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Sample records for parathion exposure alters

  1. Alteration of the kidney membrane proteome of Mizuhopecten yessoensis induced by low-level methyl parathion exposure.

    PubMed

    Huang, Xiang; Huang, He-Qing

    2012-06-15

    Methyl parathion (MP) is a widely used organophosphorus pesticide that causes severe health and environmental effects. We investigated the alteration of the proteomic profile in the membrane enriched fraction of the kidneys of the scallop Mizuhopecten yessoensis exposed to low-level MP. Gas chromatography analysis showed that MP residues were significantly accumulated in the kidneys and the digestive glands of the scallops. According to two-dimensional electrophoresis, 17 proteins were differentially modulated under MP exposure. The mRNA expressions of 12 differential proteins were analyzed using quantitative PCR, and 10 showed consistent alteration of mRNA level with that of protein expression level. Altered expressions of two proteins (mitochondrial processing peptidase and α-tubulin) were also examined using Western blotting, showing that the mitochondrial processing peptidase was down-regulated but α-tubulin remained unchanged in response to MP exposure. Subcellular locations of all the identified proteins that were predicted using bioinformatics tools indicate that few of them are permanently located in the membrane. The differentially expressed proteins are involved in several critical biological processes, and their relevance to human health has been illuminated. These data taken together have provided some novel insights into the chronic toxicity mechanism of MP and have suggested mitochondrial processing peptidase as a potential biomarker for human health and environmental monitoring.

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

    PubMed Central

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

    2009-01-01

    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 of systemic toxicity. In adulthood, animals were either maintained on standard chow or switched to a high-fat diet for seven weeks. We assessed serum leptin and adiponectin, tumor necrosis factor-α (TNFα) in adipose tissues, and thiobarbituric acid reactive species (TBARS) in peripheral tissues and brain regions. Neonatal parathion exposure uncoupled serum leptin levels from their dependence on body weight, suppressed adiponectin and elevated TNFα in white adipose tissue. Some of the effects were offset by a high-fat diet. Parathion reduced TBARS in the adipose tissues, skeletal muscle and temporal/occipital cortex but not in heart, liver, kidney or frontal/parietal cortex; it elevated TBARS in the cerebellum; the high-fat diet again reversed many of the effects. Neonatal parathion exposure disrupts the regulation of adipokines that communicate metabolic status between adipose tissues and the brain, while also evoking an inflammatory adipose response. Our results are consistent with impaired fat utilization and prediabetes, as well as exposing a potential relationship between effects on fat metabolism and on synaptic function in the brain. PMID:19615431

  3. Parathion alters incubation behavior of laughing gulls

    USGS Publications Warehouse

    White, D.H.; Mitchell, C.A.; Hill, E.F.

    1983-01-01

    One member of each pair of incubating laughing gulls at 9 nests was trapped, orally dosed with either 6 mg/kg parathion in corn oil or corn oil alone, and marked about the neck with red dye. Each nest was marked with a numbered stake and the treatment was recorded. A pilot study with captive laughing gulls had determined the proper dosage of parathion that would significantly inhibit their brain AChE activity (about 50% of normal) without overt signs of poisoning. After dosing, birds were released and the nests were observed for 2 1/2 days from a blind on the nesting island. The activities of the birds at each marked nest were recorded at 10-minute intervals. Results indicated that on the day of treatment there was no difference (P greater than 0.05, Chi-square test) in the proportion of time spent on the nest between treated and control birds. However, birds dosed with 6 mg/kg parathion spent significantly less time incubating on days 2 and 3 than did birds receiving only corn oil. By noon on the third day, sharing of nest duties between pair members in the treated group had approached normal, indicating recovery from parathion intoxication. These findings suggest that sublethal exposure of nesting birds to an organophosphate (OP) insecticide, such as parathion, may result in decreased nest attentiveness, thereby making the clutch more susceptible to predation or egg failure. Behavioral changes caused by sublethal OP exposure could be especially detrimental in avian species where only one pair member incubates or where both members are exposed in species sharing nest duties.

  4. Neonatal Organophosphorus Pesticide Exposure Alters the Developmental Trajectory of Cell-Signaling Cascades Controlling Metabolism: Differential Effects of Diazinon and Parathion

    PubMed Central

    Adigun, Abayomi A.; Wrench, Nicola; Seidler, Frederic J.; Slotkin, Theodore A.

    2010-01-01

    Background Organophosphorus pesticides (OPs) are developmental neurotoxicants but also produce lasting effects on metabolism. Objectives/methods We administered diazinon (DZN) or parathion (PRT) to rats on postnatal days 1–4 at doses straddling the threshold for systemic signs of exposure and assessed the effects on hepatic and cardiac cell signaling mediated through the adenylyl cyclase (AC) cascade. Results In the liver, DZN elicited global sensitization, characterized by parallel up-regulation of AC activity itself and of the responses to stimulants acting at β-adrenergic receptors, glucagon receptors, or G-proteins. The effects intensified over the course from adolescence to adulthood. In contrast, PRT elicited up-regulation in adolescence that waned by adulthood. Superimposed on these general patterns were effects on glucagon receptor coupling to AC and on responses mediated through the Gi inhibitory protein. The effects on the liver were more substantial than those in the heart, which displayed only transient effects of DZN on AC function in adolescence and no significant effects of PRT. Furthermore, the hepatic effects were greater in magnitude than those in a brain region (cerebellum) that shares similar AC cascade elements. Conclusions These findings indicate that OPs alter the trajectory of hepatic cell signaling in a manner consistent with the observed emergence of prediabetes-like metabolic dysfunction. Notably, the various OPs differ in their net impact on peripheral AC signaling, making it unlikely that the effects on signaling reflect their shared property as cholinesterase inhibitors. PMID:20123610

  5. External and internal exposure of wine growers spraying methyl parathion.

    PubMed

    Muttray, Axel; Bäcker, Gerhard; Jung, Detlev; Hill, Georg; Letzel, Stephan

    2006-04-10

    Organophosphates, used in agriculture, are readily absorbed through the skin. We investigated the relationship between dermal and inhalative methyl parathion exposure and the plasma levels. Twenty-three healthy wine growers sprayed the insecticide for 50 min. Fluorescent brilliant sulfoflavin was added to the spraying fluids and filter papers were fixed on the subjects. The filter papers were used to evaluate the amount of brilliant sulfoflavine on the unprotected skin fluorometrically. Inhalative exposure was measured with personal air sampler. Plasma concentrations of methyl parathion and its metabolite methyl paraoxon were determined with gas chromatography. Cholinesterase activity in serum and erythrocytes was measured before and after exposure. Some wine growers wore protective clothes, none protective gloves. Dermal exposure ranged up to 12,044 microg, inhalative to 22 microg. Maximum plasma concentration of methyl parathion was 12.1 microg/l. Methyl paraoxon was not detectable. Cholinesterase activity did not decrease. Dermal exposure correlated with the methyl parathion plasma level (Spearman's rho=0.72, p<0.001). In conclusion, dermal exposure exceeded inhalative exposure considerably. Measuring dermal deposition with the brilliant sulfoflavin technique may provide a good estimate of the internal load with methyl parathion. Preventive measures should be improved as toxic effects of repeated exposure to low doses of methyl parathion cannot be excluded.

  6. Parathion

    Integrated Risk Information System (IRIS)

    Parathion ; CASRN 56 - 38 - 2 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Effects

  7. Neonatal Parathion Exposure Disrupts Serotonin and Dopamine Synaptic Function in Rat Brain Regions

    PubMed Central

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

    2009-01-01

    The consequences of exposure to developmental neurotoxicants are influenced by environmental factors. In the present study, we examined the role of dietary fat intake. We administered parathion to neonatal rats and then evaluated whether a high-fat diet begun in adulthood could modulate the persistent effects on 5HT and DA systems. Neonatal rats received parathion on postnatal days 1-4 at 0.1 or 0.2 mg/kg/day, straddling the cholinesterase inhibition threshold. In adulthood, half the animals in each exposure group were given a high-fat diet for 8 weeks. We assessed 5HT and DA concentrations and turnover in brain regions containing their respective cell bodies and projections. In addition, we monitored 5HT1A and 5HT2 receptor binding and the concentration of 5HT presynaptic transporters. Neonatal parathion exposure evoked widespread increases in neurotransmitter turnover, indicative of presynaptic hyperactivity, further augmented by 5HT receptor upregulation. In control rats, consumption of a high-fat diet recapitulated many of the changes seen with neonatal parathion exposure; the effects represented convergent mechanisms, since the high-fat diet often obtunded further increases caused by parathion. Neonatal parathion exposure causes lasting hyperactivity of 5HT and DA systems accompanied by 5HT receptor upregulation, consistent with “miswiring” of neuronal projections. A high-fat diet obtunds the effect of parathion, in part by eliciting similar changes itself. Thus, dietary factors may produce similar synaptic changes as do developmental neurotoxicants, potentially contributing to the increasing incidence in neurodevelopmental disorders. PMID:19616088

  8. Enhancement of parathion toxicity to quail by heat and cold exposure

    USGS Publications Warehouse

    Rattner, B.A.; Becker, J.M.; Nakatsugawa, T.

    1987-01-01

    Effects of ambient temperature on the acute oral toxicity of parathion were investigated in Japanese quail (Coturnix japonica) maintained at thermoneutral temperature (26.degree. C) or exposed to elevated (37.degree. C) or reduced (4.degree. C) temperatures commonly encountered by free-ranging wild birds. Based upon estimates of the median lethal dosage, there was up to a two-fold enhancement of parathion toxicity in birds chronically exposed to heat or cold. Twenty-four hours after administration of a low dosage (4 mg/kg body wt, po), there was markedly greater cholinesterase inhibition in surviving heat-exposed quail compared with those reared at 26.degree. C (e.g., brain acetylcholinesterase depression of 42% versus 12%). There were no differences in hepatic activities of parathion oxidase, paraoxonase, or paraoxon deethylase which could account for greater toxicity to chronically heat-exposed birds. In contrast, 4 mg parathion/kg wt elicited less plasma cholinesterase inhibition in cold-exposed quail compared to thermoneutral controls (e.g., < 10% versus 48% depression after 24 hr). Increased liver weight and a doubling of paraoxonase activity may have been associated with greater tolerance to sublethal doses of parathion in chronically cold-exposed quail. These findings, together with limited field observations, indicate that the hazard associated with anticholinesterase exposure of wild birds is substantially influenced by environmental temperature.

  9. Children's exposure to chlorpyrifos and parathion in an agricultural community in central Washington State.

    PubMed Central

    Fenske, Richard A; Lu, Chensheng; Barr, Dana; Needham, Larry

    2002-01-01

    We measured two diethyl organophosphorus (OP) pesticides--chlorpyrifos and parathion--in residences, and their metabolic by-products, in the urine of children 6 years old or younger in a central Washington State agricultural community. Exposures to two dimethyl OP pesticides (azinphos-methyl and phosmet) in this same population have been reported previously. We categorized children by parental occupation and by household proximity to pesticide-treated farmland. Median chlorpyrifos house dust concentrations were highest for the 49 applicator homes (0.4 microg/g), followed by the 12 farm-worker homes (0.3 microg/g) and the 14 nonagricultural reference homes (0.1 microg/g), and were statistically different (p < 0.001); we observed a similar pattern for parathion in house dust. Chlorpyrifos was measurable in the house dust of all homes, whereas we found parathion in only 41% of the homes. Twenty-four percent of the urine samples from study children had measurable 3,5,6-trichloro-2-pyridinol (TCPy) concentrations [limits of quantitation (LOQ) = 8 microg/L], and 7% had measurable 4-nitrophenol concentrations (LOQ = 9 microg/L). Child urinary metabolite concentrations did not differ across parental occupational classifications. Homes in close proximity (200 ft/60 m) to pesticide-treated farmland had higher chlorpyrifos (p = 0.01) and parathion (p = 0.014) house dust concentrations than did homes farther away, but this effect was not reflected in the urinary metabolite data. Use of OP pesticides in the garden was associated with an increase in TCPy concentrations in children's urine. Parathion concentrations in house dust decreased 10-fold from 1992 to 1995, consistent with the discontinued use of this product in the region in the early 1990s. PMID:12003762

  10. Children's exposure to chlorpyrifos and parathion in an agricultural community in central Washington State.

    PubMed

    Fenske, Richard A; Lu, Chensheng; Barr, Dana; Needham, Larry

    2002-05-01

    We measured two diethyl organophosphorus (OP) pesticides--chlorpyrifos and parathion--in residences, and their metabolic by-products, in the urine of children 6 years old or younger in a central Washington State agricultural community. Exposures to two dimethyl OP pesticides (azinphos-methyl and phosmet) in this same population have been reported previously. We categorized children by parental occupation and by household proximity to pesticide-treated farmland. Median chlorpyrifos house dust concentrations were highest for the 49 applicator homes (0.4 microg/g), followed by the 12 farm-worker homes (0.3 microg/g) and the 14 nonagricultural reference homes (0.1 microg/g), and were statistically different (p < 0.001); we observed a similar pattern for parathion in house dust. Chlorpyrifos was measurable in the house dust of all homes, whereas we found parathion in only 41% of the homes. Twenty-four percent of the urine samples from study children had measurable 3,5,6-trichloro-2-pyridinol (TCPy) concentrations [limits of quantitation (LOQ) = 8 microg/L], and 7% had measurable 4-nitrophenol concentrations (LOQ = 9 microg/L). Child urinary metabolite concentrations did not differ across parental occupational classifications. Homes in close proximity (200 ft/60 m) to pesticide-treated farmland had higher chlorpyrifos (p = 0.01) and parathion (p = 0.014) house dust concentrations than did homes farther away, but this effect was not reflected in the urinary metabolite data. Use of OP pesticides in the garden was associated with an increase in TCPy concentrations in children's urine. Parathion concentrations in house dust decreased 10-fold from 1992 to 1995, consistent with the discontinued use of this product in the region in the early 1990s.

  11. Hormonal responses and tolerance to cold of female quail following parathion ingestion

    USGS Publications Warehouse

    Rattner, B.A.; Sileo, L.; Scanes, C.G.

    1982-01-01

    Thirty-week-old female bobwhite quail (Colinus virginianus), maintained at 26 + 1?C, were provided diets containing 0,25, or 100 ppm parathion ad libitum. After 10 days, birds were exposed to mild cold (6 + 1?C) for 4,8, 12, 24, or 48 hr. Brain acetylcholinesterase activity was inhibited in a dose-dependent manner in birds receiving 25 and 100 ppm parathion. Body weight, egg production, and plasma luteinizing hormone and progesterone concentrations were reduced in birds receiving 100 ppm parathion compared with other groups. Cold exposure did not alter plasma corticosterone levels in the 0- and 25-ppm parathion groups, but a two- to five fold elevation of plasma corticosterone was observed in birds fed 100 ppm parathion. These findings indicate that (i) short-term ingestion of parathion can impair reproduction possibly by altering gonadotropin or steroid secretion, and (ii) tolerance to cold may be reduced following ingestion of this organophosphate.

  12. Evaluation of sublethal biomarkers in Litopenaeus vannamei on foodborne exposure to methyl parathion.

    PubMed

    Comoglio, L; Amin, O; Roque, A; Betancourt-Lozano, M; Anguas, D; Haro, B M

    2005-09-01

    Sublethal effects of foodborne exposure to methyl parathion (0.62 and 1.31 microg methyl parathion*g(-1) dry weight of food) on juveniles of Litopenaeus vannamei using integrated biochemical (acetylcholinesterase (AChE) and ATPases) and physiological (feeding rate (FR), egestion rate (ER), and hepatosomatic index (HI)) biomarkers were evaluated. The HI was significantly higher in controls than in pesticide treatments. The FR was significantly lower in controls than in pesticide treatments while no significant differences were detected in the ER. AChE activity was significantly higher in controls than in pesticide treatments (control = 0.11 +/- 0.02; solvent control = 0.11 +/- 0.03; 0.62 = 0.07 +/- 0.01; 1.31 = 0.08 +/- 0.02 microM*min(-1)*mgprotein(-1)). The total-ATPase activity was significantly lower in controls than in pesticide treatments (control=77.90+/-12.41; solvent control = 83.69 +/- 22.05; 0.62 = 110.03 +/- 22.17; 1.31 = 121.54 +/- 19.84 microM P(i)*h(-1)*mgprotein(-1)). The Mg(2+)-ATPase activity was significantly higher in treatments than in controls (control = 65.14+/-10.76; solvent control = 75.12 +/- 21.10; 0.62 = 100.53 +/- 20.97; 1.31 = 108.94 +/- 17.26 microM P(i)*h(-1)*mgprotein(-1)). Finally, the results obtained for the Na(+)/K(+)-ATPase activity were significantly higher in control and in 1.31 than in solvent control and in 0.62 (control = 14.06+/-2.63; solvent control=7.30 +/- 4.13; 0.62 = 7.60 +/- 3.81; 1.31 = 13.42 +/- 2.88 microM P(i)*h(-1)*mgprotein(-1)). The results in this study showed that pulse exposures to methyl parathion via food could elicit measurable effects on the marine shrimp L. vannamei, indicating that foodborne exposure can be a reliable toxicological procedure and, if combined with pulse exposures, could also simulate more realistic exposure scenarios.

  13. Alterations of protein profile in zebrafish liver cells exposed to methyl parathion: a membrane proteomics approach.

    PubMed

    Huang, Qingyu; Huang, He-Qing

    2012-03-01

    Methyl parathion (MP) is an extensively used organophosphorus pesticide, which has been associated with a wide spectrum of toxic effects on environmental organisms. The aim of this study is to investigate the alterations of membrane protein profiles in zebrafish liver (ZFL) cell line exposed to MP for 24 h using proteomic approaches. Two-dimensional gel electrophoresis revealed a total of 13 protein spots, whose expression levels were significantly altered by MP. These differential proteins were subjected to matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry analysis, and nine proteins were identified to be membrane proteins, among which seven were up-regulated, while two were down-regulated. In addition, the mRNA levels corresponding to these differential membrane proteins were further analyzed by quantitative real-time PCR. And the differential expression of arginase-2 was specially validated via Western blotting. Regarding the physiological functions, these proteins are involved in molecular chaperon, cytoskeleton system, cell metabolism, signal transduction, transport and hormone receptor respectively, suggesting the complexity of MP-mediated toxicity to ZFL cell. These data could provide useful insights for better understanding the hepatotoxic mechanisms of MP and develop novel protein biomarkers for effectively monitoring MP contamination level in aquatic environment.

  14. Interactive toxicity of chlorpyrifos and parathion in neonatal rats: Role of esterases in exposure sequence-dependent toxicity

    SciTech Connect

    Kacham, R.; Karanth, S.; Baireddy, P.; Liu, J.; Pope, C. . E-mail: carey.pope@okstate.edu

    2006-01-15

    We previously reported that sequence of exposure to chlorpyrifos and parathion in adult rats can markedly influence toxic outcome. In the present study, we evaluated the interactive toxicity of chlorpyrifos (8 mg/kg, po) and parathion (0.5 mg/kg, po) in neonatal (7 days old) rats. Rats were exposed to the insecticides either concurrently or sequentially (separated by 4 h) and sacrificed at 4, 8, and 24 h after the first exposure for biochemical measurements (cholinesterase activity in brain, plasma, and diaphragm and carboxylesterase activity in plasma and liver). The concurrently-exposed group showed more cumulative lethality (15/24) than either of the sequential dosing groups. With sequential dosing, rats treated initially with chlorpyrifos prior to parathion (C/P) exhibited higher lethality (7/23) compared to those treated with parathion before chlorpyrifos (P/C; 1/24). At 8 h after initial dosing, brain cholinesterase inhibition was significantly greater in the C/P group (59%) compared to the P/C group (28%). Diaphragm and plasma cholinesterase activity also followed a relatively similar pattern of inhibition. Carboxylesterase inhibition in plasma and liver was relatively similar among the treatment groups across time-points. Similar sequence-dependent differences in brain cholinesterase inhibition were also noted with lower binary exposures to chlorpyrifos (2 mg/kg) and parathion (0.35 mg/kg). In vitro and ex vivo studies compared relative oxon detoxification of carboxylesterases (calcium-insensitive) and A-esterases (calcium-sensitive) in liver homogenates from untreated and insecticide pretreated rats. Using tissues from untreated rats, carboxylesterases detoxified both chlorpyrifos oxon and paraoxon, while A-esterases only detoxified chlorpyrifos oxon. With parathion pretreatment, A-esterases still detoxified chlorpyrifos oxon while liver from chlorpyrifos pretreated rats had little apparent effect on paraoxon. We conclude that while neonatal rats are less

  15. Effects of Exposure to Methyl Parathion on Egg Hatchability and Eggshell Chemical Composition in Podocnemis expansa (Testudines, Podocnemididae).

    PubMed

    Valdes, Sady Alexis Chavauty; Vieira, Lucélia Gonçalves; Ferreira, Caio Henrique; dos Santos Mendonça, Juliana; Ribeiro, Priscilla Rosa Queiroz; de Abreu Fernandes, Evandro; Santos, André Luiz Quagliatto

    2015-04-01

    Eggshell evaluation may serve as an indicator of the effect of substances released in the environment, which may change eggshell shape, size, structure, and/or chemical composition. Additionally, exposure may interfere with hatching rates in contaminated eggs. The objective of this study was to better understand how exposure to the insecticide methyl parathion interferes with chemical changes in eggshells of Podocnemis expansa throughout their artificial incubation, as well as with egg hatchability. A total of 343 P. expansa eggs were collected in a natural reproduction area for the species. These eggs were transferred to and artificially incubated in the Wild Animal Teaching and Research Laboratory at Universidade Federal de Uberlândia. On the first day of artificial incubation, 0, 35, 350, and 3500 ppb of methyl parathion were incorporated to the substrate. Eggs were collected every three days for chemical analysis of eggshells. Hatchability was evaluated as the number of hatchlings in each treatment, for the eggs that were not used in the chemical analysis. Student's T-test was used for data on eggshell chemical composition, and the Binomial Test for Two Proportions was used in the hatchability analysis, at a 5% significance level. It was observed that the incorporation of methyl parathion to the substrate on the first day of artificial incubation of P. expansa eggs reduced the levels of total fat in the shells throughout their incubation, besides reducing egg hatchability.

  16. Neonatal parathion exposure disrupts serotonin and dopamine synaptic function in rat brain regions: modulation by a high-fat diet in adulthood.

    PubMed

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

    2009-01-01

    The consequences of exposure to developmental neurotoxicants are influenced by environmental factors. In the present study, we examined the role of dietary fat intake. We administered parathion to neonatal rats and then evaluated whether a high-fat diet begun in adulthood could modulate the persistent effects on 5HT and DA systems. Neonatal rats received parathion on postnatal days 1-4 at 0.1 or 0.2 mg/kg/day, straddling the cholinesterase inhibition threshold. In adulthood, half the animals in each exposure group were given a high-fat diet for 8 weeks. We assessed 5HT and DA concentrations and turnover in brain regions containing their respective cell bodies and projections. In addition, we monitored 5HT1A and 5HT2 receptor binding and the concentration of 5HT presynaptic transporters. Neonatal parathion exposure evoked widespread increases in neurotransmitter turnover, indicative of presynaptic hyperactivity, further augmented by 5HT receptor upregulation. In control rats, consumption of a high-fat diet recapitulated many of the changes seen with neonatal parathion exposure; the effects represented convergent mechanisms, since the high-fat diet often obtunded further increases caused by parathion. Neonatal parathion exposure causes lasting hyperactivity of 5HT and DA systems accompanied by 5HT receptor upregulation, consistent with "miswiring" of neuronal projections. A high-fat diet obtunds the effect of parathion, in part by eliciting similar changes itself. Thus, dietary factors may produce similar synaptic changes as do developmental neurotoxicants, potentially contributing to the increasing incidence of neurodevelopmental disorders.

  17. Altering the substrate specificity of methyl parathion hydrolase with directed evolution.

    PubMed

    Ng, Tee-Kheang; Gahan, Lawrence R; Schenk, Gerhard; Ollis, David L

    2015-05-01

    Many organophosphates (OPs) are used as pesticides in agriculture. They pose a severe health hazard due to their inhibitory effect on acetylcholinesterase. Therefore, detoxification of water and soil contaminated by OPs is important. Metalloenzymes such as methyl parathion hydrolase (MPH) from Pseudomonas sp. WBC-3 hold great promise as bioremediators as they are able to hydrolyze a wide range of OPs. MPH is highly efficient towards methyl parathion (1 × 10(6) s(-1) M(-1)), but its activity towards other OPs is more modest. Thus, site saturation mutagenesis (SSM) and DNA shuffling were performed to find mutants with improved activities on ethyl paraxon (6.1 × 10(3) s(-1) M(-1)). SSM was performed on nine residues lining the active site. Several mutants with modest activity enhancement towards ethyl paraoxon were isolated and used as templates for DNA shuffling. Ultimately, 14 multiple-site mutants with enhanced activity were isolated. One mutant, R2F3, exhibited a nearly 100-fold increase in the kcat/Km value for ethyl paraoxon (5.9 × 10(5) s(-1) M(-1)). These studies highlight the 'plasticity' of the MPH active site that facilitates the fine-tuning of its active site towards specific substrates with only minor changes required. MPH is thus an ideal candidate for the development of an enzyme-based bioremediation system.

  18. Consumption of a High-Fat Diet in Adulthood Ameliorates the Effects of Neonatal Parathion Exposure on Acetylcholine Systems in Rat Brain Regions

    PubMed Central

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

    2009-01-01

    Background Developmental exposure to a wide variety of developmental neurotoxicants, including organophosphate pesticides, evokes late-emerging and persistent abnormalities in acetylcholine (ACh) systems. We are seeking interventions that can ameliorate or reverse the effects later in life. Objectives We administered parathion to neonatal rats and then evaluated whether a high-fat diet begun in adulthood could reverse the effects on ACh systems. Methods Neonatal rats received parathion on postnatal days 1–4 at 0.1 or 0.2 mg/kg/day, straddling the cholinesterase inhibition threshold. In adulthood, half the animals were switched to a high-fat diet for 8 weeks. We assessed three indices of ACh synaptic function: nicotinic ACh receptor binding, choline acetyltransferase activity, and hemicholinium-3 binding. Determinations were performed in brain regions comprising all the major ACh projections and cell bodies. Results Neonatal parathion exposure evoked widespread abnormalities in ACh synaptic markers, encompassing effects in brain regions possessing ACh projections and ACh cell bodies. In general, males were affected more than females. Of 17 regional ACh marker abnormalities (10 male, 7 female), 15 were reversed by the high-fat diet. Conclusions A high-fat diet reverses neurodevelopmental effects of neonatal parathion exposure on ACh systems. This points to the potential for nonpharmacologic interventions to offset the effects of developmental neurotoxicants. Further, cryptic neurodevelopmental deficits evoked by environmental exposures may thus engender a later preference for a high-fat diet to maintain normal ACh function, ultimately contributing to obesity. PMID:19590683

  19. Methyl parathion

    Integrated Risk Information System (IRIS)

    Methyl parathion ; CASRN 298 - 00 - 0 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic

  20. A receptor binding assay applied to monitoring the neurotoxicity of parathion to Peromyscus after oral exposure

    USGS Publications Warehouse

    Jett, D.A.; Eldefrawi, A.T.; Eldefrawi, M.E.

    1993-01-01

    Many naturally occurring toxins, as well as pesticides, metals, and other compounds that occur in our environment from anthropogenic activities, stimulate or antagonize neuro-receptors to produce acute and/or chronic toxicities. Recent advances in laboratory instrumentation and the availability of a variety of radiolabeled ligands and type-specific drugs for numerous receptors make it possible to easily screen large numbers of samples and detect changes in sensitivity and density of receptor types and subtypes. A receptor binding assay for examining the chronic dietary toxicity of parathion will be used as a model to describe the methodology.

  1. Interaction of ethanol and the organophosphorus insecticide parathion.

    PubMed

    O'Shaughnessy, J A; Sultatos, L G

    1995-11-27

    Phosphorothioate insecticides such as parathion (O,O-diethyl-O-p-nitrophenyl phosphorothioate) undergo P450-dependent oxidative desulfuration, leading to both activation and detoxification of these compounds. Consequently, alterations in P450-dependent oxidative desulfuration may affect the acute toxicities of these insecticides. In the present study, pretreatment of mice with 15% ethanol in the drinking water for 6 days antagonized the acute toxicity of parathion, but not its toxic metabolite paraoxon (O,O-diethyl-O-p-nitrophenyl phosphate), suggesting that ethanol affected the oxidative desulfuration of this insecticide. The presence of ethanol within hepatic microsomal incubations did not alter the P450-dependent formation of paraoxon (activation) and p-nitrophenol (detoxification), although p-nitrophenol levels were increased in the presence of ethanol as a result of inhibition of its biotransformation to 4-nitrocatechol by CYP2E1. Ethanol exposure reduced hepatic pyruvate levels, but had no effect on levels of lactate, isocitrate, alpha-ketoglutarate, and malate. Calculation of cytosolic NAD+/NADH and cytosolic NADP+/NADPH redox ratios did not reveal any detectable difference in redox state between control and ethanol-treated mice. Since ethanol did not alter directly the P450-dependent activation or detoxification of parathion, and did not decrease NADPH levels, ethanol's antagonism of the acute toxicity of parathion may result from reduced availability of O2.

  2. Down-regulation of muscarinic receptors and the m3 subtype in white-footed mice by dietary exposure to parathion

    USGS Publications Warehouse

    Jett, D.A.; Hill, E.F.; Fernando, J.C.; Eldefrawi, M.E.; Eldefrawi, A.T.

    1993-01-01

    The effect of ad libitum dietary exposure (as occurs in the field) to parathion for 14 d was investigated on the muscarinic acetylcholine receptor (mAChR) in brains and submaxillary glands of adults of a field species, the white-footed mouse Peromyscus leucopus. Immunoprecipitation using subtype selective antibodies revealed that the relative ratios of the m1-m5 mAChR subtypes in Peromyscus brain were similar to those in rat brain. There was little variability in acetylcholinesterase (AChE) activity in control mice brains but large variability in 39 exposed mice, resulting from differences in food ingestion and parathion metabolism. Accordingly, data on radioligand binding to mAChRs in each mouse brain were correlated with brain AChE activity in the same mouse, and AChE inhibition served as a biomarker of exposure reflecting in situ paraoxon concentrations. Exposure to parathion for 14 d reduced maximal binding (Bmax) of [3H]quinuclidinyl benzilate ([3H]QNB), [3H]-N-methylscopolamine ([3H]NMS), and [3H]-4-diphenylacetoxy-N-methylpiperidine methiodide ([3H]-4-DAMP) by up to approximately 58% without affecting receptor affinities for these ligands. Maximal reduction in Bmax of [3H]QNB and [3H]-4-DAMP binding occurred in mice with highest AChE inhibition, while equivalent maximal reduction in Bmax of [3H]NMS occurred in mice with only approximately 10% AChE inhibition, without further change at higher parathion doses. This is believed to be due to the hydrophilicity of [3H]NMS, which limits its accessibility to internalized desensitized receptors. In submaxillary glands (mAChRs are predominantly m3 subtype), there were significant dose-dependent reductions in [3H]QNB binding and m3 mRNA levels in exposed mice, revealed by Northern blot analyses. The reduction in m3 receptors is suggested to result mostly from reduced synthesis at the transcription level, rather than from translational or posttranslational events. The data suggest that down-regulation of mAChRs occurs

  3. Neonatal Parathion Exposure and Interactions with a High-Fat Diet in Adulthood: Adenylyl Cyclase-Mediated Cell Signaling in Heart, Liver and Cerebellum

    PubMed Central

    Adigun, Abayomi A.; Wrench, Nicola; Levin, Edward D.; Seidler, Frederic J.; Slotkin, Theodore A.

    2010-01-01

    Organophosphates are developmental neurotoxicants but recent evidence points to additional adverse effects on metabolism and cardiovascular function. One common mechanism is disrupted cell signaling mediated through cyclic AMP, targeting neurohumoral receptors, G-proteins and adenylyl cyclase (AC) itself. Earlier, we showed that neonatal parathion evokes later upregulation of the hepatic AC pathway in adolescence but that the effect wanes by young adulthood; nevertheless metabolic changes resembling prediabetes persist. Here, we administered parathion to neonatal rats (postnatal days 1-4, 0.1 or 0.2 mg/kg/day), straddling the threshold for cholinesterase inhibition, but we extended the studies to much later, 5 months of age. In addition, we investigated whether metabolic challenge imposed by consuming a high-fat diet for 7 weeks would exacerbate neonatal parathion’s effects. Parathion alone increased the expression or function of Gi, thus reducing AC responses to fluoride. Receptors controlling AC activity were also affected: β-adrenergic receptors (βARs) in skeletal muscle were increased, whereas those in the heart were decreased, and the latter also showed an elevation of m2-muscarinic acetylcholine receptors, which inhibit AC. The high-fat diet also induced changes in AC signaling, enhancing the hepatic AC response to glucagon while impairing the cardiac response to fluoride or forskolin, and suppressing βARs and m2-muscarinic receptors; the only change in the cerebellum was a decrease in βARs. Although there were no significant interactions between neonatal parathion exposure and a high-fat diet, their convergent effects on the same signaling cascade indicate that early OP exposure, separately or combination with dietary factors, may contribute to the worldwide increase in the incidence of obesity and diabetes. PMID:20074626

  4. Oviposition and the plasma concentrations of LH, progesterone, and corticosterone in bobwhite quail (Colinus virginianus) fed parathion

    USGS Publications Warehouse

    Rattner, B.A.; Sileo, L.; Scanes, C.G.

    1982-01-01

    Bobwhite quail were fed concentrations of parathion (0,50, 100, 200 or 400 p.p.m.) for 10 days. Food intake, body weight change, brain acetylcholinesterase activity, egg production, and ovary weight were reduced in a dose-dependent manner. In a second experiment, birds were fed 0, 25 or 100 p.p.m. parathion or pair-fed control food to equate consumption in the 100 p.p.m. group. Egg production was not affected in birds fed 25 p.p.m. or in the pair-fed group, but the daily time of oviposition was more variable than in the control group. Cessation of egg production, inhibition of follicular development, and reduced plasma LH concentration were observed in birds fed 100 p.p.m. parathion. These findings indicate that exposure to parathion can impair reproduction, possibly by altering gonadotrophin secretion.

  5. Acute responses of American kestrels to methyl parathion and fenvalerate

    USGS Publications Warehouse

    Rattner, B.A.; Franson, J.C.

    1984-01-01

    Physiological and toxicological effects of p.o, methyl parathion (0.375-3.0 mg/kg) or fenvalerate (1000-4000 mg/kg) were examined over a 10 h period in American kestrels (Falco sparverius) maintained in thermoneutral (22?.C) and cold (-5?.C) environments. Methyl parathion was highly toxic (LD50=3.08 mg/kg, 95% confidence limits=2.29-4.l4 mg/kg, producing overt intoxication (abnormal posture, ataxia, paresis), dose-dependent inhibition (26-67%) of brain acetylcholinesterase activity, hyperglycemia, and elevated plasma corticosterone concentration. Transient but pronounced hypothermia was associated with plasma cholinesterase inhibition in excess of 50% (2 h after intubation), although this response was highly variable (plasma ChE inhibition vs. A cloacal temperature, r=-0.60). Fenvalerate, at doses far exceeding those encountered in the environment, caused mild intoxication (irregular head movement) and elevated plasma alanine aminotransferase activity, but did not alter cloacal temperature, plasma activities of CK, U-HBDH, and LDK, or concentrations of corticosterone, glucose, triiodothyronine, and uric acid. Cold exposure intensified methyl parathion toxicity, but did not affect that of fenvalerate. It would thus appear that the organophosphorus insecticide methyl parathion poses far greater hazard than the pyrethroid fenvalerate to raptorial birds.

  6. Methyl parathion inhibits the nuclear maturation, decreases the cytoplasmic quality in oocytes and alters the developmental potential of embryos of Swiss albino mice

    SciTech Connect

    Nair, Ramya; Singh, Vikram Jeet; Salian, Sujith Raj; Kalthur, Sneha Guruprasad; D'Souza, Antony Sylvan; Shetty, Pallavi K.; Mutalik, Srinivas; Kalthur, Guruprasad; Adiga, Satish Kumar

    2014-09-15

    Methyl parathion (MP) is one of the most commonly used and extremely toxic organophosphorous group of pesticide. A large number of studies in the literature suggest that it has adverse effects on the male reproductive system. However, there is limited information about its toxicity to the female reproductive system. In the present study we report the toxic effects of methyl parathion on the female reproductive system using Swiss albino mice as the experimental model. The female mice were administered orally with 5, 10 and 20 mg/kg of MP. One week later, the mice were superovulated with pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG) to study the quality of the oocytes, spindle organization, developmental potential of early embryos and the DNA integrity in blastocysts. MP exposure resulted in a non-significant decrease in the number of primordial follicles and increased DNA damage in granulosa cells. Though MP did not have any effect on the ovulation it had a significant inhibitory effect on the nuclear maturity of oocytes which was associated with spindle deformity. In addition, the oocytes had higher cytoplasmic abnormalities with depleted glutathione level. Even though it did not have any effect on the fertilization and blastocyst rate at lower doses, at 20 mg/kg MP it resulted in a significant decrease in blastocyst hatching, decrease in cell number and high DNA damage. While low body weight gain was observed in F1 generation from 5 mg/kg group, at higher dose, the body weight in F1 generation was marginally higher than control. Post-natal death in F1 generation was observed only in mice treated with 20 mg/kg MP. In conclusion, we report that MP has adverse effects on the oocyte quality, developmental potential of the embryo and reproductive outcome. - Highlights: • Methyl parathion induces severe cytoplasmic abnormalities in oocytes. • Inhibits nuclear maturation and spindle damage • Poor blastocyst quality and high DNA

  7. Differential protein profile in zebrafish (Danio rerio) brain under the joint exposure of methyl parathion and cadmium.

    PubMed

    Ling, Xue-Ping; Lu, Ying-Hua; Huang, He-Qing

    2012-11-01

    As different chemicals, methyl parathion (MP) and cadmium (Cd) can induce neurotoxicity on the brain of aquatic ecosystems. This study aims to explore the differential expression proteins in the brain induced by their joint stress and their joint effects, which are poorly reported, and devotes finding novel biomarkers for monitoring their contamination in water and assessing their neurological effects. The bioaccumulation of MP and Cd in tissues after 96 h of exposure was first analyzed by GC and inductively coupled plasma-MS to provide insights into the interaction. Protein profile changes in the brains of the zebrafish (Danio rerio) exposed to MP and Cd were further investigated using the proteomic approach. The correlation of gene expression on the transcription level of mRNA and the translation level of protein was examined by real-time quantitative PCR and Western blotting analysis. It showed that Cd and MP have an interaction on their bioaccumulation, which suggests that their joint effect over 96 h might be antagonistic. Proteomics revealed that 22 protein spots changed their expression levels under stress, of which 16 proteins were identified using MS. These proteins were involved in oxidation/reduction, metabolism, energy production, receptor activity, and cytoskeleton assembly. Among them, five proteins with a remarkable abundance change are significantly suggested to play important roles in the joint effect. This work demonstrates that there exists an interaction between MP and Cd toxicities, which may aid in our understanding of the mechanism of neurotoxicity induced by joint stress. The results may also provide the possibility of the establishment of candidate biomarkers for monitoring MP and Cd contamination in water.

  8. Methyl parathion inhibits the nuclear maturation, decreases the cytoplasmic quality in oocytes and alters the developmental potential of embryos of Swiss albino mice.

    PubMed

    Nair, Ramya; Singh, Vikram Jeet; Salian, Sujith Raj; Kalthur, Sneha Guruprasad; D'Souza, Antony Sylvan; Shetty, Pallavi K; Mutalik, Srinivas; Kalthur, Guruprasad; Adiga, Satish Kumar

    2014-09-15

    Methyl parathion (MP) is one of the most commonly used and extremely toxic organophosphorous group of pesticide. A large number of studies in the literature suggest that it has adverse effects on the male reproductive system. However, there is limited information about its toxicity to the female reproductive system. In the present study we report the toxic effects of methyl parathion on the female reproductive system using Swiss albino mice as the experimental model. The female mice were administered orally with 5, 10 and 20mg/kg of MP. One week later, the mice were superovulated with pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG) to study the quality of the oocytes, spindle organization, developmental potential of early embryos and the DNA integrity in blastocysts. MP exposure resulted in a non-significant decrease in the number of primordial follicles and increased DNA damage in granulosa cells. Though MP did not have any effect on the ovulation it had a significant inhibitory effect on the nuclear maturity of oocytes which was associated with spindle deformity. In addition, the oocytes had higher cytoplasmic abnormalities with depleted glutathione level. Even though it did not have any effect on the fertilization and blastocyst rate at lower doses, at 20 mg/kg MP it resulted in a significant decrease in blastocyst hatching, decrease in cell number and high DNA damage. While low body weight gain was observed in F1 generation from 5mg/kg group, at higher dose, the body weight in F1 generation was marginally higher than control. Post-natal death in F1 generation was observed only in mice treated with 20mg/kg MP. In conclusion, we report that MP has adverse effects on the oocyte quality, developmental potential of the embryo and reproductive outcome.

