dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels, and dopamine transporter (DAT) gene expression in zebrafish. Adult zebrafish received an i.p. injection of either 10 mg/kg (Pq10) or 20 mg/kg (Pq20) of Pq every 3 days for a total of six injections. Locomotion and distance traveled decreased at 24 h after each injection in both treatment doses. In addition, both Pq10- and Pq20-treated animals exhibited differential effects on the absolute turn angle. Nonmotor behaviors were also evaluated, and no changes were observed in anxiety-related behaviors or social interactions in Pq-treated zebrafish. However, Pq-treated animals demonstrated impaired acquisition and consolidation of spatial memory in the Y-maze task. Interestingly, dopamine levels increased while DOPAC levels decreased in the zebrafish brain after both treatments. However, DAT expression decreased in the Pq10-treated group, and there was no change in the Pq20-treated group. The amount of TH protein showed no significant difference in the treated group. Our study establishes a new model to study Parkinson-associated symptoms in zebrafish that have been chronically treated with Pq.

  2. Select Prenatal Environmental Exposures and Subsequent Alterations of Gene-Specific and Repetitive Element DNA Methylation in Fetal Tissues.

    Science.gov (United States)

    Green, Benjamin B; Marsit, Carmen J

    2015-06-01

    Strong evidence implicates maternal environmental exposures in contributing to adverse outcomes during pregnancy and later in life through the developmental origins of health and disease hypothesis. Recent research suggests these effects are mediated through the improper regulation of DNA methylation in offspring tissues, specifically placental tissue, which plays a critical role in fetal development. This article reviews the relevant literature relating DNA methylation in multiple tissues at or near delivery to several prenatal environmental toxicants and stressors, including cigarette smoke, endocrine disruptors, heavy metals, as well as maternal diet. These human studies expand upon previously reported outcomes in animal model interventions and include effects on both imprinted and non-imprinted genes. We have also noted some of the strengths and limitations in the approaches used, and consider the appropriate interpretation of these findings in terms of their effect size and their relationship to differential gene expression and potential health outcomes. The studies suggest an important role of DNA methylation in mediating the effects of the intrauterine environment on children's health and a need for additional research to better clarify the role of this epigenetic mechanism as well as others. PMID:26231362

  3. Exposure to contaminated sediments induces alterations in the gill epithelia in juvenile Solea senegalensis: a comparative in situ and ex situ study

    Directory of Open Access Journals (Sweden)

    Carla Martins

    2014-06-01

    contaminated sediments. Hypertrophied chloride cells are a consequence of a hindered osmotic regulation by the impairment of ionic active transport, leading to loss-of-function and excessive fluid retention in the cytoplasm. On its turn, a reduction in number and size of gill mucous cells likely reduced the protection provided by mucous to these delicate structures. In general, the alterations were more pronounced in the ex situ study than in situ bioassays, which is probably linked to differences in contaminant bioavailability between laboratory and field scenarios. This variation is likely related to, for instance, estuarine hydrodynamics and sediment steady-state parameters. Interestingly, the results suggest that time of exposure is a key factor, since fewer alterations were observed in animals sampled at the end of the assay (28 days compared to the mid-term (14 days, revealing adaptation to toxicological challenge. In conclusion, mixed sediment contamination can cause physiological alterations in fish gill epithelia that can be determined histologically. These subtle changes may affect the health status of animals by impairing key vital functions such as osmotic balance. As such, physiological alterations to fish gill epithelia may reflect, as in the present case, estuarine sediment contamination even when severe gill lesions are reduced or absent, which mandates caution when interpreting histopathological data in fish for the purpose of environmental risk assessment.

  4. Carcinogenic alterations in murine liver, lung, and uterine tumors induced by in utero exposure to ionizing radiation.

    Science.gov (United States)

    Lumniczky, K; Antal, S; Unger, E; Wunderlich, L; Hidvégi, E J; Sáfrány, G

    1998-02-01

    The atomic bombing of Hiroshima and Nagasaki and the nuclear accident at Chernobyl raised the question of prenatal sensitivity to ionizing radiation-induced cancer. In this study, mice were exposed to single doses of gamma-radiation (0.2-2.0 Gy) at different embryonic stages. The tumor incidence increased with dose from 15% in control mice to 35% in mice irradiated with 2.0 Gy on 18 d of prenatal life. Various oncogenic events were investigated in lymphoid, liver, lung, and uterine tumors. We observed threefold to fivefold increases in myc expression in 25% of the lymphomas, and the expression of Ha-ras and p53 genes decreased in 40% and 60% of the lung tumors by twofold to fivefold. Point mutations were tissue specific: Ha-ras codon 61 mutations were found in about 40% of the liver adenocarcinomas, Ki-ras codon 12 mutations in about 17% of lung tumors, and p53 mutations in about 15% of the lymphomas. Amplification and rearrangement of the p53, myc, and Ha-, Ki- and N-ras genes were not detected. Loss of heterozygosity on chromosome 4 at the multiple tumor suppressor 1 and 2 genes was observed in all types of malignancies. Allelic losses on chromosome 11 at the p53 locus were found in lymphoid, liver, and lung tumors, but they were absent from uterine tumors. Multiple oncogenic changes were often detected. The frequency of carcinogenic alterations was similar in spontaneous and radiation-induced lymphoid, liver, and uterine tumors. In radiation-induced lung adenocarcinomas, however, the incidences of many oncogenic changes were different from those found in their spontaneous counterparts. This suggests that different oncogenic pathways are activated during spontaneous and in utero gamma-radiation-induced murine lung carcinogenesis. PMID:9496910