  9. Covalent fabrication of methyl parathion hydrolase on gold nanoparticles modified carbon substrates for designing a methyl parathion biosensor.

    PubMed

    Liu, Guozhen; Guo, Wenqi; Yin, Zhang

    2014-03-15

    A biosensor based on AuNP modified GC electrodes has been developed for direct detection of methyl parathion. AuNP can be introduced to mixed monolayers of aryldiazonium salt modified GC electrodes by Au-C bonding through aryldiazonium salt chemistry, which provides a stable interface showing efficient electron transfer between biomolecules and electrodes. PEG molecules were introduced to the interface to resist non-specific protein adsorption. AuNP surfaces were further modified with 4-carboxyphenyl followed by covalent immobilization of methyl parathion hydrolase (MPH), a specific biocatalytic enzyme to methyl parathion. Exposure of this interface to methyl parathion resulted in a change in amperometric signal due to the MPH catalytic hydrolysis of methyl parathion producing electroactive compound 4-nitrophenol. This biosensor shows high selectivity, specificity, reproducibility and stability, and is functional for the detection of methyl parathion in real samples. The linear range for detection of methyl parathion is 0.2-100 ppb with a detection limit of 0.07 ppb in 0.1M phosphate buffer at pH 7.0.

  10. Protective effects of vitamins C and E against hepatotoxicity induced by methyl parathion in rats.

    PubMed

    Uzunhisarcikli, Meltem; Kalender, Yusuf

    2011-10-01

    Male rats were given vitamins C+E, methyl parathion, or both daily via gavage for seven weeks. Body weight was decreased while liver weight increased significantly at the end of fourth and seventh weeks in the methyl parathion- and methyl parathion plus vitamin-treated groups. Serum total protein, albumin, triglyceride, low density lipoprotein-cholesterol (VLDL-cholesterol) levels decreased, and serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl-transferase (GGT), lactate dehydrogenase (LDH), and total cholesterol levels increased significantly in the methyl parathion- and the methyl parathion plus vitamin-treated rats. There was a statistically significant difference for all biochemical parameters when the methyl parathion plus vitamin-treated group was compared with methyl parathion-treated group. In electron microscopic investigation, cytopathological alterations were observed in hepatocytes of the methyl parathion- and the methyl parathion plus vitamin-treated rats. As a result, methyl parathion-induced hepatotoxicity is reduced by vitamins C+E, but vitamins C+E did not provide complete protection.

  11. Reductive transformation of parathion and methyl parathion by Bacillus sp.

    PubMed

    Yang, Chao; Dong, Ming; Yuan, Yulan; Huang, Yao; Guo, Xinmin; Qiao, Chuanling

    2007-03-01

    Based on the results of phenotypic features, phylogenetic similarity of 16S rRNA gene sequences and BIOLOG test, a soil bacterium was identified as Bacillus sp. DM-1. Using either growing cells or a cell-free extract, it transformed parathion and methyl parathion to amino derivatives by reducing the nitro group. Pesticide transformation by a cell-free extract was specifically inhibited by three nitroreductase inhibitors, indicating the presence of nitroreductase activity. The nitroreductase activity was NAD(P)H-dependent, O(2)-insensitive, and exhibited the substrate specificity for parathion and methyl parathion. Reductive transformation significantly decreased the toxicity of pesticides.

  12. Comparative analyses of genotoxicity, oxidative stress and antioxidative defence system under exposure of methyl parathion and hexaconazole in barley (Hordeum vulgare L.).

    PubMed

    Dubey, Pragyan; Mishra, Amit Kumar; Singh, Ashok Kumar

    2015-12-01

    The present study aims to evaluate the comparative effects of methyl parathion and hexaconazole on genotoxicity, oxidative stress, antioxidative defence system and photosynthetic pigments in barley (Hordeum vulgare L. variety karan-16). The seeds were exposed with three different concentrations, i.e. 0.05, 0.1 and 0.5 % for 6 h after three pre-soaking durations 7, 17 and 27 h which represents G1, S and G2 phases of the cell cycle, respectively. Ethyl methane sulphonate, a well-known mutagenic agent and double distilled water, was used as positive and negative controls, respectively. The results indicate significant decrease in mitotic index with increasing concentrations of pesticides, and the extent was higher in methyl parathion. Chromosomal aberrations were found more frequent in methyl parathion than hexaconazole as compared to their respective controls. Treatment with the pesticides induced oxidative stress which was evident with higher contents of H2O2 and lipid peroxidation, and the increase was more prominent in methyl parathion. Contents of total phenolics were increased; however, soluble protein content showed a reverse trend. Among the enzymatic antioxidants, activities of superoxide dismutase and peroxidase were significantly up-regulated, and more increase was noticed in hexaconazole. Increments in total chlorophyll and carotenoid contents were observed up to 0.1 % but decreased at higher concentration (0.5 %), and the reductions were more prominent in methyl parathion than hexaconazole as compared to their respective controls. Methyl parathion treatment caused more damage in the plant cells of barley as compared to hexaconazole, which may be closely related to higher genotoxicity and oxidative stress.

  13. Involvement of oxidative stress in methyl parathion and parathion-induced toxicity and genotoxicity to human liver carcinoma (HepG₂) cells.

    PubMed

    Edwards, Falicia L; Yedjou, Clement G; Tchounwou, Paul B

    2013-06-01

    Methyl parathion (C₈H₁₀NO₅PS) and parathion (C₁₀H14 NO₅PS) are both organophosphate insecticides (OPI) widely used for household and agricultural applications. They are known for their ability to irreversibly inhibit acetylcholinesterase which often leads to a profound effect on the nervous system of exposed organisms. Many recently published studies have indicated that human exposure to OPI may be associated with neurologic, hematopoietic, cardiovascular, and reproductive adverse effects. Studies have also linked OPI exposure to a number of degenerative diseases including Parkinson's, Alzheimer's, and amyotrophic lateral sclerosis. Also, oxidative stress (OS) has been reported as a possible mechanism of OPI toxicity in humans. Hence, the aim of the present investigation was to use human liver carcinoma (HepG₂) cells as a test model to evaluate the role of OS in methyl parathion- and parathion-induced toxicity. To achieve this goal, we performed the MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] assay for cell viability, lipid peroxidation assay for malondialdehyde (MDA) production, and Comet assay for DNA damage, respectively. Results from MTT assay indicated that methyl parathion and parathion gradually reduce the viability of HepG₂ cells in a dose-dependent manner, showing 48 h-LD₅₀ values of 26.20 mM and 23.58 mM, respectively. Lipid peroxidation assay resulted in a significant increase (P < 0.05) of MDA level in methyl parathion- and parathion-treated HepG₂ cells compared with controls, suggesting that OS plays a key role in OPI-induced toxicity. Comet assay indicated a significant increase in genotoxicity at higher concentrations of OPI exposure. Overall, we found that methyl-parathion is slightly less toxic than parathion to HepG₂ cells. The cytotoxic effect of these OPI was found to be associated, at least in part, with oxidative cell/tissue damage.

  14. Involvement of Oxidative Stress in Methyl Parathion and Parathion-Induced Toxicity and Genotoxicity to Human Liver Carcinoma (HepG2) Cells

    PubMed Central

    Edwards, Falicia L.; Yedjou, Clement G.; Tchounwou, Paul B.

    2013-01-01

    Methyl parathion (C8H10NO5PS) and parathion (C10H14NO5PS) are both organophosphate insecticides (OPI) widely used for household and agricultural applications. They are known for their ability to irreversibly inhibit acetylcholinesterase which often leads to a profound effect on the nervous system of exposed organisms. Many recently published studies have indicated that human exposure to OPI may be associated with neurologic, hematopoietic, cardiovascular, and reproductive adverse effects. Studies have also linked OPI exposure to a number of degenerative diseases including Parkinson's, Alzheimer's, and amyotrophic lateral sclerosis. Also, oxidative stress (OS) has been reported as a possible mechanism of OPI toxicity in humans. Hence, the aim of the present investigation was to use human liver carcinoma (HepG2) cells as a test model to evaluate the role of OS in methyl parathion- and parathion-induced toxicity. To achieve this goal, we performed the MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] assay for cell viability, lipid peroxidation assay for malondialdehyde (MDA) production, and Comet assay for DNA damage, respectively. Results from MTT assay indicated that methyl parathion and parathion gradually reduce the viability of HepG2 cells in a dose-dependent manner, showing 48 h-LD50 values of 26.20 mM and 23.58 mM, respectively. Lipid peroxidation assay resulted in a significant increase (p<0.05) of MDA level in methyl parathion- and parathion-treated HepG2 cells compared to controls, suggesting that OS plays a key role in OPI-induced toxicity. Comet assay indicated a significant increase in genotoxicity at higher concentrations of OPI exposure. Overall, we found that methyl-parathion is slightly less toxic than parathion to HepG2 cells. The cytotoxic effect of these OPI was found to be associated, at least in part, with oxidative cell/tissue damage. PMID:21544925

  15. DDE increased the toxicity of parathion to coturnix quail

    USGS Publications Warehouse

    Ludke, J.L.

    1977-01-01

    Adult male Japanese quail (Coturnix coturnix) were exposed to DDE or chlordane in the diet and subsequently dosed with parathion or paraoxon. Pretreatment with 5 or 50 ppm DDE in the diet for 12 weeks resulted in increased cholinesterase (ChE) activity in plasma, but not in the brain. Dietary concentrations of 5 and 50 ppm DDE caused increased susceptibility of quail that were challenged with parathion or paraoxon. The increased mortality resulting from DDE pretreatment was reflected in brain ChE inhibition. The synergistic action of DDE was apparent after 3 days of exposure to 50 ppm DDE and 1 week of exposure to 5 ppm DDE. Birds exposed for 3 weeks to 5 or 50 ppm DDE retained their DDE-potentiated sensitivity to parathion after 2 weeks on clean diet. Chlordane pretreatment resulted in decreased susceptibility (antagonism) to parathion, but not to paraoxon dosage. Implications of differing responses in ChE and mortality among controls, DDE-, and chlordane-pretreated birds after parathion or paraoxon dosage are discussed.

  16. Parathion Poisoning from Flannelette Sheets

    PubMed Central

    Anderson, L. S.; Warner, D. L.; Parker, J. E.; Bluman, N.; Page, B. D.

    1965-01-01

    Two small boys were admitted to the Lions Gate Hospital in coma and acute respiratory distress. They improved and the first boy was sent home; after two nights he was back in hospital in a worsened state. Poisoning with organic phosphate was suspected, and after investigation some flannelette sheets were taken from his home for testing. They proved to have been contaminated with parathion (“nerve gas”) in the hold of a ship sailing from Antwerp to Vancouver; the parathion had been offloaded in California. The remainder of the sheets were traced. The symptomatology and treatment of organic phosphate ester poisoning and the chemical testing of parathion are discussed. PMID:14272498

  17. Effects of methyl parathion on Chasmagnathus granulatus hepatopancreas: protective role of sesamol.

    PubMed

    Bianchini, Adalto; Monserrat, José Maria

    2007-05-01

    The protective role of sesamol, an inhibitor of the mixed function oxygenase (MFO) system, against histopathological effects of methyl parathion in the hepatopancreas of the estuarine crab, Chasmagnathus granulatus, was studied. Exposure (72 h) to a sublethal dose (0.05 mg/kg/day; 10% of 72 h-LD50) of injected methyl parathion increased the percentage of damaged hepatopancreatic tubules. Presence of melanin-like deposits in the connective tissue between hepatopancreatic tubules was also observed. Antioxidant enzyme activities (catalase and glutathione S-transferase) and lipid peroxidation (LPO) levels were also increased in hepatopancreas of crabs injected with methyl parathion. Pretreatment with sesamol (0.85 mg/kg/day) significantly protected against all these effects. These findings suggest that the hepatopancreatic damages induced by methyl parathion are due to LPO of hepatopancreatocytes membranes, as a consequence of the oxidative stress generated after methyl parathion oxidative biotransformation mediated by the MFO system.

  18. Macrophage TNF-α mediates parathion-induced airway hyperreactivity in guinea pigs

    PubMed Central

    Bruun, Donald A.; Jacoby, David B.; van Rooijen, Nico; Lein, Pamela J.; Fryer, Allison D.

    2013-01-01

    Organophosphorus pesticides (OPs) are implicated in human asthma. We previously demonstrated that, at concentrations that do not inhibit acetylcholinesterase activity, the OP parathion causes airway hyperreactivity in guinea pigs as a result of functional loss of inhibitory M2 muscarinic receptors on parasympathetic nerves. Because macrophages are associated with asthma, we investigated whether macrophages mediate parathion-induced M2 receptor dysfunction and airway hyperreactivity. Airway physiology was measured in guinea pigs 24 h after a subcutaneous injection of parathion. Pretreatment with liposome-encapsulated clodronate induced alveolar macrophage apoptosis and prevented parathion-induced airway hyperreactivity in response to electrical stimulation of the vagus nerves. As determined by qPCR, TNF-α and IL-1β mRNA levels were increased in alveolar macrophages isolated from parathion-treated guinea pigs. Parathion treatment of alveolar macrophages ex vivo did not significantly increase IL-1β and TNF-α mRNA but did significantly increase TNF-α protein release. Consistent with these data, pretreatment with the TNF-α inhibitor etanercept but not the IL-1β receptor inhibitor anakinra prevented parathion-induced airway hyperreactivity and protected M2 receptor function. These data suggest a novel mechanism of OP-induced airway hyperreactivity in which low-level parathion activates macrophages to release TNF-α-causing M2 receptor dysfunction and airway hyperreactivity. These observations have important implications regarding therapeutic approaches for treating respiratory disease associated with OP exposures. PMID:23377347

  19. Modulation of parathion toxicity by glucose feeding: Is nitric oxide involved?

    SciTech Connect

    Liu Jing . E-mail: jing.pope@okstate.edu; Gupta, Ramesh C.; Goad, John T.; Karanth, Subramanya; Pope, Carey

    2007-03-15

    Glucose feeding can markedly exacerbate the toxicity of the anticholinesterase insecticide, parathion. We determined the effects of parathion on brain nitric oxide and its possible role in potentiation of toxicity by glucose feeding. Adult rats were given water or 15% glucose in water for 3 days and challenged with vehicle or parathion (18 mg/kg, s.c.) on day 4. Functional signs, plasma glucose and brain cholinesterase, citrulline (an indicator of nitric oxide production) and high-energy phosphates (HEPs) were measured 1-3 days after parathion. Glucose feeding exacerbated cholinergic toxicity. Parathion increased plasma glucose (15-33%) and decreased cortical cholinesterase activity (81-90%), with no significant differences between water and glucose treatment groups. In contrast, parathion increased brain regional citrulline (40-47%) and decreased HEPs (18-40%) in rats drinking water, with significantly greater changes in glucose-fed rats (248-363% increase and 31-61% decrease, respectively). We then studied the effects of inhibiting neuronal nitric oxide synthase (nNOS) by 7-nitroindazole (7NI, 30 mg/kg, i.p. x4) on parathion toxicity and its modulation by glucose feeding. Co-exposure to parathion and 7NI led to a marked increase in cholinergic signs of toxicity and lethality, regardless of glucose intake. Thus, glucose feeding enhanced the accumulation of brain nitric oxide following parathion exposure, but inhibition of nitric oxide synthesis was ineffective at counteracting increased parathion toxicity associated with glucose feeding. Evidence is therefore presented to suggest that nitric oxide may play both toxic and protective roles in cholinergic toxicity, and its precise contribution to modulation by glucose feeding requires further investigation.

  20. Neural alterations from lead exposure in zebrafish.

    PubMed

    Roy, Nicole M; DeWolf, Sarah; Schutt, Alexius; Wright, Ashia; Steele, Latina

    2014-01-01

    Lead was used extensively as a gas additive and pesticide, in paints, batteries, lead shot, pipes, canning and toy manufacturing. Although uses of lead have been restricted, lead persists in our environment especially in older homes, and generally in soil and water. Although extensive studies have determined that fetal and childhood exposures to lead have been associated with childhood and adolescent memory impairments and learning disabilities, there are limited studies investigating early neural and morphological effects that may lead to these behavioral and learning abnormalities. Here we utilize the zebrafish vertebrate model system to study early effects of lead exposure on the brain. We treat embryos with 0.2mM lead for 24, 48 and 72 h and analyze neural structures through live imagery and transgenic approaches. We find structural abnormalities in the hindbrain region as well as changes in branchiomotor neuron development and altered neural vasculature. Additionally, we find areas of increased apoptosis. We conclude that lead is developmentally neurotoxic to a specific region of the brain, the hindbrain and is toxic to branchiomotor neurons residing in rhombomeres 2 through 7 of the hindbrain and hindbrain central artery vasculature.

  1. Depression of plasma luteinizing hormone concentration in quail by the anticholinesterase insecticide parathion

    USGS Publications Warehouse

    Rattner, B.A.; Clarke, R.N.; Ottinger, M.A.

    1986-01-01

    1. To examine the effects of parathion on basal plasma luteinizing hormone (LH) concentration, male Japanese quail (Coturnix japonica) were orally intubated with 0, 5 or 10 mg/kg parathion and sacrificed after 4, 8 and 24 hr.2. At the 5 mg/kg dose, plasma LH levels were reduced at 4 and 8 hr, but returned to control values by 24 hr. Brain acetylcholinesterase activity was substantially reduced by 10 mg/kg parathion (52, 75 and 37% inhibition at 4, 8 and 24 hr, respectively) and plasma LH concentration remained depressed through the 24-hr period.3. These findings suggest that the organophosphorus insecticide parathion may alter plasma LH concentration in a manner which might impair reproductive activity, and provide indirect evidence for a cholinergic component in the regulation of LH secretion in quail.

  2. Depression of plasma luteinizing hormone concentration in quail by the anticholinesterase insecticide parathion

    USGS Publications Warehouse

    Rattner, B.A.; Clarke, R.N.; Ottinger, M.A.

    1986-01-01

    To examine the effects of parathion on basal plasma luteinizing hormone (LH) concentration, male Japanese quail (Coturnix japonica) were orally intubated with 0, 5 or 10 mg/kg parathion and sacrificed after 4, 8 and 24 hr. At the 5 mg/kg dose, plasma LH levels were reduced at 4 and 8 hr, but returned to control values by 24 hr. Brain acetylcholinesterase activity was substantially reduced by 10 mg/kg parathion (52, 75 and 37% inhibition at 4, 8 and 24 hr, respectively) and plasma LH concentration remained depressed through the 24-hr period. These findings suggest that the organophosphorus insecticide parathion may alter plasma LH concentration in a manner which might impair reproductive activity, and provide indirect evidence for a cholinergic component in the regulation of LH secretion in quail.

  3. Exposure to Environmental Ozone Alters Semen Quality

    PubMed Central

    Sokol, Rebecca Z.; Kraft, Peter; Fowler, Ian M.; Mamet, Rizvan; Kim, Elizabeth; Berhane, Kiros T.

    2006-01-01

    Idiopathic male infertility may be due to exposure to environmental toxicants that alter spermatogenesis or sperm function. We studied the relationship between air pollutant levels and semen quality over a 2-year period in Los Angeles, California, by analyzing repeated semen samples collected by sperm donors. Semen analysis data derived from 5,134 semen samples from a sperm donor bank were correlated with air pollutant levels (ozone, nitrogen dioxide, carbon monoxide, and particulate matter < 10 μm in aerodynamic diameter) measured 0–9, 10–14, and 70–90 days before semen collection dates in Los Angeles between January 1996 and December 1998. A linear mixed-effects model was used to model average sperm concentration and total motile sperm count for the donation from each subject. Changes were analyzed in relationship to biologically relevant time points during spermatogenesis, 0–9, 10–14, and 70–90 days before the day of semen collection. We estimated temperature and seasonality effects after adjusting for a base model, which included donor’s date of birth and age at donation. Forty-eight donors from Los Angeles were included as subjects. Donors were included if they collected repeated semen samples over a 12-month period between January 1996 and December 1998. There was a significant negative correlation between ozone levels at 0–9, 10–14, and 70–90 days before donation and average sperm concentration, which was maintained after correction for donor’s birth date, age at donation, temperature, and seasonality (p < 0.01). No other pollutant measures were significantly associated with sperm quality outcomes. Exposure to ambient ozone levels adversely affects semen quality. PMID:16507458

  4. Parathion poisoning of Mississippi kites in Oklahoma

    USGS Publications Warehouse

    Franson, J. Christian

    1994-01-01

    Parathion(phosphorothioic acid O, O-diethyl O-[4-nitrophenyl] ester) is a broad spectrum organophosphorus insecticide, used on a variety of crops and occasionally for mosquito control, and is highly toxic to birds (Smith 1987). Intentional poisoning with parathion is reported to have killed more than 8000 red-winged blackbirds (Agelaius phoeniceus), common grackles (Quiscalus quiscula), brown-headed cowbirds (Molothrus ater) and European starlings (Sturnus vulgaris) in two separate instances (Stone et al. 1984). Use of parathion on wheat fields has resulted in the mortality of about 1600 Canada geese (Branta canadensis) and other waterfowl in one instance (White et al. 1982) and about 200 Canada geese in another (Flickinger et al. 1991). More than 200 laughing gulls (Larus atricilla) died near cotton fields treated with parathion (White et al. 1979). Secondary poisoning of raptors resulting from the consumption of prey exposed to parathion, has been reported experimentally and in the field. Stone et al. (1984) found two dead red-tailed hawks (Buteo jamaicensis), a Cooper's hawk (Accipiter cooperii) and an American kestrel (Falco sparverius) that had fed on blackbirds killed by parathion. One of four American kestrels died after being fed cricket frogs (Acris crepitans) that had been exposed to 10ppm parathion for 96 hr (Fleming et al. 1982). The Mississippi kite (Ictinia mississippensis) is highly insectivorous (Brown and Amadon 1968) and is thus subject to secondary poisoning resulting from consumption of insects exposed to pesticides. I report here an instance of secondary parathion poisoning in wild Mississippi kites.

  5. Bioconcentration and Acute Intoxication of Brazilian Freshwater Fishes by the Methyl Parathion Organophosphate Pesticide.

    PubMed

    de Salles, João Bosco; Lopes, Renato Matos; de Salles, Cristiane M C; Cassano, Vicente P F; de Oliveira, Manildo Marcião; Bastos, Vera L F Cunha; Bastos, Jayme Cunha

    2015-01-01

    Three species of freshwater Brazilian fishes (pacu, Piaractus mesopotamicus; piavussu, Leporinus macrocephalus, and curimbatá, Prochilodus lineatus) were exposed to an acute dose of 5 ppm methyl parathion organophosphate pesticide. Three to five individuals per species were exposed, one at a time, to 40 liters tap water spiked with Folidol 600. Pesticide concentrations and cholinesterase (ChE) activities were evaluated in serum, liver, brain, heart, and muscle. The bioconcentration of methyl parathion was similar for all studied fishes. Brain tissue showed the highest pesticide concentration, reaching 80 ppm after exposure for 30 min to methyl parathion. Three to 5 hours of 5 ppm methyl parathion exposure provoked the death of all P. lineatus at 92% brain AChE inhibition, whereas fish from the other two species survived for up to 78 hours with less than 80% brain AChE inhibition. Our results indicate that acute toxic effects of methyl parathion to fish are correlated with brain AChE sensitivity to methyl paraoxon.

  6. Bioconcentration and Acute Intoxication of Brazilian Freshwater Fishes by the Methyl Parathion Organophosphate Pesticide

    PubMed Central

    Bosco de Salles, João; Matos Lopes, Renato; de Salles, Cristiane M. C.; Cassano, Vicente P. F.; de Oliveira, Manildo Marcião; Cunha Bastos, Vera L. F.; Bastos, Jayme Cunha

    2015-01-01

    Three species of freshwater Brazilian fishes (pacu, Piaractus mesopotamicus; piavussu, Leporinus macrocephalus, and curimbatá, Prochilodus lineatus) were exposed to an acute dose of 5 ppm methyl parathion organophosphate pesticide. Three to five individuals per species were exposed, one at a time, to 40 liters tap water spiked with Folidol 600. Pesticide concentrations and cholinesterase (ChE) activities were evaluated in serum, liver, brain, heart, and muscle. The bioconcentration of methyl parathion was similar for all studied fishes. Brain tissue showed the highest pesticide concentration, reaching 80 ppm after exposure for 30 min to methyl parathion. Three to 5 hours of 5 ppm methyl parathion exposure provoked the death of all P. lineatus at 92% brain AChE inhibition, whereas fish from the other two species survived for up to 78 hours with less than 80% brain AChE inhibition. Our results indicate that acute toxic effects of methyl parathion to fish are correlated with brain AChE sensitivity to methyl paraoxon. PMID:26339593

  7. Toxicity of parathion to captive European starlings (Sturnus vulgaris)-absence of seasonal effects

    USGS Publications Warehouse

    Rattner, B.A.; Grue, C.E.

    1990-01-01

    The effects of season on the toxicity of the prototypic organophosphorus insecticide parathion was evaluated using adult European starlings (Sturnus vulgaris) housed in outdoor pens. Groups of birds received oral doses of parathion in the fall, winter, spring and summer. Median lethal dosage, and brain and plasma cholinesterase inhibition, were found to be quite similar among seasons. Parathion may have been more toxic during hot weather (winter vs. summer LD50 estimate: 160 vs. 118 mg/kg; p < 0.1). In view of previous reports in which ambient temperature extremes and harsh weather have enhanced organophosphorus insecticide toxicity to birds, it is concluded that circannual toxicity studies should include measures of sensitivity (acute oral exposure) and vulnerability (dietary exposure) to better predict responses of free-ranging birds.

  8. Structural Alterations in the Cornea from Exposure to Infrared Radiation

    DTIC Science & Technology

    1985-07-01

    mylar disks that were preformed - 4- to match the corneal curvature. The disks were attached 0 at their edges to excised corneas using cyanoacrylate ...ICFIECOP JHU/APL TG 1364 JULY 1985 (0 FINAL Technical Memorandum STRUCTURAL ALTERATIONS IN THE CORNEA FROM EXPOSURE TO INFRARED RADIATION R. A...Structural Alterations in the Cornea from Exposure to Infrared Radiation 12. PERSONAL AUTHOR(S) R. A. Farrell, R. L. McCally, C. B. Bargeron, and W. R. Green

  9. A rat mammary tumor model induced by the organophosphorous pesticides parathion and malathion, possibly through acetylcholinesterase inhibition.

    PubMed Central

    Cabello, G; Valenzuela, M; Vilaxa, A; Durán, V; Rudolph, I; Hrepic, N; Calaf, G

    2001-01-01

    Environmental chemicals may be involved in the etiology of breast cancers. Many studies have addressed the association between cancer in humans and agricultural pesticide exposure. Organophosphorous pesticides have been used extensively to control mosquito plagues. Parathion and malathion are organophosphorous pesticides extensively used to control a wide range of sucking and chewing pests of field crops, fruits, and vegetables. They have many structural similarities with naturally occurring compounds, and their primary target of action in insects is the nervous system; they inhibit the release of the enzyme acetylcholinesterase at the synaptic junction. Eserine, parathion, and malathion are cholinesterase inhibitors responsible for the hydrolysis of body choline esters, including acetylcholine at cholinergic synapses. Atropine, a parasympatholytic alkaloid, is used as an antidote to acetylcholinesterase inhibitors. The aim of this study was to examine whether pesticides were able to induce malignant transformation of the rat mammary gland and to determine whether alterations induced by these substances increase the cholinergic activation influencing such transformation. These results showed that eserine, parathion, and malathion increased cell proliferation of terminal end buds of the 44-day-old mammary gland of rats, followed by formation of 8.6, 14.3, and 24.3% of mammary carcinomas, respectively, after about 28 months. At the same time, acetylcholinesterase activity decreased in the serum of these animals from 9.78 +/- 0.78 U/mL in the control animals to 3.05 +/- 0.06 U/mL; 2.57 +/- 0.15 U/mL; and 3.88 +/- 0.44 U/mL in the eserine-, parathion-, and malathion-treated groups, respectively. However, atropine alone induced a significant (p < 0.05) decrease in the acetylcholinesterase activity from the control value of 9.78 +/- 0.78 to 4.38 +/- 0.10 for atropine alone, to 1.32 +/- 0.06 for atropine in combination with eserine, and 2.39 +/- 0.29 for atropine with

  10. Urinary paranitrophenol, a metabolite of methyl parathion, in Thai farmer and child populations.

    PubMed

    Panuwet, Parinya; Prapamontol, Tippawan; Chantara, Somporn; Thavornyuthikarn, Prasak; Bravo, Roberto; Restrepo, Paula; Walker, Robert D; Williams, Bryan L; Needham, Larry L; Barr, Dana B

    2009-10-01

    Human exposure to methyl parathion can be assessed by measuring the concentration of its metabolite paranitrophenol (PNP) in urine. Our biologic monitoring study in Chiang Mai, Thailand, measured PNP and dialkylphosphate metabolites (i.e., dimethylphosphate [DMP] and dimethylthiophosphate [DMTP]) of methyl parathion in urine samples collected from 136 farmers (age 20 to 65 years) and 306 school children (age 10 to 15 years) in 2006. Participants came from two topographically different areas: one was colder and mountainous, whereas the other was alluvial with climate fluctuations depending on the monsoon season. Both children and farmers were recruited from each area. Despite methyl parathion's prohibited use in agriculture in 2004, we detected PNP in >90% of all samples analyzed. We applied a nonparametric correlation test (PNP vs. DMP and DMTP) to determine whether the PNP found in most of the samples tested resulted from exposures to methyl parathion. DMP (Spearman's rho = 0.601 [p = 0.001] for farmers and Spearman's rho = 0.263 [p <0.001] for children) and DMTP (Spearman's rho = 0.296 [p = 0.003] for farmers and Spearman's rho = 0.304 [p<0.001] for children) were positively correlated with PNP, suggesting a common source for the three analytes, presumably methyl parathion or related environmental degradates. Although we found a modest correlation between the metabolites, our findings suggest that despite the prohibition, at least a portion (approximately 25% to 60%) of the PNP detected among farmers and children in Thailand may be attributed to exposure from continued methyl parathion use.

  11. Effects on wildlife of ethyl and methyl parathion applied to California rice fields

    USGS Publications Warehouse

    Custer, T.W.; Hill, E.F.; Ohlendorf, H.M.

    1985-01-01

    Selected rice fields on the Sacramento National Wildlife Refuge Complex were aerially sprayed one time during May or June 1982 with either ethyl (0.11 kg Al/ha) or methyl (0.84 kg AI/ha) parathion for control of tadpole shrimp, Triops longicaudatus. No sick or dead vertebrate wildlife were found or adjacent to the treated rice fields after spraying. Specimens of the following birds and mammals were assayed for brain cholinesterase (ChE) activity to determine exposure to either form of parathion; house mouse, Mus musculus; black-tailed jackrabbit, Lepus californicus; mallard, Anas platyrhynchos; ring-necked pheasant, Phasianus colchicus; American coot, Fulica americana; and red-winged blackbird, Agelaius phoeniceus. Both mice and pheasants from methyl parathion-treated fields had overall mean ChE activities that were significantly (P < 0.05) inhibited compared with controls, and 7, 40, 54 and 57% of individual blackbirds, pheasant, mice, and coots, respectively, had inhibited brain ChE activities (i.e., less than -2 SD of control mean). Although no overall species effect was detected for ethyl parathoid treatment, pheasants (43%), coots (33%), and mice (37%) had significantly inhibited brain ChE activities. Neither of the parathion treatment appeared acutely hazardous to wildlife in or adjacent to rice fields, but sufficient information on potential hazards was obtained to warrant caution in use of these chemicals, especially methyl parathion, in rice fields.

  12. Effects of wildlife of ethyl and methyl parathion applied to California USA rice fields

    USGS Publications Warehouse

    Custer, T.W.; Hill, E.F.; Ohlendorf, H.M.

    1985-01-01

    Selected rice fields on the Sacramento National Wildlife Refuge Complex were aerially sprayed one time during May or June 1982 with either ethyl (0.11 kg Al/ha) or methyl (0.84 kg AI/ha) parathion for control of tadpole shrimp, Triops longicaudatus. No sick or dead vertebrate wildlife were found or adjacent to the treated rice fields after spraying. Specimens of the following birds and mammals were assayed for brain cholinesterase (ChE) activity to determine exposure to either form of parathion; house mouse, Mus musculus; black-tailed jackrabbit, Lepus californicus; mallard, Anas platyrhynchos; ring-necked pheasant, Phasianus colchicus; American coot, Fulica americana; and red-winged blackbird, Agelaius phoeniceus. Both mice and pheasants from methyl parathion-treated fields had overall mean ChE activities that were significantly (P < 0.05) inhibited compared with controls, and 7, 40, 54 and 57% of individual blackbirds, pheasant, mice, and coots, respectively, had inhibited brain ChE activities (i.e., less than -2 SD of control mean). Although no overall species effect was detected for ethyl parathoid treatment, pheasants (43%), coots (33%), and mice (37%) had significantly inhibited brain ChE activities. Neither of the parathion treatment appeared acutely hazardous to wildlife in or adjacent to rice fields, but sufficient information on potential hazards was obtained to warrant caution in use of these chemicals, especially methyl parathion, in rice fields.

  13. Parathion accumulation in cricket frogs and its effect on American kestrels

    USGS Publications Warehouse

    Fleming, W.J.; de Chacin, H.; Pattee, O.H.; Lamont, T.G.

    1982-01-01

    Adult cricket frogs (Acris crepitans) were held individually for 96 h in static systems containing initial concentrations of either 0, 0.1, 1.0, or 10 ppm parathion in 10 ml water. Mortality of cricket frogs was directly related to the parathion concentration in the water. Frogs from the 1.0- and 10-ppm groups accumulated 0.08 and 4.6 ppm parathion, respectively. One of four American kestrels (Falco sparverius) fed frogs from the 10-ppm group died from organophosphate poisoning less than 3 h after consuming five frogs. Mortality did not occur in kestrels fed frogs from the other treatment groups, which represented more environmentally realistic levels of exposure.

  14. Volatilization of parathion and chlorothalonil from a potato crop simulated by the PEARL model.

    PubMed

    Leistra, Minze; van den Berg, Frederik

    2007-04-01

    The volatilization of pesticides from crop canopies in the field should be modeled within the context of evaluating environmental exposure. A model concept based on diffusion through a laminar air-boundary layer was incorporated into the PEARL model (pesticide emission assessment at regional and local scales) and used to simulate volatilization of the pesticides parathion and chlorothalonil from a potato crop in a field experiment. Rate coefficients for the competing processes of plant penetration, wash off, and phototransformation in the canopy had to be derived from a diversity of literature data. Cumulative volatilization of the moderately volatile parathion (31% of the dosage in 7.6 days) could be simulated after calibrating two input data derived for the related compound parathion-methyl. The less volatile and more slowly transformed chlorothalonil showed 5% volatilization in 7.6 days, which could be explained by the simulation. Simulated behavior of the pesticides in the crop canopy roughly corresponded to published data.

  15. Effects of malathion, diazinon, and parathion on mallard embryo development and cholinesterase activity

    USGS Publications Warehouse

    Hoffman, D.J.; Eastin, W.C.

    1981-01-01

    The effects of external exposure of mallard (Anas platyrhynchos) eggs to malathion, diazinon, and parathion were examined using formulations and concentrations similar to field applications. Treatment with aqueous emulsion simulated exposure at the rate of 100 gal per acre (153 liters/hectare) with three to six different doses per compound with treatment at 3 and 8 days of embryonic development. Treatment with a nontoxic oil vehicle simulated exposure at the rate of 11 gal per acre (16.8 liters/hectare) with three to six different doses per compound. The order of embryotoxicity on a pounds-per-acre basis was parathion > diazinon > malathion with either vehicle. However, the potential hazard under conditions of up to five times the maximum field level of application was greater for malathion because of the high permissible level of application for malathion on certain crops. Parathion, the most embryotoxic of the three, had the most pronounced effects when an oil vehicle was used, as reflected by an LC50 of about 2 lb of active ingredient per acre, stunted growth, and a high frequency of malformations involving distortion of the axial skeleton, particularly in the cervical region. All three compounds resulted in significant depression of plasma and brain cholinesterase activity, but parathion caused the most depression throughout development, which was still apparent in hatchlings. Treatment with either distilled water or oil vehicle alone did not result in any of these effects seen with organophosphorous insecticides.

  16. Atrazine exposure elicits copy number alterations in the zebrafish genome.

    PubMed

    Wirbisky, Sara E; Freeman, Jennifer L

    2017-04-01

    Atrazine is an agricultural herbicide used throughout the Midwestern United States that frequently contaminates potable water supplies resulting in human exposure. Using the zebrafish model system, an embryonic atrazine exposure was previously reported to decrease spawning rates with an increase in progesterone and ovarian follicular atresia in adult females. In addition, alterations in genes associated with distinct molecular pathways of the endocrine system were observed in brain and gonad tissue of the adult females and males. Current hypotheses for mechanistic changes in the developmental origins of health and disease include genetic (e.g., copy number alterations) or epigenetic (e.g., DNA methylation) mechanisms. As such, in the current study we investigated whether an atrazine exposure would generate copy number alterations (CNAs) in the zebrafish genome. A zebrafish fibroblast cell line was used to limit detection to CNAs caused by the chemical exposure. First, cells were exposed to a range of atrazine concentrations and a crystal violet assay was completed, showing confluency decreased by ~60% at 46.3μM. Cells were then exposed to 0, 0.463, 4.63, or 46.3μM atrazine and array comparative genomic hybridization completed. Results showed 34, 21, and 44 CNAs in the 0.463, 4.63, and 46.3μM treatments, respectively. Furthermore, CNAs were associated with previously reported gene expression alterations in adult male and female zebrafish. This study demonstrates that atrazine exposure can generate CNAs that are linked to gene expression alterations observed in adult zebrafish exposed to atrazine during embryogenesis providing a mechanism of the developmental origins of atrazine endocrine disruption. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Methyl-parathion decreases sperm function and fertilization capacity after targeting spermatocytes and maturing spermatozoa.

    PubMed

    Piña-Guzmán, B; Sánchez-Gutiérrez, M; Marchetti, F; Hernández-Ochoa, I; Solís-Heredia, M J; Quintanilla-Vega, B

    2009-07-15

    Paternal germline exposure to organophosphorous pesticides (OP) has been associated with reproductive failures and adverse effects in the offspring. Methyl-parathion (Me-Pa), a worldwide-used OP, has reproductive adverse effects and is genotoxic to sperm, possibly via oxidative damage. This study investigated the stages of spermatogenesis susceptible to be targeted by Me-Pa exposure that impact on spermatozoa function and their ability to fertilize. Male mice were exposed to Me-Pa (20 mg/kg bw, i.p.) and spermatozoa from epididymis-vas deferens were collected at 7 or 28 days post-treatment (dpt) to assess the effects on maturing spermatozoa and spermatocytes, respectively. Spermatozoa were examined for DNA damage by nick translation (NT-positive cells) and SCSA (%DFI), lipoperoxidation (LPO) by malondialdehyde production, sperm function by spontaneous- and induced-acrosome reactions (AR), mitochondrial membrane potential (MMP) by using the JC-1 fluorochrome, and fertilization ability by an in vitro assay and in vivo mating. Alterations on DNA integrity (%DFI and NT-positive cells) in spermatozoa collected at 7 and 28 dpt, and decreases in sperm quality and induced-AR were observed; reduced MMP and LPO were observed at 7 dpt only. Negative correlations between LPO and sperm alterations were found. Altered sperm functional parameters evaluated either in vitro or in vivo were associated with reduced fertilization rates at both times. These results show that Me-Pa exposure of maturing spermatozoa and spermatocytes affects many sperm functional parameters that result in a decreased fertilizing capacity. Oxidative stress seems to be a likely mechanism of the detrimental effects of Me-Pa exposure in male germ cells.

  18. Microbial degradation of parathion. Ph.D. Thesis

    NASA Technical Reports Server (NTRS)

    Gibson, W. L.