  5. Microcystin-LR acute exposure does not alter in vitro and in vivo ATP, ADP and AMP hydrolysis in adult zebrafish (Danio rerio brain membranes

    Directory of Open Access Journals (Sweden)

    Luiza Wilges Kist

    2012-10-01

    Full Text Available Microcystins (MCs are toxins produced by cyanobacteria during the blooms that could accumulate in aquatic animals and be relocated to higher trophic levels. Adenosine triphosphate (ATP acts as an excitatory neurotransmitter and/or a neuromodulator in the extracellular space playing important roles in physiological and pathological conditions. The aim of this study was, therefore, to evaluate the acute effects of different concentrations of MC-LR on nucleoside triphosphate diphosphohydrolases and 5’-nucleotidade in adult zebrafish (Danio rerio brain membranes. The results have shown no significant changes in ATP, adenosine diphosphate (ADP and adenosine monophosphate (AMP hydrolysis in zebrafish brain membranes. MC-LR in vitro also did not alter ATP, ADP and AMP hydrolysis in the concentrations tested. These findings show that acute exposure to MC-LR did not modulate ectonucleotidase activity in the conditions tested. However, additional studies including chronic exposure should be performed in order to achieve a better understanding about MC-LR toxicity mechanisms in the central nervous system.

  6. Exposure of C57BL/6J mice to long photoperiod during early life stages increases body weight and alters plasma metabolomic profiles in adulthood.

    Science.gov (United States)

    Uchiwa, Tatsuhiro; Takai, Yusuke; Tashiro, Ayako; Furuse, Mitsuhiro; Yasuo, Shinobu

    2016-09-01

    Perinatal photoperiod is an important regulator of physiological phenotype in adulthood. In this study, we demonstrated that postnatal (0-4 weeks old) exposure of C57BL/6J mice to long photoperiod induced persistent increase in body weight until adulthood, compared with the mice maintained under short photoperiod. The expression of peroxisome proliferator-activated receptor δ, a gene involved in fatty acid metabolism, was decreased in 10-week-old mice exposed to long photoperiod during 0-4 or 4-8 weeks of age. Plasma metabolomic profiles of adult mice exposed to a long photoperiod during the postnatal period (0-4 LD) were compared to those in the mice exposed to short photoperiod during the same period. Cluster analysis revealed that both carbon metabolic pathway and nucleic acid pathway were altered by the postnatal photoperiod. Levels of metabolites involved in glycolysis were significantly upregulated in 0-4 LD, suggesting that the mice in 0-4 LD use the glycolytic pathway for energy expenditure rather than the fatty acid oxidation pathway. In addition, the mice in 0-4 LD exhibited high levels of purine metabolites, which have a role in neuroprotection. In conclusion, postnatal exposure of C57BL/6J mice to long photoperiod induces increase in body weight and various changes in plasma metabolic profiles during adulthood. PMID:27650252

  7. Chronic exposure to triclosan sustains microbial community shifts and alters antibiotic resistance gene levels in anaerobic digesters.

    Science.gov (United States)

    Carey, Daniel E; Zitomer, Daniel H; Kappell, Anthony D; Choi, Melinda J; Hristova, Krassimira R; McNamara, Patrick J

    2016-08-10

    Triclosan, an antimicrobial chemical found in consumer personal care products, has been shown to stimulate antibiotic resistance in pathogenic bacteria. Although many studies focus on antibiotic resistance pertinent to medical scenarios, resistance developed in natural and engineered environments is less studied and has become an emerging concern for human health. In this study, the impacts of chronic triclosan (TCS) exposure on antibiotic resistance genes (ARGs) and microbial community structure were assessed in lab-scale anaerobic digesters. TCS concentrations from below detection to 2500 mg kg(-1) dry solids were amended into anaerobic digesters over 110 days and acclimated for >3 solid retention time values. Four steady state TCS concentrations were chosen (30-2500 mg kg(-1)). Relative abundance of mexB, a gene coding for a component of a multidrug efflux pump, was significantly higher in all TCS-amended digesters (30 mg kg(-1) or higher) relative to the control. TCS selected for bacteria carrying tet(L) and against those carrying erm(F) at concentrations which inhibited digester function; the pH decrease associated with digester failure was suspected to cause this selection. Little to no impact of TCS was observed on intI1 relative abundance. Microbial communities were also surveyed by high-throughput 16S rRNA gene sequencing. Compared to the control digesters, significant shifts in community structure towards clades containing commensal and pathogenic bacteria were observed in digesters containing TCS. Based on these results, TCS should be included in studies and risk assessments that attempt to elucidate relationships between chemical stressors (e.g. antibiotics), antibiotic resistance genes, and public health. PMID:27291499

  8. Prenatal glucocorticoid exposure alters hypothalamic-pituitary-adrenal function and blood pressure in mature male guinea pigs.

    Science.gov (United States)

    Banjanin, Sonja; Kapoor, Amita; Matthews, Stephen G

    2004-07-01

    Pregnant guinea pigs were treated with dexamethasone (1 mg kg(-1)) or vehicle on days 40-41, 50-51 and 60-61 of gestation, after which animals delivered normally. Adult male offspring were catheterized at 145 days of age and subjected to tests of hypothalamic-pituitary-adrenal (HPA) axis function in basal and activated states. Animals exposed to dexamethasone in utero (mat-dex) exhibited increased hippocampus-to-brain weight ratio, increased adrenal-to-body weight ratio and increased mean arterial pressure. There were no effects on gestation length, birth weight and postnatal growth. There were no overall differences in diurnal plasma adrenocorticotropic hormone (ACTH) and cortisol profiles, though there were subtle differences during the subjective afternoon between control and mat-dex offspring. A significant decrease in initial ACTH suppression was observed following dexamethasone injection in mat-dex offspring compared to control offspring. Molecular analysis revealed significantly increased MR mRNA expression in the limbic system and particularly in the dentate gyrus in mat-dex offspring. In the anterior pituitary, both pro-opiomelanocortin (POMC) and glucocorticoid receptor (GR) mRNA levels were significantly elevated in mat-dex offspring. In conclusion, (1) repeated prenatal treatment with synthetic glucocorticoid (sGC) permanently programmes organ growth, blood pressure and HPA regulation in mature male offspring and these changes involve modification of corticosteroid receptor expression in the brain and pituitary; (2) the effects of prenatal sGC exposure on HPA function appear to change as a function of age, indicating the importance of investigating HPA and cardiovascular outcome at multiple time points throughout life.

  9. Chronic exposure to triclosan sustains microbial community shifts and alters antibiotic resistance gene levels in anaerobic digesters.

    Science.gov (United States)

    Carey, Daniel E; Zitomer, Daniel H; Kappell, Anthony D; Choi, Melinda J; Hristova, Krassimira R; McNamara, Patrick J

    2016-08-10

    Triclosan, an antimicrobial chemical found in consumer personal care products, has been shown to stimulate antibiotic resistance in pathogenic bacteria. Although many studies focus on antibiotic resistance pertinent to medical scenarios, resistance developed in natural and engineered environments is less studied and has become an emerging concern for human health. In this study, the impacts of chronic triclosan (TCS) exposure on antibiotic resistance genes (ARGs) and microbial community structure were assessed in lab-scale anaerobic digesters. TCS concentrations from below detection to 2500 mg kg(-1) dry solids were amended into anaerobic digesters over 110 days and acclimated for >3 solid retention time values. Four steady state TCS concentrations were chosen (30-2500 mg kg(-1)). Relative abundance of mexB, a gene coding for a component of a multidrug efflux pump, was significantly higher in all TCS-amended digesters (30 mg kg(-1) or higher) relative to the control. TCS selected for bacteria carrying tet(L) and against those carrying erm(F) at concentrations which inhibited digester function; the pH decrease associated with digester failure was suspected to cause this selection. Little to no impact of TCS was observed on intI1 relative abundance. Microbial communities were also surveyed by high-throughput 16S rRNA gene sequencing. Compared to the control digesters, significant shifts in community structure towards clades containing commensal and pathogenic bacteria were observed in digesters containing TCS. Based on these results, TCS should be included in studies and risk assessments that attempt to elucidate relationships between chemical stressors (e.g. antibiotics), antibiotic resistance genes, and public health.

  10. Chronic exposure to low levels of inorganic arsenic causes alterations in locomotor activity and in the expression of dopaminergic and antioxidant systems in the albino rat.

    Science.gov (United States)

    Rodríguez, Verónica Mireya; Limón-Pacheco, Jorge Humberto; Carrizales, Leticia; Mendoza-Trejo, María Soledad; Giordano, Magda

    2010-01-01

    Several studies have associated chronic arsenicism with decreases in IQ and sensory and motor alterations in humans. Likewise, studies of rodents exposed to inorganic arsenic ((i)As) have found changes in locomotor activity, brain neurochemistry, behavioral tasks, oxidative stress, and in sensory and motor nerves. In the current study, male Sprague-Dawley rats were exposed to environmentally relevant doses of (i)As (0.05, 0.5 mg (i)As/L) and to a high dose (50 mg (i)As/L) in drinking water for one year. Hypoactivity and increases in the striatal dopamine content were found in the group treated with 50 mg (i)As/L. Exposure to 0.5 and 50 mg (i)As/L increased the total brain content of As. Furthermore, (i)As exposure produced a dose-dependent up-regulation of mRNA for Mn-SOD and Trx-1 and a down-regulation of DAR-D₂ mRNA levels in the nucleus accumbens. DAR-D₁ and Nrf2 mRNA expression were down-regulated in nucleus accumbens in the group exposed to 50 mg (i)As/L. Trx-1 mRNA levels were up-regulated in the cortex in an (i)As dose-dependent manner, while DAR-D₁ mRNA expression was increased in striatum in the 0.5 mg (i)As/L group. These results show that chronic exposure to low levels of arsenic causes subtle but region-specific changes in the nervous system, especially in antioxidant systems and dopaminergic elements. These changes became behaviorally evident only in the group exposed to 50 mg (i)As/L.

  11. Daily Exposure to Sucrose Impairs Subsequent Learning About Food Cues: A Role for Alterations in Ghrelin Signaling and Dopamine D2 Receptors.