    1972-01-01

    An organism capable of utilizing parathion as the sole carbon and energy source was isolated by enrichment culture techniques. The bacterium was characterized and tentatively classified as Pseudomonas aeruginosa. A pH of 7.0 - 7.5 and temperature of 30 C were found to be optimum for the consumption of parathion. Virtually no oxygen utilization was observed with resting cell suspensions when nonsolubilized parathion was employed. The use of ethanol as solvent for parathion in resting cell studies or preincubation of cells in ethanol obviated this problem and rapid parathion oxidation was demonstrable. Approximately 80% of the parathion consumed by resting cells was present terminally as carbon dioxide. Permeability of the cell to parathion or its metabolites was contingent upon the use of ethanol as either solvent or denaturant. Metabolites were tentatively identified by thin layer chromatography.

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

    SciTech Connect

    Morrow, L.A.; Ryan, C.M.; Hodgson, M.J.; Robin, N. )

    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.

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

    PubMed Central

    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 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. PMID:25276823

  1. Chemodynamics of methyl parathion and ethyl parathion: adsorption models for sustainable agriculture.

    PubMed

    Tabassum, Noshabah; Rafique, Uzaira; Balkhair, Khaled S; Ashraf, Muhammad Aqeel

    2014-01-01

    The toxicity of organophosphate insecticides for nontarget organism has been the subject of extensive research for sustainable agriculture. Pakistan has banned the use of methyl/ethyl parathions, but they are still illegally used. The present study is an attempt to estimate the residual concentration and to suggest remedial solution of adsorption by different types of soils collected and characterized for physicochemical parameters. Sorption of pesticides in soil or other porous media is an important process regulating pesticide transport and degradation. The percentage removal of methyl parathion and ethyl parathion was determined through UV-Visible spectrophotometer at 276 nm and 277 nm, respectively. The results indicate that agricultural soil as compared to barren soil is more efficient adsorbent for both insecticides, at optimum batch condition of pH 7. The equilibrium between adsorbate and adsorbent was attained in 12 hours. Methyl parathion is removed more efficiently (by seven orders of magnitude) than ethyl parathion. It may be attributed to more available binding sites and less steric hindrance of methyl parathion. Adsorption kinetics indicates that a good correlation exists between distribution coefficient (Kd) and soil organic carbon. A general increase in Kd is noted with increase in induced concentration due to the formation of bound or aged residue.

  2. Chemodynamics of Methyl Parathion and Ethyl Parathion: Adsorption Models for Sustainable Agriculture

    PubMed Central

    Rafique, Uzaira; Balkhair, Khaled S.; Ashraf, Muhammad Aqeel

    2014-01-01

    The toxicity of organophosphate insecticides for nontarget organism has been the subject of extensive research for sustainable agriculture. Pakistan has banned the use of methyl/ethyl parathions, but they are still illegally used. The present study is an attempt to estimate the residual concentration and to suggest remedial solution of adsorption by different types of soils collected and characterized for physicochemical parameters. Sorption of pesticides in soil or other porous media is an important process regulating pesticide transport and degradation. The percentage removal of methyl parathion and ethyl parathion was determined through UV-Visible spectrophotometer at 276 nm and 277 nm, respectively. The results indicate that agricultural soil as compared to barren soil is more efficient adsorbent for both insecticides, at optimum batch condition of pH 7. The equilibrium between adsorbate and adsorbent was attained in 12 hours. Methyl parathion is removed more efficiently (by seven orders of magnitude) than ethyl parathion. It may be attributed to more available binding sites and less steric hindrance of methyl parathion. Adsorption kinetics indicates that a good correlation exists between distribution coefficient (Kd) and soil organic carbon. A general increase in Kd is noted with increase in induced concentration due to the formation of bound or aged residue. PMID:24689059

  3. Genetic damage caused by methyl-parathion in mouse spermatozoa is related to oxidative stress

    SciTech Connect

    Pina-Guzman, B.; Solis-Heredia, M.J.; Rojas-Garcia, A.E.; Uriostegui-Acosta, M.; Quintanilla-Vega, B. . E-mail: mquintan@cinvestav.mx

    2006-10-15

    Organophosphorous (OP) pesticides are considered genotoxic mainly to somatic cells, but results are not conclusive. Few studies have reported OP alterations on sperm chromatin and DNA, and oxidative stress has been related to their toxicity. Sperm cells are very sensitive to oxidative damage which has been associated with reproductive dysfunctions. We evaluated the effects of methyl-parathion (Me-Pa; a widely used OP) on sperm DNA, exploring the sensitive stage(s) of spermatogenesis and the relationship with oxidative stress. Male mice (10-12-weeks old) were administered Me-Pa (3-20 mg/kg bw/i.p.) and euthanized at 7- or 28-days post-treatment. Mature spermatozoa were obtained and evaluated for chromatin structure through SCSA (Sperm Chromatin Structure Assay; DNA Fragmentation Index parameters: Mean DFI and DFI%) and chromomycin-A{sub 3} (CMA{sub 3})-staining, for DNA damage through in situ-nick translation (NT-positive) and for oxidative stress through lipid peroxidation (LPO; malondialdehyde production). At 7-days post-treatment (mature spermatozoa when Me-Pa exposure), dose-dependent alterations in chromatin structure (Mean DFI and CMA{sub 3}-staining) were observed, as well as increased DNA damage, from 2-5-fold in DFI% and NT-positive cells. Chromatin alterations and DNA damage were also observed at 28-days post-treatment (cells at meiosis at the time of exposure); suggesting that the damage induced in spermatocytes was not repaired. Positive correlations were observed between LPO and sperm DNA-related parameters. These data suggest that oxidative stress is related to Me-Pa alterations on sperm DNA integrity and cells at meiosis (28-days post-treatment) and epididymal maturation (7-days post-treatment) are Me-Pa targets. These findings suggest a potential risk of Me-Pa to the offspring after transmission.

  4. Caffeine exposure alters cardiac gene expression in embryonic cardiomyocytes

    PubMed Central

    Fang, Xiefan; Mei, Wenbin; Barbazuk, William B.; Rivkees, Scott A.

    2014-01-01

    Previous studies demonstrated that in utero caffeine treatment at embryonic day (E) 8.5 alters DNA methylation patterns, gene expression, and cardiac function in adult mice. To provide insight into the mechanisms, we examined cardiac gene and microRNA (miRNA) expression in cardiomyocytes shortly after exposure to physiologically relevant doses of caffeine. In HL-1 and primary embryonic cardiomyocytes, caffeine treatment for 48 h significantly altered the expression of cardiac structural genes (Myh6, Myh7, Myh7b, Tnni3), hormonal genes (Anp and BnP), cardiac transcription factors (Gata4, Mef2c, Mef2d, Nfatc1), and microRNAs (miRNAs; miR208a, miR208b, miR499). In addition, expressions of these genes were significantly altered in embryonic hearts exposed to in utero caffeine. For in utero experiments, pregnant CD-1 dams were treated with 20–60 mg/kg of caffeine, which resulted in maternal circulation levels of 37.3–65.3 μM 2 h after treatment. RNA sequencing was performed on embryonic ventricles treated with vehicle or 20 mg/kg of caffeine daily from E6.5-9.5. Differential expression (DE) analysis revealed that 124 genes and 849 transcripts were significantly altered, and differential exon usage (DEU) analysis identified 597 exons that were changed in response to prenatal caffeine exposure. Among the DE genes identified by RNA sequencing were several cardiac structural genes and genes that control DNA methylation and histone modification. Pathway analysis revealed that pathways related to cardiovascular development and diseases were significantly affected by caffeine. In addition, global cardiac DNA methylation was reduced in caffeine-treated cardiomyocytes. Collectively, these data demonstrate that caffeine exposure alters gene expression and DNA methylation in embryonic cardiomyocytes. PMID:25354728

  5. Caffeine exposure alters cardiac gene expression in embryonic cardiomyocytes.

    PubMed

    Fang, Xiefan; Mei, Wenbin; Barbazuk, William B; Rivkees, Scott A; Wendler, Christopher C

    2014-12-15

    Previous studies demonstrated that in utero caffeine treatment at embryonic day (E) 8.5 alters DNA methylation patterns, gene expression, and cardiac function in adult mice. To provide insight into the mechanisms, we examined cardiac gene and microRNA (miRNA) expression in cardiomyocytes shortly after exposure to physiologically relevant doses of caffeine. In HL-1 and primary embryonic cardiomyocytes, caffeine treatment for 48 h significantly altered the expression of cardiac structural genes (Myh6, Myh7, Myh7b, Tnni3), hormonal genes (Anp and BnP), cardiac transcription factors (Gata4, Mef2c, Mef2d, Nfatc1), and microRNAs (miRNAs; miR208a, miR208b, miR499). In addition, expressions of these genes were significantly altered in embryonic hearts exposed to in utero caffeine. For in utero experiments, pregnant CD-1 dams were treated with 20-60 mg/kg of caffeine, which resulted in maternal circulation levels of 37.3-65.3 μM 2 h after treatment. RNA sequencing was performed on embryonic ventricles treated with vehicle or 20 mg/kg of caffeine daily from E6.5-9.5. Differential expression (DE) analysis revealed that 124 genes and 849 transcripts were significantly altered, and differential exon usage (DEU) analysis identified 597 exons that were changed in response to prenatal caffeine exposure. Among the DE genes identified by RNA sequencing were several cardiac structural genes and genes that control DNA methylation and histone modification. Pathway analysis revealed that pathways related to cardiovascular development and diseases were significantly affected by caffeine. In addition, global cardiac DNA methylation was reduced in caffeine-treated cardiomyocytes. Collectively, these data demonstrate that caffeine exposure alters gene expression and DNA methylation in embryonic cardiomyocytes.

  6. Produced water exposure alters bacterial response to biocides.

    PubMed

    Vikram, Amit; Lipus, Daniel; Bibby, Kyle

    2014-11-04

    Microbial activity during the holding and reuse of wastewater from hydraulic fracturing operations, termed produced water, may lead to issues with corrosion, sulfide release, and fouling. Biocides are applied to control biological activity, often with limited efficacy, which is typically attributed to chemical interactions with the produced water. However, it is unknown whether there is a biologically driven mechanism to biocide tolerance in produced water. Here, we demonstrate that produced water exposure results in an enhanced tolerance against the typically used biocide glutaraldehyde and increased susceptibility to the oxidative biocide hypochlorite in a native and a model bacteria and that this altered resistance is due to the salinity of the produced water. In addition, we elucidate the genetic response of the model organism Pseudomonas fluorescens to produced water exposure to provide a mechanistic interpretation of the altered biocide resistance. The RNA-seq data demonstrated the induction of genes involved in osmotic stress, energy production and conversion, membrane integrity, and protein transport following produced water exposure, which facilitates bacterial survival and alters biocide tolerance. Efforts to fundamentally understand biocide resistance mechanisms, which enable the optimization of biocide application, hold significant implications for greening of the fracturing process through encouraging produced water recycling. Specifically, these results suggest the necessity of optimizing biocide application at the level of individual shale plays, rather than historical experience, based upon produced water characteristics and salinity.

  7. Perinatal exposure to polychlorinated biphenyls alters social behaviors in rats

    PubMed Central

    Jolous-Jamshidi, Banafsheh; Cromwell, Howard C.; McFarland, Ashley M.; Meserve, Lee A.

    2014-01-01

    Perinatal exposure to polychlorinated biphenyls (PCBs) leads to significant alterations of neural and hormonal systems. These alterations have been shown to impair motor and sensory development. Less is known about the influence of PCB exposure on developing emotional and motivational systems involved in social interactions and social learning. The present study examined the impact of perinatal PCB exposure (mixture of congeners 47 and 77) on social recognition in juvenile animals, conspecific-directed investigation in adults and on neural and hormonal systems involved in social functions. We used a standard habituation–dishabituation paradigm to evaluate juvenile recognition and a social port paradigm to monitor adult social investigation. Areal measures of the periventricular nucleus (PVN) of the hypothalamus were obtained to provide correlations with related hormone and brain systems. PCB exposed rats were significantly impaired in social recognition as indicated by persistent conspecific-directed exploration by juvenile animals regardless of social experience. As adults, PCB exposure led to a dampening of the isolation-induced enhancement of social investigation. There was not a concomitant alteration of social investigation in pair-housed PCB exposed animals at this stage of development. Interestingly, PVN area was significantly decreased in juvenile animals exposed to PCB during the perinatal period. Shifts in hypothalamic regulation of hormones involved in social behavior and stress could be involved in the behavioral changes observed. Overall, the results suggest that PCB exposure impairs context or experience-dependent modulation of social approach and investigation. These types of social-context deficits are similar to behavioral deficits observed in social disorders such as autism and other pervasive developmental disorders. PMID:20813172

  8. Comparative Effects of Parathion and Chlorpyrifos on Endocannabinoid and Endocannabinoid-Like Lipid Metabolites in Rat Striatum

    PubMed Central

    Liu, Jing; Parsons, Loren; Pope, Carey

    2015-01-01

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

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

    PubMed

    Liu, Jing; Parsons, Loren; Pope, Carey

    2015-09-01

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

  10. Prolonged prenatal psychotropic medication exposure alters neonatal acute pain response.

    PubMed

    Oberlander, Tim F; Eckstein Grunau, Ruth; Fitzgerald, Colleen; Ellwood, Ann-Louise; Misri, Shaila; Rurak, Dan; Riggs, Kenneth Wayne

    2002-04-01

    Selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines are frequently used to treat maternal depression during pregnancy, however the effect of increased serotonin (5HT) and gamma-amino-butyric acid (GABA) agonists in the fetal human brain remains unknown. 5HT and GABA are active during fetal neurologic growth and play early roles in pain modulation, therefore, if prolonged prenatal exposure alters neurodevelopment this may become evident in altered neonatal pain responses. To examine biologic and behavioral effects of prenatal exposure, neonatal responses to acute pain (phenylketonuria heel lance) in infants with prolonged prenatal exposure were examined. Facial action (Neonatal Facial Coding System) and cardiac autonomic reactivity derived from the relationship between respiratory activity and short term variations of heart rate (HRV) were compared between 22 infants with SSRI exposure (SE) [fluoxetine (n = 7), paroxetine (n = 11), sertraline (n = 4)]; 16 infants exposed to SSRIs and clonazepam (SE+) [paroxetine (n = 14), fluoxetine (n = 2)]; and 23 nonexposed infants during baseline, lance, and recovery periods of a heel lance. Length of maternal SSRI use did not vary significantly between exposure groups-[mean (range)] SE:SE+ 183 (31-281):141 (54-282) d (p > 0.05). Infants exposed to SE and SE+ displayed significantly less facial activity to heel lance than control infants. Mean HR increased with lance, but was significantly lower in SE infants during recovery. Using measures of HRV and the transfer relationship between heart rate and respiration, SSRI infants had a greater return of parasympathetic cardiac modulation in the recovery period, whereas a sustained sympathetic response continued in the control group. Prolonged prenatal SSRI exposure appears to be associated with reduced behavioral pain responses and increased parasympathetic cardiac modulation in recovery following an acute neonatal noxious event. Possible 5HT-mediated pain inhibition

  11. Competition of a parathion-hydrolyzing Flavobacterium with bacteria from ditch water in carbon-, nitrate- and phosphate-limited continuous cultures.

    PubMed

    Sprenger, Wander W; Dijkstra, Annereinou; Zwart, Gabriel J M; Agterveld, Miranda P; Noort, Paul C M; Parsons, John R

    2003-02-01

    Abstract The effect of competition for macroelements with bacteria from ditch water on the parathion-hydrolyzing Flavobacterium sp. ATCC 27551 (FB) was investigated within mixed continuous cultures under carbon-, nitrate- or phosphate-limited conditions. The high initial rate of parathion hydrolysis decreased rapidly in all cultures due to the loss of strain FB. Addition of 2-isopropyl-6-methyl-4-pyrimidinol (a selective source of carbon, nitrogen and energy for FB) to one nitrate- and carbon-limited chemostat caused a 20-fold increase in parathion-hydrolyzing activity compared to unamended control cultures and retention of FB. The presence of the parathion hydrolase-encoding gene could be demonstrated by a newly developed PCR detection method in all FB cultures during most of the cultivation period. These results suggest that competition effects cause the pesticide-degrading capacity of microbial communities depending on their frequency of exposure to the pesticide compounds.

  12. Mass spectrometric detection of CYP450 adducts following oxidative desulfuration of methyl parathion.

    PubMed

    Kyle, Patrick B; Smith, Stanley V; Baker, Rodney C; Kramer, Robert E

    2013-07-01

    Cytochrome P450 (CYP)-mediated desulfuration of methyl parathion results in mechanism-based inhibition of the enzyme. Although previous data suggest that reactive sulfur is released and binds to the apoprotein, the identities of neither the adduct(s) nor the affected amino acid(s) have been clearly determined. In this study, nanospray tandem mass spectroscopy was used to analyze peptide digests of CYP resolved by SDS-PAGE from liver microsomes of male rats following incubation in the absence or presence of methyl parathion. Oxidative desulfuration was confirmed by measurement of methyl paraoxon, and inhibition of specific CYP isozymes was determined by measurement of testosterone hydroxylation. Total CYP content was quantified spectrophotometrically. Incubation of microsomes with methyl parathion decreased CYP content by 58%. This effect was not associated with a comparable increase in absorbance at 420 nm, suggesting the displacement of heme from the apoprotein. Rates of testosterone 2β- and 6β-hydroxylation, respectively, were reduced to 8 and 2%, implicating CYP3A and CYP2C11 in the oxidative desulfuration of methyl parathion. Mass spectrometric analysis identified 96 amu adducts to cysteines 64 and 378 of CYP3A1. In addition, a peptide containing cysteine 433 that coordinates with heme was possibly modified as it was detected in control, but not methyl parathion samples. A comparison of rat CYP3A1 with human CYP3A4 suggests that cysteines 64 and 378 reside along the substrate channel, remote from the active site. Alteration of these residues might modulate substrate entry to the binding pocket of the enzyme.

  13. Prenatal exposure to MDMA alters noradrenergic neurodevelopment in the rat

    PubMed Central

    Thompson, V.B.; Koprich, J.B.; Chen, E.Y.; Kordower, J.H.; Terpstra, B.; Lipton, J.W.

    2011-01-01

    3,4-methylenedioxymethamphetamine (MDMA; ecstasy) binds with high affinity to the norepinephrine transporter (NET), making the noradrenergic system a potential target during fetal exposure. Recent data indicates that adult rats that had been prenatally exposed to MDMA display persistent deficits in working memory and attention; behaviors consistent with abnormal noradrenergic signaling in the forebrain. The present study was designed to investigate whether prenatal exposure to MDMA from embryonic days 14–20 affects the structure and/or function of the noradrenergic system of the rat on postnatal day 21. Offspring that were prenatally exposed to MDMA exhibited an increase in noradrenergic fiber density in the prelimbic region of the prefrontal cortex and the CA1 region of the hippocampus that was not accompanied by an increase in the number of noradrenergic neurons in the locus coeruleus. Direct tissue autoradiography using tritiated nisoxetine demonstrated that while NET binding was not altered in the prelimbic cortex, the dentate gyrus, or the locus coeruleus, it was increased in the CA1, CA2, and CA3 regions of the hippocampus. Basal levels of norepinephrine were increased in the prefrontal cortex and the nucleus accumbens of MDMA-exposed rats, as compared to saline-treated controls. These findings indicate that prenatal exposure to MDMA results in structural changes in the noradrenergic system as well as functional alterations in NE neurotransmission in structures that are critical in attentional processing. PMID:21978916

  14. Methyl-parathion decreases sperm function and fertilization capacity after targeting spermatocytes and maturing spermatozoa

    SciTech Connect

    Pina-Guzman, Belem; Sanchez-Gutierrez, M.; Marchetti, Francesco; Hernandez-Ochoa, I.; Solis-Heredia, M.J .; Quintanilla-Vega, B.

    2009-05-03

    Paternal germline exposure to organophosphorous pesticides (OP) has been associated with reproductive failures and adverse effects in the offspring. Methyl parathion (Me-Pa), a worldwide-used OP, has reproductive adverse effects and is genotoxic to sperm. Oxidative damage has been involved in the genotoxic and reproductive effects of OP. The purpose of this study was to determine the effects of Me-Pa on spermatozoa function and ability to fertilize. Male mice were exposed to Me-Pa (20 mg/kg bw, i.p.) and spermatozoa from epididymis-vas deferens were collected at 7 or 28 days post-treatment (dpt) to assess the effects on maturing spermatozoa and spermatocytes, respectively. DNA damage was evaluated by nick translation (NT-positive cells) and SCSA (percentDFI); lipoperoxidation (LPO) by malondialdehyde production; sperm function by spontaneous- and induced-acrosome reactions (AR); mitochondrial membrane potential (MMP) by using the JC-1 flurochrome; and, fertilization ability by an in vitro assay and in vivo mating. Results showed alterations in DNA integrity (percentDFI and NT-positive cells) at 7 and 28 dpt, in addition to decreased sperm quality and a decrease in induced-AR; reduced MMP and LPO was observed only at 7 dpt. We found negative correlations between LPO and all sperm alterations. Altered sperm functional parameters were associated with reduced fertilization rates at both times, evaluated either in vitro or in vivo. These results show that Me-Pa exposure of maturing spermatozoa and spermatocytes affects many sperm functional parameters that result in a decreased fertilizing capacity. Oxidative stress seems to be a likely mechanism ofthe detrimental effects of Me-Pa in male germ cells.

  15. Prenatal antiepileptic drug exposure alters seizure susceptibility in rats.

    PubMed

    Sobrian, S K; Nandedkar, A K

    1986-05-01

    An animal model is used to address the issue of prenatal exposure to certain antiepileptic drugs and seizure susceptibility in the offspring. Administration of doses established as median therapeutic doses in humans of phenobarbital, valproate and clonazepam to pregnant rats during the last third of gestation produced sexually dimorphic alterations in pentylenetetrazol (PTZ)-induced seizures as well as in non-convulsive (spontaneous alternation and cliff avoidance) behaviors in the offspring. Altered seizure susceptibility occurred in the absence of overtly recognizable morphological abnormalities and did not appear to reflect differences in the status of circulating drug-binding plasma proteins. Possible neural and/or metabolic mechanisms responsible for these behavioral changes are discussed.

  16. Tributyltin exposure alters cytokine levels in mouse serum.

    PubMed

    Lawrence, Shanieek; Pellom, Samuel T; Shanker, Anil; Whalen, Margaret M

    2016-11-01

    Tributyltin (TBT), a toxic environmental contaminant, has been widely utilized for various industrial, agricultural and household purposes. Its usage has led to a global contamination and its bioaccumulation in aquatic organisms and terrestrial mammals. Previous studies suggest that TBT has debilitating effects on the overall immune function of animals, rendering them more vulnerable to diseases. TBT (at concentrations that have been detected in human blood) alters secretion of inflammatory cytokines from human lymphocytes ex vivo. Thus, it is important to determine if specified levels of TBT can alter levels of cytokines in an in vivo system. Mice were exposed to biologically relevant concentrations of TBT (200, 100 or 25 nM final concentrations). The quantitative determination of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL2, IL5, IL7, IL12βp40, IL13, IL15, keratinocyte chemoattractant (KC), macrophage inflammatory protein 1β (MIP), MIP2 and regulated on activation normal T-cell-expressed and secreted (RANTES) was performed in mouse sera by MAGPIX analysis and Western blot. Results indicated alterations (both decreases and increases) in several cytokines. The pro-inflammatory cytokines IFNγ, TNFα, IL-1β, IL-2, IL5, IL12βp40 and IL-15 were altered as were the chemokines MIP-1 and RANTES and the anti-inflammatory cytokine IL-13. Increases in IFNγ and TNFα were seen in the serum of mice exposed to TBT for less than 24 h. Levels of IL1β, IL-12 βp40, IL-5 and IL-15 were also modulated in mouse serum, depending on the specific experiment and exposure level. IL-2 was consistently decreased in mouse serum when animals were exposed to TBT. There were also TBT-induced increases in MIP-1β, RANTES and IL-13. These results from human and murine samples clearly suggest that TBT exposures modulate the secretion inflammatory cytokines.

  17. Radiation Exposure Alters Expression of Metabolic Enzyme Genes In Mice

    NASA Technical Reports Server (NTRS)

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

    2010-01-01

    Most 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. Because of the importance of the liver in drug metabolism it is important to understand the effects of spaceflight on the enzymes of the liver. Exposure to cosmic radiation is one aspect of spaceflight that can be modeled in ground experiments. This study is an effort to examine the effects of adaptive mechanisms that may be triggered by early exposure to low radiation doses. Using procedures approved by the JSC Animal Care & Use Committee, C57 male mice were exposed to Cs-137 in groups: controls, low dose (50 mGy), high dose (6Gy) and a fourth group that received both radiation doses separated by 24 hours. Animals were anesthetized and sacrificed 4 hours after their last radiation exposure. Livers were removed immediately and flash-frozen in liquid nitrogen. Tissue was homogenized, RNA extracted and purified (Absolutely RNA, Agilent). Quality of RNA samples was evaluated (Agilent Bioanalyzer 2100). Complementary DNA was prepared from high-quality RNA samples, and used to run RT-qPCR screening arrays for DNA Repair and Drug Metabolism (SuperArray, SABiosciences/Qiagen; BioRad Cfx96 qPCR System). Of 91 drug metabolism genes examined, expression of 7 was altered by at least one treatment condition. Genes that had elevated expression include those that metabolize promethazine and steroids (4-8-fold), many that reduce oxidation products, and one that reduces heavy metal exposure (greater than 200-fold). Of the 91 DNA repair and general metabolism genes examined, expression of 14 was altered by at least one treatment condition. These gene expression changes are likely homeostatic and could lead to development of new radioprotective countermeasures.

  18. Vanadium exposure-induced neurobehavioral alterations among Chinese workers.

    PubMed

    Li, Hong; Zhou, Dinglun; Zhang, Qin; Feng, Chengyong; Zheng, Wei; He, Keping; Lan, Yajia

    2013-05-01

    Vanadium-containing products are manufactured and widely used in the modern industry. Yet the neurobehavioral toxicity due to occupational exposure to vanadium remained elusive. This cross-sectional study was designed to examine the neurotoxic effects of occupational vanadium exposure. A total of 463 vanadium-exposed workers (exposed group) and 251 non-exposed workers (control group) were recruited from a Steel and Iron Group in Sichuan, China. A WHO-recommended neurobehavioral core test battery (NCTB) and event-related auditory evoked potentials test (P300) were used to assess the neurobehavioral functions of all study subjects. A general linear model was used to compare outcome scores between the two groups while controlling for possible confounders. The exposed group showed a statistically significant neurobehavioral alteration more than the control group in the NCTB tests. The exposed workers also exhibited an increased anger-hostility, depression-dejection and fatigue-inertia on the profile of mood states (p<0.05). Performances in the simple reaction time, digit span, benton visual retention and pursuit aiming were also poorer among exposed workers as compared to unexposed control workers (p<0.05). Some of these poor performances in tests were also significantly related to workers' exposure duration. P300 latencies were longer in the exposed group than in the control (p<0.05). Longer mean reaction times and more counting errors were also found in the exposed workers (p<0.05). Given the findings of our study and the limitations of neurobehavioral workplace testing, we found evidence of altered neurobehavioral outcomes by occupational exposure to vanadium.

  19. Exposure to hog barn dust alters airway epithelial ciliary beating.

    PubMed

    Wyatt, T A; Sisson, J H; Von Essen, S G; Poole, J A; Romberger, D J

    2008-06-01

    Swine confinement workers are at increased risk of airway diseases, including mucus membrane irritation syndrome, chronic rhinosinusitis and chronic bronchitis. Dust extracts from swine confinement facilities stimulate the production of pro-inflammatory cytokines in bronchial epithelial cells, including interleukin (IL)-8. As IL-8 is capable of blocking beta-agonist-stimulated increases in cilia beating, which impacts on mucociliary clearance, it was hypothesised that hog barn-dust exposure might alter cilia responses to stimulation. To test this hypothesis, ciliated bovine bronchial epithelial cell cultures were exposed to hog barn-dust extract (HDE) and ciliary beat frequency (CBF) was assayed. An elevation in baseline CBF was observed. This effect appeared to be independent of endotoxin but dependent upon nitric oxide. HDE also stimulated nitric oxide production in bronchial epithelial cells; however, stimulation of cilia beating by a beta-agonist did not occur in cells pre-exposed to HDE. These data demonstrate that hog barn dust can alter normal stimulation of cilia, suggesting a mechanism for the abrogation of stimulated increases in mucociliary clearance in response to inhaled dust exposure.

  20. Altering user' acceptance of automation through prior automation exposure.

    PubMed

    Bekier, Marek; Molesworth, Brett R C

    2016-08-22

    Air navigation service providers worldwide see increased use of automation as one solution to overcome the capacity constraints imbedded in the present air traffic management (ATM) system. However, increased use of automation within any system is dependent on user acceptance. The present research sought to determine if the point at which an individual is no longer willing to accept or cooperate with automation can be manipulated. Forty participants underwent training on a computer-based air traffic control programme, followed by two ATM exercises (order counterbalanced), one with and one without the aid of automation. Results revealed after exposure to a task with automation assistance, user acceptance of high(er) levels of automation ('tipping point') decreased; suggesting it is indeed possible to alter automation acceptance. Practitioner Summary: This paper investigates whether the point at which a user of automation rejects automation (i.e. 'tipping point') is constant or can be manipulated. The results revealed after exposure to a task with automation assistance, user acceptance of high(er) levels of automation decreased; suggesting it is possible to alter automation acceptance.

  1. Embryonic ethanol exposure alters synaptic properties at zebrafish neuromuscular junctions.

    PubMed

    Sylvain, Nicole J; Brewster, Daniel L; Ali, Declan W

    2011-01-01

    Pre-natal alcohol exposure induces delays in fine and gross motor skills, and deficiencies in reflex development via mechanisms that remain to be elucidated. The purpose of the present study was to investigate the effect of embryonic ethanol exposure (16-hour exposure window with 1.5%, 2% or 2.5% EtOH) on synaptic properties at the neuromuscular junction (NMJ) in 3 day post fertilization (dpf) zebrafish larvae. Immunohistochemical studies show that exposure of embryos to 2.5% ethanol for 16 h results in motor neuron axons that display abnormal branching patterns. Co-labelling embryos with pre-synaptic markers such as SV-2 or 3A10, and the post-synaptic marker, α-bungarotoxin, which irreversibly binds to nicotinic acetylcholine receptors (nAChRs), indicates that pre- and post-synaptic sites are properly aligned even when motor neuron axons display abnormal morphology. Miniature endplate currents (mEPCs) recorded from muscle fibers revealed the presence of two types of mEPCs that we dubbed fast and slow. Ethanol treated fish experienced significant changes in the frequencies of fast and slow mEPCs, and an increase in the rise time of slow mEPCs recorded from red muscle fibers. Additionally, embryonic exposure to ethanol resulted in a significant increase in the decay time of fast mEPCs recorded from white fibers. Mean mEPC amplitude was unaffected by ethanol treatment. Together, these results indicate that zebrafish embryos exposed to ethanol may experience altered synaptic properties at the NMJ.

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

    PubMed Central

    2011-01-01

    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 genes that were

  3. Arsenic exposure to killifish during embryogenesis alters muscle development.

    PubMed

    Gaworecki, Kristen M; Chapman, Robert W; Neely, Marion G; D'Amico, Angela R; Bain, Lisa J

    2012-02-01

    Epidemiological studies have correlated arsenic exposure in drinking water with adverse developmental outcomes such as stillbirths, spontaneous abortions, neonatal mortality, low birth weight, delays in the use of musculature, and altered locomotor activity. Killifish (Fundulus heteroclitus) were used as a model to help to determine the mechanisms by which arsenic could impact development. Killifish embryos were exposed to three different sodium arsenite concentrations and were collected at 32 h post-fertilization (hpf), 42 hpf, 168 hpf, or < 24 h post-hatch. A killifish oligo microarray was developed and used to examine gene expression changes between control and 25-ppm arsenic-exposed hatchlings. With artificial neural network analysis of the transcriptomic data, accurate prediction of each group (control vs. arsenic-exposed embryos) was obtained using a small subset of only 332 genes. The genes differentially expressed include those involved in cell cycle, development, ubiquitination, and the musculature. Several of the genes involved in cell cycle regulation and muscle formation, such as fetuin B, cyclin D-binding protein 1, and CapZ, were differentially expressed in the embryos in a time- and dose-dependent manner. Examining muscle structure in the hatchlings showed that arsenic exposure during embryogenesis significantly reduces the average muscle fiber size, which is coupled with a significant 2.1- and 1.6-fold upregulation of skeletal myosin light and heavy chains, respectively. These findings collectively indicate that arsenic exposure during embryogenesis can initiate molecular changes that appear to lead to aberrant muscle formation.

  4. Seizures and antiepileptic drugs: does exposure alter normal brain development?

    PubMed

    Marsh, Eric D; Brooks-Kayal, Amy R; Porter, Brenda E

    2006-12-01

    Seizures and antiepileptic drugs (AEDs) affect brain development and have long-term neurological consequences. The specific molecular and cellular changes, the precise timing of their influence during brain development, and the full extent of the long-term consequences of seizures and AEDs exposure have not been established. This review critically assesses both the basic and clinical science literature on the effects of seizures and AEDs on the developing brain and finds that evidence exists to support the hypothesis that both seizures and antiepileptic drugs influence a variety of biological process, at specific times during development, which alter long-term cognition and epilepsy susceptibility. More research, both clinical and experimental, is needed before changes in current clinical practice, based on the scientific data, can be recommended.

  5. Does metoclopramide exposure alter endometrial receptivity and decrease pregnancy rates?

    PubMed

    Çekmez, Yasemin; Korkmaz, Vakkas; Çakır, Aslı; Göçmen, Ahmet; Ergün, Yusuf; Gülşen, Serdar; Akpak, Yasam K

    2016-01-01

    The aim of this study was to investigate the effect of metoclopramide on endometrial receptivity with an immunohistochemical investigation of integrin β3 expression in pregnant rats. In the present study, the pregnant mice administrated by different doses of metoclopramide were used to explore the effect of metoclopramide on embryo implantation, especially on the endometrial receptivity. The statistical results showed that the number of implanted embryos was gradually declining along the increasing dose of metoclopramide. When the administrated dose of metoclopramide was 3 mg/kg per day, great changes were observed in the exposed uterine morphology and down-regulated integrin β3 were also found in high dose metoclopramide-exposed mice. Metoclopramide exposure, especially in high doses may alter endometrial receptivity by effecting integrin expression on decidual tissue which can decrease pregnancy rates. This drug should only be recommended for use during pregnancy when benefit outweighs the risk.

  6. Methyl parathion hydrolase based nanocomposite biosensors for highly sensitive and selective determination of methyl parathion.

    PubMed

    Chen, Shizhen; Huang, Jing; Du, Dan; Li, Jinlin; Tu, Haiyang; Liu, Deli; Zhang, Aidong

    2011-07-15

    This article reports the fabrication of a nanocomposite biosensor for the sensitive and specific detection of methyl parathion. The nanocomposite sensing film was prepared via the formation of gold nanoparticles on silica particles, mixing with multiwall carbon nanotubes and subsequent covalent immobilization of methyl parathion hydrolase. The composite of the individual materials was finely tuned to offer the sensing film with high specific surface area and high conductivity. A significant synergistic effect of nanocomposites on the biosensor performance was observed in biosensing methyl parathion. The square wave voltammetric responses displayed well defined peaks, linearly proportional to the concentrations of methyl parathion in the range from 0.001 μg mL⁻¹ to 5.0 μg mL⁻¹ with a detection limit of 0.3 ng mL⁻¹. The application of this biosensor in the analysis of spiked garlic samples was also evaluated. The proposed protocol can be used as a platform for the simple and fast construction of biosensors with good performance for the determination of enzyme-specific electroactive species.

  7. Prenatal alcohol exposure alters the patterns of facial asymmetry.

    PubMed

    Klingenberg, C P; Wetherill, L; Rogers, J; Moore, E; Ward, R; Autti-Rämö, I; Fagerlund, A; Jacobson, S W; Robinson, L K; Hoyme, H E; Mattson, S N; Li, T K; Riley, E P; Foroud, T

    2010-01-01

    Directional asymmetry, the systematic differences between the left and right body sides, is widespread in human populations. Changes in directional asymmetry are associated with various disorders that affect craniofacial development. Because facial dysmorphology is a key criterion for diagnosing fetal alcohol syndrome (FAS), the question arises whether in utero alcohol exposure alters directional asymmetry in the face. Data on the relative position of 17 morphologic landmarks were obtained from facial scans of children who were classified as either FAS or control. Shape data obtained from the landmarks were analyzed with the methods of geometric morphometrics. Our analyses showed significant directional asymmetry of facial shape, consisting primarily of a shift of midline landmarks to the right and a displacement of the landmarks around the eyes to the left. The asymmetry of FAS and control groups differed significantly and average directional asymmetry was increased in those individuals exposed to alcohol in utero. These results suggest that the developmental consequences of fetal alcohol exposure affect a wide range of craniofacial features in addition to those generally recognized and used for diagnosis of FAS.

  8. Maternal perchlorate exposure in pregnancy and altered birth outcomes.

    PubMed

    Rubin, Rainbow; Pearl, Michelle; Kharrazi, Martin; Blount, Benjamin C; Miller, Mark D; Pearce, Elizabeth N; Valentin-Blasini, Liza; DeLorenze, Gerald; Liaw, Jane; Hoofnagle, Andrew N; Steinmaus, Craig

    2017-10-01

    At high medicinal doses perchlorate is known to decrease the production of thyroid hormone, a critical factor for fetal development. In a large and uniquely exposed cohort of pregnant women, we recently identified associations between environmental perchlorate exposures and decreased maternal thyroid hormone during pregnancy. Here, we investigate whether perchlorate might be associated with birthweight or preterm birth in the offspring of these women. Maternal urinary perchlorate, serum thyroid hormone concentrations, birthweight, gestational age, and urinary nitrate, thiocyanate, and iodide were collected in 1957 mother-infant pairs from San Diego County during 2000-2003, a period when the county's water supply was contaminated with perchlorate. Associations between perchlorate exposure and birth outcomes were examined using linear and logistic regression analyses adjusted for maternal age, weight, race/ethnicity, and other factors. Perchlorate was not associated with birth outcomes in the overall population. However, in analyses confined to male infants, log10 maternal perchlorate concentrations were associated with increasing birthweight (β=143.1gm, p=0.01), especially among preterm births (β=829.1g, p<0.001). Perchlorate was associated with male preterm births ≥2500g (odds ratio=3.03, 95% confidence interval=1.09-8.40, p-trend=0.03). Similar associations were not seen in females. This is the first study to identify associations between perchlorate and increasing birthweight. Further research is needed to explore the differences we identified related to infant sex, preterm birth, and other factors. Given that perchlorate exposure is ubiquitous, and that long-term impacts can follow altered birth outcomes, future research on perchlorate could have widespread public health importance. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Ozone exposure alters tracheobronchial mucociliary function in humans

    SciTech Connect

    Foster, W.M.; Costa, D.L.; Langenback, E.G.

    1987-09-01

    Mucociliary function is a primary defense mechanism of the tracheobronchial airways, and yet the response of this system to an inhalational hazard, such as ozone, is undefined in humans. Utilizing noninvasive techniques to measure deposition and retention of insoluble radiolabeled particles on airway mucous membranes, we studied the effect on mucus transport of 0.2 and 0.4 ppm ozone compared with filtered air (FA) in seven healthy males. During 2-h chamber exposures, subjects alternated between periods of rest and light exercise with hourly spirometric measurement of lung function. Mechanical and mucociliary function responses to ozone by lung airways appeared concentration dependent. Reduction in particle retention was significant (P less than 0.005) (i.e., transport of lung mucus was increased during exposure to 0.4 ppm ozone and was coincident with impaired lung function; e.g., forced vital capacity and midmaximal flow rate fell by 12 and 16%, respectively, and forced expiratory volume at 1 s by 5%, of preexposure values). Regional analysis indicated that mucus flow from distal airways into central bronchi was significantly increased (P less than 0.025) by 0.2 ppm ozone. This peripheral effect, however, was buffered by only a marginal influence of 0.2 ppm ozone on larger bronchi, such that the resultant mucus transport for all airways of the lung in aggregate differed only slightly from FA exposures. These data may reflect differences in regional diffusion of ozone along the respiratory tract, rather than tissue sensitivity. In conclusion, mucociliary function of humans is acutely stimulated by ozone and may result from fluid additions to the mucus layer from mucosal and submucosal secretory cells and/or alteration of epithelial permeability.

  10. [Study on the analytical method of methyl-parathion and phoxim in methyl-parathion, phoxim and cypermethrin mixed formulation].