    Science.gov (United States)

    Sharpe, M J; Clemens, K J; Morris, M J; Westbrook, R F

    2016-04-01

    The prevalence of hedonic foods and associated advertising slogans has contributed to the rise of the obesity epidemic in the modern world. Research has shown that intake of these foods disrupt dopaminergic systems. It may be that a disruption of these circuits produces aberrant learning about food-cue relationships. We found that rodents given 28 days of intermittent access to sucrose exhibited a deficit in the ability to block learning about a stimulus when it is paired in compound with food and another stimulus that has already been established as predictive of the food outcome. This deficit was characterized by an approach to a cue signaling food delivery that is usually blocked by prior learning, an effect dependent on dopaminergic prediction-error signaling in the midbrain. Administering the D2 agonist quinpirole during learning restored blocking in animals with a prior history of sucrose exposure. Further, repeated central infusions of ghrelin produced a deficit in blocking in the same manner as sucrose exposure. We argue that changes in dopaminergic systems resulting from sucrose exposure are mediated by a disruption of ghrelin signaling as rodents come to anticipate delivery of the highly palatable sucrose outside of normal feeding schedules. This suggestion is supported by our finding that both sucrose and ghrelin treatments resulted in increases in amphetamine-induced locomotor responding. Thus, for the first time, we have provided evidence of a potential link between alterations in D2 receptors caused by the intake of hedonic foods and aberrant learning about cue-food relationships capable of promoting inappropriate feeding habits. In addition, we have found preliminary evidence to suggest that this is mediated by changes in ghrelin signaling, a finding that should stimulate further research into modulation of ghrelin activity to treat obesity. PMID:26365954

  12. Phytic Acid Exposure Alters AflatoxinB1-induced Reproductive and Oxidative Toxicity in Albino Rats (Rattus norvegicus).

    Science.gov (United States)

    Abu El-Saad, Abdelaziz S; Mahmoud, Hamada M

    2009-09-01

    activities were recorded. The histopathologic alterations revealed a degeneration and highly mitotic division within the spermatogenic nuclei, in addition to some karyomegaly and nuclear pyknosis. It is concluded that the reduction in the toxicity of free radicals by phytic acid might be responsible for the protective influence observed.

  13. Phytic Acid Exposure Alters AflatoxinB1-Induced Reproductive and Oxidative Toxicity in Albino Rats (Rattus norvegicus

    Directory of Open Access Journals (Sweden)

    Abdelaziz S. Abu El-Saad

    2009-01-01

    dismutase activities were recorded. The histopathologic alterations revealed a degeneration and highly mitotic division within the spermatogenic nuclei, in addition to some karyomegaly and nuclear pyknosis. It is concluded that the reduction in the toxicity of free radicals by phytic acid might be responsible for the protective influence observed.

  14. Acute exposure to ergot alkaloids from endophyte-infected tall fescue does not alter absorptive or barrier function of the isolated bovine ruminal epithelium.

    Science.gov (United States)

    Foote, A P; Penner, G B; Walpole, M E; Klotz, J L; Brown, K R; Bush, L P; Harmon, D L

    2014-07-01

    Ergot alkaloids in endophyte-infected (Neotyphodium coenophialum) tall fescue (Lolium arundinaceum) have been shown to cause a reduction in blood flow to the rumen epithelium as well as a decrease in volatile fatty acids (VFA) absorption from the washed rumen of steers. Previous data also indicates that incubating an extract of endophyte-infected tall fescue seed causes an increase in the amount of VFA absorbed per unit of blood flow, which could result from an alteration in the absorptive or barrier function of the rumen epithelium. An experiment was conducted to determine the acute effects of an endophyte-infected tall fescue seed extract (EXT) on total, passive or facilitated acetate and butyrate flux across the isolated bovine rumen as well as the barrier function measured by inulin flux and tissue conductance (G t ). Flux of ergovaline across the rumen epithelium was also evaluated. Rumen tissue from the caudal dorsal sac of Holstein steers (n=6), fed a common diet, was collected and isolated shortly after slaughter and mounted between two halves of Ussing chambers. In vitro treatments included vehicle control (80% methanol, 0.5% of total volume), Low EXT (50 ng ergovaline/ml) and High EXT (250 ng ergovaline/ml). Results indicate that there is no effect of acute exposure to ergot alkaloids on total, passive or facilitated flux of acetate or butyrate across the isolate bovine rumen epithelium (P>0.51). Inulin flux (P=0.16) and G t (P>0.17) were not affected by EXT treatment, indicating no alteration in barrier function due to acute ergot alkaloid exposure. Ergovaline was detected in the serosal buffer of the High EXT treatment indicating that the flux rate is ~0.25 to 0.44 ng/cm2 per hour. Data indicate that specific pathways for VFA absorption and barrier function of the rumen epithelium are not affected by acute exposure to ergot alkaloids from tall fescue at the concentrations tested. Ergovaline has the potential to be absorbed from the rumen of cattle that

  15. 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.

  16. Biochemical and genetic alterations in the freshwater neotropical fish Prochilodus lineatus after acute exposure to Microcystis aeruginosa

    Directory of Open Access Journals (Sweden)

    Cylene Zambrozi Garcia

    2012-09-01

    Full Text Available Microcystins are secondary metabolites produced by different species of cyanobacteria, such as Microcystis aeruginosa (MA. In this study, the biochemical and genetic effects of lyophilized MA were evaluated in the neotropical fish Prochilodus lineatus exposed to 1 or 2 mg L-1 lyophilized MA (treated group or only water (control group in static toxicity tests for 24 and 96 h. The gills and liver were used in the analysis of biotransformation enzymes and antioxidant defenses, blood and gill cells in genetic analysis and in brain and muscle it was determined the activity of acetylcholinesterase (AChE. The results showed the biotransformation pathway activation due to the increase in hepatic CYP1A and in branchial and hepatic glutathione S-transferase (GST. The antioxidant defense proved to be greatly affected by MA exposure leading to changes, both in gills and liver, in the activities of superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPx, glutathione reductase (GR and in the content of tripeptide glutathione (GSH. Lipid peroxidation was not detected, but damage to DNA molecule was observed in blood cells. In conclusion, it can be state the lyophilized MA is able to promote changes in the biochemical and genetic parameters of P. lineatus.As microcistinas são metabólitos secundários produzidos por diferentes espécies de cianobactérias, como a Microcystis aeruginosa (MA. Neste estudo, os efeitos bioquímicos e genéticos de liofilizado de MA foram avaliados para juvenis da espécie de peixe Neotropical Prochilodus lineatus expostos a 1 ou 2 mg L-1 de liofilizado de MA (grupo tratado ou apenas à água (grupo controle, em testes de toxicidade estáticos, durante 24 e 96 h. As brânquias e o fígado foram usados para as análises das enzimas de biotransformação e defesas antioxidantes, células do sangue e das brânquias para análises genéticas e no cérebro e músculo foi determinada a atividade da acetilcolinesterase (ACh

  17. 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.

  18. Combined exposure to Maneb and Paraquat alters transcriptional regulation of neurogenesis-related genes in mice models of Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Desplats Paula

    2012-09-01

    Full Text Available Abstract Background Parkinson's disease (PD is a multifactorial disease where environmental factors act on genetically predisposed individuals. Although only 5% of PD manifestations are associated with specific mutations, majority of PD cases are of idiopathic origin, where environment plays a prominent role. Concurrent exposure to Paraquat (PQ and Maneb (MB in rural workers increases the risk for PD and exposure of adult mice to MB/PQ results in dopamine fiber loss and decreased locomotor activity. While PD is characterized by neuronal loss in the substantia nigra, we previously showed that accumulation of α-synuclein in the limbic system contributes to neurodegeneration by interfering with adult neurogenesis. Results We investigated the effect of pesticides on adult hippocampal neurogenesis in two transgenic models: Line 61, expressing the human wild type SNCA gene and Line LRRK2(G2019S, expressing the human LRRK2 gene with the mutation G2019S. Combined exposure to MB/PQ resulted in significant reduction of neuronal precursors and proliferating cells in non-transgenic animals, and this effect was increased in transgenic mice, in particular for Line 61, suggesting that α-synuclein accumulation and environmental toxins have a synergistic effect. We further investigated the transcription of 84 genes with direct function on neurogenesis. Overexpresion of α-synuclein resulted in the downregulation of 12% of target genes, most of which were functionally related to cell differentiation, while LRRK2 mutation had a minor impact on gene expression. MB/PQ also affected transcription in non-transgenic backgrounds, but when transgenic mice were exposed to the pesticides, profound alterations in gene expression affecting 27% of the studied targets were observed in both transgenic lines. Gene enrichment analysis showed that 1:3 of those genes were under the regulation of FoxF2 and FoxO3A, suggesting a primary role of these proteins in the response to

  19. Reproductive toxicity of inorganic mercury exposure in adult zebrafish: Histological damage, oxidative stress, and alterations of sex hormone and gene expression in the hypothalamic-pituitary-gonadal axis.

    Science.gov (United States)

    Zhang, Qun-Fang; Li, Ying-Wen; Liu, Zhi-Hao; Chen, Qi-Liang

    2016-08-01

    Mercury (Hg) is a prominent environmental contaminant that causes a variety of adverse effects on aquatic organisms. However, the mechanisms underlying inorganic Hg-induced reproductive impairment in fish remains largely unknown. In this study, adult zebrafish were exposed to 0 (control), 15 and 30μg Hg/l (added as mercuric chloride, HgCl2) for 30days, and the effects on histological structure, antioxidant status and sex hormone levels in the ovary and testis, as well as the mRNA expression of genes involved in the hypothalamic-pituitary-gonadal (HPG) axis were analyzed. Exposure to Hg caused pathological lesions in zebrafish gonads, and changed the activities and mRNA levels of antioxidant enzymes (catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx)) as well as the content of glutathione (GSH) and malondialdehyde (MDA). In females, although ovarian 17β-estradiol (E2) content remained relatively stable, significant down-regulation of lhβ, gnrh2, gnrh3, lhr and erα were observed. In males, testosterone (T) levels in the testis significantly decreased after Hg exposure, accompanied by down-regulated expression of gnrh2, gnrh3, fshβ and lhβ in the brain as well as fshr, lhr, ar, cyp17 and cyp11b in the testis. Thus, our study indicated that waterborne inorganic Hg exposure caused histological damage and oxidative stress in the gonads of zebrafish, and altered sex hormone levels by disrupting the transcription of related HPG-axis genes, which could subsequently impair the reproduction of fish. Different response of the antioxidant defense system, sex hormone and HPG-axis genes between females and males exposed to inorganic Hg indicated the gender-specific regulatory effect by Hg. To our knowledge, this is the first time to explore the effects and mechanisms of inorganic Hg exposure on reproduction at the histological, enzymatic and molecular levels, which will greatly extend our understanding on the mechanisms underlying of reproductive

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

    Science.gov (United States)

    Gao, Yan; Chen, Shaohua; Hu, Meiying; Hu, Qiongbo; Luo, Jianjun; Li, Yanan

    2012-01-01

    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.