    PubMed

    Wang, Y; Zheng, F; Chen, F

    1999-07-01

    This paper describes an HPLC method to simultaneously determine methyl-parathion and phoxim in mixed formulation of methyl-parathion, phoxim and cypermethrin. A C8 column was used. The mobile phase was V(MeOH):V(H2O) = 70:30, Methyl-parathion and phoxim were monitored at 254 nm or 280 nm by UV detector. The average recoveries were 99.8% and 99.9% for methyl-parathion and phoxim respectively. The linearity of detector response vs concentration was calibrated in the concentration ranges from 0.1746 to 1.091 g/L for methyl-parathion and from 0.1927 to 1.205 g/L for phoxim.

  11. Chlorpyrifos-, Diisopropylphosphorofluoridate-, and Parathion-Induced Behavioral and Oxidative Stress Effects: Are They Mediated by Analogous Mechanisms of Action?

    PubMed Central

    Sánchez-Santed, Fernando

    2013-01-01

    Exposure to organophosphates (OPs) can lead to cognitive deficits and oxidative damage. Little is known about the relationship between behavioral deficits and oxidative stress within the context of such exposures. Accordingly, the first experiment was carried out to address this issue. Male Wistar rats were administered 250mg/kg of chlorpyrifos (CPF), 1.5mg/kg of diisopropylphosphorofluoridate (DFP), or 15mg/kg of parathion (PTN). Spatial learning in the water maze task was evaluated, and F2-isoprostanes (F2-IsoPs) and prostaglandin (PGE2) were analyzed in the hippocampus. A second experiment was designed to determine the degree of inhibition of brain acetylcholinesterase (AChE) activity, both the soluble and particulate forms of the enzyme, and to assess changes in AChE gene expression given evidence on alternative splicing of the gene in response to OP exposures. In addition, brain acylpeptide hydrolase (APH) activity was evaluated as a second target for OP-mediated effects. In both experiments, rats were sacrificed at various points to determine the time course of OPs toxicity in relation to their mechanism of action. Results from the first experiment suggest cognitive and emotional deficits after OPs exposure, which could be due to, at least in part, increased F2-IsoPs levels. Results from the second experiment revealed inhibition of brain AChE and APH activity at various time points post OP exposure. In addition, we observed increased brain read-through splice variant AChE (AChE-R) mRNA levels after 48h PTN exposure. In conclusion, this study provides novel data on the relationship between cognitive alterations and oxidative stress, and the diverse mechanisms of action along a temporal axis in response to OP exposures in the rat. PMID:22986948

  12. Evaluation of the susceptibility of the cultured shrimp Litopenaeus vannamei to vibriosis when orally exposed to the insecticide methyl parathion.

    PubMed

    Roque, A; Abad, S; Betancourt-Lozano, M; de la Parra, L M Garcia; Baird, D; Guerra-Flores, A L; Gomez-Gil, B

    2005-06-01

    The causes of disease in cultured shrimp are difficult to ascertain but there is evidence that disease is correlated with environmental factors. Crustaceans are particularly sensitive to insecticides due to their close phylogenetic relationship with insects. The objective of this study was to investigate whether there was an increased susceptibility of the shrimp Litopenaeus vannamei to Vibrio parahaemolyticus, when exposed to methyl parathion. The outline of the study was the following: An LC50 96 h was determined to methyl parathion orally offered to juvenile shrimp. Further experiments were carried out in order to determine a concentration that affected the shrimp (verified by measuring the acethylcholinesterase activity) while producing minimal mortalities. This sublethal concentration was used in a susceptibility experiment where methyl parathion was offered to shrimp which were later injected with V. parahaemolyticus in a dose expected to kill less than 15%. Probit analysis estimated a 96 h median lethal concentration (LC50) of 1.56 microg g(-1). Mortality and AChE activity showed a concentration-response relationship in the exposure treatments. The median inhibitory concentration (IC50) determined was 0.029 microg g(-1). These results suggested that a concentration of 0.1 microg g(-1) was appropriate for the bacteria-pesticide interaction test as it was able to elicit 11.1% mortality after 10 days of exposure, while producing an AChE inhibition of 57.12%. Cumulative mortalities were significantly increased (P<0.01) in the treatment that combined exposure to methyl parathion and V. parahaemolyticus (35.19%) in comparison with methyl parathion or V. parahaemolyticus alone (9.26% and 7.41%, respectively).

  13. Parathion utilization by bacterial symbionts in a chemostat.

    PubMed Central

    Daughton, C G; Hsieh, D P

    1977-01-01

    A continuous-culture device was used to select and enrich for microorganisms, from sewage and agricultural runoff, that were capable of using the organophosphorus insecticide parathion as a sole growth substrate. Parathion was dissimilated by the highly acclimated symbiotic activities of Pseudomonas stutzeri, which non-oxidatively and cometabolically hydrolyzed the parathion to ionic diethyl thiophosphate and p-nitrophenol, and P. aeruginosa, which utilized the p-nitrophenol as a sole carbon and energy source. Ionic diethyl thiophosphate was found to be inert to any transformations. Methyl parathion was dissimilated in an analogous way. The device functioned as a chemostat with parathion as the growth-limiting nutrient, and extraordinarily high dissimilation rates were attained for parathion (8 g/liter per day) and for p-nitrophenol (7 g/liter per day). This is the first report of parathion utilization by a defined microbial culture and by symbiotic microbial attack and of dissimilation of an organophosphorus pesticide in a chemostat. PMID:410368

  14. Hyperoxia exposure alters hepatic eicosanoid metabolism in newborn mice.

    PubMed

    Rogers, Lynette K; Tipple, Trent E; Britt, Rodney D; Welty, Stephen E

    2010-02-01

    Prematurely born infants are often treated with supraphysiologic amounts of oxygen, which is associated with lung injury and the development of diseases such as bronchopulmonary dysplasia. Complimentary responses between the lung and liver during the course of hyperoxic lung injury have been studied in adult animals, but little is known about this relationship in neonates. These studies tested the hypothesis that oxidant stress occurs in the livers of newborn mice in response to continuous hyperoxia exposure. Greater levels of glutathione disulfide and nitrotyrosine were detected in lung tissues but not liver tissues from newborn mice exposed to hyperoxia than in room air-exposed controls. However, early increases in 5-lipoxygenase and cyclooxygenases-2 protein levels and increases in total hydroxyeicosatetraenoic acid and prostaglandin levels were observed in the liver tissues of hyperoxia-exposed pups. These studies indicate that free radical oxidation occurs in the lungs of newborn pups exposed to hyperoxia, and alterations in lipid metabolism could be a primary response in the liver tissues. The findings of this study identify possible new mechanisms associated with hyperoxic lung injury in a newborn model of bronchopulmonary dysplasia and thus open opportunities for research.

  15. Genetic surface-display of methyl parathion hydrolase on Yarrowia lipolytica for removal of methyl parathion in water.

    PubMed

    Wang, Xing-Xing; Chi, Zhe; Ru, Shao-Guo; Chi, Zhen-Ming

    2012-09-01

    In this study, the mph gene encoding methyl parathion hydrolase from Pseudomonas sp. WBC-3 was expressed in Yarrowia lipolytica and the expressed methyl parathion hydrolase was displayed on cell surface of Y. lipolytica. The activity of methyl parathion hydrolase displayed on the yeast cells of the transformant Z51 was 59.5 U mg⁻¹ of cell dry cells (450.6 U per mL of the culture) in the presence of 5.0 mM of Co²⁺. The displayed methyl parathion hydrolase had the optimal pH of 9.5 and the optimal temperature of 40 °C, respectively and was stable in the pH range of 4.5-11 and up to 40 °C. The displayed methyl parathion hydrolase was also stimulated by Co²⁺, Cu²⁺, Ni²⁺ and Mn²⁺, and was not affected by Fe²⁺, Fe³⁺, Na⁺, K⁺, Ca²⁺ and Zn²⁺, but was inhibited by other cations tested. Under the optimal conditions (OD(600 nm) = 2.6, the substrate concentration = 100 mg L⁻¹ and 40 °C), 90.8 % of methyl parathion was hydrolyzed within 30 min. Under the similar conditions, 98.7, 97.0, 96.5 and 94.4 % of methyl parathion in tap water (pH 9.5), tap water (pH 6.8), seawater (pH 9.5) and natural seawater (pH 8.2) were hydrolyzed, respectively, suggesting that the methyl parathion hydrolase displayed on the yeast cells can effectively remove methyl parathion in water.

  16. A colorimetric assay for determination of methyl parathion using recombinant methyl parathion hydrolase.

    PubMed

    Anh, Dau Hung; Cheunrungsikul, Kritsananporn; Wichitwechkarn, Jesdawan; Surareungchai, Werasak

    2011-05-01

    A simple, rapid and sensitive colorimetric dipstick assay for the detection of the organophosphorous insecticide methyl parathion (MPT) residue in vegetables was developed. The assay was based on the hydrolysis of MPT by a recombinant methyl parathion hydrolase (recMPH), the encoding gene of which was isolated from Burkholderia cepacia, a soil bacterium indigenous to Thailand. This reaction generates protons leading to a change in pH that correlates with the amount of MPH present. Hence, the pH indicator bromothymol blue was used to monitor the MPH hydrolysis as the associated color changes can be observed by the naked eye. The recMPH was immobilized on a PVDF membrane to establish a dipstick assay format. The assays could detect MPT residues in spiked vegetable samples at the concentration of 1 mg/L without using analytical instrumentation. The test is reusable and stable for up to 3 months in the absence of any preservatives.

  17. Absence of circannual toxicity of parathion to starlings

    USGS Publications Warehouse

    Rattner, B.A.; Grue, C.E.

    1990-01-01

    Ambient temperature and season have been observed to influence the toxicity of several environmental pollutants in homeotherms. The circannual toxicity of ethyl parathion (EP) was examined in adult European starlings (Sturnus vulgaris). Groups of birds housed in outdoor pens received oral doses of EP (20-150 mg/kg body weight) in fall, winter, spring and summer (temperature range -3.3 to 36.7?C). The median lethal dosage (LD50), and brain and plasma cholinesterase inhibition, were found to be quite similar among seasons. There was some suggestion that EP may have been more toxic during hot weather (winter versus summer LD50 estimate [95% confidence interval]:160 [114-225] vs. 118 [102-136] mg/kg; P<0.10). In view of previous reports in which ambient temperature extremes and harsh weather have enhanced organophosphorus insecticide toxicity to birds, it is concluded that circannual toxicity studies should include measures of sensitivity (acute oral exposure) and vulnerability (dietary exposure) to better predict responses of free-ranging birds

  18. CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FAILS TO ALTER FLASH OR PATTERN REVERSAL EVOKED POTENTIALS IN RATS.

    EPA Science Inventory

    Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Visual disturbances are often reported following exposure to xenobiotics, and cholinesterase-inhibiting compounds have been reported to alter visual functi...

  19. CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FAILS TO ALTER BRAINSTEM AUDITORY EVOKED RESPONSE (BAERS) IN RATS.

    EPA Science Inventory

    Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Cholinergic transmission is involved in auditory structures in the periphery and the brainstem and is altered following chlorpyrifos exposure. This study e...

  20. CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FAILS TO ALTER FLASH OR PATTERN REVERSAL EVOKED POTENTIALS IN RATS.

    EPA Science Inventory

    Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Visual disturbances are often reported following exposure to xenobiotics, and cholinesterase-inhibiting compounds have been reported to alter visual functi...

  1. CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FAILS TO ALTER BRAINSTEM AUDITORY EVOKED RESPONSE (BAERS) IN RATS.

    EPA Science Inventory

    Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Cholinergic transmission is involved in auditory structures in the periphery and the brainstem and is altered following chlorpyrifos exposure. This study e...

  2. Methyl parathion in residential properties: relocation and decontamination methodology.

    PubMed Central

    Clark, J Milton; Bing-Canar, John; Renninger, Steve; Dollhopf, Ralph; El-Zein, Jason; Star, Dave; Zimmerman, Dea; Anisuzzaman, Abul; Boylan, Kathline; Tomaszewski, Terrence; Pearce, Ken; Yacovac, Rebecca; Erlwein, Bobby; Ward, John

    2002-01-01

    In November 1994 methyl parathion (MP), a restricted agricultural pesticide, was discovered to have been illegally sprayed within hundreds of residences in Lorain County, Ohio. Surface levels and air concentrations of MP revealed detectable levels of the pesticide 3 years after spraying. Because of the high toxicity of MP (lethal dose to 50% of rats tested [LD50] = 15 mg/kg) and long half-life indoors, risk-based relocation and decontamination criteria were created. Relocation criteria were derived based on levels of p-nitrophenol in urine, a metabolic byproduct of MP exposure. In Ohio, concentrations of MP on surfaces and in the air were also used to trigger relocations. The criteria applied in Ohio underwent refinement as cases of MP misuse were found in Mississippi and then in several other states. The MP investigation (1994-1997) was the largest pesticide misuse case in the nation, ultimately involving the sampling of 9,000 residences and the decontamination of 1,000 properties. This article describes the methodology used for relocation of residents and decontamination of properties having MP. PMID:12634141

  3. FINE PARTICLE EXPOSURE IS ASSOCIATED WITH ALTERED VENTRICULAR REPOLARIZATION

    EPA Science Inventory

    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...

  4. FINE PARTICLE EXPOSURE IS ASSOCIATED WITH ALTERED VENTRICULAR REPOLARIZATION

    EPA Science Inventory

    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...

  5. Paternal nicotine exposure alters hepatic xenobiotic metabolism in offspring.

    PubMed

    Vallaster, Markus P; Kukreja, Shweta; Bing, Xin Y; Ngolab, Jennifer; Zhao-Shea, Rubing; Gardner, Paul D; Tapper, Andrew R; Rando, Oliver J

    2017-02-14

    Paternal environmental conditions can influence phenotypes in future generations, but it is unclear whether offspring phenotypes represent specific responses to particular aspects of the paternal exposure history, or a generic response to paternal 'quality of life'. Here, we establish a paternal effect model based on nicotine exposure in mice, enabling pharmacological interrogation of the specificity of the offspring response. Paternal exposure to nicotine prior to reproduction induced a broad protective response to multiple xenobiotics in male offspring. This effect manifested as increased survival following injection of toxic levels of either nicotine or cocaine, accompanied by hepatic upregulation of xenobiotic processing genes, and enhanced drug clearance. Surprisingly, this protective effect could also be induced by a nicotinic receptor antagonist, suggesting that xenobiotic exposure, rather than nicotinic receptor signaling, is responsible for programming offspring drug resistance. Thus, paternal drug exposure induces a protective phenotype in offspring by enhancing metabolic tolerance to xenobiotics.

  6. Biotransformation of the insecticide parathion by mouse brain.

    PubMed

    Soranno, T M; Sultatos, L G

    1992-01-01

    The acute toxicity of organothiophosphate insecticides like parathion results from their metabolic activation by cytochromes P450. The present study is directed towards the characterization of cytochrome-P450-dependent metabolism of parathion by various mouse brain regions. Intraperitoneal administration of [35S]parathion to mice led to covalently bound [35S]sulfur in various tissues, indicating their capacity to oxidatively desulfurate this insecticide. Liver contained the greatest amount of covalently bound sulfur, and brain the least. Among individual brain regions the olfactory bulb and hypothalamus possessed the highest levels of sulfur binding when expressed on a per milligram tissue basis. However, when expressed on a per brain region basis, sulfur binding was greatest within the cortex as a result of the large mass of this region, compared to the hypothalamus and olfactory bulb. Incubation of the 78,000 x g fraction of mouse brain with parathion resulted in formation of p-nitrophenol, although paraoxon could not be detected. However, given the current understanding of parathion metabolism by cytochromes P450, and given that paraoxon can rapidly disappear through phosphorylation of serine hydroxyl groups, it is reasonable to assume that at least some paraoxon was formed. Production of p-nitrophenol required NADPH and was inhibited by carbon monoxide. In vitro incubations of parathion with the 78,000 x g fraction of mouse brain indicated that the hypothalamus and olfactory bulb had the greatest capacity to produce p-nitrophenol. These results demonstrate that various mouse brain regions possess different capacities to metabolize parathion.

  7. In utero and postnatal exposure to arsenic alters pulmonary structure and function

    SciTech Connect

    Lantz, R. Clark Chau, Binh; Sarihan, Priyanka; Witten, Mark L.; Pivniouk, Vadim I.; Chen, Guan Jie

    2009-02-15

    In addition to cancer endpoints, arsenic exposures can also lead to non-cancerous chronic lung disease. Exposures during sensitive developmental time points can contribute to the adult disease. Using a mouse model, in utero and early postnatal exposures to arsenic (100 ppb or less in drinking water) were found to alter airway reactivity to methacholine challenge in 28 day old pups. Removal of mice from arsenic exposure 28 days after birth did not reverse the alterations in sensitivity to methacholine. In addition, adult mice exposed to similar levels of arsenic in drinking water did not show alterations. Therefore, alterations in airway reactivity were irreversible and specific to exposures during lung development. These functional changes correlated with protein and gene expression changes as well as morphological structural changes around the airways. Arsenic increased the whole lung levels of smooth muscle actin in a dose dependent manner. The level of smooth muscle mass around airways was increased with arsenic exposure, especially around airways smaller than 100 {mu}m in diameter. This increase in smooth muscle was associated with alterations in extracellular matrix (collagen, elastin) expression. This model system demonstrates that in utero and postnatal exposure to environmentally relevant levels of arsenic can irreversibly alter pulmonary structure and function in the adults.

  8. In Utero and Postnatal Exposure to Arsenic Alters Pulmonary Structure and Function

    PubMed Central

    Lantz, R. Clark; Chau, Binh; Sarihan, Priyanka; Witten, Mark L.; Pivniouk, Vadim I.; Chen, Guan Jie

    2009-01-01

    In addition to cancer endpoints, arsenic exposures can also lead to non-cancerous chronic lung disease. Exposures during sensitive developmental time points can contribute to the adult disease. Using a mouse model, in utero and early postnatal exposures to arsenic (100 ppb or less in drinking water) were found to alter airway reactivity to methacholine challenge in 28 day old pups. Removal of mice from arsenic exposure 28 days after birth did not reverse the alterations in sensitivity to methacholine. In addition, adult mice exposed to similar levels of arsenic in drinking water did not show alterations. Therefore, alterations in airway reactivity were irreversible and specific to exposures during lung development. These functional changes correlated with protein and gene expression changes as well as morphological structural changes around the airways. Arsenic increased the whole lung levels of smooth muscle actin in a dose dependent manner. The level of smooth muscle mass around airways was increased with arsenic exposure, especially around airways smaller than 100 μm in diameter. This increase in smooth muscle was associated with alterations in extracellular matrix (collagen, elastin) expression. This model system demonstrates that in utero and postnatal exposure to environmentally relevant levels of arsenic can irreversibly alter pulmonary structure and function in the adults. PMID:19095001

  9. Paternal nicotine exposure alters hepatic xenobiotic metabolism in offspring

    PubMed Central

    Vallaster, Markus P; Kukreja, Shweta; Bing, Xin Y; Ngolab, Jennifer; Zhao-Shea, Rubing; Gardner, Paul D; Tapper, Andrew R; Rando, Oliver J

    2017-01-01

    Paternal environmental conditions can influence phenotypes in future generations, but it is unclear whether offspring phenotypes represent specific responses to particular aspects of the paternal exposure history, or a generic response to paternal ‘quality of life’. Here, we establish a paternal effect model based on nicotine exposure in mice, enabling pharmacological interrogation of the specificity of the offspring response. Paternal exposure to nicotine prior to reproduction induced a broad protective response to multiple xenobiotics in male offspring. This effect manifested as increased survival following injection of toxic levels of either nicotine or cocaine, accompanied by hepatic upregulation of xenobiotic processing genes, and enhanced drug clearance. Surprisingly, this protective effect could also be induced by a nicotinic receptor antagonist, suggesting that xenobiotic exposure, rather than nicotinic receptor signaling, is responsible for programming offspring drug resistance. Thus, paternal drug exposure induces a protective phenotype in offspring by enhancing metabolic tolerance to xenobiotics. DOI: http://dx.doi.org/10.7554/eLife.24771.001 PMID:28196335

  10. Developmental timing of perchlorate exposure alters threespine stickleback dermal bone

    PubMed Central

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

    2015-01-01

    Adequate levels of thyroid hormone are critical during development and metamorphosis, and for maintaining metabolic homeostasis. Perchlorate, a common contaminant of water sources, inhibits thyroid function in vertebrates. We utilized threespine stickleback (Gasterosteus aculeatus) to determine if timing of perchlorate exposure during development impacts adult dermal skeletal phenotypes. Fish were exposed to water contaminated with perchlorate (30 mg/L or 100 mg/L) beginning at 0, 3, 7, 14, 21, 42, 154 or 305 days post fertilization until sexual maturity at one year of age. A reciprocal treatment moved stickleback from contaminated to clean water on the same schedule providing for different stages of initial exposure and different treatment durations. Perchlorate exposure caused concentration-dependent significant differences in growth for some bony traits. Continuous exposure initiated within the first 21 days post fertilization had the greatest effects on skeletal traits. Exposure to perchlorate at this early stage can result in small traits or abnormal skeletal morphology of adult fish which could affect predator avoidance and survival. PMID:25753171

  11. Developmental timing of perchlorate exposure alters threespine stickleback dermal bone.

    PubMed

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

    2015-08-01

    Adequate levels of thyroid hormone are critical during development and metamorphosis, and for maintaining metabolic homeostasis. Perchlorate, a common contaminant of water sources, inhibits thyroid function in vertebrates. We utilized threespine stickleback (Gasterosteus aculeatus) to determine if timing of perchlorate exposure during development impacts adult dermal skeletal phenotypes. Fish were exposed to water contaminated with perchlorate (30mg/L or 100mg/L) beginning at 0, 3, 7, 14, 21, 42, 154 or 305days post fertilization until sexual maturity at 1year of age. A reciprocal treatment moved stickleback from contaminated to clean water on the same schedule providing for different stages of initial exposure and different treatment durations. Perchlorate exposure caused concentration-dependent significant differences in growth for some bony traits. Continuous exposure initiated within the first 21days post fertilization had the greatest effects on skeletal traits. Exposure to perchlorate at this early stage can result in small traits or abnormal skeletal morphology of adult fish which could affect predator avoidance and survival. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Acute Exposure to Particulate Matter (PM) Alters Physiologic ...

    EPA Pesticide Factsheets

    Human exposure to ambient PM from fossil-fuel emissions is linked to cardiovascular disease and death. This association strengthens in people with preexisting cardiopulmonary diseases—especially heart failure (HF). We previously examined the effects of PM on HF by exposing Spontaneously Hypertensive Heart Failure (SHHF) rats to residual oil fly ash (ROFA) after accelerating HF onset via isoproterenol (ISO) infusion. In that study, rats were exposed to PM 2 wks after ISO treatment ceased, which was more than 1 wk after ISO-cessation had induced a 9-d period of hypotension. Epidemiological evidence suggests that effects would be more pronounced if exposure coincided with the HF-like hypotensive period. We hypothesized that PM exposure shortly after cessation of ISO treatment would cause greater cardiopulmonary injury. SHHF rats were infused with ISO (n=24; 1.0 mg/kg/d sc) or saline (n=23) via osmotic pump for 5 wks and then 5 d later exposed by nose-only inhalation for 4 h to either air or 580 µg/m3 of the PM2.5 fraction of a synthetic PM (dried salt solution, MSO4) similar in composition to a well-studied ROFA and consisting of Fe, Ni and V sulfates. In ISO-pretreated rats only, MSO4 decreased pulse pressure (an indirect indicator of cardiac output), decreased systolic and diastolic blood pressures, and increased QA interval (inversely related to myocardial contractility) during inhalation exposure and caused post-inhalation pulmonary inflammation significantl

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

    NASA Technical Reports Server (NTRS)

    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.

  14. Acute neuroactive drug exposures alter locomotor activity in larval zebrafish

    EPA Science Inventory

    In an effort to develop a rapid in vivo screen for EPA's prioritization of toxic chemicals, we are characterizing the locomotor activity of zebrafish (Danio rerio) larvae after exposure to prototypic drugs that act on the central nervous system. MPTP (1-methyl-4phenyl- 1 ,2,3,6-...

  15. Acute neuroactive drug exposures alter locomotor activity in larval zebrafish

    EPA Science Inventory

    In an effort to develop a rapid in vivo screen for EPA's prioritization of toxic chemicals, we are characterizing the locomotor activity of zebrafish (Danio rerio) larvae after exposure to prototypic drugs that act on the central nervous system. MPTP (1-methyl-4phenyl- 1 ,2,3,6-...

  16. NGF and BDNF Alterations by Prenatal Alcohol Exposure.

    PubMed

    Carito, Valentina; Ceccanti, Mauro; Ferraguti, Giampiero; Coccurello, Roberto; Ciafrè, Stefania; Tirassa, Paola; Fiore, Marco

    2017-08-24

    It is now widely established the devastating effects of prenatal alcohol exposure on the embryo and fetus development causing marked cognitive and neurobiological deficits in the newborns. The negative effects of the gestational alcohol use have been well documented and known for some time. However, also the subtle role of alcohol consumption by fathers prior to mating is drawing special attention. Both paternal and maternal alcohol exposure have been shown to affect the neurotrophins&#039; signalling pathways in the brain and in target organs of ethanol intoxication. Neurotrophins, in particular nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), are molecules playing a pivotal role in the survival, development and function of the peripheral and central nervous systems but also in the pathogenesis of developmental defects caused by alcohol exposure. New researches from the available literature and experimental data from our laboratory are presented in this review to offer the most recent findings regarding the effects of maternal and paternal prenatal ethanol exposure especially on the neurotrophins&#039; signalling pathways. NGF and BDNF changes play a subtle role in short- and long-lasting effects of alcohol in ethanol target tissues, including neuronal cell death and severe cognitive and physiological deficits in the newborns. The review suggests a possible therapeutic intervention based on the use of specific molecules with antioxidant properties in order to induce a potential prevention of the harmful effects of the paternal and/or maternal alcohol exposure. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    PubMed

    Hanson, Miranda L; Holásková, Ida; Elliott, Meenal; Brundage, Kathleen M; Schafer, Rosana; Barnett, John B

    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(2) (10ppm) and the effects on the immune system of the offspring were assessed at two time points following birth (2 and 7weeks of age). Thymocyte and splenocyte phenotypes were analyzed by flow cytometry. Prenatal Cd exposure did not affect thymocyte populations at 2 and 7weeks 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 2weeks of age. At 7weeks 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(+)FoxP3(+)CD25(+) (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(+)CD223(+) T cells were markedly decreased in the spleens in all offspring at 7weeks of age. These findings suggest that even very low levels of Cd exposure during gestation can result in long term detrimental

  18. ABCB1 and ABCC4 efflux transporters are involved in methyl parathion detoxification in ZFL cells.

    PubMed

    Nornberg, Bruna Félix; Batista, Carolina Reyes; Almeida, Daniela Volcan; Trindade, Gilma Santos; Marins, Luis Fernando

    2015-02-01

    The multi-xenobiotics resistance (MXR) mechanisms are the first line of defense against toxic substances in aquatic organisms and present great importance in the adaptation related to contaminated environments. Methyl parathion (MP) is a widely used organophosphate pesticide, which has been associated to various toxic effects in organisms. In the present work, we studied the main genes related to efflux transporters in zebrafish liver (ZFL) cells exposed to MP with and without an inhibitor of ABC transporters (verapamil). The results concerning transporters activity showed that the MXR mechanism is activated to detoxify from methyl parathion. The toxic effects of MP on ZFL cells were increased in the presence of the efflux transporter inhibitor, once cell viability was significantly decreased in co-exposure experiments. The combined exposure to MP and the inhibitor caused an increase in gene expression of P-gp1 (Abcb1) and MRP4 (Abcc4), suggesting that these transporters isoforms are associated with MP efflux. In general, the expression of genes related to the antioxidant defense system (ADS) was significantly increased in ZFL cells co-exposed to MP and verapamil. These data provide useful insights for better understanding of MP detoxification mechanism in fish hepatocytes.

  19. ACUTE EXPOSURE TO MOLINATE ALTERS NEUROENDOCRINE CONTROL OF OVULATION IN THE RAT

    EPA Science Inventory

    Molinate, a thiocarbamate herbicide, has been shown previously to impair reproductive capability in the male rat. In a two-generation study, molinate exposure to female rats resulted in altered pregnancy outcome. However, published data is lacking on the effects of acute exposure...

  20. EXPOSURE OF CULTURED MYOCYTES TO ZINC RESULTS IN ALTERED BEAT RATE AND INTERCELLULAR COMMUNICATION.

    EPA Science Inventory

    Exposure of cultured myocytes to zinc results in altered beat rate and intercellular communication

    Graff, Donald W, Devlin, Robert B, Brackhan, Joseph A, Muller-Borer, Barbara J, Bowman, Jill S, Cascio, Wayne E.

    Exposure to ambient air pollution particulate matter (...

  1. EXPOSURE OF CULTURED MYOCYTES TO ZINC RESULTS IN ALTERED BEAT RATE AND INTERCELLULAR COMMUNICATION.

    EPA Science Inventory

    Exposure of cultured myocytes to zinc results in altered beat rate and intercellular communication

    Graff, Donald W, Devlin, Robert B, Brackhan, Joseph A, Muller-Borer, Barbara J, Bowman, Jill S, Cascio, Wayne E.

    Exposure to ambient air pollution particulate matter (...

  2. ACUTE EXPOSURE TO MOLINATE ALTERS NEUROENDOCRINE CONTROL OF OVULATION IN THE RAT

    EPA Science Inventory

    Molinate, a thiocarbamate herbicide, has been shown previously to impair reproductive capability in the male rat. In a two-generation study, molinate exposure to female rats resulted in altered pregnancy outcome. However, published data is lacking on the effects of acute exposure...

  3. Exposure to metals mixtures: Genomic alterations of infectious ...

    EPA Pesticide Factsheets

    Exposure to toxic metals can have harmful health effects, particularly in children. Although studies have investigated the individual effects toxic metals have on gene expression and health outcomes, there are no studies assessing the effect of metal mixtures on gene expression profiles. Here, we assessed the mixture effect of six toxic metals (arsenic, beryllium, cadmium, chromium, mercury, and lead) on gene expression profiles in children in Detroit, Michigan. As part of the Mechanistic Indicators of Childhood Asthma (MICA) cross sectional study, we assessed metal exposure in 131 children in Detroit using fingernail metals levels. A metals mixture score was calculated and compared to gene expression profiles across the population adjusting for age and race. There were 145 unique genes that were significantly differentially expressed when comparing children exposed to low and high levels of the metals mixture. Of the genes differentially expressed, 107 (74%) had increased expression while 38 (26%) had decreased expression. The main biological function associated with multiple metals was infectious disease. Within that group, genes were associated with infection of respiratory tract (P < 10-6) severe acute respiratory syndrome (P < 10-5), and sepsis (P < 10-3). Taken together, these data demonstrate that exposure to metals mixtures may activate gene networks related to infectious disease response. This abstract does not necessarily reflect the views or policie

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

    SciTech Connect

    Hanson, Miranda L.; Holásková, Ida; Elliott, Meenal; Brundage, Kathleen M.; Schafer, Rosana; Barnett, John B.

    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. Alterations in splanchnic blood flow following chronic ethanol exposure.

    PubMed

    Piano, M R; Ferguson, J L; Melchior, C L

    1990-08-01

    The purpose of these experiments was to determine whether or not tolerance develops to the effect of 3.0 g/kg ethanol on total and regional splanchnic blood flow in male Wistar rats. The animals were given the Lieber-DeCarli liquid diet containing ethanol for 10 days; ethanol-fed animals were withdrawn 24 hr prior to experiments. Regional blood flow and cardiac output (CO) were measured by the reference microsphere technique after an intraperitoneal injection of 3.0 g/kg of ethanol. Acute ethanol administration produced early nonsustained increases in portal vein blood flow in animals fed ethanol for 10 days and withdrawn for 24 hr and in control animals. However, after chronic exposure to ethanol, the pattern of increase in blood flow in response to ethanol in the splanchnic organs was different between the ethanol-fed and control groups. Increases in portal vein flow in control groups were due to concomitant increases in small intestinal, colonic, and cecal blood flow while the increase in the ethanol-fed group was due to a rise in small intestinal and stomach blood flow. The increase in stomach blood flow that occurred in the animals treated chronically with ethanol may be viewed as a conditioned response to ethanol, since this was not found in the control group. These results, demonstrate that the pattern of increase in blood flow in the splanchnic organs produced by an acute dose of ethanol depends on the animal's previous exposure to ethanol.

  6. Exposure to bisphenol A in young adult mice does not alter ovulation but does alter the fertilization ability of oocytes.

    PubMed

    Moore-Ambriz, Teresita Rocio; Acuña-Hernández, Deyanira Guadalupe; Ramos-Robles, Brenda; Sánchez-Gutiérrez, Manuel; Santacruz-Márquez, Ramsés; Sierra-Santoyo, Adolfo; Piña-Guzmán, Belem; Shibayama, Mineko; Hernández-Ochoa, Isabel

    2015-12-15

    Follicle growth culminates in ovulation, which allows for the expulsion of fertilizable oocytes and the formation of corpora lutea. Bisphenol A (BPA) is present in many consumer products, and it has been suggested that BPA impairs ovulation; however, the underlying mechanisms are unknown. Therefore, this study first evaluated whether BPA alters ovulation by affecting folliculogenesis, the number of corpora lutea or eggs shed to the oviduct, ovarian gonadotropin responsiveness, hormone levels, and estrous cyclicity. Because it has been suggested (but not directly confirmed) that BPA exerts toxic effects on the fertilization ability of oocytes, a second aim was to evaluate whether BPA impacts the oocyte fertilization rate using an in vitro fertilization assay and mating. The possible effects on early zygote development were also examined. Young adult female C57BL/6J mice (39 days old) were orally dosed with corn oil (vehicle) or 50 μg/kgbw/day BPA for a period encompassing the first three reproductive cycles (12-15 days). BPA exposure did not alter any parameters related to ovulation. Moreover, BPA exposure reduced the percentage of fertilized oocytes after either in vitro fertilization or mating, but it did not alter the zygotic stages. The data indicate that exposure to the reference dose of BPA does not impact ovulation but that it does influence the oocyte quality in terms of its fertilization ability.

  7. Alteration of catecholamine concentrations in rat testis after methamphetamine exposure.

    PubMed

    Janphet, S; Nudmamud-Thanoi, S; Thanoi, S

    2017-03-01

    Methamphetamine (METH) is an illicit drug that can lead to changes in catecholamines in the brain. It also has substantial effects on reproductive function. We investigated whether rat models of METH abuse could induce changes in the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), norepinephrine (NE) and its metabolite, 3,4-dihydroxyphenylglycol (DHPG), in testis. Four groups of rats received vehicle, acute dose (AB), escalating dose (ED) or ED with an acute high dose (ED-binge) METH. DOPAC, NE and DHPG were determined using HPLC. DOPAC was significantly increased in the AB while NE was significantly decreased in the ED-binge. DHPG was also significantly decreased in the ED and ED-binge. METH induces alterations of DOPAC, NE and DHPG testicular concentrations that may result in male reproductive dysfunction.

  8. The interaction of the phosphorothioate insecticides chlorpyrifos and parathion and their oxygen analogues with bovine serum albumin.

    PubMed

    Sultatos, L G; Basker, K M; Shao, M; Murphy, S D

    1984-07-01

    The distribution and subsequent toxicity of hazardous chemicals can be influenced by their interactions with plasma proteins. In the present study reversible binding of the phosphorothioate insecticides chlorpyrifos and parathion to fatty acid-free bovine serum albumin (BSA) was examined using the technique of equilibrium dialysis. Computer analyses of the binding data revealed that chlorpyrifos and parathion each bound reversibly to a single class of binding sites on BSA, with apparent KD values of 3.4 +/- 0.1 and 11.1 +/- 0.3 microM, respectively. Additionally, the maximal number of binding sites for each insecticide per molecule of BSA was one. Displacement studies using both chlorpyrifos and parathion indicated that each was a competitive inhibitor of the other's binding, suggesting that they were bound to the same site. Incubation of chlorpyrifos oxon or paraoxon with a 1% solution of BSA resulted in limited, EDTA-insensitive formation of 3,5,6-trichloro-2-pyridinol or p-nitrophenol, respectively. Pretreatment of BSA with 5 mM paraoxon, chlorpyrifos oxon, or 1 mM diisopropylfluorophosphate did not alter this activity, suggesting that these reactions resulted from an esterase-like capacity of BSA, and not from phosphorylation of BSA by these oxons.

  9. Effect of prenatal haloperidol exposure on behavioral alterations in rats.

    PubMed

    Singh, K P; Singh, Mandavi

    2002-01-01

    Pregnant Charles-Foster rats were exposed to haloperidol (HAL), a neuroleptic drug that binds to and blocks dopamine (DA) receptor subtypes at a dose of 2.5 mg/kg body weight (intraperitoneally) from Gestation Day (GD) 12 to 20. The animals from both treated as well as vehicle control groups were allowed to deliver on GD 21. The offspring culled at birth on the basis of sex and weight were subjected to behavioral tests at the age of 8 weeks. The HAL-treated rat offspring showed a significant increase in anxiogenic behavior on the open field, elevated plus-maze and elevated zero-maze tests when compared with the vehicle-treated (control) rat offspring of the same age group. These findings suggest that prenatal exposure to HAL during a critical period of brain development leaves a lasting imprint on the brain, resulting in abnormal anxiety states, possibly through dopaminergic neurotransmission mechanisms.

  10. Prenatal chlorpyrifos exposure in rats causes persistent behavioral alterations.

    PubMed

    Levin, Edward D; Addy, Nii; Baruah, Avanti; Elias, Alana; Christopher, N Channelle; Seidler, Frederic J; Slotkin, Theodore A

    2002-01-01

    Use of chlorpyrifos (CPF) has been curtailed due to its developmental neurotoxicity. In rats, postnatal CPF administration produces lasting changes in cognitive performance, but less information is available about the effects of prenatal exposure. We administered CPF to pregnant rats on gestational days (GD) 17-20, a peak period of neurogenesis, using doses (1 or 5 mg/kg/day) below the threshold for fetal growth impairment. We then evaluated performance in the T-maze, Figure-8 apparatus and 16-arm radial maze, beginning in adolescence and continuing into adulthood. CPF elicited initial locomotor hyperactivity in the T-maze. Females showed slower habituation in the Fig. 8 maze; no effects were seen in males. In the radial-arm maze, females showed impaired choice accuracy for both working and reference memory and again, males were unaffected. Despite the deficits, all animals eventually learned the maze with continued training. At that point, we challenged them with the muscarinic antagonist, scopolamine, to determine the dependence of behavioral performance on cholinergic function. Whereas control females showed impairment with scopolamine, CPF-exposed females did not, implying that the delayed acquisition of the task had been accomplished through alternative mechanisms. The differences were specific to muscarinic circuits, as control and CPF groups responded similarly to the nicotinic antagonist, mecamylamine. Surprisingly, adverse effects of CPF were greater in the group receiving 1 mg/kg as compared to 5 mg/kg. Promotional effects of acetylcholine (ACh) on cell differentiation may thus help to offset CPF-induced developmental damage that occurs through other noncholinergic mechanisms. Our results indicate that late prenatal exposure to CPF induces long-term changes in cognitive performance that are distinctly gender-selective. Additional defects may be revealed by similar strategies that subject the animals to acute challenges, thus, uncovering the adaptive

  11. An approach for the quantitative consideration of genetic polymorphism data in chemical risk assessment: examples with warfarin and parathion.

    PubMed

    Gentry, P Robinan; Hack, C Eric; Haber, Lynne; Maier, Andrew; Clewell, Harvey J

    2002-11-01

    In recent years, a great deal of research has been conducted to identify genetic polymorphisms. One focus has been to characterize variability in metabolic enzyme systems that could impact internal doses of pharmaceuticals or environmental pollutants. Methods are needed for using this metabolic information to estimate the resulting variability in tissue doses associated with chemical exposure. We demonstrate here the use of physiologically based pharmacokinetic (PBPK) modeling in combination with Monte Carlo analysis to incorporate information on polymorphisms into the analysis of toxicokinetic variability. Warfarin and parathion were used as case studies to demonstrate this approach. Our results suggest that polymorphisms in the PON1 gene, that give rise to allelic variants of paraoxonase, which is involved in the metabolism of paraoxon (a metabolite of parathion), make only a minor contribution to the overall variability in paraoxon tissue dose, while polymorphisms in the CYP2C9 gene, which gives rise to allelic variants of the major metabolic enzyme for warfarin, account for a significant portion of the overall variability in (S)-warfarin tissue dose. These analyses were used to estimate chemical-specific adjustment factors (CSAFs) for the human variability in toxicokinetics for both parathion and warfarin. Implications of alternatives in the calculation of CSAFs are explored. Key decision points for applying the PBPK-Monte Carlo approach to evaluate toxicokinetic variability for other chemicals are also discussed.