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

    Science.gov (United States)

    Daam, Michiel A; Crum, Steven J H; Van den Brink, Paul J; Nogueira, António J A

    2008-12-01

    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 relatively small, with the major part in the top layer (depth, 1.5 cm). Application of chlorpyrifos led to significant changes in freshwater biological communities. Clam shrimps (Conchostraca) and the cladoceran Moina micrura were the most susceptible species (no-observed-effect concentration [NOEC], 0.1 microg/L) and macroinvertebrates the most sensitive community (NOEC, 0.1 microg/L). These results are in agreement with those from semifield experiments with chlorpyrifos in temperate regions. The results of an in situ bioassay were used to calculate a NOEC of 0.1 microg/L and a 48-h median lethal concentration of 0.6 microg/L for M. micrura, which are similar to toxicity values reported for Daphnia magna in studies in temperate regions. Overall, these findings support the use of toxicity data from temperate regions for the risk assessment of low-persistent insecticides like chlorpyrifos for aquatic communities in tropical regions. PMID:18699699

  2. Sex differences in the adult HPA axis and affective behaviors are altered by perinatal exposure to a low dose of bisphenol A.

    Science.gov (United States)

    Chen, Fang; Zhou, Libin; Bai, Yinyang; Zhou, Rong; Chen, Ling

    2014-07-01

    Bisphenol A (BPA), an estrogen-mimicking endocrine disrupter, when administered perinatally can affect affective behaviors in adult rodents, however the underlying mechanisms remain largely unclear. Postnatal day (PND) 80 vehicle-injected control female rats showed more obvious depression- and anxiety-like behaviors than males, indicative of sexually dimorphic affective behaviors. When female breeders were subcutaneously injected with BPA (2µg/kg) from gestation day 10 to lactation day 7, sex difference of affective behaviors was impaired in their offspring (PND80 BPA-rats), as results that female BPA-rats showed a visible "antianxiety-like" behavior, and male BPA-rats increased depression-like behavior compared to vehicle-injected controls. Notably, basal levels of serum corticosterone and adrenocorticotropin (ACTH), and corticotropin-releasing hormone mRNA were increased in male BPA-rats, but not in female BPA-rats, in comparison with vehicle-injected controls. Following mild-stressor the elevation of corticosterone or ACTH levels was higher in male BPA-rats, whereas it was lower in female BPA-rats than vehicle-injected controls. In comparison with vehicle-injected controls, the level of glucocorticoid receptor (GR) mRNA in hippocampus or hypothalamic paraventricular nucleus was increased in female BPA-rats, while decreased in male BPA-rats. In addition, the levels of hippocampal mineralocorticoid receptor (MR) mRNA, neuronal nitric oxide synthase (nNOS) and phospho-cAMP response element binding protein (p-CREB) were increased in female BPA-rats, but were decreased in male BPA-rats. Furthermore, the testosterone level was reduced in male BPA-rats. The results indicate that the perinatal exposure to BPA through altering the GR and MR expression disrupts the GR-mediated feedback of hypothalamic-pituitary-adrenal (HPA) axis and MR-induced nNOS-CREB signaling, which alters sex difference in affective behaviors. PMID:24857958

  3. 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

  4. Dietary exposures to selected metals and pesticides.

    OpenAIRE

    MacIntosh, D L; Spengler, J D; Ozkaynak, H; Tsai, L.; Ryan, P B

    1996-01-01

    Average daily dietary exposures to 11 contaminants were estimated for approximately 120,000 U.S. adults by combining data on annual diet, as measured by a food frequency questionnaire, with contaminant residue data for table-ready foods that were collected as part of the annual U.S. Food and Drug Administration Total Diet Study. The contaminants included in the analysis were four heavy metals (arsenic, cadmium, lead, mercury), three organophosphate pesticides (chlorpyrifos, diazinon, malathio...

  5. Prenatal exposure to moderate levels of ethanol alters social behavior in adult rats: Relationship to structural plasticity and immediate early gene expression in frontal cortex

    Science.gov (United States)

    Hamilton, Derek A.; Akers, Katherine G.; Rice, James P.; Johnson, Travis E.; Candelaria-Cook, Felicha T.; Maes, Levi I.; Rosenberg, Martina; Valenzuela, C. Fernando; Savage, Daniel D.

    2009-01-01

    The goals of the present study were to characterize the effects of prenatal exposure to moderate levels of ethanol on adult social behavior, and to evaluate fetal-ethanol-related effects on dendritic morphology, structural plasticity and activity-related immediate early gene (IEG) expression in the agranular insular (AID) and prelimbic (Cg3) regions of frontal cortex. Baseline fetal-ethanol-related alterations in social behavior were limited to reductions in social investigation in males. Repeated experience with novel cage-mates resulted in comparable increases in wrestling and social investigation among saccharin- and ethanol-exposed females, whereas social behavioral effects among males were more evident in ethanol-exposed animals. Male ethanol-exposed rats also displayed profound increases in wrestling when social interaction was motivated by 24 hours of isolation. Baseline decreases in dendritic length and spine density in AID were observed in ethanol-exposed rats that were always housed with the same cage-mate. Modest experience-related decreases in dendritic length and spine density in AID were observed in saccharin-exposed rats housed with various cage-mates. In contrast, fetal-ethanol-exposed rats displayed experience-related increases in dendritic length in AID, and no experience-related changes in spine density. The only effect observed in Cg3 was a baseline increase in basilar dendritic length among male ethanol-exposed rats. Robust increases in activity-related IEG expression in AID (c-fos and Arc) and Cg3 (c-fos) were observed following social interaction in saccharin-exposed rats, however, activity-related increases in IEG expression were not observed in fetal-ethanol-exposed rats in either region. The results indicate that deficits in social behavior are among the long-lasting behavioral consequences of moderate ethanol exposure during brain development, and implicate AID, and to a lesser degree Cg3, in fetal-ethanol-related social behavior

  6. In Utero Exposure to a Cardiac Teratogen Causes Reversible Deficits in Postnatal Cardiovascular Function, But Altered Adaptation to the Burden of Pregnancy.