  12. Exposure to mercury alters early activation events in fish leukocytes.

    PubMed Central

    MacDougal, K C; Johnson, M D; Burnett, K G

    1996-01-01

    Although fish in natural populations may carry high body burdens of both organic and inorganic mercury, the effects of this divalent metal on such lower vertebrates is poorly understood. In this report, inorganic mercury in the form of mercuric chloride (HgCl2) is shown to produce both high-dose inhibition and low-dose activation of leukocytes in a marine teleost fish, Sciaenops ocellatus. Concentrations of inorganic mercury > or = 10 microM suppressed DNA synthesis and induced rapid influx of radiolabeled calcium, as well as tyrosine phosphorylation of numerous cellular proteins. Lower concentrations (0.1-1 microM) of HgCl2 that activated cell growth also induced a slow sustained rise in intracellular calcium in cells loaded with the calcium indicator dye fura-2, but did not produce detectable tyrosine phosphorylation of leukocyte proteins. These studies support the possibility that subtoxic doses of HgCl2 may inappropriately activate teleost leukocytes, potentially altering the processes that regulate the magnitude and specificity of the fish immune response to environmental pathogens. Images Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. Figure 7. PMID:8930553

  13. Developmental exposure to paracetamol causes biochemical alterations in medulla oblongata.

    PubMed

    Blecharz-Klin, Kamilla; Joniec-Maciejak, Ilona; Jawna, Katarzyna; Pyrzanowska, Justyna; Piechal, Agnieszka; Wawer, Adriana; Widy-Tyszkiewicz, Ewa

    2015-09-01

    The effect and safety of prenatal and early life administration of paracetamol - routinely used over-the-counter antipyretic and analgesic medication on monoamines content and balance of amino acids in the medulla oblongata is still unknown. In this study we have determined the level of neurotransmitters in this structure in two-month old Wistar male rats exposed to paracetamol in the dose of 5 (P5, n=10) or 15mg/kg b.w. (P15, n=10) during prenatal period, lactation and till the end of the second month of life. Control group received drinking water (Con, n=10). Monoamines, their metabolites and amino acids concentration in medulla oblongata of rats were determined using high performance liquid chromatography (HPLC) in 60 postnatal day (PND60). This experiment shows that prenatal and early life paracetamol exposure modulates neurotransmission associated with serotonergic, noradrenergic and dopaminergic system in medulla oblongata. Reduction of alanine and taurine levels has also been established. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Exposure to high ambient temperatures alters embryology in rabbits

    NASA Astrophysics Data System (ADS)

    García, M. L.; Argente, M. J.

    2017-09-01

    High ambient temperatures are a determining factor in the deterioration of embryo quality and survival in mammals. The aim of this study was to evaluate the effect of heat stress on embryo development, embryonic size and size of the embryonic coats in rabbits. A total of 310 embryos from 33 females in thermal comfort zone and 264 embryos of 28 females in heat stress conditions were used in the experiment. The traits studied were ovulation rate, percentage of total embryos, percentage of normal embryos, embryo area, zona pellucida thickness and mucin coat thickness. Traits were measured at 24 and 48 h post-coitum (hpc); mucin coat thickness was only measured at 48 hpc. The embryos were classified as zygotes or two-cell embryos at 24 hpc, and 16-cells or early morulae at 48 hpc. The ovulation rate was one oocyte lower in heat stress conditions than in thermal comfort. Percentage of normal embryos was lower in heat stress conditions at 24 hpc (17.2%) and 48 hpc (13.2%). No differences in percentage of zygotes or two-cell embryos were found at 24 hpc. The embryo development and area was affected by heat stress at 48 hpc (10% higher percentage of 16-cells and 883 μm2 smaller, respectively). Zona pellucida was thicker under thermal stress at 24 hpc (1.2 μm) and 48 hpc (1.5 μm). No differences in mucin coat thickness were found. In conclusion, heat stress appears to alter embryology in rabbits.

  15. Exposure to high ambient temperatures alters embryology in rabbits

    NASA Astrophysics Data System (ADS)

    García, M. L.; Argente, M. J.

    2017-03-01

    High ambient temperatures are a determining factor in the deterioration of embryo quality and survival in mammals. The aim of this study was to evaluate the effect of heat stress on embryo development, embryonic size and size of the embryonic coats in rabbits. A total of 310 embryos from 33 females in thermal comfort zone and 264 embryos of 28 females in heat stress conditions were used in the experiment. The traits studied were ovulation rate, percentage of total embryos, percentage of normal embryos, embryo area, zona pellucida thickness and mucin coat thickness. Traits were measured at 24 and 48 h post-coitum (hpc); mucin coat thickness was only measured at 48 hpc. The embryos were classified as zygotes or two-cell embryos at 24 hpc, and 16-cells or early morulae at 48 hpc. The ovulation rate was one oocyte lower in heat stress conditions than in thermal comfort. Percentage of normal embryos was lower in heat stress conditions at 24 hpc (17.2%) and 48 hpc (13.2%). No differences in percentage of zygotes or two-cell embryos were found at 24 hpc. The embryo development and area was affected by heat stress at 48 hpc (10% higher percentage of 16-cells and 883 μm2 smaller, respectively). Zona pellucida was thicker under thermal stress at 24 hpc (1.2 μm) and 48 hpc (1.5 μm). No differences in mucin coat thickness were found. In conclusion, heat stress appears to alter embryology in rabbits.

  16. Exposure to high ambient temperatures alters embryology in rabbits.

    PubMed

    García, M L; Argente, M J

    2017-03-22

    High ambient temperatures are a determining factor in the deterioration of embryo quality and survival in mammals. The aim of this study was to evaluate the effect of heat stress on embryo development, embryonic size and size of the embryonic coats in rabbits. A total of 310 embryos from 33 females in thermal comfort zone and 264 embryos of 28 females in heat stress conditions were used in the experiment. The traits studied were ovulation rate, percentage of total embryos, percentage of normal embryos, embryo area, zona pellucida thickness and mucin coat thickness. Traits were measured at 24 and 48 h post-coitum (hpc); mucin coat thickness was only measured at 48 hpc. The embryos were classified as zygotes or two-cell embryos at 24 hpc, and 16-cells or early morulae at 48 hpc. The ovulation rate was one oocyte lower in heat stress conditions than in thermal comfort. Percentage of normal embryos was lower in heat stress conditions at 24 hpc (17.2%) and 48 hpc (13.2%). No differences in percentage of zygotes or two-cell embryos were found at 24 hpc. The embryo development and area was affected by heat stress at 48 hpc (10% higher percentage of 16-cells and 883 μm(2) smaller, respectively). Zona pellucida was thicker under thermal stress at 24 hpc (1.2 μm) and 48 hpc (1.5 μm). No differences in mucin coat thickness were found. In conclusion, heat stress appears to alter embryology in rabbits.

  17. Accumulation, metabolism and toxicity of parathion in tadpoles

    SciTech Connect

    Hall, R.J. )

    1990-04-01

    Earlier work exposing tadpoles to organophosphorus pesticides indicated the great resistance of tadpoles of the bullfrog (Rana catesbeiana) to these chemicals and their surprising ability to accumulate parathion and fenthion from water. These qualities seemed to make them an ideal model with which to test a hypothesis advanced by Burke and Ferguson, who noted that parathion is more toxic to resistant mosquitofish in static water than in flowing water--a reversal of the pattern normally seen. They believed that highly toxic metabolite paraoxon was produced by the fish and that its buildup in static systems resulted in the unexpected mortality. Amphibians have been shown to produce paraoxon and to accumulate the parent compound parathion to levels that are potentially hazardous to other organisms. In the course of examining paraoxon production by tadpoles, it would also be possible to learn more about their patterns of parathion uptake and elimination. Retention of residues is also a matter of concern given the high levels observed in the earlier studies.

  18. 40 CFR 180.122 - Parathion; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Parathion; tolerances for residues. 180.122 Section 180.122 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances...

  19. 40 CFR 180.122 - Parathion; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Parathion; tolerances for residues. 180.122 Section 180.122 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances...

  20. Perinatal sulfur dioxide exposure alters brainstem parasympathetic control of heart rate.

    PubMed

    Woerman, Amanda L; Mendelowitz, David

    2013-07-01

    Sulfur dioxide (SO₂) is an air pollutant that impedes neonatal development and induces adverse cardiorespiratory health effects, including tachycardia. Here, an animal model was developed that enabled characterization of (i) in vivo alterations in heart rate and (ii) altered activity in brainstem neurons that control heart rate after perinatal SO₂ exposure. Pregnant Sprague-Dawley dams and their pups were exposed to 5 parts per million SO₂ for 1 h daily throughout gestation and 6 days postnatal. Electrocardiograms were recorded from pups at 5 days postnatal to examine changes in basal and diving reflex-evoked changes in heart rate following perinatal SO₂ exposure. In vitro studies employed whole-cell patch-clamp electrophysiology to examine changes in neurotransmission to cardiac vagal neurons within the nucleus ambiguus upon SO₂ exposure using a preparation that maintains fictive inspiratory activity recorded from the hypoglossal rootlet. Perinatal SO₂ exposure increased heart rate and blunted the parasympathetic-mediated diving reflex-evoked changes in heart rate. Neither spontaneous nor inspiratory-related inhibitory GABAergic or glycinergic neurotransmission to cardiac vagal neurons was altered by SO₂ exposure. However, excitatory glutamatergic neurotransmission was decreased by 51.2% upon SO₂ exposure. This diminished excitatory neurotransmission was tetrodotoxin-sensitive, indicating SO₂ exposure impaired the activity of preceding glutamatergic neurons that synapse upon cardiac vagal neurons. Diminished glutamatergic, but unaltered inhibitory neurotransmission to cardiac vagal neurons provides a mechanism for the observed SO₂-induced elevated heart rate via an impairment of brainstem cardioinhibitory parasympathetic activity to the heart.

  1. DNA damage associated with ultrastructural alterations in rat myocardium after loud noise exposure.

    PubMed Central

    Lenzi, Paola; Frenzilli, Giada; Gesi, Marco; Ferrucci, Michela; Lazzeri, Gloria; Fornai, Francesco; Nigro, Marco

    2003-01-01

    Noise exposure causes changes at different levels in human organs, particularly the cardiovascular system, where it is responsible for increasing heart rate, peripheral vascular resistance, and blood pressure. In this study, we evaluated the effect of noise exposure on DNA integrity and ultrastructure of rat cardiomyocytes. The exposure to loud noise (100 dBA) for 12 hr caused a significant increase of DNA damage, accompanied by swelling of mitochondrial membranes, dilution of the matrix, and cristolysis. These alterations were concomitant with increased in situ noradrenaline levels and utilization. Genetic and ultrastructural alterations did not decrease 24 hr after the cessation of the stimulus. An elevated oxyradical generation, possibly related to altered sympathetic innervation, is hypothesized as responsible for the induction and persistence of noise-induced cellular damage. PMID:12676600

  2. Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism and inhibits parathion intoxication.

    PubMed

    Jan, Yi-Hua; Richardson, Jason R; Baker, Angela A; Mishin, Vladimir; Heck, Diane E; Laskin, Debra L; Laskin, Jeffrey D

    2015-10-01

    Parathion, a widely used organophosphate insecticide, is considered a high priority chemical threat. Parathion toxicity is dependent on its metabolism by the cytochrome P450 system to paraoxon (diethyl 4-nitrophenyl phosphate), a cytotoxic metabolite. As an effective inhibitor of cholinesterases, paraoxon causes the accumulation of acetylcholine in synapses and overstimulation of nicotinic and muscarinic cholinergic receptors, leading to characteristic signs of organophosphate poisoning. Inhibition of parathion metabolism to paraoxon represents a potential approach to counter parathion toxicity. Herein, we demonstrate that menadione (methyl-1,4-naphthoquinone, vitamin K3) is a potent inhibitor of cytochrome P450-mediated metabolism of parathion. Menadione is active in redox cycling, a reaction mediated by NADPH-cytochrome P450 reductase that preferentially uses electrons from NADPH at the expense of their supply to the P450s. Using human recombinant CYP 1A2, 2B6, 3A4 and human liver microsomes, menadione was found to inhibit the formation of paraoxon from parathion. Administration of menadione bisulfite (40mg/kg, ip) to rats also reduced parathion-induced inhibition of brain cholinesterase activity, as well as parathion-induced tremors and the progression of other signs and symptoms of parathion poisoning. These data suggest that redox cycling compounds, such as menadione, have the potential to effectively mitigate the toxicity of organophosphorus pesticides including parathion which require cytochrome P450-mediated activation.

  3. Alteration of Rat Fetal Cerebral Cortex Development after Prenatal Exposure to Polychlorinated Biphenyls

    PubMed Central

    Naveau, Elise; Pinson, Anneline; Gérard, Arlette; Nguyen, Laurent; Charlier, Corinne; Thomé, Jean-Pierre; Zoeller, R. 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 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. PMID:24642964

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

    PubMed

    Naveau, Elise; Pinson, Anneline; Gérard, Arlette; Nguyen, Laurent; Charlier, Corinne; Thomé, Jean-Pierre; Zoeller, R 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 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.

  5. Isolation of Methyl Parathion-Degrading Strain M6 and Cloning of the Methyl Parathion Hydrolase Gene

    PubMed Central

    Zhongli, Cui; Shunpeng, Li; Guoping, Fu

    2001-01-01

    A degradative bacterium, M6, was isolated and presumptively identified as Plesiomonas sp. strain M6 was able to hydrolyze methyl parathion to p-nitrophenol. A novel organophosphate hydrolase gene designated mpd was selected from its genomic library prepared by shotgun cloning. The nucleotide sequence of the mpd gene was determined. The gene could be effectively expressed in Esherichia coli. PMID:11571204

  6. PRENATAL EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE ALTERS GENE EXPRESSION IN THE DEVELOPING MURINE HIPPOCAMPUS

    PubMed Central

    Mukhopadhyay, Partha; Horn, Kristin H.; Greene, Robert M.; Pisano, M. Michele

    2010-01-01

    Background Little is known about the effects of passive smoke exposures on the developing brain. Objective The purpose of the current study was to identify changes in gene expression in the murine hippocampus as a consequence of in utero exposure to sidestream cigarette smoke (an experimental equivalent of environmental tobacco smoke (ETS)) at exposure levels that do not result in fetal growth inhibition. Methods A whole body smoke inhalation exposure system was utilized to deliver ETS to pregnant C57BL/6J mice for six hours/day from gestational days 6–17 (gd 6–17) [for microarray] or gd 6–18.5 [for fetal phenotyping]. Results There were no significant effects of ETS exposure on fetal phenotype. However, 61 “expressed” genes in the gd 18.5 fetal hippocampus were differentially regulated (up- or down-regulated by 1.5 fold or greater) by maternal exposure to ETS. Of these 61 genes, 25 genes were upregulated while 36 genes were downregulated. A systems biology approach, including computational methodologies, identified cellular response pathways, and biological themes, underlying altered fetal programming of the embryonic hippocampus by in utero cigarette smoke exposure. Conclusions Results from the present study suggest that even in the absence of effects on fetal growth, prenatal smoke exposure can alter gene expression during the “early” period of hippocampal growth and may result in abnormal hippocampal morphology, connectivity, and function. PMID:19969065

  7. Prenatal exposure to environmental tobacco smoke alters gene expression in the developing murine hippocampus.

    PubMed

    Mukhopadhyay, Partha; Horn, Kristin H; Greene, Robert M; Michele Pisano, M

    2010-04-01

    Little is known about the effects of passive smoke exposures on the developing brain. The purpose of the current study was to identify changes in gene expression in the murine hippocampus as a consequence of in utero exposure to sidestream cigarette smoke (an experimental equivalent of environmental tobacco smoke (ETS)) at exposure levels that do not result in fetal growth inhibition. A whole body smoke inhalation exposure system was utilized to deliver ETS to pregnant C57BL/6J mice for 6 h/day from gestational days 6-17 (gd 6-17) [for microarray] or gd 6-18.5 [for fetal phenotyping]. There were no significant effects of ETS exposure on fetal phenotype. However, 61 "expressed" genes in the gd 18.5 fetal hippocampus were differentially regulated (up- or down-regulated by 1.5-fold or greater) by maternal exposure to ETS. Of these 61 genes, 25 genes were upregulated while 36 genes were down-regulated. A systems biology approach, including computational methodologies, identified cellular response pathways, and biological themes, underlying altered fetal programming of the embryonic hippocampus by in utero cigarette smoke exposure. Results from the present study suggest that even in the absence of effects on fetal growth, prenatal smoke exposure can alter gene expression during the "early" period of hippocampal growth and may result in abnormal hippocampal morphology, connectivity, and function. Copyright 2009 Elsevier Inc. All rights reserved.

  8. Embryonic atrazine exposure alters zebrafish and human miRNAs associated with angiogenesis, cancer, and neurodevelopment.

    PubMed

    Wirbisky, Sara E; Weber, Gregory J; Schlotman, Kelly E; Sepúlveda, Maria S; Freeman, Jennifer L

    2016-12-01

    MicroRNAs (miRNAs) are short, single-stranded RNA that regulate post-transcriptional control of mRNA translation. Knowledge on the role of these critical regulators in toxicological responses in increasing, but is still limited. Atrazine is a herbicide used throughout the Midwestern US that is reported to frequently contaminate potable water supplies above the maximum contaminant level of 3 parts per billion. Atrazine is a suspected endocrine disrupting chemical and studies have begun to investigate the genetic mechanisms of toxicity; however, studies investigating epigenetic mechanisms are limited. In this study both zebrafish and human miRNAs were significantly altered in response to an embryonic atrazine exposure of 0.3, 3, or 30 ppb in zebrafish. Altered miRNAs are known to play a role in angiogenesis, cancer, or neuronal development, differentiation, and maturation. Targeted analysis of altered human miRNAs with genes previously identified to be altered by atrazine exposure revealed several targets linked to cell cycle and cell signaling. Further analysis of hsa-miRNA-126-3p, which had altered expression in all three atrazine treatments at 72 hpf, revealed alterations also occurred at 60 hpf in the 30 ppb treatment group. Results from this study indicate miRNA deregulation in zebrafish and human miRNAs following an embryonic atrazine exposure in zebrafish. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Alterations in fetal thymic and liver hematopoietic cells as indicators of exposure to developmental immunotoxicants.

    PubMed Central

    Holladay, S D; Luster, M I

    1996-01-01

    Recent studies indicate that immune development in humans and other species may be altered after perinatal exposure to immunotoxic environmental contaminants. However, limited information is available regarding appropriate tests that may adequately detect developmental immunotoxic compounds. Experiments in which pregnant laboratory rodents were exposed to a variety of immunotoxic environmental agents indicate that fetal thymus and liver immune cells may be quantitatively and qualitatively altered by immunotoxicant exposure and, thus, may serve as sensitive markers of developmental immunotoxicant exposure. In particular, depression of fetal thymic cell counts appears to be a common event following gestational exposure to immunotoxicants that produce this response in adult animals. Total hematopoietic cell counts in fetal liver, however, may be a poor indicator of immunotoxicant exposure. Altered marker expression in both fetal thymus and liver appears to be a highly sensitive indicator of gestational immunotoxicant exposure. Together, these reports suggest that immune tests with high predictability for immunosuppression in adults may also be appropriate for the detection of developmental immunotoxic agents. PMID:8880003

  10. Alterations in lung clearance mechanisms due to single and repeated nitrogen dioxide exposures in the rabbit

    SciTech Connect

    Vollmuth, T.A.

    1986-01-01

    Tracheobronchial mucociliary clearance was assessed following single, two-hour exposures to either 0.3, 1.0, 3.0, or 10.0 ppm NO/sub 2/, or 14 daily two hour exposures to 0.3, 1.0, 3.0 ppm NO/sub 2/. No significant changes in the mean residence time of tracer particles in the tracheobronchial region were produced under any exposure condition, indicating no effect upon mucociliary clearance. Macrophage functional properties were examined in vitro at select times following single, two hour in vivo exposures to 1.0 and 10.0 ppm NO/sub 2/. Macrophage number and viability were not affected; however, significant dose-related differences in phagocytosis and mobility were observed. These changes were associated with altered in vivo alveolar clearance patterns. Additional studies examined the effects of in vitro exposure to nitrite and hydrogen ion, two known NO/sub 2/ reaction products in the lung, on macrophage phagocytosis. While hydrogen ion had no effect at the levels used, nitrate was shown to enhance phagocytosis. These results demonstrate that alveolar clearance and macrophage function are altered by short-term NO/sub 2/ exposure at realistic, environmental levels. These data also provide insight into the mechanisms of NO/sub 2/-induced alteration in lung clearance pathways.

  11. Human hepatic cytochrome P450-specific metabolism of the organophosphorus pesticides methyl parathion and diazinon.

    PubMed

    Ellison, Corie A; Tian, Yuan; Knaak, James B; Kostyniak, Paul J; Olson, James R

    2012-01-01

    Organophosphorus pesticides (OPs) are a public health concern due to their worldwide use and documented human exposures. Phosphorothioate OPs are metabolized by cytochrome P450s (P450s) through either a dearylation reaction to form an inactive metabolite, or through a desulfuration reaction to form an active oxon metabolite, which is a potent cholinesterase inhibitor. This study investigated the rate of desulfuration (activation) and dearylation (detoxification) of methyl parathion and diazinon in human liver microsomes. In addition, recombinant human P450s were used to determine the P450-specific kinetic parameters (K(m) and V(max)) for each compound for future use in refining human physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) models of OP exposure. The primary enzymes involved in bioactivation of methyl parathion were CYP2B6 (K(m) = 1.25 μM; V(max) = 9.78 nmol · min(-1) · nmol P450(-1)), CYP2C19 (K(m) = 1.03 μM; V(max) = 4.67 nmol · min(-1) · nmol P450(-1)), and CYP1A2 (K(m) = 1.96 μM; V(max) = 5.14 nmol · min(-1) · nmol P450(-1)), and the bioactivation of diazinon was mediated primarily by CYP1A1 (K(m) = 3.05 μM; V(max) = 2.35 nmol · min(-1) · nmol P450(-1)), CYP2C19 (K(m) = 7.74 μM; V(max) = 4.14 nmol · min(-1) · nmol P450(-1)), and CYP2B6 (K(m) = 14.83 μM; V(max) = 5.44 nmol · min(-1) · nmol P450(-1)). P450-mediated detoxification of methyl parathion only occurred to a limited extent with CYP1A2 (K(m) = 16.8 μM; V(max) = 1.38 nmol · min(-1) · nmol P450(-1)) and 3A4 (K(m) = 104 μM; V(max) = 5.15 nmol · min(-1) · nmol P450(-1)), whereas the major enzyme involved in diazinon detoxification was CYP2C19 (K(m) = 5.04 μM; V(max) = 5.58 nmol · min(-1) · nmol P450(-1)). The OP- and P450-specific kinetic values will be helpful for future use in refining human PBPK/PD models of OP exposure.

  12. Human Hepatic Cytochrome P450-Specific Metabolism of the Organophosphorus Pesticides Methyl Parathion and Diazinon

    PubMed Central

    Tian, Yuan; Knaak, James B.; Kostyniak, Paul J.; Olson, James R.

    2012-01-01

    Organophosphorus pesticides (OPs) are a public health concern due to their worldwide use and documented human exposures. Phosphorothioate OPs are metabolized by cytochrome P450s (P450s) through either a dearylation reaction to form an inactive metabolite, or through a desulfuration reaction to form an active oxon metabolite, which is a potent cholinesterase inhibitor. This study investigated the rate of desulfuration (activation) and dearylation (detoxification) of methyl parathion and diazinon in human liver microsomes. In addition, recombinant human P450s were used to determine the P450-specific kinetic parameters (Km and Vmax) for each compound for future use in refining human physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) models of OP exposure. The primary enzymes involved in bioactivation of methyl parathion were CYP2B6 (Km = 1.25 μM; Vmax = 9.78 nmol · min−1 · nmol P450−1), CYP2C19 (Km = 1.03 μM; Vmax = 4.67 nmol · min−1 · nmol P450−1), and CYP1A2 (Km = 1.96 μM; Vmax = 5.14 nmol · min−1 · nmol P450−1), and the bioactivation of diazinon was mediated primarily by CYP1A1 (Km = 3.05 μM; Vmax = 2.35 nmol · min−1 · nmol P450−1), CYP2C19 (Km = 7.74 μM; Vmax = 4.14 nmol · min−1 · nmol P450−1), and CYP2B6 (Km = 14.83 μM; Vmax = 5.44 nmol · min−1 · nmol P450−1). P450-mediated detoxification of methyl parathion only occurred to a limited extent with CYP1A2 (Km = 16.8 μM; Vmax = 1.38 nmol · min−1 · nmol P450−1) and 3A4 (Km = 104 μM; Vmax = 5.15 nmol · min−1 · nmol P450−1), whereas the major enzyme involved in diazinon detoxification was CYP2C19 (Km = 5.04 μM; Vmax = 5.58 nmol · min−1 · nmol P450−1). The OP- and P450-specific kinetic values will be helpful for future use in refining human PBPK/PD models of OP exposure. PMID:21969518

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

    PubMed

    Kroener, Sven; Mulholland, Patrick J; New, Natasha N; Gass, Justin T; Becker, Howard C; Chandler, L Judson

    2012-01-01

    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.

  14. Chronic Alcohol Exposure Alters Behavioral and Synaptic Plasticity of the Rodent Prefrontal Cortex

    PubMed Central

    Kroener, Sven; Mulholland, Patrick J.; New, Natasha N.; Gass, Justin T.; Becker, Howard C.; Chandler, L. Judson

    2012-01-01

    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. PMID:22666364

  15. FINE AMBIENT AIR PARTICULAR MATTER EXPOSURE INDUCES MOLECULAR ALTERATIONS INDICATIVE OF CARDIOVASCULAR DISEASE PROGRESSION IN ATHEROSCLEROTIC SUSCEPTIBLE MICE

    EPA Science Inventory

    Epidemiological, clinical, and toxicological studies have demonstrated that exposure to ambient air particulate matter (PM) can alter cardiovascular function and may influence cardiovascular disease (CVD). It has been shown that exposure to concentrated ambient air particles (CA...

  16. FINE AMBIENT AIR PARTICULAR MATTER EXPOSURE INDUCES MOLECULAR ALTERATIONS INDICATIVE OF CARDIOVASCULAR DISEASE PROGRESSION IN ATHEROSCLEROTIC SUSCEPTIBLE MICE

    EPA Science Inventory

    Epidemiological, clinical, and toxicological studies have demonstrated that exposure to ambient air particulate matter (PM) can alter cardiovascular function and may influence cardiovascular disease (CVD). It has been shown that exposure to concentrated ambient air particles (CA...

  17. Poisoning of Canada geese in Texas by parathion sprayed for control of Russian wheat aphid

    USGS Publications Warehouse

    Flickinger, Edward L.; Juenger, Gary; Roffe, Thomas J.; Smith, Milton R.; Irwin, Roy J.

    1991-01-01

    Approximately 200 Canada geese (Branta canadensis) died at a playa lake in the Texas Panhandle shortly after a winter wheat field in the basin adjacent to the lake was treated with parathion to control newly invading Russian wheat aphids (Diuraphis noxia). No evidence of infectious disease was diagnosed during necropsies of geese. Brain ChE activities were depressed up to 77% below normal. Parathion residues in GI tract contents of geese ranged from 4 to 34 ppm. Based on this evidence, parathion was responsible for the goose mortalities. Parathion applications to winter wheat will undoubtedly increase if parathion is applied for control of both Russian wheat aphids and greenbugs (Schizaphis graminum). Geese may potentially be exposed to widespread applications of parathion from fall to spring, essentially their entire wintering period.

  18. Constitutive Androgen Receptor-Null Mice Are Sensitive to the Toxic Effects of Parathion: Association with Reduced Cytochrome P450-Mediated Parathion MetabolismS⃞

    PubMed Central

    Mota, Linda C.; Hernandez, Juan P.

    2010-01-01

    Constitutive androgen receptor (CAR) is activated by several chemicals and in turn regulates multiple detoxification genes. Our research demonstrates that parathion is one of the most potent, environmentally relevant CAR activators with an EC50 of 1.43 μM. Therefore, animal studies were conducted to determine whether CAR was activated by parathion in vivo. Surprisingly, CAR-null mice, but not wild-type (WT) mice, showed significant parathion-induced toxicity. However, parathion did not induce Cyp2b expression, suggesting that parathion is not a CAR activator in vivo, presumably because of its short half-life. CAR expression is also associated with the expression of several drug-metabolizing cytochromes P450 (P450). CAR-null mice demonstrate lower expression of Cyp2b9, Cyp2b10, Cyp2c29, and Cyp3a11 primarily, but not exclusively in males. Therefore, we incubated microsomes from untreated WT and CAR-null mice with parathion in the presence of esterase inhibitors to determine whether CAR-null mice show perturbed P450-mediated parathion metabolism compared with that in WT mice. The metabolism of parathion to paraoxon and p-nitrophenol (PNP) was reduced in CAR-null mice with male CAR-null mice showing reduced production of both paraoxon and PNP, and female CAR-null mice showing reduced production of only PNP. Overall, the data indicate that CAR-null mice metabolize parathion slower than WT mice. These results provide a potential mechanism for increased sensitivity of individuals with lower CAR activity such as newborns to parathion and potentially other chemicals due to decreased metabolic capacity. PMID:20573718

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

    EPA Science Inventory

    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...

  20. PERINATAL EXPOSURE TO THE PESTICIDE HEPTACHLOR PRODUCES ALTERATIONS IN IMMUNE FUNCTION PARAMETERS IN SPRAGUE DAWLEY RATS

    EPA Science Inventory

    PERINATAL EXPOSURE TO THE PESTICIDE HEPTACHLOR PRODUCES ALTERATIONS IN IMMUNE FUNCTION PARAMETERS IN SPRAGUE DAWLEY RATS. R A Matulka1, AA Rooney3, W Williams2, CB Copeland2, and R J Smialowicz2. 1Curriculum in Toxicology, UNC, Chapel Hill, NC, USA; 2US EPA, ITB, ETD, NHEERL, RT...

  1. Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver

    EPA Science Inventory

    Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver D.B. Johnson, 1 W.O. Ward, 2 V.L. Bass, 2 M.C.J. Schladweiler, 2A.D. Ledbetter, 2 D. Andrews, and U.P. Kodavanti 2 1 Curriculum in Toxicology, UNC School of Medicine, Cha...

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

    EPA Science Inventory

    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...

  3. GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE (EDS) ALTERS DEVELOPMENT OF THE MOUSE TESTIS

    EPA Science Inventory

    GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE (EDS) ALTERS DEVELOPMENT OF THE MOUSE TESTIS. D.K. Tarka*1,2, J.D. Suarez*2, N.L. Roberts*2, J.M. Rogers*1,2, M.P. Hardy3, and G.R. Klinefelter1,2. 1University of North Carolina, Curriculum in Toxicology, Chapel Hill, NC; 2USEPA,...

  4. PERINATAL EXPOSURE TO THE PESTICIDE HEPTACHLOR PRODUCES ALTERATIONS IN IMMUNE FUNCTION PARAMETERS IN SPRAGUE DAWLEY RATS

    EPA Science Inventory

    PERINATAL EXPOSURE TO THE PESTICIDE HEPTACHLOR PRODUCES ALTERATIONS IN IMMUNE FUNCTION PARAMETERS IN SPRAGUE DAWLEY RATS. R A Matulka1, AA Rooney3, W Williams2, CB Copeland2, and R J Smialowicz2. 1Curriculum in Toxicology, UNC, Chapel Hill, NC, USA; 2US EPA, ITB, ETD, NHEERL, RT...

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

    EPA Science Inventory

    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...

  6. GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE (EDS) ALTERS DEVELOPMENT OF THE MOUSE TESTIS

    EPA Science Inventory

    GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE (EDS) ALTERS DEVELOPMENT OF THE MOUSE TESTIS. D.K. Tarka*1,2, J.D. Suarez*2, N.L. Roberts*2, J.M. Rogers*1,2, M.P. Hardy3, and G.R. Klinefelter1,2. 1University of North Carolina, Curriculum in Toxicology, Chapel Hill, NC; 2USEPA,...

  7. Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver

    EPA Science Inventory

    Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver D.B. Johnson, 1 W.O. Ward, 2 V.L. Bass, 2 M.C.J. Schladweiler, 2A.D. Ledbetter, 2 D. Andrews, and U.P. Kodavanti 2 1 Curriculum in Toxicology, UNC School of Medicine, Cha...

  8. Adaptive Responses to Prochloraz Exposure That Alter Dose-Response and Time-Course Behaviors

    EPA Science Inventory

    Dose response and time-course (DRTC) are, along with exposure, the major determinants of health risk. Adaptive changes within exposed organisms in response to environmental stress are common, and alter DRTC behaviors to minimize the effects caused by stressors. In this project, ...

  9. Adaptive Responses to Prochloraz Exposure That Alter Dose-Response and Time-Course Behaviors

    EPA Science Inventory

    Dose response and time-course (DRTC) are, along with exposure, the major determinants of health risk. Adaptive changes within exposed organisms in response to environmental stress are common, and alter DRTC behaviors to minimize the effects caused by stressors. In this project, ...

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

    EPA Science Inventory

    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...

  11. Comparative effects of parathion and chlorpyrifos on extracellular endocannabinoid levels in rat hippocampus: Influence on cholinergic toxicity

    SciTech Connect

    Liu, Jing; Parsons, Loren; Pope, Carey

    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

  12. Pulmonary biochemical and histological alterations after repeated low-level blast overpressure exposures.

    PubMed

    Elsayed, Nabil M; Gorbunov, Nikolai V

    2007-01-01

    Blast overpressure (BOP), also known as high energy impulse noise, is a damaging outcome of explosive detonations and firing of weapons. Exposure to BOP shock waves alone results in injury predominantly to the hollow organ systems such as auditory, respiratory, and gastrointestinal systems. In recent years, the hazards of BOP that once were confined to military and professional settings have become a global societal problem as terrorist bombings and armed conflicts involving both military and civilian populations increased significantly. We have previously investigated the effects of single BOP exposures at different peak pressures. In this study, we examined the effects of repeated exposure to a low-level BOP and whether the number of exposures or time after exposure would alter the injury outcome. We exposed deeply anesthetized rats to simulated BOP at 62 +/- 2 kPa peak pressure. The lungs were examined immediately after one exposure (1 + 0), or 1 h after one (1 + 1), two (2 + 1), or three (3 + 1) consecutive exposures at 3-min interval. In one group of animals, we examined the effects of repeated exposure on lung weight, methemoglobin, transferrin, antioxidants, and lipid peroxidation. In a second group, the lungs were fixed inflated at 25 cm water, sectioned, and examined histologically after one to three repeated exposures, or after one exposure at 1, 6, and 24 h. We found that single BOP exposure causes notable changes after 1 h, and that repeating BOP exposure did not add markedly to the effect of the first one. However, the effects increased significantly with time from 1 to 24 h. These observations have biological and occupational implications, and emphasize the need for protection from low-level BOP, and for prompt treatment within the first hour following BOP exposure.

  13. Symptoms from masked acrolein exposure suggest altered trigeminal reactivity in chemical intolerance.

    PubMed

    Claeson, Anna-Sara; Andersson, Linus

    2017-05-01

    Chemical intolerance (CI) is a widespread occupational and public health problem characterized by symptoms that reportedly result from low-levels of chemical exposure. The mechanisms behind CI are unknown, however modifications of the chemical senses (rather than toxic processes) have been suggested as key components. The aim of this study was to investigate whether individuals with self-reported CI report more sensory irritation during masked acrolein exposure compared to controls without CI. Individuals with CI (n=18) and controls without CI (n=19) were exposed in an exposure chamber. Each participant took part in two exposure conditions - one with heptane (the masking compound), and one with heptane and acrolein at a dose below previously reported sensory irritation thresholds. The exposures lasted for 60min. Symptoms and confidence ratings were measured continuously throughout the exposure as were measurements of electrodermal activity and self-reported tear-film break-up time. Participants were blind to exposure condition. Individuals with CI, compared with controls reported greater sensory irritation in the eyes, nose and throat when exposed to acrolein masked with heptane. There was no difference during exposure to heptane. Masked exposure to acrolein at a concentration below the previously reported detection threshold is perceived as more irritating by individuals with CI compared with controls. The results indicate that there is altered trigeminal reactivity in those with CI compared to controls. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Epigenetic alterations and occupational exposure to benzene, fibers, and heavy metals associated with tumor development (Review).

    PubMed

    Salemi, Rossella; Marconi, Andrea; Di Salvatore, Valentina; Franco, Sabrina; Rapisarda, Venerando; Libra, Massimo

    2017-05-01

    The chronic occupational exposure to contaminants and carcinogens leads to the development of cancer. Over the past decades, many carcinogens have been found in the occupational environment and their presence is often associated with an increased incidence of cancer. According to the International Agency for Research on Cancer (IARC), the majority of carcinogens are classified as 'probable' and 'possible' human carcinogens, while, direct evidence of carcinogenicity is provided in epidemiological and experimental studies. Additionally, accumulating evidence suggests that epigenetic alterations may be early indicators of genotoxic and non-genotoxic carcinogen exposure. In the present review, the relationship between exposures to benzene, mineral fibers, metals and epigenetic alterations are discussed as the most important cancer risk factors during work activities.

  15. Bioavailability of methyl parathion adsorbed on clay minerals and iron oxide.

    PubMed

    Cai, Peng; He, Xiaomin; Xue, Aifang; Chen, Hao; Huang, Qiaoyun; Yu, Jun; Rong, Xinming; Liang, Wei

    2011-01-30

    Adsorption, desorption and degradation by Pseudomonas putida of methyl parathion (O,O-dimethyl O-p-nitrophenyl phosphorothioate) on montmorillonite, kaolinite and goethite were studied. Metabolic activities of methyl parathion-degrading bacteria P. putida in the presence of minerals were also monitored by microcalorimetry to determine the degradation mechanism of methyl parathion. Montmorillonite presented higher adsorption capacity and affinity for methyl parathion than kaolinite and goethite. The percentage of degradation of methyl parathion adsorbed on minerals by P. putida was in the order of montmorillonite>kaolinite>goethite. The presence of minerals inhibited the exponential growth and the metabolic activity of P. putida. Among the examined minerals, goethite exhibited the greatest inhibitory effect on bacterial activity, while montmorillonite was the least depressing. The biodegradation of adsorbed methyl parathion by P. putida is apparently not controlled by the adsorption affinity of methyl parathion on minerals and may be mainly governed by the activity of the methyl parathion-degrading bacteria. The information obtained in this study is of fundamental significance for the understanding of the behavior of methyl parathion in soil environments.

  16. Caspofungin exposure alters the core septin AspB interactome of Aspergillus fumigatus.

    PubMed

    Vargas-Muñiz, José M; Renshaw, Hilary; Waitt, Greg; Soderblom, Erik J; Moseley, M Arthur; Palmer, Jonathan M; Juvvadi, Praveen R; Keller, Nancy P; Steinbach, William J

    2017-04-01

    Aspergillus fumigatus, the main etiological agent of invasive aspergillosis, is a leading cause of death in immunocompromised patients. Septins, a conserved family of GTP-binding proteins, serve as scaffolding proteins to recruit enzymes and key regulators to different cellular compartments. Deletion of the A. fumigatus septin aspB increases susceptibility to the echinocandin antifungal caspofungin. However, how AspB mediates this response to caspofungin is unknown. Here, we characterized the AspB interactome under basal conditions and after exposure to a clinically relevant concentration of caspofungin. While A. fumigatus AspB interacted with 334 proteins, including kinases, cell cycle regulators, and cell wall synthesis-related proteins under basal growth conditions, caspofungin exposure altered AspB interactions. A total of 69 of the basal interactants did not interact with AspB after exposure to caspofungin, and 54 new interactants were identified following caspofungin exposure. We generated A. fumigatus deletion strains for 3 proteins (ArpB, Cyp4, and PpoA) that only interacted with AspB following exposure to caspofungin that were previously annotated as induced after exposure to antifungal agents, yet only PpoA was implicated in the response to caspofungin. Taken together, we defined how the septin AspB interactome is altered in the presence of a clinically relevant antifungal.

  17. Effects of the organophosphorus pesticide Folisuper 600 (methyl parathion) on the heart function of bullfrog tadpoles, Lithobates catesbeianus (Shaw, 1802).

    PubMed

    Costa, M J; Ribeiro, L R; Salla, R F; Gamero, F U; Alves, L M L M; Silva-Zacarin, E C M

    2015-11-01

    The aim of this work was to evaluate whether the heart function of bullfrog tadpoles (25 Gosner stage) is affected by their acute exposure (48 h) to a sub-lethal concentration (10 µg.L-1) of the active principle of the organophosphorus pesticide Folisuper 600R (methyl parathion - MP). Our results demonstrated that MP causes not only a reduction in tadpoles' cardiac ventricular mass, resulting in a marked reduction in their cardiac twitch force, but also impairs their swimming performance, irrespective of increasing their heart rate. Together, these findings indicate that low and realistic concentration of MP have a negative impact on tadpoles' performance, jeopardizing their survival.

  18. [Terahertz spectroscopic investigation of organophosphorus pesticide parathion-methyl].

    PubMed

    Yan, Zhi-Gang; Zheng, Song; Xie, Qiang-Jun; Zhou, Ze-Kui

    2009-10-01

    The present paper reports the theoretical and experimental vibrational spectra of organophosphorus pesticide parathion-methyl in the frequency range from 0.2 to 2.0 THz respectively. Under the room temperature and nitrogen conditions, the absorption peaks were found at 0.65, 1.33, 1.81 and 1.91 THz, and the average refractive index was 1.39 based on the terahertz time-domain spectroscopy (THz-TDS). In parallel with the experimental study, density functional theory (DFT) was applied to obtain the structure and vibrational frequencies of parathion-methyl in the terahertz region. The calculated results are in reasonable agreement with the experimental data. The absorption features are caused by the collective vibrational and torsional modes, and the different absorption peaks correspond to different vibrational modes.

  19. Acute nitrite exposure alters the metabolism of thyroid hormones in grass carp (Ctenopharyngodon idellus).

    PubMed

    Xiao, Chen; Liu, Zidong; Li, Dapeng; Refaey, Mohamed M; Tang, Rong; Li, Li; Zhang, Xi

    2017-08-08

    Nitrite has the potential to disturb thyroid hormone homeostasis, but little is known about the underlying mechanisms. In the present study, juvenile grass carp (Ctenopharyngodon idellus) were exposed to various concentrations of nitrite (0, 0.5, 1, 4, and 16 mg/L, respectively). Serum concentrations of triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), 3,3,5'-triiodothyronine (rT3), thyroid-stimulating hormone (TSH), and the activity of iodothyronine deiodinases were assayed at 0, 12, 24, 48, and 96 h after exposure. It was found that acute nitrite exposure significantly altered the TH levels and iodothyronine deiodinase activities. The rT3 levels were significantly increased in the treatment groups, whereas the concentrations of T3, FT3, FT4, and TSH decreased significantly. The concentration of T4 was elevated in the lower-dose exposure group, but was reduced in the higher-dose exposure group. Increases in type I iodothyronine deiodinase (ID1) and type III iodothyronine deiodinase (ID3) activities were observed in the exposure groups. The activity of type II iodothyronine deiodinase (ID2) decreased at 12 and 24 h after exposure. A decrease of colloid in the thyroid follicles was observed in the exposure group. The results indicate that acute nitrite exposure has the potential to disturb the homeostasis of thyroid hormone metabolism, leading to a hypothyroidism state in the juvenile grass carp. Copyright © 2017. Published by Elsevier Ltd.

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

    PubMed

    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.

  1. Parathion, a cholinesterase-inhibiting plaguicide induces changes in tertiary villi of placenta of women exposed: a scanning electron microscopy study.

    PubMed

    Levario-Carrillo, M; Feria-Velasco, A; De Celis, R; Ramos-Martínez, E; Córdova-Fierro, L; Solís, F J

    2001-01-01

    The objective of this work was to describe the anatomy of placentas from women who were at risk of exposure to parathion during their pregnancy, when examined with the light and scanning electron microscopes. Twenty term placentas were analyzed; 10 from women living in an agricultural area, who were at risk of exposure to parathion during their pregnancy, and 10 from women living in an urban area, not expressly exposed to pesticides. Each sample was examined with both light and scanning electron microscopes. Cholinesterase activity was significantly reduced in blood from women of the exposed group. In some placentas of women exposed to parathion, recent microinfarctions, microcalcifications and increased deposition of fibrinoid material were seen, along with a larger proportion of atypical characteristics of villi, such as bullous and balloon-like formations with nonhomogeneous surface, and other areas devoid of microvilli. These observations suggest that in chronic exposure to pesticides, the rate of atypical characteristics of placental villi increases, which could be related to changes in the fetus biology. In this study, one newborn from the exposed group showed intrauterine growth retardation and another one, some signs of hypoxia.

  2. Altered Hepatic Transport by Fetal Arsenite Exposure in Diet-Induced Fatty Liver Disease.

    PubMed

    Ditzel, Eric J; Li, Hui; Foy, Caroline E; Perrera, Alec B; Parker, Patricia; Renquist, Benjamin J; Cherrington, Nathan J; Camenisch, Todd D

    2016-07-01

    Non-alcoholic fatty liver disease can result in changes to drug metabolism and disposition potentiating adverse drug reactions. Furthermore, arsenite exposure during development compounds the severity of diet-induced fatty liver disease. This study examines the effects of arsenite potentiated diet-induced fatty liver disease on hepatic transport in male mice. Changes were detected for Mrp2/3/4 hepatic transporter gene expression as well as for Oatp1a4/2b1/1b2. Plasma concentrations of Mrp and Oatp substrates were increased in arsenic exposure groups compared with diet-only controls. In addition, murine embryonic hepatocytes and adult primary hepatocytes show significantly altered transporter expression after exposure to arsenite alone: a previously unreported phenomenon. These data indicate that developmental exposure to arsenite leads to changes in hepatic transport which could increase the risk for ADRs during fatty liver disease.

  3. Acute alcohol exposure during mouse gastrulation alters lipid metabolism in placental and heart development: Folate prevention

    PubMed Central

    Han, Mingda

    2016-01-01

    Background Embryonic acute exposure to ethanol (EtOH), lithium, and homocysteine (HCy) induces cardiac defects at the time of exposure; folic acid (FA) supplementation protects normal cardiogenesis (Han et al., 2009, 2012; Serrano et al., 2010). Our hypothesis is that EtOH exposure and FA protection relate to lipid and FA metabolism during mouse cardiogenesis and placentation. Methods On the morning of conception, pregnant C57BL/6J mice were placed on either of two FA‐containing diets: a 3.3 mg health maintenance diet or a high FA diet of 10.5 mg/kg. Mice were injected a binge level of EtOH, HCy, or saline on embryonic day (E) 6.75, targeting gastrulation. On E15.5, cardiac and umbilical blood flow were examined by ultrasound. Embryonic cardiac tissues were processed for gene expression of lipid and FA metabolism; the placenta and heart tissues for neutral lipid droplets, or for medium chain acyl‐dehydrogenase (MCAD) protein. Results EtOH exposure altered lipid‐related gene expression on E7.5 in comparison to control or FA‐supplemented groups and remained altered on E15.5 similarly to changes with HCy, signifying FA deficiency. In comparison to control tissues, the lipid‐related acyl CoA dehydrogenase medium length chain gene and its protein MCAD were altered with EtOH exposure, as were neutral lipid droplet localization in the heart and placenta. Conclusion EtOH altered gene expression associated with lipid and folate metabolism, as well as neutral lipids, in the E15.5 abnormally functioning heart and placenta. In comparison to controls, the high FA diet protected the embryo and placenta from these effects allowing normal development. Birth Defects Research (Part A) 106:749–760, 2016. © 2016 The Authors Birth Defects Research Part A: Clinical and Molecular Teratology Published by Wiley Periodicals, Inc. PMID:27296863

  4. Ozone Exposure Alters Serotonin and Serotonin Receptor Expression in the Developing Lung

    PubMed Central

    Van Winkle, Laura S.

    2013-01-01

    Ozone, a pervasive environmental pollutant, adversely affects functional lung growth in children. Animal studies demonstrate that altered lung development is associated with modified signaling within the airway epithelial mesenchymal trophic unit, including mediators that can change nerve growth. We hypothesized that ozone exposure alters the normal pattern of serotonin, its transporter (5-HTT), and two key receptors (5-HT2A and 5-HT4), a pathway involved in postnatal airway neural, epithelial, and immune processes. We exposed monkeys to acute or episodic ozone during the first 2 or 6 months of life. There were three exposure groups/age: (1) filtered air, (2) acute ozone challenge, and (3) episodic ozone + acute ozone challenge. Lungs were prepared for compartment-specific qRT-PCR, immunohistochemistry, and stereology. Airway epithelial serotonin immunopositive staining increased in all exposure groups with the most prominent in 2-month midlevel and 6-month distal airways. Gene expression of 5-HTT, 5-HT2AR, and 5-HT4R increased in an age-dependent manner. Overall expression was greater in distal compared with midlevel airways. Ozone exposure disrupted both 5-HT2AR and 5-HT4R protein expression in airways and enhanced immunopositive staining for 5-HT2AR (2 months) and 5-HT4R (6 months) on smooth muscle. Ozone exposure increases serotonin in airway epithelium regardless of airway level, age, and exposure history and changes the spatial pattern of serotonin receptor protein (5-HT2A and 5-HT4) and 5-HTT gene expression depending on compartment, age, and exposure history. Understanding how serotonin modulates components of reversible airway obstruction exacerbated by ozone exposure sets the foundation for developing clinically relevant therapies for airway disease. PMID:23570994

  5. Acrolein Inhalation Alters Myocardial Synchrony and Performance at and Below Exposure Concentrations that Cause Ventilatory Responses.

    PubMed

    Thompson, Leslie C; Ledbetter, Allen D; Haykal-Coates, Najwa; Cascio, Wayne E; Hazari, Mehdi S; Farraj, Aimen K

    2017-04-01

    Acrolein is an irritating aldehyde generated during combustion of organic compounds. Altered autonomic activity has been documented following acrolein inhalation, possibly impacting myocardial synchrony and function. Given the ubiquitous nature of acrolein in the environment, we sought to better define the immediate and delayed functional cardiac effects of acrolein inhalation in vivo. We hypothesized that acrolein inhalation would increase markers of cardiac mechanical dysfunction, i.e., myocardial dyssynchrony and performance index in mice. Male C57Bl/6J mice were exposed to filtered air (FA) or acrolein (0.3 or 3.0 ppm) for 3 h in whole-body plethysmography chambers (n = 6). Echocardiographic analyses were performed 1 day before exposure and at 1 and 24 h post-exposure. Speckle tracking echocardiography revealed that circumferential strain delay (i.e., dyssynchrony) was increased at 1 and 24 h following exposure to 3.0 ppm, but not 0.3 ppm, when compared to pre-exposure and/or FA exposure. Pulsed wave Doppler of transmitral blood flow revealed that acrolein exposure at 0.3 ppm, but not 3.0 ppm, increased the Tei index of myocardial performance (i.e., decreased global heart performance) at 1 and 24 h post-exposure compared to pre-exposure and/or FA exposure. We conclude that short-term inhalation of acrolein can acutely modify cardiac function in vivo and that echocardiographic evaluation of myocardial synchrony and performance following exposure to other inhaled pollutants could provide broader insight into the health effects of air pollution.

  6. Alterations in adult behavioral responses to cocaine and dopamine transporters following juvenile exposure to methamphetamine.

    PubMed

    McFadden, Lisa; Yamamoto, Bryan K; Matuszewich, Leslie

    2011-01-20

    The present experiment assessed whether preadolescent exposure to methamphetamine would alter adult behavioral responses to cocaine and dopamine transporter immunoreactivity in the striatum of male and female rats. Juvenile rats were injected once daily with 0 or 2 mg/kg methamphetamine from postnatal days 21 to 35 and tested in adulthood. Male rats, but not female rats, exposed to methamphetamine showed an increase in responsiveness to cocaine in the open field and an increase in dopamine transporter immunoreactivity in the striatum. These findings suggest that early exposure to methamphetamine can lead to sex specific altered responses to psychostimulants in adulthood, which may contribute to later vulnerability to drug use. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Prenatal exposure to methylmercury alters development of adrenergic receptor binding sites in peripheral sympathetic target tissues

    SciTech Connect

    Slotkin, T.A.; Orband, L.; Cowdery, T.; Kavlock, R.J.; Bartolome, J.

    1987-01-01

    In order to assess the impact of prenatal exposure to methylmercury on sympathetic neurotransmission, effects on development of adrenergic receptor binding sites in peripheral tissues was evaluated. In the liver, methylmercury produced a dose-dependent increase in alpha/sub 1/, alpha/sub 2/, and beta-receptor binding of radioliganda throughout the first 5 weeks of postnatal life. Similarly, renal alpha-receptor subtypes showed increased binding capabilities, but binding to alpha-receptor sites was reduced. At least some of the changes in receptors appear to be of functional significance, as physiological reactivity to adrenergic stimulation is altered in the same directions in these two tissues. The actions of methylmercury displayed tissue specificity in that the same receptor populations were largely unaffected in other tissues (lung, heart). These results suggest that methylmercury exposure in utero alters adrenergic responses through targeted effects on postsynaptic receptor populations in specific tissues.

  8. Alterations in Skeletal Muscle Cell Homeostasis in a Mouse Model of Cigarette Smoke Exposure

    PubMed Central

    Caron, Marc-André; Morissette, Mathieu C.; Thériault, Marie-Eve; Nikota, Jake K.; Stämpfli, Martin R.; Debigaré, Richard

    2013-01-01

    Background Skeletal muscle dysfunction is common in chronic obstructive pulmonary disease (COPD), a disease mainly caused by chronic cigarette use. An important proportion of patients with COPD have decreased muscle mass, suggesting that chronic cigarette smoke exposure may interfere with skeletal muscle cellular equilibrium. Therefore, the main objective of this study was to investigate the kinetic of the effects that cigarette smoke exposure has on skeletal muscle cell signaling involved in protein homeostasis and to assess the reversibility of these effects. Methods A mouse model of cigarette smoke exposure was used to assess skeletal muscle changes. BALB/c mice were exposed to cigarette smoke or room air for 8 weeks, 24 weeks or 24 weeks followed by 60 days of cessation. The gastrocnemius and soleus muscles were collected and the activation state of key mediators involved in protein synthesis and degradation was assessed. Results Gastrocnemius and soleus were smaller in mice exposed to cigarette smoke for 8 and 24 weeks compared to room air exposed animals. Pro-degradation proteins were induced at the mRNA level after 8 and 24 weeks. Twenty-four weeks of cigarette smoke exposure induced pro-degradation proteins and reduced Akt phosphorylation and glycogen synthase kinase-3β quantity. A 60-day smoking cessation period reversed the cell signaling alterations induced by cigarette smoke exposure. Conclusions Repeated cigarette smoke exposure induces reversible muscle signaling alterations that are dependent on the duration of the cigarette smoke exposure. These results highlights a beneficial aspect associated with smoking cessation. PMID:23799102

  9. Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors

    PubMed Central

    Fordahl, Steve; Cooney, Paula; Qiu, Yunping; Xie, Guoxiang; Jia, Wei; Erikson, Keith M.

    2011-01-01

    Overexposure to waterborne manganese (Mn) is linked with cognitive impairment in children and neurochemical abnormalities in other experimental models. In order to characterize the threshold between Mn-exposure and altered neurochemistry, it is important to identify biomarkers that positively correspond with brain Mn-accumulation. The objective of this study was to identify Mn-induced alterations in plasma, liver, and brain metabolites using liquid/gas chromatography-time of flight-mass spectrometry metabolomic analyses; and to monitor corresponding Mn-induced behavior changes. Weanling Sprague-Dawley rats had access to deionized drinking water either Mn-free or containing 1g Mn/L for six weeks. Behaviors were monitored during the sixth week for a continuous 24h period while in a home cage environment using video surveillance. Mn-exposure significantly increased liver, plasma, and brain Mn concentrations compared to control, specifically targeting the globus pallidus (GP). Mn significantly altered 98 metabolites in the brain, liver, and plasma; notably shifting cholesterol and fatty acid metabolism in the brain (increased oleic and palmitic acid; 12.57 and 15.48 fold change (FC), respectively), and liver (increased oleic acid, 14.51 FC; decreased hydroxybutyric acid, −14.29 FC). Additionally, Mn-altered plasma metabolites homogentisic acid, chenodeoxycholic acid, and aspartic acid correlated significantly with GP and striatal Mn. Total distance traveled was significantly increased and positively correlated with Mn-exposure, while nocturnal stereotypic and exploratory behaviors were reduced with Mn-exposure and performed largely during the light cycle compared to unexposed rats. These data provide putative biomarkers for Mn-neurotoxicity and suggest that Mn disrupts the circadian cycle in rats. PMID:22056924

  10. Formaldehyde exposure alters miRNA expression profiles in the olfactory bulb.

    PubMed

    Li, Guifa; Yang, Jing; Ling, Shucai

    2015-01-01

    It has been reported that inhaling formaldehyde (FA) causes damage to the central nervous system. However, it is unclear whether FA can disturb the function of the olfactory bulb. Using a microarray, we found that FA inhalation altered the miRNA expression profile. Functional enrichment analysis of the predicted targets of the changed miRNA showed that the enrichment canonical pathways and networks associated with cancer and transcriptional regulation. FA exposure disrupts miRNA expression profiles within the olfactory bulb.

  11. Developmental Exposure to Pesticides Alters Motor Activity and Coordination in Rats: Sex Differences and Underlying Mechanisms.

    PubMed

    Gómez-Giménez, B; Felipo, V; Cabrera-Pastor, A; Agustí, A; Hernández-Rabaza, V; Llansola, M

    2017-10-03

    It has been proposed that developmental exposure to pesticides contributes to increasing prevalence of neurodevelopmental disorders in children, such as attention deficit with hyperactivity (ADHD) and to alterations in coordination skills. However, the mechanisms involved in these alterations remain unclear. We analyzed the effects on spontaneous motor activity and motor coordination of developmental exposure to a representative pesticide of each one of the four main chemical families: organophosphates (chlorpyrifos), carbamates (carbaryl), organochlorines (endosulfan), and pyrethroids (cypermethrin). Pesticides were administered once a day orally, in a sweet jelly, from gestational day 7 to post natal day 21. Spontaneous motor activity was assessed by an actimeter and motor coordination using the rotarod, when rats were adults. The effects were analyzed separately in males and females. Extracellular GABA in cerebellum and NMDA receptor subunits in hippocampus were assessed as possible underlying mechanisms of motor alterations. Motor coordination was impaired by developmental exposure to endosulfan, cypermethrin, and chlorpyrifos in females but not in males. The effect of endosulfan and cypermethrin would be due to increased extracellular GABA in cerebellum, which remains unaltered in male rats. Chlorpyrifos increased motor activity in males and females. Cypermethrin decreased motor activity mainly in males. In male rats, but not in females, expression of the NR2B subunit of NMDA receptor in hippocampus correlated with motor activity. These results show sex-specific effects of different pesticides on motor activity and coordination, associated with neurotransmission alterations. These data contribute to better understand the relationship between developmental exposure to the main pesticide families and motor disorders in children.

  12. CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FALLS TO ALTER SOMATOSENSORY EVOKED POTENTIALS, COMPOUND NERVE ACTION POTENTIALS, OR NERVE CONDUCTION VELOCITY IN RATS.

    EPA Science Inventory

    Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Cholinergic transmission is involved in sensory modulation in the cortex and cerebellum, and therefore may be altered following chlorpyrifos (CPF) exposure...

  13. CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FALLS TO ALTER SOMATOSENSORY EVOKED POTENTIALS, COMPOUND NERVE ACTION POTENTIALS, OR NERVE CONDUCTION VELOCITY IN RATS.

    EPA Science Inventory

    Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Cholinergic transmission is involved in sensory modulation in the cortex and cerebellum, and therefore may be altered following chlorpyrifos (CPF) exposure...

  14. Maternal and fetal metabonomic alterations in prenatal nicotine exposure-induced rat intrauterine growth retardation.

    PubMed

    Feng, Jiang-hua; Yan, You-e; Liang, Gai; Liu, Yan-song; Li, Xiao-jun; Zhang, Ben-jian; Chen, Liao-bin; Yu, Hong; He, Xiao-hua; Wang, Hui

    2014-08-25

    Prenatal nicotine exposure causes adverse birth outcome. However, the corresponding metabonomic alterations and underlying mechanisms of nicotine-induced developmental toxicity remain unclear. The aims of this study were to characterize the metabolic alterations in biofluids in nicotine-induced intrauterine growth retardation (IUGR) rat model. In the present study, pregnant Wistar rats were intragastrically administered with different doses of nicotine (0.5, 1.0 and 2.0 mg/kg d) from gestational day (GD) 11-20. The metabolic profiles of the biofluids, including maternal plasma, fetal plasma and amniotic fluid, were analyzed using (1)H nuclear magnetic resonance (NMR)-based metabonomic techniques. Prenatal nicotine exposure caused noticeably lower body weights, higher IUGR rates of fetal rats, and elevated maternal and fetal corticosterone (CORT) levels compared to the controls. The correlation analysis among maternal, fetal serum CORT levels and fetal bodyweight suggested that the levels of maternal and fetal serum CORT presented a positive correlation (r=0.356, n=32, P<0.05), while there was a negative correlation between fetal (r=-0.639, n=32, P<0.01) and maternal (r=-0.530, n=32, P<0.01) serum CORT level and fetal bodyweight. The fetal metabonome alterations included the stimulation of lipogenesis and the decreased levels of glucose and amino acids. The maternal metabonome alterations involved the enhanced blood glucose levels, fatty acid oxygenolysis, proteolysis and amino acid accumulation. These results suggested that prenatal nicotine exposure is associated with an altered maternal and fetal metabonome, which may be related to maternal increased glucocorticoid level induced by nicotine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Progression of micronutrient alteration and hepatotoxicity following acute PCB126 exposure.

    PubMed

    Klaren, W D; Gadupudi, G S; Wels, B; Simmons, D L; Olivier, A K; Robertson, L W

    2015-12-02

    Polychlorinated Biphenyls (PCBs) are industrial chemicals that have become a persistent threat to human health due to ongoing exposure. A subset of PCBs, known as dioxin-like PCBs, pose a special threat given their potent hepatic effects. Micronutrients, especially Cu, Zn and Se, homeostatic dysfunction is commonly seen after exposure to dioxin-like PCBs. This study investigates whether micronutrient alteration is the byproduct of the ongoing hepatotoxicity, marked by lipid accumulation, or a concurrent, yet independent event of hepatic damage. A time course study was carried out using male Sprague-Dawley rats with treatments of PCB126, the prototypical dioxin-like PCB, resulting in 6 different time points. Animals were fed a purified diet, based on AIN-93G, for three weeks to ensure micronutrient equilibration. A single IP injection of either tocopherol-stripped soy oil vehicle (5 mL/kg) or 5 μmol/kg PCB126 dose in vehicle was given at various time points resulting in exposures of 9h, 18 h, 36 h, 3 days, 6 days, and 12 days. Mild hepatic vacuolar change was seen as early as 36 h with drastic changes at the later time points, 6 and 12 days. Micronutrient alterations, specifically Cu, Zn, and Se, were not seen until after day 3 and only observed in the liver. No alterations were seen in the duodenum, suggesting that absorption and excretion may not be involved. Micronutrient alterations occur with ROS formation, lipid accumulation, and hepatomegaly. To probe the mechanistic underpinnings, alteration of gene expression of several copper chaperones was investigated; only metallothionein appeared elevated. These data suggest that the disruption in micronutrient status is a result of the hepatic injury elicited by PCB126 and is mediated in part by metallothionein.

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

    PubMed

    Herring, M J; Putney, L F; St George, J A; Avdalovic, M V; Schelegle, E S; Miller, L A; Hyde, D M

    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 (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.

  17. Fetal alcohol exposure alters neurosteroid levels in the developing rat brain.

    PubMed

    Caldeira, Jerri C; Wu, Yan; Mameli, Manuel; Purdy, Robert H; Li, Pui-Kai; Akwa, Yvette; Savage, Daniel D; Engen, John R; Valenzuela, C Fernando

    2004-09-01

    Neurosteroids are modulators of neuronal function that may play important roles in brain maturation. We determined whether chronic prenatal ethanol exposure altered neurosteroid levels in the developing brain. Rat dams were exposed to: (i) a 5% ethanol-containing liquid diet that produces peak maternal blood alcohol levels near the legal intoxication limit (approximately 0.08 g/dL); (ii) an isocaloric liquid diet containing maltose-dextrin instead of ethanol with pair-feeding; (iii) rat chow ad libitum. Neurosteroid levels were assessed in offspring brains using radioimmunoassay or gas chromatography-mass spectrometry techniques. A prenatal ethanol exposure-induced increase in pregnenolone sulfate levels, but not dehydroepiandrosterone sulfate levels, was evident at the earliest time point studied (embryonic day 14). This effect lasted until post-natal day 5. Levels of other neurosteroids were assessed at embryonic day 20; pregnenolone levels, but not allopregnanolone levels, were elevated. Pregnenolone sulfate levels were not altered in the maternal brain. Neither pregnenolone nor pregnenolone sulfate levels were significantly altered in the fetal liver, placenta and maternal blood, indicating that the effect of ethanol is not secondary to accumulation of peripherally-produced steroids. Fetal ethanol exposure has been shown to decrease both cellular and behavioral responsiveness to neurosteroids, and our findings provide a plausible explanation for this effect.

  18. Gestational exposure to perfluorooctanoic acid (PFOA): Alterations in motor related behaviors.

    PubMed

    Goulding, David R; White, Sally S; McBride, Sandra J; Fenton, Suzanne E; Harry, G Jean

    2017-01-01

    Perfluoroalkyl and polyfluoroalkyl substances are used in commercial applications and developmental exposure has been implicated in alterations in neurobehavioral functioning. While associations between developmental perfluorooctanoic acid (PFOA) exposure and human outcomes have been inconsistent, studies in experimental animals suggest alterations in motor related behaviors. To examine a dose-response pattern of neurobehavioral effects following gestational exposure to PFOA, pregnant CD-1 mice received PFOA (0, 0.1, 0.3, 1.0mg/kg/day) via oral gavage from gestational day 1-17 and the male offspring examined. Motor activity assessments on postnatal day (PND)18, 19, and 20 indicated a shift in the developmental pattern with an elevated activity level observed in the 1.0mg/kg/day dose group on PND18. In the adult, no alterations were observed in body weights, activity levels, diurnal pattern of running wheel activity, startle response, or pre-pulse startle inhibition. In response to a subcutaneous injection of saline or nicotine (80μg/kg), all animals displayed a transient increase in activity likely associated with handling with no differences observed across dose groups. Inhibition of motor activity over 18days of 400μg/kg nicotine injection was not significantly different across dose groups. Hyperactivity induced by 2mg/kg (+)-methamphetamine hydrochloride intraperitoneal injection was significantly lower in the 1.0mg/kg/day PFOA dose group as compared to controls. Taken together, these data suggest that the effects on motor-related behaviors with gestational PFOA exposure do not mimic those reported for acute postnatal exposure. Changes were not observed at dose levels under 1.0mg/kg/day PFOA. Further examination of pathways associated with methamphetamine-induced activity is warranted. Published by Elsevier B.V.

  19. Altered myelination and axonal integrity in adults with childhood lead exposure: a diffusion tensor imaging study.

    PubMed

    Brubaker, Christopher J; Schmithorst, Vincent J; Haynes, Erin N; Dietrich, Kim N; Egelhoff, John C; Lindquist, Diana M; Lanphear, Bruce P; Cecil, Kim M

    2009-11-01

    Childhood lead exposure is associated with adverse cognitive, neurobehavioral and motor outcomes, suggesting altered brain structure and function. The purpose of this work was to assess the long-term impact of childhood lead exposure on white matter integrity in young adults. We hypothesized that childhood lead exposure would alter adult white matter architecture via deficits in axonal integrity and myelin organization. Adults (22.9+/-1.5 years, range 20.0-26.1 years) from the Cincinnati Lead Study were recruited to undergo a study employing diffusion tensor imaging (DTI). The anatomic regions of association between water diffusion characteristics in white matter and mean childhood blood lead level were determined for 91 participants (52 female). Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured on an exploratory voxel-wise basis. In adjusted analyses, mean childhood blood lead levels were associated with decreased FA throughout white matter. Regions of the corona radiata demonstrated highly significant lead-associated decreases in FA and AD and increases in MD and RD. The genu, body, and splenium of the corpus callosum demonstrated highly significant lead-associated decreases in RD, smaller and less significant decreases in MD, and small areas with increases in AD. The results of this analysis suggest multiple insults appear as distinct patterns of white matter diffusion abnormalities in the adult brain. Neurotoxic insults from the significant lead burden the participants experienced throughout childhood affect neural elements differently and may be related to the developmental stage of myelination at periods of exposure. This study indicates that childhood lead exposure is associated with a significant and persistent impact on white matter microstructure as quantified with diffusivity changes suggestive of altered myelination and axonal integrity.

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

    PubMed Central

    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

  1. The volitional nature of nicotine exposure alters anandamide and oleoylethanolamide levels in the ventral tegmental area.

    PubMed

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

    2013-03-01

    Cannabinoid-1 receptors (CB(1)) 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 CB(1) (by AEA and 2-AG) and non-CB(1) (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.

  2. Abiotic degradation of methyl parathion by manganese dioxide: Kinetics and transformation pathway.

    PubMed

    Liao, Xiaoping; Zhang, Caixiang; Liu, Yuan; Luo, Yinwen; Wu, Sisi; Yuan, Songhu; Zhu, Zhenli

    2016-05-01

    Methyl parathion, a widely used insecticide around the world, has aroused gradually extensive concern of researchers due to its degradation product such as methyl paraoxon, with higher toxicity for mammals and more recalcitrant. Given the ubiquity of manganese dioxide (MnO2) in soils and aquatic sediments, the abiotic degradation of methyl parathion by α-MnO2 was investigated in batch experiments. It was found that methyl parathion was decomposed up to 90% by α-MnO2 in 30 h and the removal efficiency of methyl parathion depended strongly on the loading of α-MnO2 and pH value in the solution where the reactions followed pseudo-first-order model well. The coexisting metal ions (such as Ca(2+), Mg(2+) and Mn(2+)) weakened markedly the degradation of methyl parathion by α-MnO2. However, the effect of dissolved organic matter (HA-Na) on reaction rates presented two sides: to improve hydrolysis rate but deteriorate oxidation rate of methyl parathion. Based on the degradation products identified by gas chromatography-mass spectrometer (GC/MS) and liquid chromatography high-resolution mass spectrometer (LC/HRMS), both hydrolysis and oxidation processes were proposed to be two predominant reaction mechanisms contributing to methyl parathion degradation by α-MnO2. This study provided meaningful information to elucidate the abiotic dissipation of methyl parathion by manganese oxide minerals in the environment.

  3. 75 FR 41482 - Methyl Parathion; Cancellation Order for Certain Pesticide Registrations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-16

    ...; the chemical industry; pesticide users; and members of the public interested in the sale, distribution... organophosphates as a class of chemicals, and does not specifically refer to this cancellation action for methyl... methyl parathion. USA Rice would like EPA to expedite a replacement chemical for methyl parathion, and...

  4. Prenatal xenobiotic exposure and intrauterine hypothalamus-pituitary-adrenal axis programming alteration.

    PubMed

    Zhang, Chong; Xu, Dan; Luo, Hanwen; Lu, Juan; Liu, Lian; Ping, Jie; Wang, Hui

    2014-11-05

    The hypothalamic-pituitary-adrenal (HPA) axis is one of the most important neuroendocrine axes and plays an important role in stress defense responses before and after birth. Prenatal exposure to xenobiotics, including environmental toxins (such as smoke, sulfur dioxide and carbon monoxide), drugs (such as synthetic glucocorticoids), and foods and beverage categories (such as ethanol and caffeine), affects fetal development indirectly by changing the maternal status or damaging the placenta. Certain xenobiotics (such as caffeine, ethanol and dexamethasone) may also affect the fetus directly by crossing the placenta into the fetus due to their lipophilic properties and lower molecular weights. All of these factors probably result in intrauterine programming alteration of the HPA axis, which showed a low basal activity but hypersensitivity to chronic stress. These alterations will, therefore, increase the susceptibility to adult neuropsychiatric (such as depression and schizophrenia) and metabolic diseases (such as hypertension, diabetes and non-alcoholic fatty liver disease). The "over-exposure of fetuses to maternal glucocorticoids" may be the main initiation factor by which the fetal HPA axis programming is altered. Meantime, xenobiotics can directly induce abnormal epigenetic modifications and expression on the important fetal genes (such as hippocampal glucocorticoid receptor, adrenal steroidogenic acute regulatory protein, et al) or damage by in situ oxidative metabolism of fetal adrenals, which may also be contributed to the programming alteration of fetal HPA axis.

  5. Cholinergic Synaptic Transmissions Were Altered after Single Sevoflurane Exposure in Drosophila Pupa

    PubMed Central

    Chen, Rongfa; Zhang, Tao; Kuang, Liting; Chen, Zhen; Ran, Dongzhi; Niu, Yang; Gu, Huaiyu

    2015-01-01

    Purpose. Sevoflurane, one of the most used general anesthetics, is widely used in clinical practice all over the world. Previous studies indicated that sevoflurane could induce neuron apoptosis and neural deficit causing query in the safety of anesthesia using sevoflurane. The present study was designed to investigate the effects of sevoflurane on electrophysiology in Drosophila pupa whose excitatory neurotransmitter is acetylcholine early after sevoflurane exposure using whole brain recording technique. Methods. Wide types of Drosophila (canton-s flies) were allocated to control and sevoflurane groups randomly. Sevoflurane groups (1% sevoflurane; 2% sevoflurane; 3% sevoflurane) were exposed to sevoflurane and the exposure lasted 5 hours, respectively. All flies were subjected to electrophysiology experiment using patch clamp 24 hours after exposure. Results. The results showed that, 24 hours after sevoflurane exposure, frequency but not the amplitude of miniature excitatory postsynaptic currents (mEPSCs) was significantly reduced (P < 0.05). Furthermore, we explored the underlying mechanism and found that calcium currents density, which partially regulated the frequency of mEPSCs, was significantly reduced after sevoflurane exposure (P < 0.05). Conclusions. All these suggested that sevoflurane could alter the mEPSCs that are related to synaptic plasticity partially through modulating calcium channel early after sevoflurane exposure. PMID:25705662

  6. Cholinergic synaptic transmissions were altered after single sevoflurane exposure in Drosophila pupa.

    PubMed

    Chen, Rongfa; Zhang, Tao; Kuang, Liting; Chen, Zhen; Ran, Dongzhi; Niu, Yang; Xu, Kangqing; Gu, Huaiyu

    2015-01-01

    . Sevoflurane, one of the most used general anesthetics, is widely used in clinical practice all over the world. Previous studies indicated that sevoflurane could induce neuron apoptosis and neural deficit causing query in the safety of anesthesia using sevoflurane. The present study was designed to investigate the effects of sevoflurane on electrophysiology in Drosophila pupa whose excitatory neurotransmitter is acetylcholine early after sevoflurane exposure using whole brain recording technique. Wide types of Drosophila (canton-s flies) were allocated to control and sevoflurane groups randomly. Sevoflurane groups (1% sevoflurane; 2% sevoflurane; 3% sevoflurane) were exposed to sevoflurane and the exposure lasted 5 hours, respectively. All flies were subjected to electrophysiology experiment using patch clamp 24 hours after exposure. The results showed that, 24 hours after sevoflurane exposure, frequency but not the amplitude of miniature excitatory postsynaptic currents (mEPSCs) was significantly reduced (P < 0.05). Furthermore, we explored the underlying mechanism and found that calcium currents density, which partially regulated the frequency of mEPSCs, was significantly reduced after sevoflurane exposure (P < 0.05). All these suggested that sevoflurane could alter the mEPSCs that are related to synaptic plasticity partially through modulating calcium channel early after sevoflurane exposure.

  7. Urinary excretion of metabolites following a single dermal dose of [14C]methyl parathion in pregnant rats.

    PubMed

    Abu-Qare, A W; Abou-Donia, M B

    2000-09-07

    The identification and kinetics of urinary excretion of metabolites of uniformly phenyl-labeled O,O-dimethyl O-4-nitrophenyl phosphorothioate ([14C]methyl parathion) were carried out following a single dermal dose of 10.0 mg (10 microCi)/kg in pregnant Sprague-Dawley rats at 14-18 days of gestation. Urine was collected at each time interval of 1, 2, 4, 12, 24, 48, 72, and 96 h after dosing. Total p-nitrophenol in the conjugated and non-conjugated metabolites was measured as a marker of methyl parathion exposure. Elimination of radioactivity in the urine was rapid. Of the total 14C urinary excretion, 30% of the dose was excreted within 4 h, while 50 and 90% of the dose were recovered in the urine by 24 and 96 h, respectively. Excretion rate of total radioactivity was 60 microgram methyl parathion equivalent/h (1.4 mg/day). By the end of the 96-h experiment, conjugated and non-conjugated metabolites accounted for 78.1 and 21.9%, respectively. Of the non-conjugated metabolites, p-nitrophenol and O,O-dimethyl O-4-nitrophenyl phosphate (methyl paraoxon) were identified by high performance liquid chromatography (HPLC) that accounted for 20%, and 1.9% of total urinary excretion, respectively. Appearance and disappearance rate constants of p-nitrophenol in urine were 0.12 and 0.048 microgram/h, respectively. Conjugated metabolites were classified as: glucuronides 12% of urinary excretion, sulfates 3%, hot sulfuric acid hydrolysable residues 47% and 16.1% remained as unidentified water soluble metabolites. Direct hot acid hydrolysis of urine yielded 49% of extractable 14C-radioactivity compared to 62% when hot acid hydrolysis followed the enzymatic hydrolysis. The presence of the conjugated metabolites as the major class of metabolites of the total excretion indicates that determining only unbound p-nitrophenol as a biological marker for methyl parathion exposure underestimates total urinary excretion of p-nitrophenol. Sequential enzymatic and acid hydrolyses of urine prior

  8. Embryonic Atrazine Exposure Elicits Alterations in Genes Associated with Neuroendocrine Function in Adult Male Zebrafish

    PubMed Central

    Wirbisky, Sara E.; Sepúlveda, Maria S.; Weber, Gregory J.; Jannasch, Amber S.; Horzmann, Katharine A.; Freeman, Jennifer L.

    2016-01-01

    The developmental origins of health and disease (DOHaD) hypothesis states that exposure to environmental stressors early in life can elicit genome and epigenome changes resulting in an increased susceptibility of a disease state during adulthood. Atrazine, a common agricultural herbicide used throughout the Midwestern United States, frequently contaminates potable water supplies and is a suspected endocrine disrupting chemical. In our previous studies, zebrafish was exposed to 0, 0.3, 3, or 30 parts per billion (μg/l) atrazine through embryogenesis, rinsed, and allowed to mature to adulthood. A decrease in spawning was observed with morphological alterations in offspring. In addition, adult females displayed an increase in ovarian progesterone and follicular atresia, alterations in levels of a serotonin metabolite and serotonin turnover in brain tissue, and transcriptome changes in brain and ovarian tissue supporting neuroendocrine alterations. As reproductive dysfunction is also influenced by males, this study assessed testes histology, hormone levels, and transcriptomic profiles of testes and brain tissue in the adult males. The embryonic atrazine exposure resulted in no alterations in body or testes weight, gonadosomatic index, testes histology, or levels of 11-ketotestosterone or testosterone. To further investigate potential alterations, transcriptomic profiles of adult male testes and brain tissue was completed. This analysis demonstrated alterations in genes associated with abnormal cell and neuronal growth and morphology; molecular transport, quantity, and production of steroid hormones; and neurotransmission with an emphasis on the hypothalamus–pituitary–adrenal and hypothalamus–pituitary–thyroid axes. Overall, this data indicate future studies should focus on additional neuroendocrine endpoints to determine potential functional impairments. PMID:27413107

  9. Environmentally Realistic Exposure to the Herbicide Atrazine Alters Some Sexually Selected Traits in Male Guppies

    PubMed Central

    Shenoy, Kausalya

    2012-01-01

    Male mating signals, including ornaments and courtship displays, and other sexually selected traits, like male-male aggression, are largely controlled by sex hormones. Environmental pollutants, notably endocrine disrupting compounds, can interfere with the proper functioning of hormones, thereby impacting the expression of hormonally regulated traits. Atrazine, one of the most widely used herbicides, can alter sex hormone levels in exposed animals. I tested the effects of environmentally relevant atrazine exposures on mating signals and behaviors in male guppies, a sexually dimorphic freshwater fish. Prolonged atrazine exposure reduced the expression of two honest signals: the area of orange spots (ornaments) and the number of courtship displays performed. Atrazine exposure also reduced aggression towards competing males in the context of mate competition. In the wild, exposure levels vary among individuals because of differential distribution of the pollutants across habitats; hence, differently impacted males often compete for the same mates. Disrupted mating signals can reduce reproductive success as females avoid mating with perceptibly suboptimal males. Less aggressive males are at a competitive disadvantage and lose access to females. This study highlights the effects of atrazine on ecologically relevant mating signals and behaviors in exposed wildlife. Altered reproductive traits have important implications for population dynamics, evolutionary patterns, and conservation of wildlife species. PMID:22312428

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

    PubMed

    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. © The Author(s) 2014.