    Science.gov (United States)

    Aasa, Kristiina L; Maciver, Rebecca D; Ramchandani, Shyamlal; Adams, Michael A; Ozolinš, Terence R S

    2015-11-01

    Congenital heart defects (CHD) are the most common birth anomaly and while many resolve spontaneously by 1 year of age, the lifelong burden on survivors is poorly understood. Using a rat model of chemically induced CHD that resolve postnatally, we sought to characterize the postnatal changes in cardiac function, and to investigate whether resolved CHD affects the ability to adapt to the increased the cardiovascular (CV) burden of pregnancy. To generate rats with resolved CHD, pregnant rats were administered distilled water or dimethadione (DMO) [300 mg/kg b.i.d. on gestation day (gd) 9 and 10] and pups delivered naturally. To characterize structural and functional changes in the heart, treated and control offspring were scanned by echocardiography on postnatal day 4, 21, and 10-12 weeks. Radiotelemeters were implanted for continuous monitoring of hemodynamics. Females were mated and scanned by echocardiography on gd12 and gd18 during pregnancy. On gd18, maternal hearts were collected for structural and molecular assessment. Postnatal echocardiography revealed numerous structural and functional differences in treated offspring compared with control; however, these resolved by 10-12 weeks of age. The CV demand of pregnancy revealed differences between treated and control offspring with respect to mean arterial pressure, CV function, cardiac strain, and left ventricular gene expression. In utero exposure to DMO also affected the subsequent generation. Gd18 fetal and placental weights were increased in treated F2 offspring. This study demonstrates that in utero chemical exposure may permanently alter the capacity of the postnatal heart to adapt to pregnancy and this may have transgenerational effects.

  7. Hematobiochemical and pathological alterations due to chronic chlorpyrifos intoxication in indigenous chicken

    Directory of Open Access Journals (Sweden)

    Shameem Ara Begum

    2015-01-01

    Results: A significant (P < 0.01 increase of Hb, TEC, TLC, and heterophil percent and decrease of lymphocyte percent was observed. Serum ALP, AST, ALT, and uric acid increased significantly and CHE values decreased significantly in CPF treated birds. The protein level remained similar. Uric acid level was found to be increased significantly in the treated group. The results indicate that chronic CPF intoxication produces hematological, biochemical, and pathological changes in treated birds.

  8. Behavioral swimming effects and acetylcholinesterase activity changes in Jenynsia multidentata exposed to chlorpyrifos and cypermethrin individually and in mixtures.

    Science.gov (United States)

    Bonansea, Rocío Inés; Wunderlin, Daniel Alberto; Amé, María Valeria

    2016-07-01

    The pesticides cypermethrin (CYP) and chlorpyrifos (CPF) were found together in water bodies located in agricultural and urban areas. However, the impact to non-target biota from exposure to mixtures has received little attention. In the current study, we evaluated changes in swimming behavior and cholinesterase enzymes activity in Jenynsia multidentata, to investigate the possible effects of these insecticides individually and in mixtures. Moreover, differences between technical and commercial mixtures of the pesticides were evaluated. Females of J. multidentata were exposed over 96-h to CYP (0.04 and 0.4µgL(-1)), CPF (0.4 and 4µgL(-1)), individually and in a technical and commercial mixtures. Swimming behavior was recorded after 24h and 96h of exposure. Also, we measured cholinesterase enzymes activity in brain and muscle after 96h of exposure. Exposure to CYP increased the exploratory activity of J. multidentata in the upper area of the aquarium. Fish exposed to CPF (4µg L(-1)) showed a decrease in swimming activity and an increase in the time spent at the bottom of the aquarium. Interestingly, fish exposed to the technical and commercial mixture of CYP and CPF displayed a different behavior based on the concentration of exposure. Low concentration of pesticides elicited an increase in J. multidentata swimming activity with preference for the upper area of the aquarium, and high concentrations caused decrease in swimming activity with preference for the bottom area of the aquarium. Based on the response of cholinesterase enzymes, acetylcholinesterase in muscle was more sensitive to exposure to CYP, CPF and their mixtures than in brain. A decrease in swimming behavior correlates significantly with the inhibition of acetylcholinesterase activity in muscle of J. multidentata exposed to high concentrations of pesticides. These results draw attention to the need of more studies on the potential ecotoxicological impact of pesticides and its mixtures at

  9. 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.