  11. Neonatal exposure to monosodium glutamate induces morphological alterations in suprachiasmatic nucleus of adult rat.

    PubMed

    Rojas-Castañeda, Julio César; Vigueras-Villaseñor, Rosa María; Chávez-Saldaña, Margarita; Rojas, Patricia; Gutiérrez-Pérez, Oscar; Rojas, Carolina; Arteaga-Silva, Marcela

    2016-02-01

    Neonatal exposure to monosodium glutamate (MSG) induces circadian disorders in several physiological and behavioural processes regulated by the suprachiasmatic nucleus (SCN). The objective of this study was to evaluate the effects of neonatal exposure to MSG on locomotor activity, and on morphology, cellular density and expression of proteins, as evaluated by optical density (OD), of vasopressin (VP)-, vasoactive intestinal polypeptide (VIP)- and glial fibrillary acidic protein (GFAP)-immunoreactive cells in the SCN. Male Wistar rats were used: the MSG group was subcutaneously treated from 3 to 10 days of age with 3.5 mg/g/day. Locomotor activity was evaluated at 90 days of age using 'open-field' test, and the brains were processed for immunohistochemical studies. MSG exposure induced a significant decrease in locomotor activity. VP- and VIP-immunoreactive neuronal densities showed a significant decrease, while the somatic OD showed an increase. Major axes and somatic area were significantly increased in VIP neurons. The cellular and optical densities of GFAP-immunoreactive sections of SCN were significantly increased. These results demonstrated that newborn exposure to MSG induced morphological alterations in SCN cells, an alteration that could be the basis for behavioural disorders observed in the animals.

  12. Rat hippocampal alterations could underlie behavioral abnormalities induced by exposure to moderate noise levels.

    PubMed

    Uran, S L; Aon-Bertolino, M L; Caceres, L G; Capani, F; Guelman, L R

    2012-08-30

    Noise exposure is known to affect auditory structures in living organisms. However, it should not be ignored that many of the effects of noise are extra-auditory. Previous findings of our laboratory demonstrated that noise was able to induce behavioral alterations that are mainly related to the cerebellum (CE) and the hippocampus (HC). Therefore, the aim of this work was to reveal new data about the vulnerability of developing rat HC to moderate noise levels through the assessment of potential histological changes and hippocampal-related behavioral alterations. Male Wistar rats were exposed to noise (95-97 dB SPL, 2h daily) either for 1 day (acute noise exposure, ANE) or between postnatal days 15 and 30 (sub-acute noise exposure, SANE). Hippocampal histological evaluation as well as short (ST) and long term (LT) habituation and recognition memory assessments were performed. Results showed a mild disruption in the different hippocampal regions after ANE and SANE schemes, along with significant behavioral abnormalities. These data suggest that exposure of developing rats to noise levels of moderate intensity is able to trigger changes in the HC, an extra-auditory structure of the Central Nervous System (CNS), that could underlie the observed behavioral effects.

  13. Embryo-larval exposure to atrazine reduces viability and alters oxidative stress parameters in Drosophila melanogaster.

    PubMed

    Figueira, Fernanda Hernandes; Aguiar, Lais Mattos de; Rosa, Carlos Eduardo da

    2017-01-01

    The herbicide atrazine has been used worldwide with subsequent residual contamination of water and food, which may cause adverse effects on non-target organisms. Animal exposure to this herbicide may affect development, reproduction and energy metabolism. Here, the effects of atrazine regarding survival and redox metabolism were assessed in the fruit fly D. melanogaster exposed during embryonic and larval development. The embryos (newly fertilized eggs) were exposed to different atrazine concentrations (10μM and 100μM) in the diet until the adult fly emerged. Pupation and emergence rates, developmental time and sex ratio were determined as well as oxidative stress parameters and gene expression of the antioxidant defence system were evaluated in newly emerged male and female flies. Atrazine exposure reduced pupation and emergence rates in fruit flies without alterations to developmental time and sex ratio. Different redox imbalance patterns were observed between males and females exposed to atrazine. Atrazine caused an increase in oxidative damage, reactive oxygen species generation and antioxidant capacity and decreased thiol-containing molecules. Further, atrazine exposure altered the mRNA expression of antioxidant genes (keap1, sod, sod2, cat, irc, gss, gclm, gclc, trxt, trxr-1 and trxr-2). Reductions in fruit fly larval and pupal viability observed here are likely consequences of the oxidative stress induced by atrazine exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Prenatal betamethasone exposure alters renal function in immature sheep: sex differences in effects

    PubMed Central

    Bi, Jianli; Valego, Nancy; Carey, Luke; Figueroa, Jorge; Chappell, Mark; Rose, James C.

    2010-01-01

    Synthetic glucocorticoids are commonly given to pregnant women when premature delivery threatens. Antenatal administration of clinically relevant doses of betamethasone to pregnant sheep causes sex-specific compromises of renal function and increases in blood pressure in adult offspring. However, it is unclear whether such effects are present in immature lambs. Therefore, the aims of the present study were to determine whether antenatal betamethasone at 80–81 days of gestation increases blood pressure and adversely impacts renal function in adolescent ewes and rams. Prenatal steroid exposure increased blood pressure significantly in the young male (84 ± 2 vs. 74 ± 3 mmHg) and female sheep (88 ± 5 vs. 79 ± 4), but it did not alter basal glomerular filtration rate, renal blood flow (RBF), or sodium excretion in either sex. However, antenatal betamethasone exposure blocked increases in RBF (P = 0.001), and enhanced excretion of an acute Na load (P < 0.05) in response to systemic infusions of angiotensin (ANG)-(1–7) at 10 pmol·kg−1·min−1 in males. In females, the natriuretic response to combined ANG-(1–7), and Na load was significantly altered by prenatal betamethasone exposure. These findings indicate that blood pressure is increased in immature animals in response to antenatal steroid exposure and that sex-specific effects on renal function also exist. These changes may reflect greater risk for further loss of renal function with age. PMID:20554936

  15. Arsenic Exposure and Epigenetic Alterations: Recent Findings Based on the Illumina 450K DNA Methylation Array.

    PubMed

    Argos, Maria

    2015-06-01

    Arsenic is a major public health concern worldwide. While it is an established carcinogen and associated with a number of other adverse health outcomes, the molecular mechanisms underlying arsenic toxicity are not completely clarified. There is mounting evidence from human studies suggesting that arsenic exposure is associated with epigenetic alterations, including DNA methylation. In this review, we summarize several recent human studies that have evaluated arsenic exposure using the Illumina HumanMethylation 450K BeadChip, which interrogates more than 485,000 methylation sites across the genome. Many of these studies have observed novel regions of the genome associated with arsenic exposure. However, few studies have evaluated the biological and functional relevance of these DNA methylation changes, which are still needed. We emphasize the need for future studies to replicate the identified DNA methylation signals as well as assess whether these markers are associated with risk of arsenic-related diseases.

  16. Proteolytic activity is altered in brain tissue of rats upon chronic exposure to ozone

    SciTech Connect

    Benuck, M.; Banay-Schwartz, M.; Lajtha, A. )

    1993-01-01

    Tissue from pons medulla of rats exposed in vivo to various levels of ozone was assayed for calpain and cathepsin D activity. Chronic exposure to ozone increased calpain activity, which was 35% to 46% higher in the homogenates of animals exposed to 1.0 ppm ozone than in those of animals exposed to 0.5 ppm ozone or of controls. An increase in activity of 26% was also observed in the soluble supernatant. The increase in activity did not seem to be caused by ozone effects on calpastatin. Addition of 32 mM carnitine to the incubation mixture increased total activity 3-4 fold, making the differences in activity proportionately smaller. Cathepsin D activity was little altered. Changes in calpain activity and in the generation of free oxygen radicals have been implicated in the aging process, long-term exposure to ozone may magnify changes. Ozone exposure may cause changes in brain protein metabolism. 15 refs., 2 tabs.

  17. Cigarette smoke exposure-associated alterations to non-coding RNA.

    PubMed

    Maccani, Matthew A; Knopik, Valerie S

    2012-01-01

    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 non-coding 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 non-coding 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 ncRNA, assesses how such alterations may have consequences throughout the life course, and proposes future directions for this intriguing field of research.

  18. Prenatal arsenic exposure alters the programming of the glucocorticoid signaling system during embryonic development.

    PubMed

    Caldwell, Katharine E; Labrecque, Matthew T; Solomon, Benjamin R; Ali, Abdulmehdi; Allan, Andrea M

    2015-01-01

    The glucocorticoid system, which plays a critical role in a host of cellular functions including mood disorders and learning and memory, has been reported to be disrupted by arsenic. In previous work we have developed and characterized a prenatal moderate arsenic exposure (50ppb) model and identified several deficits in learning and memory and mood disorders, as well as alterations within the glucocorticoid receptor signaling system in the adolescent mouse. In these present studies we assessed the effects of arsenic on the glucocorticoid receptor (GR) pathway in both the placenta and the fetal brain in response at two critical periods, embryonic days 14 and 18. The focus of these studies was on the 11β-hydroxysteroid dehydrogenase enzymes (11β-HSD1 and 11β-HSD2) which play a key role in glucorticoid synthesis, as well as the expression and set point of the GR negative feedback regulation. Negative feedback regulation is established early in development. At E14 we found arsenic exposure significantly decreased expression of both protein and message in brain of GR and the 11β-HSD1, while 11β-HSD2 enzyme protein levels were increased but mRNA levels were decreased in the brain. These changes in brain protein continued into the E18 time point, but mRNA levels were no longer significantly altered. Placental HSD11B2 mRNA was not altered by arsenic treatment but protein levels were elevated at E14. GR placental protein levels were decreased at E18 in the arsenic exposed condition. This suggests that arsenic exposure may alter GR expression levels as a consequence of a prolonged developmental imbalance between 11β-HSD1 and 11β-HSD2 protein expression despite decreased 11HSDB2 mRNA. The suppression of GR and the failure to turn down 11β-HSD2 protein expression during fetal development may lead to an altered set point for GR signaling throughout adulthood. To our knowledge, these studies are the first to demonstrate that gestational exposure to moderate levels of

  19. Prenatal arsenic exposure alters the programming of the glucocorticoid signaling system during embryonic development

    PubMed Central

    Caldwell, Katharine E.; Labrecque, Matthew T.; Solomon, Benjamin R.; Ali, Abdulmehdi; Allan, Andrea M.

    2015-01-01

    The glucocorticoid system, which plays a critical role in a host of cellular functions including mood disorders and learning and memory, has been reported to be disrupted by arsenic. In previous work we have developed and characterized a prenatal moderate arsenic exposure (50 ppb) model and identified several deficits in learning and memory and mood disorders, as well as alterations within the glucocorticoid receptor signaling system in the adolescent mouse. In these present studies we assessed the effects of arsenic on the glucocorticoid receptor (GR) pathway in both the placenta and the fetal brain in response at two critical periods, embryonic days 14 and 18. The focus of these studies was on the 11β-hydroxysteroid dehydrogenase enzymes (11β-HSD1 and 11β-HSD2) which play a key role in glucorticoid synthesis, as well as the expression and set point of the GR negative feedback regulation. Negative feedback regulation is established early in development. At E14 we found arsenic exposure significantly decreased expression of both protein and message in brain of GR and the 11β-HSD1, while 11β-HSD2 enzyme protein levels were increased but mRNA levels were decreased in the brain. These changes in brain protein continued into the E18 time point, but mRNA levels were no longer significantly altered. Placental HSD11B2 mRNA was not altered by arsenic treatment but protein levels were elevated at E14. GR placental protein levels were decreased at E18 in the arsenic exposed condition. This suggests that arsenic exposure may alter GR expression levels as a consequence of a prolonged developmental imbalance between 11β-HSD1 and 11β-HSD2 protein expression despite decreased 11HSDB2 mRNA. The suppression of GR and the failure to turn down 11β-HSD2 protein expression during fetal development may lead to an altered set point for GR signaling throughout adulthood. To our knowledge, these studies are the first to demonstrate that gestational exposure to moderate levels of

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

    PubMed

    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.

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

    PubMed Central

    Al-Maleki, Anis Rageh; Mariappan, Vanitha; Vellasamy, Kumutha Malar; Tay, Sun Tee; Vadivelu, Jamuna

    2015-01-01

    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. PMID:25996927

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

    PubMed Central

    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

  3. Moderate blast exposure alters gene expression and levels of amyloid precursor protein

    PubMed Central

    Cashion, Ann; Osier, Nicole; Arcurio, Lindsay; Motamedi, Vida; Dell, Kristine C.; Carr, Walter; Kim, Hyung-Suk; Yun, Sijung; Walker, Peter; Ahlers, Stephen; LoPresti, Matthew; Yarnell, Angela

    2017-01-01

    Objective: To explore gene expression after moderate blast exposure (vs baseline) and proteomic changes after moderate- (vs low-) blast exposure. Methods: Military personnel (N = 69) donated blood for quantification of protein level, and peak pressure exposures were detected by helmet sensors before and during a blast training program (10 days total). On day 7, some participants (n = 29) sustained a moderate blast (mean peak pressure = 7.9 psi) and were matched to participants with no/low-blast exposure during the training (n = 40). PAXgene tubes were collected from one training site at baseline and day 10; RNA-sequencing day 10 expression was compared with each participant's own baseline samples to identify genes and pathways differentially expressed in moderate blast-exposed participants. Changes in amyloid precursor protein (APP) from baseline to the day of blast and following 2 days were evaluated. Symptoms were assessed using a self-reported form. Results: We identified 1,803 differentially expressed genes after moderate blast exposure; the most altered network was APP. Significantly reduced levels of peripheral APP were detected the day after the moderate blast exposure and the following day. Protein concentrations correlated with the magnitude of the moderate blast exposure on days 8 and 9. APP concentrations returned to baseline levels 3 days following the blast, likely due to increases in the genetic expression of APP. Onset of concentration problems and headaches occurred after moderate blast. Conclusions: Moderate blast exposure results in a signature biological profile that includes acute APP reductions, followed by genetic expression increases and normalization of APP levels; these changes likely influence neuronal recovery. PMID:28975156

  4. Parathion degradation and its intermediate formation by Fenton process in neutral environment.

    PubMed

    Fan, Chihhao; Tsui, Lo; Liao, Ming-Chu

    2011-01-01

    The purpose of this study is to investigate parathion degradation by Fenton process in neutral environment. The initial parathion concentration for all the degradation experiments was 20 ppm. For hydrogen ion effect on Fenton degradation, the pH varied from 2 to 8 at the [H₂O₂] to [Fe²(+)] ratio of 2-2 mM, and the result showed pH 3 as the most effective environment for parathion degradation by Fenton process. Apparent degradation was also observed at pH 7. The subsequent analysis for parathion degradation was conducted at pH 7 because most environmental parathion exists in the neutral environment. Comparing the parathion degradation results at various Fenton dosages revealed that at Fe²(+) concentrations of 0.5, 1.0 and 1.5 mM, the Fenton reagent ratio ([H₂O₂]/[Fe²(+)]) for best-removing performance were found as 4, 3, and 2, resulting in the removal efficiencies of 19%, 48% and 36%, respectively. Further increase in Fe²(+) concentration did not cause any increase of the optimum Fenton reagent ratio for the best parathion removal. The result from LC-MS also indicated that hydroxyl radicals might attack the PS double bond, the single bonds connecting nitro-group, nitrophenol, or the single bond within ethyl groups of parathion molecules forming paraoxons, nitrophenols, nitrate/nitrite, thiophosphates, and other smaller molecules. Lastly, the parathion degradation by Fenton process at the presence of humic acids was investigated, and the results showed that the presence of 10 mg L⁻¹ of humic acids in the aqueous solution enhanced the parathion removal by Fenton process twice as much as that without the presence of humic acids.

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

    PubMed

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Olivary Climbing Fiber Alterations in PN40 Rat Cerebellum Following Postnatal Ethanol Exposure

    PubMed Central

    Pierce, Dwight R.; Hayar, Abdallah; Williams, D. Keith; Light, Kim Edward

    2011-01-01

    Developmental ethanol exposure in rats during postnatal days (PN) 4–6 is known to cause significant loss of cerebellar Purkinje cells. It is not known what happens to the surviving neurons as they continue to develop. This study was designed to quantify the interactions between the olivary climbing fibers and the Purkinje cells when the cerebellar circuits have matured. Rat pups were treated with a daily dose of ethanol (4.5 g/kg body weight) delivered by intragastric intubation on PN4, PN4-6, or PN7-9. The interactions between climbing fibers and Purkinje cells were examined on PN40 using confocal microscopy. Mid-vermal cerebellar sections were stained with antibodies to calbindin-D28k (to visualize Purkinje cells) and vesicular glutamate transporter 2 (VGluT2, to visualize climbing fibers). Confocal z-stack images were obtained from Lobule 1 and analyzed with Imaris software to quantify the staining of the two antibodies. The VGluT2 immunostaining was significantly reduced and this was associated with alterations in the synaptic integrity, and synaptic number per Purkinje cell with only a single exposure on PN4 enough to cause the alterations. Previously, we demonstrated similar deficits in climbing fiber innervation when analyzed on PN14 (Pierce, Hayar, Williams, and Light, 2010). The present study confirms that these alterations are sustained and further identifies the decreased synaptic density as well as alterations to the general morphology of the molecular layer of the cerebellar cortex that are the result of the binge ethanol exposure. PMID:21241681

  7. Genistein Exposure Inhibits Growth and Alters Steroidogenesis in Adult Mouse Antral Follicles

    PubMed Central

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

    2016-01-01

    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 36 μM) for 18 – 96 hours (h). Every 24 h, 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 (36 μM) inhibits growth of mouse antral follicles. Additionally, genistein (6.0 and 36 μM) 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 96 h, and the expression of cell cycle regulators at 18 h. 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

  8. Subchronic arsenic exposure through drinking water alters vascular redox homeostasis and affects physical health in rats.

    PubMed

    Waghe, Prashantkumar; Sarath, Thengumpallil Sasindran; Gupta, Priyanka; Kutty, Harikumar Sankaran; Kandasamy, Kannan; Mishra, Santosh Kumar; Sarkar, Souvendra Nath

    2014-12-01

    We evaluated whether arsenic can alter vascular redox homeostasis and modulate antioxidant status, taking rat thoracic aorta as a model vascular tissue. In addition, we evaluated whether the altered vascular biochemical homeostasis could be associated with alterations in the physical indicators of toxicity development. Rats were exposed to arsenic as 25, 50, and 100 ppm of sodium arsenite through drinking water for 90 consecutive days. Body weight, food intake, and water consumption were recorded weekly. On the 91st day, rats were sacrificed; vital organs and thoracic aorta were collected. Lipid peroxidation, reactive oxygen species generation, and antioxidants were assessed in the thoracic aorta. Arsenic increased aortic lipid peroxidation and hydrogen peroxide generation while decreased reduced glutathione content in a dose-dependent manner. The activities of the enzymatic antioxidants superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were decreased. Further, arsenic at 100 ppm decreased feed intake, water consumption, and body weight from the 11th week onward. At this concentration, arsenic increased the relative weights of the liver and kidney. The results suggest that arsenic causes dose-dependent oxidative stress, reduction in antioxidative defense systems, and body weight loss with alteration in hepato-renal organosomatic indices. Overall, subchronic arsenic exposure through drinking water causes alteration in vascular redox homeostasis and at high concentration affects physical health.

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

    SciTech Connect

    Herring, M.J.; Putney, L.F.; St George, J.A.; Avdalovic, M.V.; Schelegle, E.S.; Miller, L.A.; Hyde, D.M.

    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)

  10. Parental Exposure to Dim Light at Night Prior to Mating Alters Offspring Adaptive Immunity

    PubMed Central

    Cissé, Yasmine M.; Russart, Kathryn L.G.; Nelson, Randy J.

    2017-01-01

    Exposure to dim light at night (dLAN) disrupts natural light/dark cycles and impairs endogenous circadian rhythms necessary to maintain optimal biological function, including the endocrine and immune systems. We have previously demonstrated that white dLAN compromises innate and cell mediated immune responses in adult Siberian hamsters (Phodopus sungorus). We hypothesized that dLAN has transgenerational influences on immune function. Adult male and female Siberian hamsters were exposed to either dark nights (DARK) or dLAN (~5 lux) for 9 weeks, then paired in full factorial design, mated, and thereafter housed under dark nights. Offspring were gestated and reared in dark nights, then tested as adults for cell-mediated and humoral immunity. Maternal exposure to dLAN dampened delayed type hypersensitivity (DTH) responses in male offspring. Maternal and paternal exposure to dLAN reduced DTH responses in female offspring. IgG antibodies to a novel antigen were elevated in offspring of dams exposed to dLAN. Paternal exposure to dLAN decreased splenic endocrine receptor expression and global methylation in a parental sex-specific manner. Together, these data suggest that exposure to dLAN has transgenerational effects on endocrine-immune function that may be mediated by global alterations in the epigenetic landscape of immune tissues. PMID:28361901

  11. A Complex Interaction Between Reduced Reelin Expression and Prenatal Organophosphate Exposure Alters Neuronal Cell Morphology.

    PubMed

    Mullen, Brian R; Ross, Brennan; Chou, Joan Wang; Khankan, Rana; Khialeeva, Elvira; Bui, Kimberly; Carpenter, Ellen M

    2016-06-01

    Genetic and environmental factors are both likely to contribute to neurodevelopmental disorders including schizophrenia, autism spectrum disorders, and major depressive disorders. Prior studies from our laboratory and others have demonstrated that the combinatorial effect of two factors-reduced expression of reelin protein and prenatal exposure to the organophosphate pesticide chlorpyrifos oxon-gives rise to acute biochemical effects and to morphological and behavioral phenotypes in adolescent and young adult mice. In the current study, we examine the consequences of these factors on reelin protein expression and neuronal cell morphology in adult mice. While the cell populations that express reelin in the adult brain appear unchanged in location and distribution, the levels of full length and cleaved reelin protein show persistent reductions following prenatal exposure to chlorpyrifos oxon. Cell positioning and organization in the hippocampus and cerebellum are largely normal in animals with either reduced reelin expression or prenatal exposure to chlorpyrifos oxon, but cellular complexity and dendritic spine organization is altered, with a skewed distribution of immature dendritic spines in adult animals. Paradoxically, combinatorial exposure to both factors appears to generate a rescue of the dendritic spine phenotypes, similar to the mitigation of behavioral and morphological changes observed in our prior study. Together, our observations support an interaction between reelin expression and chlorpyrifos oxon exposure that is not simply additive, suggesting a complex interplay between genetic and environmental factors in regulating brain morphology. © The Author(s) 2016.

  12. Methamphetamine exposure during brain development alters the brain acetylcholine system in adolescent mice.

    PubMed

    Siegel, Jessica A; Park, Byung S; Raber, Jacob

    2011-10-01

    Children exposed to methamphetamine during brain development as a result of maternal drug use have long-term hippocampus-dependent cognitive impairments, but the mechanisms underlying these impairments are not understood. The acetylcholine system plays an important role in cognitive function and potential methamphetamine-induced acetylcholine alterations may be related to methamphetamine-induced cognitive impairments. In this study, we investigated the potential long-term effects of methamphetamine exposure during hippocampal development on the acetylcholine system in adolescence mice on postnatal day 30 and in adult mice on postnatal day 90. Methamphetamine exposure increased the density of acetylcholine neurons in regions of the basal forebrain and the area occupied by acetylcholine axons in the hippocampus in adolescent female mice. In contrast, methamphetamine exposure did not affect the density of GABA cells or total neurons in the basal forebrain. Methamphetamine exposure also increased the number of muscarinic acetylcholine receptors in the hippocampus of adolescent male and female mice. Our results demonstrate for the first time that methamphetamine exposure during hippocampal development affects the acetylcholine system in adolescent mice and that these changes are more profound in females than males. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  13. Prenatal Exposure to Lipopolysaccharide Alters Renal DNA Methyltransferase Expression in Rat Offspring

    PubMed Central

    Chen, Rui; Deng, Youcai; Liao, Xi; Wei, Yanling; Li, Xiaohui; Su, Min; Yu, Jianhua; Yi, Ping

    2017-01-01

    Prenatal exposure to inflammation results in hypertension during adulthood but the mechanisms are not well understood. Maternal exposure to lipopolysaccharide (LPS) alters interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels in the fetal environment. As reported in many recent studies, IL-6 regulates DNA methyltransferases (DNMTs) through the transcription factor friend leukemia virus integration 1 (Fli-1). The present study explores the role of intrarenal DNMTs during development of hypertension induced by prenatal exposure to LPS. Pregnant rats were randomly divided into four treatment groups: control, LPS, pyrrolidine dithiocarbamate (PDTC, a NF-κB inhibitor), and the combination of LPS and PDTC. Expression of IL-6, Fli-1, TNF-α, DNMT1 and DNMT3B was significantly increased in the offspring of LPS-treated rats. Global DNA methylation level of renal cortex also increased dramatically in rat offspring of the LPS group. Prenatal PDTC administration reversed the increases in gene expression and global DNA methylation level. These findings suggest that prenatal exposure to LPS may result in changes of intrarenal DNMTs through the IL-6/Fli-1 pathway and TNF-α, which probably involves hypertension in offspring due to maternal exposure to inflammation. PMID:28103274

  14. A Complex Interaction Between Reduced Reelin Expression and Prenatal Organophosphate Exposure Alters Neuronal Cell Morphology

    PubMed Central

    Mullen, Brian R.; Ross, Brennan; Chou, Joan Wang; Khankan, Rana; Khialeeva, Elvira; Bui, Kimberly

    2016-01-01

    Genetic and environmental factors are both likely to contribute to neurodevelopmental disorders including schizophrenia, autism spectrum disorders, and major depressive disorders. Prior studies from our laboratory and others have demonstrated that the combinatorial effect of two factors—reduced expression of reelin protein and prenatal exposure to the organophosphate pesticide chlorpyrifos oxon—gives rise to acute biochemical effects and to morphological and behavioral phenotypes in adolescent and young adult mice. In the current study, we examine the consequences of these factors on reelin protein expression and neuronal cell morphology in adult mice. While the cell populations that express reelin in the adult brain appear unchanged in location and distribution, the levels of full length and cleaved reelin protein show persistent reductions following prenatal exposure to chlorpyrifos oxon. Cell positioning and organization in the hippocampus and cerebellum are largely normal in animals with either reduced reelin expression or prenatal exposure to chlorpyrifos oxon, but cellular complexity and dendritic spine organization is altered, with a skewed distribution of immature dendritic spines in adult animals. Paradoxically, combinatorial exposure to both factors appears to generate a rescue of the dendritic spine phenotypes, similar to the mitigation of behavioral and morphological changes observed in our prior study. Together, our observations support an interaction between reelin expression and chlorpyrifos oxon exposure that is not simply additive, suggesting a complex interplay between genetic and environmental factors in regulating brain morphology. PMID:27364165

  15. Acute exposure to 2,4-dinitrophenol alters zebrafish swimming performance and whole body triglyceride levels.

    PubMed

    Marit, Jordan S; Weber, Lynn P

    2011-06-01

    While swimming endurance (critical swimming speed or U(crit)) and lipid stores have both been reported to acutely decrease after exposure to a variety of toxicants, the relationship between these endpoints has not been clearly established. In order to examine these relationships, adult zebrafish (Danio rerio) were aqueously exposed to solvent control (ethanol) or two nominal concentrations of 2,4-dinitrophenol (DNP), a mitochondrial electron transport chain uncoupler, for a 24-h period. Following exposure, fish were placed in a swim tunnel in clean water for swimming testing or euthanized immediately without testing, followed by analysis of whole body triglyceride levels. U(crit) decreased in both the 6 mg/L and 12 mg/L DNP groups, with 12 mg/L approaching the LC₅₀. A decrease in tail beat frequency was observed without a significant change in tail beat amplitude. In contrast, triglyceride levels were elevated in a concentration-dependent manner in the DNP exposure groups, but only in fish subjected to swimming tests. This increase in triglyceride stores may be due to a direct interference of DNP on lipid catabolism as well as increased triglyceride production when zebrafish were subjected to the co-stressors of swimming and toxicant exposure. Future studies should be directed at determining how acute DNP exposure combines with swimming to cause alterations in triglyceride accumulation.

  16. Prenatal exposure to antidepressants and depressed maternal mood alter trajectory of infant speech perception.

    PubMed

    Weikum, Whitney M; Oberlander, Tim F; Hensch, Takao K; Werker, Janet F

    2012-10-16

    Language acquisition reflects a complex interplay between biology and early experience. Psychotropic medication exposure has been shown to alter neural plasticity and shift sensitive periods in perceptual development. Notably, serotonin reuptake inhibitors (SRIs) are antidepressant agents increasingly prescribed to manage antenatal mood disorders, and depressed maternal mood per se during pregnancy impacts infant behavior, also raising concerns about long-term consequences following such developmental exposure. We studied whether infants' language development is altered by prenatal exposure to SRIs and whether such effects differ from exposure to maternal mood disturbances. Infants from non-SRI-treated mothers with little or no depression (control), depressed but non-SRI-treated (depressed-only), and depressed and treated with an SRI (SRI-exposed) were studied at 36 wk gestation (while still in utero) on a consonant and vowel discrimination task and at 6 and 10 mo of age on a nonnative speech and visual language discrimination task. Whereas the control infants responded as expected (success at 6 mo and failure at 10 mo) the SRI-exposed infants failed to discriminate the language differences at either age and the depressed-only infants succeeded at 10 mo instead of 6 mo. Fetuses at 36 wk gestation in the control condition performed as expected, with a response on vowel but not consonant discrimination, whereas the SRI-exposed fetuses showed accelerated perceptual development by discriminating both vowels and consonants. Thus, prenatal depressed maternal mood and SRI exposure were found to shift developmental milestones bidirectionally on infant speech perception tasks.

  17. Alterations in the Striatal Dopamine System During Intravenous Methamphetamine Exposure: Effects of Contingent and Noncontingent Administration

    PubMed Central

    Laćan, Goran; Hadamitzky, Martin; Kuczenski, Ronald; Melega, William P.

    2014-01-01

    The continuing spread of methamphetamine (METH) abuse has stimulated research aimed at understanding consequences of its prolonged exposure. Alterations in nigrostriatal dopamine (DA) system parameters have been characterized in experimental studies after discontinuation of long term METH but fewer studies have included similar assessments during METH exposure. Here, we report METH plasma pharmacokinetics and striatal DA system alterations in rat after noncontingent and contingent METH administration for 7.5 weeks. Escalating METH exposure was delivered by dynamic infusion (DI) that incorporated a ‘humanized’ plasma METH half life, or by intravenous self-administration (IVSA) that included binge intakes. Kinetic modeling of DI and IVSA for 24 h periods during the final week of METH exposure showed that plasma METH levels remained between 0.7–1.5 μM. Animals were sacrificed during their last METH administration for autoradiography assessment using [3H]ligands and D2 agonist-induced [35S]GTPγS binding. DA transporter binding was decreased (DI, 34%; IVSA, 15%) while vesicular monoamine transporter binding and substantia nigra DA cell numbers were unchanged. Decreases were measured for D2 receptor (DI and IVSA, 15–20%) and [35S]GTPγS binding (DI, 35%; IVSA, 18%). These similar patterns of DI and IVSA associated decreases in striatal DA markers reflect consequences of cumulative METH exposure and not the drug delivery method. For METH IVSA, individual differences were observed, yet each animal’s total intake was similar within and across three 24 h binges. IVSA rodent models may be useful for identifying molecular mechanisms that are associated with METH binges in humans. PMID:23417852

  18. Alterations in the striatal dopamine system during intravenous methamphetamine exposure: effects of contingent and noncontingent administration.

    PubMed

    Laćan, Goran; Hadamitzky, Martin; Kuczenski, Ronald; Melega, William P

    2013-08-01

    The continuing spread of methamphetamine (METH) abuse has stimulated research aimed at understanding consequences of its prolonged exposure. Alterations in nigrostriatal dopamine (DA) system parameters have been characterized in experimental studies after discontinuation of long-term METH but fewer studies have included similar assessments during METH exposure. Here, we report METH plasma pharmacokinetics and striatal DA system alterations in rat after noncontingent and contingent METH administration for 7.5 weeks. Escalating METH exposure was delivered by dynamic infusion (DI) that incorporated a "humanized" plasma METH half life or by intravenous self-administration (IVSA) that included binge intakes. Kinetic modeling of DI and IVSA for 24 h periods during the final week of METH exposure showed that plasma METH levels remained between 0.7 and 1.5 µM. Animals were sacrificed during their last METH administration for autoradiography assessment using [³H]ligands and D2 agonist-induced [³⁵S]GTPγS binding. DA transporter binding was decreased (DI, 34%; IVSA, 15%) while vesicular monoamine transporter binding and substantia nigra DA cell numbers were unchanged. Decreases were measured for D2 receptor (DI and IVSA, 15-20%) and [³⁵S]GTPγS binding (DI, 35%; IVSA, 18%). These similar patterns of DI and IVSA associated decreases in striatal DA markers reflect consequences of cumulative METH exposure and not the drug delivery method. For METH IVSA, individual differences were observed, yet each animal's total intake was similar within and across three 24-h binges. IVSA rodent models may be useful for identifying molecular mechanisms that are associated with METH binges in humans. Copyright © 2013 Wiley Periodicals, Inc.

  19. Prenatal exposure to antidepressants and depressed maternal mood alter trajectory of infant speech perception

    PubMed Central

    Weikum, Whitney M.; Oberlander, Tim F.; Hensch, Takao K.; Werker, Janet F.

    2012-01-01

    Language acquisition reflects a complex interplay between biology and early experience. Psychotropic medication exposure has been shown to alter neural plasticity and shift sensitive periods in perceptual development. Notably, serotonin reuptake inhibitors (SRIs) are antidepressant agents increasingly prescribed to manage antenatal mood disorders, and depressed maternal mood per se during pregnancy impacts infant behavior, also raising concerns about long-term consequences following such developmental exposure. We studied whether infants’ language development is altered by prenatal exposure to SRIs and whether such effects differ from exposure to maternal mood disturbances. Infants from non–SRI-treated mothers with little or no depression (control), depressed but non–SRI-treated (depressed-only), and depressed and treated with an SRI (SRI-exposed) were studied at 36 wk gestation (while still in utero) on a consonant and vowel discrimination task and at 6 and 10 mo of age on a nonnative speech and visual language discrimination task. Whereas the control infants responded as expected (success at 6 mo and failure at 10 mo) the SRI-exposed infants failed to discriminate the language differences at either age and the depressed-only infants succeeded at 10 mo instead of 6 mo. Fetuses at 36 wk gestation in the control condition performed as expected, with a response on vowel but not consonant discrimination, whereas the SRI-exposed fetuses showed accelerated perceptual development by discriminating both vowels and consonants. Thus, prenatal depressed maternal mood and SRI exposure were found to shift developmental milestones bidirectionally on infant speech perception tasks. PMID:23045665

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

    PubMed

    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.

  1. Gestational exposure to yellow fever vaccine at different developmental stages induces behavioral alterations in the progeny.

    PubMed

    Marianno, P; Salles, M J S; Sonego, A B; Costa, G A; Galvão, T C; Lima, G Z; Moreira, E G

    2013-01-01

    The most effective method to prevent yellow fever and control the disease is a vaccine made with attenuated live virus. Due to the neurological tropism of the virus, preventive vaccination is not recommended for infants under 6 months and for pregnant women. However there is a paucity of data regarding the safety for pregnant women and there are no experimental studies investigating adverse effects to the offspring after maternal exposure to the vaccine. This study aimed to investigate, in mice, the effects of maternal exposure to the yellow fever vaccine at three different gestational ages on the physical and behavioral development of the offspring. Pregnant Swiss mice received a single subcutaneous injection of water for injection (control groups) or 2 log Plaque Forming Units (vaccine-treated groups) of the yellow fever vaccine on gestational days (GD) 5, 10 or 15. Neither maternal signs of toxicity nor alterations in physical development and reflex ontogeny of the offspring were observed in any of the groups. Data from behavioral evaluation indicated that yellow fever vaccine exposure induced motor hypoactivity in 22-day-old females independent of the day of exposure; and in 60-day-old male and female pups exposed at GD 10. Moreover, 22-day-old females also presented with a deficit in habituation memory. Altogether, these results indicate that in utero exposure to the yellow fever vaccine may induce behavioral alterations in the pups that may persist to adulthood in the absence of observed maternal toxicity or disruption of physical development milestones or reflex ontogeny. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Perinatal exposure to diethylstilbestrol alters the functional differentiation of the adult rat uterus.

    PubMed

    Bosquiazzo, Verónica L; Vigezzi, Lucía; Muñoz-de-Toro, Mónica; Luque, Enrique H

    2013-11-01

    The exposure to endocrine disrupters and female reproductive tract disorders has not been totally clarified. The present study assessed the long-term effect of perinatal (gestation+lactation) exposure to diethylstilbestrol (DES) on the rat uterus and the effect of estrogen replacement therapy. DES (5μg/kg bw/day) was administered in the drinking water from gestational day 9 until weaning and we studied the uterus of young adult (PND90) and adult (PND360) females. To investigate whether perinatal exposure to DES modified the uterine response to a long-lasting estrogen treatment, 12-month-old rats exposed to DES were ovariectomized and treated with 17β-estradiol for 3 months (PND460). In young adult rats (PND90), the DES treatment decreased both the proliferation of glandular epithelial cells and the percentage of glandular perimeter occupied by α-smooth muscle actin-positive cells. The other tissue compartments remained unchanged. Cell apoptosis was not altered in DES-exposed females. In control adult rats (PND360), there were some morphologically abnormal uterine glands. In adult rats exposed to DES, the incidence of glands with cellular anomalies increased. In response to estrogens (PND460), the incidence of cystic glands increased in the DES group. We observed glands with daughter glands and conglomerates of glands only on PND460 and in response to estrogen replacement therapy, independently of DES exposure. The p63 isoforms were expressed without changes on PND460. Estrogen receptors α and β showed no changes, while the progesterone receptor decreased in the subepithelial stroma of DES-exposed animals with estrogen treatment. The long-lasting effects of perinatal exposure to DES included the induction of abnormalities in uterine tissues of aged female rats and an altered response of the adult uterus to estradiol. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Developmental alcohol exposure impairs synaptic plasticity without overtly altering microglial function in mouse visual cortex.