  10. Exposure of human JEG-3 cell line to TCDD alters progesterone secretion but does not act on their viability and apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Augustowska, K.; Gregoraszczuk, E.L. [Jagiellonian Univ., Krakow (Poland)

    2004-09-15

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related compounds are lipophilic and difficult to metabolize. Any environmental exposure of living organisms to these congeners results in their accumulation in fat tissue and bioconcentration in humans via the food chain. TCDD acts as an endocrine disrupter to alter differentiation and function of the reproductive system. Therefore, these compounds represent a serious health risk, especially to the fetus and infants, whose enzymatic and metabolic systems are not yet mature. Our previous data showed high accumulation of TCDD in cultured human placental tissue which caused a decrease in hormone secretion. However, the mechanism of this action is still unclear. JEG-3 cell line from malignant placental tissue has been used as an in vitro model for investigation of the effects of xenobiotics on placenta toxicity. These cells are morphologically similar to their origin, the trophoblast of the normal first trimester placenta, and produce many peptides and steroid hormones found in normal trophoblast cells, such as hCG, GhRH, progesterone. The aim of the present study was firstly, to show dose- and time-dependent effects of TCDD on progesterone production by JEG-3 cells and secondly, to examine mechanism of its action on cell viability and apoptosis.

  11. Histopathological alterations and induction of hsp70 in ramshorn snail (Marisa cornuarietis) and zebrafish (Danio rerio) embryos after exposure to PtCl(2).

    Science.gov (United States)

    Osterauer, Raphaela; Köhler, Heinz-R; Triebskorn, Rita

    2010-08-01

    The platinum group metals (PGMs) platinum (Pt), palladium (Pd), and rhodium (Rh) are used in automobile catalytic converters, from which they have been emitted into the environment to an increasing degree during the last 20 years. Despite the bioavailability of these metals to plants and animals, studies determining the effects of PGMs on organisms are extremely rare. In the present study, effects of various concentrations of PtCl(2) (0.1, 1, 10, 50 and 100 microg/L) were investigated with respect to the induction of hsp70 and histopathological alterations in the zebrafish, Danio rerio and the ramshorn snail, Marisa cornuarietis. Histopathological investigations revealed effects of Pt on both species, which varied between slight and strong cellular reactions, depending on the PtCl(2) concentration. The hsp70 level in M. cornuarietis did not show an increase following Pt exposure whereas it was significantly elevated at 100 micorg/L PtCl(2) in D. rerio. PMID:20444508

  12. Prenatal alcohol exposure alters p35, CDK5 and GSK3β in the medial frontal cortex and hippocampus of adolescent mice

    Directory of Open Access Journals (Sweden)

    Samantha L. Goggin

    2014-01-01

    Full Text Available Fetal alcohol spectrum disorders (FASDs are the number one cause of preventable mental retardation. An estimated 2–5% of children are diagnosed as having a FASD. While it is known that children prenatally exposed to alcohol experience cognitive deficits and a higher incidence of psychiatric illness later in life, the pathways underlying these abnormalities remain uncertain. GSK3β and CDK5 are protein kinases that are converging points for a vast number of signaling cascades, including those controlling cellular processes critical to learning and memory. We investigated whether levels of GSK3β and CDK5 are affected by moderate prenatal alcohol exposure (PAE, specifically in the hippocampus and medial frontal cortex of the adolescent mouse. In the present work we utilized immunoblotting techniques to demonstrate that moderate PAE increased hippocampal p35 and β-catenin, and decreased total levels of GSK3β, while increasing GSK3β Ser9 and Tyr216 phosphorylation. Interestingly, different alterations were seen in the medial frontal cortex where p35 and CDK5 were decreased and increased total GSK3β was accompanied by reduced Tyr216 of the enzyme. These results suggest that kinase dysregulation during adolescence might be an important contributing factor to the effects of PAE on hippocampal and medial frontal cortical functioning; and by extension, that global modulation of these kinases may produce differing effects depending on brain region.

  13. 妊娠早期暴露低浓度毒死蜱对子代鼠海马脑区及体觉皮层的影响%Effects of low concentration of chlorpyrifos prenatal exposure on generation mouse brain hippocam-pus and somatosensory cortex

    Institute of Scientific and Technical Information of China (English)

    陈晓萍; 金建龙; 李传武; 王飞石

    2009-01-01

    目的 探讨小鼠妊娠早期暴露低浓度有机磷农药毒死蜱对子代鼠脑结构发育的影响.方法 在母鼠妊娠7.5~11.5 d时,以每天皮下注射5 mg/kg毒死蜱,连续5 d,将子代鼠在出生第35天处死,取脑作定位切片,HE及尼氏染色,显微镜下测量海马CA1、CA3区、DG区厚度,计数大脑皮层S1区神经元和胶质细胞数量及比例.结果 出生35 d的子代鼠海马CA 1区平均厚度下降22.37%,CA3区平均厚度下降25.66%,而DG区平均厚度增加24.14%,与对照组比较,差异均有统计学意义(P<0.01).S1区神经元,胶质细胞比值由81.77%下降至74.61%.结论 小鼠妊娠早期低浓度有机磷农药毒死蜱持续暴露可导致子代鼠脑结构细微损伤.%Objective To observe the effects of low concentration of organophosphate pesticide chlor-pyrifos(CPF) prenatal exposure on generation mouse brain development. Methods 5 mg/kg CPF was admin-istered daily on gestation days (GD) 7.5~11.5. On postnatal clay (PD) 35, quantitative morphologic examines were measured in CA1, CA3, dentate gyrus regions of the hippocampus and somatosensory cortex. Results After CPF prenatal exposure, selective morphology impairments were observed, showing 22.37%, 25.66 % thinning of the CA1 and CA3 layers, 24.14% enlargement of the dentate guys and 81.77% to 74.61% decreas-ing of the ratio of neuron/glial of the somatosensory cortex. Conclusion There maybe slight morphological changes after prenatal low concentration pesticide exposure even without obviously systemic toxicity.

  14. 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

  15. 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.

  16. 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

  17. 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.