    PubMed

    Wong, Elissa L; Lutz, Nina M; Hogan, Victoria A; Lamantia, Cassandra E; McMurray, Helene R; Myers, Jason R; Ashton, John M; Majewska, Ania K

    2017-09-14

    Fetal alcohol spectrum disorder (FASD), caused by gestational ethanol (EtOH) exposure, is one of the most common causes of non-heritable and life-long mental disability worldwide, with no standard treatment or therapy available. While EtOH exposure can alter the function of both neurons and glia, it is still unclear how EtOH influences brain development to cause deficits in sensory and cognitive processing later in life. Microglia play an important role in shaping synaptic function and plasticity during neural circuit development and have been shown to mount an acute immunological response to EtOH exposure in certain brain regions. Therefore, we hypothesized that microglial roles in the healthy brain could be permanently altered by early EtOH exposure leading to deficits in experience-dependent plasticity. We used a mouse model of human third trimester high binge EtOH exposure, administering EtOH twice daily by subcutaneous injections from postnatal day 4 through postnatal day 9 (P4-:P9). Using a monocular deprivation model to assess ocular dominance plasticity, we found an EtOH-induced deficit in this type of visually driven experience-dependent plasticity. However, using a combination of immunohistochemistry, confocal microscopy, and in vivo two-photon microscopy to assay microglial morphology and dynamics, as well as fluorescence activated cell sorting (FACS) and RNA-seq to examine the microglial transcriptome, we found no evidence of microglial dysfunction in early adolescence. We also found no evidence of microglial activation in visual cortex acutely after early ethanol exposure, possibly because we also did not observe EtOH-induced neuronal cell death in this brain region. We conclude that early EtOH exposure caused a deficit in experience-dependent synaptic plasticity in the visual cortex that was independent of changes in microglial phenotype or function. This demonstrates that neural plasticity can remain impaired by developmental ethanol exposure even in

  4. Alterations in the Rat Serum Proteome Induced by Prepubertal Exposure to Bisphenol A and Genistein

    PubMed Central

    2015-01-01

    Humans are exposed to an array of chemicals via the food, drink and air, including a significant number that can mimic endogenous hormones. One such chemical is Bisphenol A (BPA), a synthetic chemical that has been shown to cause developmental alterations and to predispose for mammary cancer in rodent models. In contrast, the phytochemical genistein has been reported to suppress chemically induced mammary cancer in rodents, and Asians ingesting a diet high in soy containing genistein have lower incidence of breast and prostate cancers. In this study, we sought to: (1) identify protein biomarkers of susceptibility from blood sera of rats exposed prepubertally to BPA or genistein using Isobaric Tandem Mass Tags quantitative mass spectrometry (TMT-MS) combined with MudPIT technology and, (2) explore the relevance of these proteins to carcinogenesis. Prepubertal exposures to BPA and genistein resulted in altered expression of 63 and 28 proteins in rat sera at postnatal day (PND) 21, and of 9 and 18 proteins in sera at PND35, respectively. This study demonstrates the value of using quantitative proteomic techniques to explore the effect of chemical exposure on the rat serum proteome and its potential for unraveling cellular targets altered by BPA and genistein involved in carcinogenesis. PMID:24552547

  5. Chronic exposure to pentachlorophenol alters thyroid hormones and thyroid hormone pathway mRNAs in zebrafish.

    PubMed

    Yu, Li-Qin; Zhao, Gao-Feng; Feng, Min; Wen, Wu; Li, Kun; Zhang, Pan-Wei; Peng, Xi; Huo, Wei-Jie; Zhou, Huai-Dong

    2014-01-01

    Pentachlorophenol (PCP) is frequently detected in the aquatic environment and has been implicated as an endocrine disruptor in fish. In the present study, 4-month-old zebrafish (Danio rerio) were exposed to 1 of 4 concentrations of PCP (0.1, 1, 9, and 27 µg/L) for 70 d. The effects of PCP exposure on plasma thyroid hormone levels, and the expression levels of selected genes, were measured in the brain and liver. The PCP exposure at 27 µg/L resulted in elevated plasma thyroxine concentrations in male and female zebrafish and depressed 3, 5, 3'-triiodothyronine concentrations in males only. In both sexes, PCP exposure resulted in decreased messenger RNA (mRNA) expression levels of thyroid-stimulating hormone β-subunit (tshβ) and thyroid hormone receptor β (trβ) in the brain, as well as increased liver levels of uridine diphosphoglucuronosyl transferase (ugt1ab) and decreased deiodinase 1 (dio1). The authors also identified several sex-specific effects of PCP exposure, including changes in mRNA levels for deiodinase 2 (dio2), cytosolic sulfotransferase (sult1 st5), and transthyretin (ttr) genes in the liver. Environmental PCP exposure also caused an increased malformation rate in offspring that received maternal exposure to PCP. The present study demonstrates that chronic exposure to environmental levels of PCP alters plasma thyroid hormone levels, as well as the expression of genes associated with thyroid hormone signaling and metabolism in the hypothalamic-pituitary-thyroid (HPT) axis and liver, resulting in abnormal zebrafish development.

  6. Urinary metabolomics revealed arsenic exposure related to metabolic alterations in general Chinese pregnant women.

    PubMed

    Li, Han; Wang, Mu; Liang, Qiande; Jin, Shuna; Sun, Xiaojie; Jiang, Yangqian; Pan, Xingyun; Zhou, Yanqiu; Peng, Yang; Zhang, Bin; Zhou, Aifen; Zhang, Yiming; Chen, Zhong; Cao, Jiangxia; Zhang, Hongling; Xia, Wei; Zheng, Tongzhang; Cai, Zongwei; Li, Yuanyuan; Xu, Shunqing

    2017-01-06

    Arsenic exposure is considered a major environmental threat to human health. It is already known that high-level arsenic exposure has adverse effects on human health. Since the pregnant women are known to be more susceptible to some chemical exposures than ordinary people, the understanding regarding the health effects of low-level arsenic exposure on pregnant women is critical and remains unclear. The aim of this study is to investigate the urinary metabolic changes of pregnant women exposed to low-dose arsenic, and to identify biomarkers from metabolomics analysis. Urine samples of 246 pregnant women were collected in the first trimester of pregnancy and were divided into three groups based on the tertile distribution of urinary arsenic concentrations which were determined using inductively coupled plasma mass spectrometry (ICP-MS). Changes in the metabolite profile were measured using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF MS). Arsenic- related metabolic biomarkers were investigated by comparing the samples of the first and third tertiles of arsenic exposure classifications using a partial least-squares discriminant model (PLS-DA). Nine urine potential biomarkers were putatively identified, including LysoPC (14:0), glutathione, 18-carboxy-dinor-LTE4, 20-COOH-LTE4, cystathionine ketimin, 1-(beta-d-ribofuranosyl)-1,4-dihydronicotinamide, thiocysteine, p-cresol glucuronide and vanillactic acid. The obtained results showed that environmental arsenic exposure, even at low levels, could cause metabolite alterations in pregnant women which might be associated with adverse health outcomes. This is the first report on metabolic changes in pregnant women for arsenic exposure. The findings may be valuable for the arsenic risk assessment for pregnant women. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Mephedrone exposure in adolescent rats alters the rewarding effect of morphine in adults.

    PubMed

    Joanna, Listos; Sylwia, Talarek; Magdalena, Gryzinska; Piotr, Listos; Ewa, Kedzierska; Jolanta, Orzelska-Gorka; Malgorzata, Dylewska; Malgorzata, Lupina; Kotlinska, Jolanta H

    2017-09-05

    An increasing number of data show that exposure to mephedrone in adolescence can have long-lasting implication on brain activity and on peripheral organs/tissues. The aim of this study was to investigate whether adolescent exposure to mephedrone (10mg/kg, i.p.) has influence upon the rewarding effect of morphine (5mg/kg, i.p.) in adult rats. Thus, the adolescent rats (on the 30th PND) were treated with mephedrone for 7 consecutive days. When the animals were adult (on the 60th PND) the morphine-induced conditioned place preference (CPP) test was performed. After that, the level of DNA methylation in the striatum was investigated. DNA methylation is one of the epigenetic mechanisms which produces changes in the genome. These alterations may affect the phenotype, without effect on DNA sequences, and has influence on drug addiction. Additionally, in order to check the toxic properties of mephedrone on the peripheral organs, the histopathological examination of kidney and liver was carried out. The present experiments demonstrated that: 1) adolescent mephedrone exposure may intensify the rewarding effect of morphine in adult rats in the CPP test; 2) mephedrone may induce the alterations in DNA methylation in striatum of adult rats leading to changes in gene activity; 3) mephedrone may produce some retrogressive disturbances in kidney and liver, which confirms the toxic properties of this substance. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Prenatal exposure to low levels of carbon monoxide alters sciatic nerve myelination in rat offspring.

    PubMed

    Carratù, M R; Cagiano, R; Desantis, S; Labate, M; Tattoli, M; Trabace, L; Cuomo, V

    2000-08-25

    Prenatal exposure to low concentrations of carbon monoxide (CO, 75 and 150 ppm from day 0 to day 20 of gestation), resulting in maternal blood HbCO concentrations equivalent to those maintained by human cigarette smokers, leads to subtle myelin alterations in the sciatic nerve of male rat offspring. The rapid growth spurt in pup body weight was related to the period of maximal increase in myelin sheath thickness in both control and CO-exposed animals. A significant reduction in myelin sheath thickness of sciatic nerve fibers, paralleled by changes in the frequency distribution, occurred in both 40- and 90-day-old rats exposed in utero to CO (75 and 150 ppm). Myelin deficit observed in 75 and 150 ppm CO-exposed animals showed up only after the major spurt in myelination but not early during development. The subtle myelin alterations observed in CO-exposed offspring were not accompanied by changes in developmental pattern of axon diameters and did not result in a gross impairment of motor activity. These results suggest that the myelination process is selectively targeted by a prenatal exposure model simulating the CO exposure observed in human cigarette smokers.

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

    PubMed Central

    Mullen, Brian R.; Khialeeva, Elvira; Hoffman, Daniel B.; Ghiani, Cristina A.; Carpenter, Ellen M.

    2013-01-01

    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. PMID:23298182

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

    PubMed

    Mullen, Brian R; Khialeeva, Elvira; Hoffman, Daniel B; Ghiani, Cristina A; Carpenter, Ellen M

    2012-02-18

    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.

  11. Alterations induced by chronic lead exposure on the cells of circadian pacemaker of developing rats

    PubMed Central

    Rojas-Castañeda, Julio César; Vigueras-Villaseñor, Rosa María; Rojas, Patricia; Chávez-Saldaña, Margarita; Pérez, Oscar Gutiérrez; Montes, Sergio; Ríos, Camilo

    2011-01-01

    Lead (Pb) exposure alters the temporal organization of several physiological and behavioural processes in which the suprachiasmatic nucleus (SCN) of the hypothalamus plays a fundamental role. In this study, we evaluated the effects of chronic early Pb exposure (CePbe) on the morphology, cellular density and relative optical density (OD) in the cells of the SCN of male rats. Female Wistar rats were exposed during gestation and lactation to a Pb solution containing 320 ppm of Pb acetate through drinking water. After weaning, the pups were maintained with the same drinking water until sacrificed at 90 days of age. Pb levels in the blood, hypothalamus, hippocampus and prefrontal cortex were significantly increased in the experimental group. Chronic early Pb exposure induced a significant increase in the minor and major axes and somatic area of vasoactive intestinal polypeptide (VIP)- and vasopressin (VP)-immunoreactive neurons. The density of VIP-, VP- and glial fibrillary acidic protein (GFAP)-immunoreactive cells showed a significant decrease in the experimental group. OD analysis showed a significant increase in VIP neurons of the experimental group. The results showed that CePbe induced alterations in the cells of the SCN, as evidenced by modifications in soma morphology, cellular density and OD in circadian pacemaker cells. These findings provide a morphological and cellular basis for deficits in circadian rhythms documented in Pb-exposed animals. PMID:21324006

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

    SciTech Connect

    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 by

  13. Removal of methyl parathion in water, by Dugesia dorotocephala.

    PubMed

    Amaya-Chávez, A; López-López, E; Galar-Martínez, M; Gómez-Oliván, L M; García-Fabila, M M

    2009-09-01

    The aim of this study was to determine the efficiency of Dugesia dorotocephala on Methyl parathion removal. An initial concentration of 1.25 microg mL(-1) of MeP was used to evaluate the removal capacity of planarian. A first-order removal kinetics was obtained with a disappearance rate constant (k(r)) of 0.49 days(-1) and 69% efficiency on contaminant removal. This is significantly different (p < 0.5) from the degradation occurring in control systems, leading us to conclude that D. dorotocephala effectively removes MeP from contaminated water.

  14. Epigenetic Alterations May Regulate Temporary Reversal of CD4+ T Cell Activation Caused by Trichloroethylene Exposure

    PubMed Central

    Gilbert, Kathleen M.; Nelson, Ashley R.; Cooney, Craig A.; Reisfeld, Brad; Blossom, Sarah J.

    2012-01-01

    Previous studies have shown that short-term (4 weeks) or chronic (32 weeks) exposure to trichloroethylene (TCE) in drinking water of female MRL+/+ mice generated CD4+ T cells that secreted increased levels of interferon (IFN)-γ and expressed an activated (CD44hiCD62Llo) phenotype. In contrast, the current study of subchronic TCE exposure showed that midway in the disease process both of these parameters of CD4+ T cell activation were reversed. This phase of the disease process may represent an attempt by the body to counteract the inflammatory effects of TCE. The decrease in CD4+ T cell production of IFN-γ following subchronic TCE exposure could not be attributed to skewing toward a Th2 or Th17 phenotype or to an increase in Treg cells. Instead, the suppression corresponded to alterations in markers used to assess DNA methylation, namely increased expression of retrotransposons Iap (intracisternal A particle) and Muerv (murine endogenous retrovirus). Also observed was an increase in the expression of Dnmt1 (DNA methyltransferase-1) and decreased expression of several genes known to be downregulated by DNA methylation, namely Ifng, Il2, and Cdkn1a. CD4+ T cells from a second study in which MRL+/+ mice were treated for 17 weeks with TCE showed a similar increase in Iap and decrease in Cdkn1a. In addition, DNA collected from the CD4+ T cells in the second study showed TCE-decreased global DNA methylation. Thus, these results described the biphasic nature of TCE-induced alterations in CD4+ T cell function and suggested that these changes represented potentially reversible alterations in epigenetic processes. PMID:22407948

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

    PubMed

    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.

  16. Secretion of interferon gamma from human immune cells is altered by exposure to tributyltin and dibutyltin.

    PubMed

    Lawrence, Shanieek; Reid, Jacqueline; Whalen, Margaret

    2015-05-01

    Tributyltin (TBT) and dibutyltin (DBT) are widespread environmental contaminants found in food, beverages, and human blood samples. Both of these butyltins (BTs) interfere with the ability of human natural killer (NK) cells to lyse target cells and alter secretion of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) from human immune cells in vitro. The capacity of BTs to interfere with secretion of other pro-inflammatory cytokines has not been examined. Interferon gamma (IFNγ) is a modulator of adaptive and innate immune responses, playing an important role in overall immune competence. This study shows that both TBT and DBT alter secretion of IFNγ from human immune cells. Peripheral blood cell preparations that were increasingly reconstituted were used to determine if exposures to either TBT or DBT affected IFNγ secretion and how the makeup of the cell preparation influenced that effect. IFNγ secretion was examined after 24 h, 48 h, and 6 day exposures to TBT (200 - 2.5 nM) and DBT (5 - 0.05 µM) in highly enriched human NK cells, a monocyte-depleted preparation of PBMCs, and monocyte-containing PBMCs. Both BTs altered IFNγ secretion from immune cells at most of the conditions tested (either increasing or decreasing secretion). However, there was significant variability among donors as to the concentrations and time points that showed changes as well as the baseline secretion of IFNγ. The majority of donors showed an increase in IFNγ secretion in response to at least one concentration of TBT or DBT at a minimum of one length of exposure.

  17. Acetylcholinesterase activity and antioxidant capacity of zebrafish brain is altered by heavy metal exposure.

    PubMed

    Richetti, S K; Rosemberg, D B; Ventura-Lima, J; Monserrat, J M; Bogo, M R; Bonan, C D

    2011-01-01

    Pollution is a world problem with immeasurable consequences. Heavy metal compounds are frequently found as components of anthropogenic pollution. Here we evaluated the effects of the treatment with cadmium acetate, lead acetate, mercury chloride, and zinc chloride in acetylcholinesterase activity and gene expression pattern, as well as the effects of these treatments in antioxidant competence in the brain of an aquatic and well-established organism for toxicological analysis, zebrafish (Danio rerio, Cyprinidae). Mercury chloride and lead acetate promoted a significant decrease in acetylcholinesterase activity whereas they did not alter the gene expression pattern. In addition, the antioxidant competence was decreased after exposure to mercury chloride. The data presented here allowed us to hypothesize a signal transmission impairment, through alterations in cholinergic transmission, and also in the antioxidant competence of zebrafish brain tissue as some of the several effects elicited by these pollutants. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Ancestral vinclozolin exposure alters the epigenetic transgenerational inheritance of sperm small noncoding RNAs

    PubMed Central

    Schuster, Andrew; Skinner, Michael K.; Yan, Wei

    2016-01-01

    Exposure to the agricultural fungicide vinclozolin during gestation promotes a higher incidence of various diseases in the subsequent unexposed F3 and F4 generations. This phenomenon is termed epigenetic transgenerational inheritance and has been shown to in part involve alterations in DNA methylation, but the role of other epigenetic mechanisms remains unknown. The current study investigated the alterations in small noncoding RNA (sncRNA) in the sperm from F3 generation control and vinclozolin lineage rats. Over 200 differentially expressed sncRNAs were identified and the tRNA-derived sncRNAs, namely 5′ halves of mature tRNAs (5′ halves), displayed the most dramatic changes. Gene targets of the altered miRNAs and tRNA 5′ halves revealed associations between the altered sncRNAs and differentially DNA methylated regions. Dysregulated sncRNAs appear to correlate with mRNA profiles associated with the previously observed vinclozolin-induced disease phenotypes. Data suggest potential connections between sperm-borne RNAs and the vinclozolin-induced epigenetic transgenerational inheritance phenomenon. PMID:27390623

  19. Ancestral vinclozolin exposure alters the epigenetic transgenerational inheritance of sperm small noncoding RNAs.

    PubMed

    Schuster, Andrew; Skinner, Michael K; Yan, Wei

    Exposure to the agricultural fungicide vinclozolin during gestation promotes a higher incidence of various diseases in the subsequent unexposed F3 and F4 generations. This phenomenon is termed epigenetic transgenerational inheritance and has been shown to in part involve alterations in DNA methylation, but the role of other epigenetic mechanisms remains unknown. The current study investigated the alterations in small noncoding RNA (sncRNA) in the sperm from F3 generation control and vinclozolin lineage rats. Over 200 differentially expressed sncRNAs were identified and the tRNA-derived sncRNAs, namely 5' halves of mature tRNAs (5' halves), displayed the most dramatic changes. Gene targets of the altered miRNAs and tRNA 5' halves revealed associations between the altered sncRNAs and differentially DNA methylated regions. Dysregulated sncRNAs appear to correlate with mRNA profiles associated with the previously observed vinclozolin-induced disease phenotypes. Data suggest potential connections between sperm-borne RNAs and the vinclozolin-induced epigenetic transgenerational inheritance phenomenon.

  20. Adolescent Alcohol Exposure Alters GABAA Receptor Subunit Expression in Adult Hippocampus

    PubMed Central

    Centanni, Samuel W.; Teppen, Tara; Risher, Mary-Louise; Fleming, Rebekah L.; Moss, Julia L.; Acheson, Shawn K.; Mulholland, Patrick J.; Pandey, Subhash C.; Chandler, L. Judson; Swartzwelder, H. Scott

    2014-01-01

    Background The long-term consequences of adolescent alcohol abuse that persist into adulthood are poorly understood and have not been widely investigated. We have shown that intermittent exposure to alcohol during adolescence decreased the amplitude of GABAA receptor-mediated tonic currents in hippocampal dentate granule cells in adulthood. The aim of the present study was to investigate the enduring effects of chronic intermittent alcohol exposure during adolescence or adulthood on the expression of hippocampal GABAA receptors (GABAARs). Methods We used a previously characterized tissue fractionation method to isolate detergent resistant membranes and soluble fractions, followed by western blots to measure GABAAR protein expression. We also measured mRNA levels of GABAAR subunits using quantitative real-time PCR. Results Although the protein levels of α1-, α4- and δ-GABAAR subunits remained stable between postnatal day (PD) 30 (early adolescence) and PD71 (adulthood), the α5-GABAAR subunit was reduced across that period. In rats that were subjected to adolescent intermittent ethanol (AIE) exposure between PD30–46, there was a significant reduction in the protein levels of the δ-GABAAR, in the absence of any changes in mRNA levels, at 48 hours and 26 days after the last ethanol exposure. Protein levels of the α4-GABAAR subunit were significantly reduced, but mRNA levels were increased, 26 days (but not 48 hours) after the last AIE exposure. Protein levels of α5-GABAAR were not changed by AIE, but mRNA levels were reduced at 48hrs but normalized 26 days after AIE. In contrast to the effects of AIE, chronic intermittent exposure to ethanol during adulthood (CIE) had no effect on expression of any of the GABAAR subunits examined. Conclusions AIE produced both short- and long-term alterations of GABAAR subunits mRNA and protein expression in the hippocampus, whereas CIE produced no long lasting effects on those measures. The observed reduction of protein

  1. Environmental pollutants parathion, paraquat and bisphenol A show distinct effects towards nuclear receptors-mediated induction of xenobiotics-metabolizing cytochromes P450 in human hepatocytes.

    PubMed

    Vrzal, Radim; Zenata, Ondrej; Doricakova, Aneta; Dvorak, Zdenek

    2015-10-01

    Environmental pollutants parathion, bisphenol A and paraquat were not systematically studied towards the effects on the expression of phase I xenobiotics-metabolizing cytochromes P450 (CYPs). We monitored their effects on the expression of selected CYPs in primary cultures of human hepatocytes. Moreover, we investigated their effects on the receptors regulating these CYPs, particularly arylhydrocarbon receptor (AhR), pregnane X receptor (PXR) and glucocorticoid receptor (GR) by gene reporter assays. We found that parathion and bisphenol A are the activators of AhR. Moreover, they are the inducers of CYP1A1 mRNA in hepatoma cells HepG2 as well as in human hepatocytes by AhR-dependent mechanism via formation of AhR-DNA-binding complex, as revealed by gel shift assay. All three compounds possessed anti-glucocorticoid action as revealed by GR-dependent gene reporter assay and a decline in tyrosine aminotransferase (TAT) gene expression in human hepatocytes. Moreover, parathion and bisphenol A are the activators of PXR and inducers of CYP3A4 mRNA and protein in the primary cultures of human hepatocytes. In conclusion, the studied compounds displayed distinct activities towards nuclear receptors involved in many biological processes and these findings may help us to better understand their adverse actions in pathological states followed after their exposure. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Neonatal exposure to bisphenol A or diethylstilbestrol alters the ovarian follicular dynamics in the lamb.

    PubMed

    Rivera, Oscar E; Varayoud, Jorgelina; Rodríguez, Horacio A; Muñoz-de-Toro, Mónica; Luque, Enrique H

    2011-11-01

    We hypothesized that neonatal xenoestrogen exposure affects the ovarian follicular dynamics in lambs. Female lambs were exposed from postnatal day (PND) 1-14 to low doses of diethylstilbestrol (DES) or bisphenol A (BPA). At PND 30, the follicular dynamics and ovarian biomarkers (ERα, ERβ, AR, Ki67, p27) were evaluated. Lambs exposed to DES or BPA showed a decline in the stock of primordial follicles with stimulation of follicular development. BPA reduced ovarian weight and increased the number of multioocyte follicles. BPA promoted proliferation of granulosa/theca cells in antral follicles, and increased both the number of antral atretic follicles and p27 expression. Neonatal exposure to BPA or DES reduced the primordial follicle pool by stimulating their initial recruitment and subsequent follicle development until antral stage. In prepubertal lambs, the accelerated folliculogenesis resulted in increased incidence of atretic follicles. These alterations may affect the ovarian function in the adult. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Alterations in cytochrome P-450 levels in adult rats following neonatal exposure to xenobiotics

    SciTech Connect

    Zangar, R.C. Pacific Northwest Laboratories, Richland, WA ); Springer, D.L. ); Buhler, D.R. )

    1993-01-01

    Neonatal exposure to certain xenobiotics has been shown to alter hepatic metabolism in adult rats in a manner that indicates long-term changes in enzyme regulation. Previously, the authors have observed changes in adult testosterone metabolism and in cytochrome P-450 (P-450) mRNA levels in animals neonatally exposed to phenobarbital (PB) or diethylstilbestrol (DES). In order to test for other enzyme alterations, they used Western blot procedures for specific P-450s to analyze hepatic microsomes from adult rats (24 wk old) that had been exposed neonatally to DES, PB, 7,12-dimethylbenz[a]anthracene (DMBA), or pregnenolone 16[alpha]-carbonitrile (PCN). The most striking effects were observed in the DES-treated males: P-4502C6 and an immunologically similar protein were increased 60 and 90%, respectively, relative to control values, but P-4503A2 was decreased by 44%. No changes were observed in the DES-treated males in levels of P-4502E1, P-4502B, or the male-specific P-4502C13. Adult males neonatally treated with PB had 150% increase in levels of anti-P4502B-reactive protein without significant changes in the other enzymes. The DES- and DMBA-treated females had increased levels of the female-specific P-4502C12 of 38 and 48%, respectively, but no other observed alterations. The results confirm that neonatal exposure to DES or PB can cause alterations in adult hepatic cytochrome P-450 levels but show that these chemicals act on different enzymes. Neonatal DMBA resulted in changes in adult females similar to those produced by the synthetic estrogen DES, but did so at about two-thirds lower dose. 37 refs., 5 figs.

  4. Chronic ultraviolet exposure-induced p53 gene alterations in sencar mouse skin carcinogenesis model

    SciTech Connect

    Tong, Ying; Smith, M.A.; Tucker, S.B.

    1997-06-27

    Alterations of the tumor suppressor gene p53 have been found in ultraviolet radiation (UVR) related human skin cancers and in UVR-induced murine skin tumors. However, links between p53 gene alterations and the stages of carcinogenesis induced by UVR have not been clearly defined. We established a chronic UVR exposure-induced Sencar mouse skin carcinogenesis model to determine the frequency of p53 gene alterations in different stages of carcinogenesis, including UV-exposed skin, papillomas, squamous-cell carcinomas (SCCs), and malignant spindle-cell tumors (SCTs). A high incidence of SCCs and SCTs were found in this model. Positive p53 nuclear staining was found in 10137 (27%) of SCCs and 12124 (50%) of SCTs, but was not detected in normal skin or papillomas. DNA was isolated from 40 paraffin-embedded normal skin, UV-exposed skin, and tumor sections. The p53 gene (exons 5 and 6) was amplified from the sections by using nested polymerase chain reaction (PCR). Subsequent single-strand conformation polymorphism (SSCP) assay and sequencing analysis revealed one point mutation in exon 6 (coden 193, C {r_arrow} A transition) from a UV-exposed skin sample, and seven point mutations in exon 5 (codens 146, 158, 150, 165, and 161, three C {r_arrow} T, two C {r_arrow} A, one C {r_arrow} G, and one A {r_arrow} T transition, respectively) from four SCTs, two SCCs and one UV-exposed skin sample. These experimental results demonstrate that alterations in the p53 gene are frequent events in chronic UV exposure-induced SCCs and later stage SCTs in Sencar mouse skin. 40 refs., 5 figs., 1 tab.

  5. Early postnatal diazepam exposure alters sex differences in the rat brain.

    PubMed

    Segovia, S; Pérez-Laso, C; Rodríguez-Zafra, M; Calés, J M; Del Abril, A; De Blas, M R; Collado, P; Valencia, A; Guillamón, A

    1991-06-01

    The volume and neuron number of the sexually dimorphic accessory olfactory bulb and locus coeruleus are altered by early postnatal exposure (from the day of birth to postnatal day 16) to diazepam. After diazepam treatment, both volume and neuron number were decreased in the male accessory olfactory bulb and in the female locus coeruleus. These results indicate that early postnatal diazepam administration can bear gender-dependent teratogenic effects upon sexually dimorphic nuclei and suggest that endogenous benzodiazepines may be involved in the sexual differentiation of the brain.

  6. Common behaviors alterations after extremely low-frequency electromagnetic field exposure in rat animal model.

    PubMed

    Mahdavi, Seyed Mohammad; Sahraei, Hedayat; Rezaei-Tavirani, Mostafa; Najafi Abedi, Akram

    2016-01-01

    Naturally, the presence of electromagnetic waves in our living environment affects all components of organisms, particularly humans and animals, as the large part of their body consists of water. In the present study, we tried to investigate the relation between exposure to the extremely low-frequency electromagnetic field (ELF-EMF) and common behaviors such as body weight, food and water intake, anorexia (poor appetite), plasma glucose concentration, movement, rearing and sniffing in rats. For this purpose, rats were exposed to 40  Hz ELF-EMF once a day for 21 days, then at days 1, 3, 7, 14 and 21 after exposure, any changes in the above-mentioned items were assessed in the exposed rats and compared to the non-exposed group as control. Body weight of irradiated rats significantly increased only a week after exposure and decreased after that. No significant change was observed in food and water intake of irradiated rats compared to the control, and the anorexia parameter in the group exposed to ELF-EMF was significantly decreased at one and two weeks after irradiation. A week after exposure, the level of glucose was significantly increased but at other days these changes were not significant. Movements, rearing and sniffing of rats at day 1 after exposure were significantly decreased and other days these changes did not follow any particular pattern. However, the result of this study demonstrated that exposure to ELF-EMF can alter the normal condition of animals and may represent a harmful impact on behavior.

  7. Perinatal bisphenol A exposure promotes dose-dependent alterations of the mouse methylome

    PubMed Central

    2014-01-01

    Background Environmental factors during perinatal development may influence developmental plasticity and disease susceptibility via alterations to the epigenome. Developmental exposure to the endocrine active compound, bisphenol A (BPA), has previously been associated with altered methylation at candidate gene loci. Here, we undertake the first genome-wide characterization of DNA methylation profiles in the liver of murine offspring exposed perinatally to multiple doses of BPA through the maternal diet. Results Using a tiered focusing approach, our strategy proceeds from unbiased broad DNA methylation analysis using methylation-based next generation sequencing technology to in-depth quantitative site-specific CpG methylation determination using the Sequenom EpiTYPER MassARRAY platform to profile liver DNA methylation patterns in offspring maternally exposed to BPA during gestation and lactation to doses ranging from 0 BPA/kg (Ctr), 50 μg BPA/kg (UG), or 50 mg BPA/kg (MG) diet (N = 4 per group). Genome-wide analyses indicate non-monotonic effects of DNA methylation patterns following perinatal exposure to BPA, corroborating previous studies using multiple doses of BPA with non-monotonic outcomes. We observed enrichment of regions of altered methylation (RAMs) within CpG island (CGI) shores, but little evidence of RAM enrichment in CGIs. An analysis of promoter regions identified several hundred novel BPA-associated methylation events, and methylation alterations in the Myh7b and Slc22a12 gene promoters were validated. Using the Comparative Toxicogenomics Database, a number of candidate genes that have previously been associated with BPA-related gene expression changes were identified, and gene set enrichment testing identified epigenetically dysregulated pathways involved in metabolism and stimulus response. Conclusions In this study, non-monotonic dose dependent alterations in DNA methylation among BPA-exposed mouse liver samples and their relevant pathways

  8. Low-dose, Chronic Exposure to Silver Nanoparticles Causes Mild Mitochondrial Alterations in the Liver of Sprague-Dawley Rat

    DTIC Science & Technology

    2014-05-10

    AFRL-AFOSR-UK-TR-2014-0032 Low-dose, chronic exposure to silver nanoparticles causes mild mitochondrial alterations in the liver...TITLE AND SUBTITLE Low-dose, chronic exposure to silver nanoparticles causes mild mitochondrial alterations in the liver of Sprague-Dawley rat 5a...Approved for public release; distribution is unlimited. 13. SUPPLEMENTARY NOTES 14. ABSTRACT Nanoparticles (NPs) are, by definition

  9. Nicotine exposure in adolescence alters the response of serotonin systems to nicotine administered subsequently in adulthood.

    PubMed

    Slotkin, Theodore A; Seidler, Frederic J

    2009-01-01

    Developmental nicotine exposure produces lasting changes in serotonin (5-HT) function. We gave nicotine to adolescent rats (postnatal days, PD, 30-47), simulating plasma levels in smokers, and then examined the subsequent effects of nicotine given again in young adulthood (PD 90-107), focusing on 5-HT(1A) and 5-HT(2) receptors and the 5-HT transporter during nicotine treatment (PD 105) and withdrawal (PD 110, 120, 130), and long-term changes (PD 180). Adolescent nicotine exposure by itself evoked long-term elevations in cerebrocortical binding parameters in males that emerged in young adulthood. Nicotine given in adulthood produced transient elevations in 5-HT receptor expression in both males and females during withdrawal, and persistent upregulation in the male cerebral cortex. In contrast, females showed decrements in cerebrocortical 5-HT receptors by PD 180. Adolescent nicotine exposure altered the responses to nicotine given in adulthood, sensitizing the initial effects and changing both the withdrawal response and long-term actions. Our results thus provide mechanistic evidence that nicotine exposure, during the period in which nearly all smokers begin to use tobacco, reprograms the future response of 5-HT systems to nicotine.

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

    PubMed

    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. © 2016 The Author(s).

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

    PubMed

    Dietrich, Grzegorz J; Dietrich, Mariola; Kowalski, R K; Dobosz, Stefan; Karol, Halina; Demianowicz, Wiesław; Glogowski, Jan

    2010-05-10

    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 4h of exposure. Although mercury ions affected sperm motility parameters immediately after dilution with milt as well as at 4h of exposure, no differences in sperm motility parameters were found between intact and mercury-treated milt after 24h 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.

  12. MicroRNA expression profiling altered by variant dosage of radiation exposure.

    PubMed

    Lee, Kuei-Fang; Chen, Yi-Cheng; Hsu, Paul Wei-Che; Liu, Ingrid Y; Wu, Lawrence Shih-Hsin

    2014-01-01

    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.

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

    PubMed Central

    Lee, Kuei-Fang; Hsu, Paul Wei-Che; Liu, Ingrid Y.; Wu, Lawrence Shih-Hsin

    2014-01-01

    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. PMID:25313363

  14. Developmental and Lactational Exposure to Dieldrin Alters Mammary Tumorigenesis in Her2/neu Transgenic Mice

    PubMed Central

    Cameron, Heather L.; Foster, Warren G.

    2009-01-01

    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 µg/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. PMID:19173004

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

    PubMed

    Cameron, Heather L; Foster, Warren G

    2009-01-01

    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.

  16. Short-term cigarette smoke exposure leads to metabolic alterations in lung alveolar cells.

    PubMed

    Agarwal, Amit R; Yin, Fei; Cadenas, Enrique

    2014-08-01

    Cigarette smoke (CS)-induced alveolar destruction and energy metabolism changes are known contributors to the pathophysiology of chronic obstructive pulmonary disease (COPD). This study examines the effect of CS exposure on metabolism in alveolar type II cells. Male A/J mice (8 wk old) were exposed to CS generated from a smoking machine for 4 or 8 weeks, and a recovery group was exposed to CS for 8 weeks and allowed to recover for 2 weeks. Alveolar type II cells were isolated from air- or CS- exposed mice. Acute CS exposure led to a reversible airspace enlargement in A/J mice as measured by the increase in mean linear intercept, indicative of alveolar destruction. The effect of CS exposure on cellular respiration was studied using the XF Extracellular Flux Analyzer. A decrease in respiration while metabolizing glucose was observed in the CS-exposed group, indicating altered glycolysis that was compensated by an increase in palmitate utilization; palmitate utilization was accompanied by an increase in the expression of CD36 and carnitine-palmitoyl transferase 1 in type II alveolar cells for the transport of palmitate into the cells and into mitochondria, respectively. The increase in palmitate use for energy production likely affects the surfactant biosynthesis pathway, as evidenced by the decrease in phosphatidylcholine levels and the increase in phospholipase A2 activity after CS exposure. These findings help our understanding of the mechanism underlying the surfactant deficiency observed in smokers and provide a target to delay the onset of COPD.

  17. Biochemical alterations induced by oral subchronic exposure to fipronil, fluoride and their combination in buffalo calves.

    PubMed

    Gill, Kamalpreet Kaur; Dumka, Vinod Kumar

    2013-11-01

    The effects of various pesticides and minerals on biochemical parameters have been explored in different species, but hardly any data exist regarding the combined toxicological effect of pesticides and minerals on these parameters in animals. The present study investigated the effects of fipronil and fluoride co-exposure on biochemical parameters in buffalo calves. Twenty-four healthy male buffalo calves divided into four groups were treated for 98 consecutive days. Group I, receiving no treatment served as the control. Animals of groups II and III were orally administered with fipronil @ 0.5mg/kg/day and sodium fluoride (NaF) @ 6.67 mg/kg/day, respectively, for 98 days. An additional group IV was co-administered fipronil and NaF at the same dosages as groups II and III. Administration of fipronil alone produced mild toxic signs, significant elevation in plasma proteins, blood glucose, blood urea nitrogen (BUN) and significant decline in the plasma cholesterol levels. NaF exposure produced toxic signs specifically of muscle weakness and brown and black discoloration of teeth. Significant elevation was seen in whole blood cholinesterase, BUN and creatinine levels. However, it produced significant decline in blood glucose, cholesterol and plasma protein levels. Combined exposure to fipronil and sodium fluoride produced toxic signs with greater intensity while biochemical alterations produced were similar to those that were produced by their individual exposures.

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

    PubMed Central

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

    2016-01-01

    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

  19. Adaptations of the vestibular system to short and long-term exposures to altered gravity

    NASA Astrophysics Data System (ADS)

    Bruce, L. L.

    2003-10-01

    Long-term space flight creates unique environmental conditions to which the vestibular system must adapt for optimal survival of a given organism. The development and maintenance of vestibular connections are controlled by environmental gravitational stimulation as well as genetically controlled molecular interactions. This paper describes the effects of hypergravity on axonal growth and dendritic morphology, respectively. Two aspects of this vestibular adaptation are examined: (1) How does long-term exposure to hypergravity affect the development of vestibular axons? (2) How does short-term exposure to extremely rapid changes in gravity, such as those that occur during shuttle launch and landing, affect dendrites of the vestibulocerebellar system? To study the effects of longterm exposures to altered gravity, embryonic rats that developed in hypergravity were compared to microgravity-exposed and control rats. Examination of the vestibular projections from epithelia devoted to linear and angular acceleration revealed that the terminal fields segregate differently in rat embryos that gestated in each of the gravitational environments.To study the effects of short-term exposures to altered gravity, mice were exposed briefly to strong vestibular stimuli and the vestibulocerebellum was examined for any resulting morphological changes. My data show that these stimuli cause intense vestibular excitation of cerebellar Purkinje cells, which induce up-regulation of clathrin-mediated endocytosis and other morphological changes that are comparable to those seen in long-term depression. This system provides a basis for studying how the vestibular environment can modify cerebellar function, allowing animals to adapt to new environments.

  20. Exposure to nicotine during periadolescence or early adulthood alters aversive and physiological effects induced by ethanol.

    PubMed

    Rinker, Jennifer A; Hutchison, Mary Anne; Chen, Scott A; Thorsell, Annika; Heilig, Markus; Riley, Anthony L

    2011-07-01

    The majority of smokers begin their habit during adolescence, which often precedes experimentation with alcohol. Interestingly, very little preclinical work has been done examining how exposure to nicotine during periadolescence impacts the affective properties of alcohol in adulthood. Understanding how periadolescent nicotine exposure influences the aversive effects of alcohol might help to explain why it becomes more acceptable to this preexposed population. Thus, Experiment 1 exposed male Sprague Dawley rats to either saline or nicotine (0.4mg/kg, IP) from postnatal days 34 to 43 (periadolescence) and then examined changes in the aversive effects of alcohol (0, 0.56, 1.0 and 1.8g/kg, IP) in adulthood using the conditioned taste aversion (CTA) design. Changes in blood alcohol concentration (BAC) as well as alcohol-induced hypothermia and locomotor suppression were also assessed. To determine if changes seen were specific to nicotine exposure during periadolescence, the procedures were replicated in adults (Experiment 2). Preexposure to nicotine during periadolescence attenuated the acquisition of the alcohol-induced CTAs (at 1.0g/kg) and the hypothermic effects of alcohol (1.0g/kg). Adult nicotine preexposure produced similar attenuation in alcohol's aversive (at 1.8g/kg) and hypothermic (1.8g/kg) effects. Neither adolescent nor adult nicotine preexposure altered BACs or alcohol-induced locomotor suppression. These results suggest that nicotine may alter the aversive and physiological effects of alcohol, regardless of the age at which exposure occurs, possibly increasing its overall reinforcing value and making it more likely to be consumed.

  1. Bisphenol A Exposure Alters Developmental Gene Expression in the Fetal Rhesus Macaque Uterus

    PubMed Central

    Calhoun, Kathryn C.; Padilla-Banks, Elizabeth; Jefferson, Wendy N.; Liu, Liwen; Gerrish, Kevin E.; Young, Steven L.; Wood, Charles E.; Hunt, Patricia A.; VandeVoort, Catherine A.; Williams, Carmen J.

    2014-01-01

    Bisphenol A (BPA) exposure results in numerous developmental and functional abnormalities in reproductive organs in rodent models, but limited data are available regarding BPA effects in the primate uterus. To determine if maternal oral BPA exposure affects fetal uterine development in a non-human primate model, pregnant rhesus macaques carrying female fetuses were exposed orally to 400 µg/kg BPA or vehicle control daily from gestation day (GD) 50–100 or GD100–165. Fetal uteri were collected at the completion of treatment (GD100 or GD165); tissue histology, cell proliferation, and expression of estrogen receptor alpha (ERα) and progesterone receptor (PR) were compared to that of controls. Gene expression analysis was conducted using rhesus macaque microarrays. There were no significant differences in histology or in the percentage of cells expressing the proliferation marker Ki-67, ERα, or PR in BPA-exposed uteri compared to controls at GD100 or GD165. Minimal differences in gene expression were observed between BPA-exposed and control GD100 uteri. However, at GD165, BPA-exposed uteri had significant differences in gene expression compared to controls. Several of the altered genes, including HOXA13, WNT4, and WNT5A, are critical for reproductive organ development and/or adult function. We conclude that second or third trimester BPA exposure does not significantly affect fetal uterus development based on morphological, proliferation, and steroid hormone receptor assessments. However, differences in expression of key developmental genes after third trimester exposure suggest that BPA could alter transcriptional signals influencing uterine function later in life. PMID:24465770

  2. Exposure to Nicotine During Periadolescence or Early Adulthood Alters Aversive and Physiological Effects Induced by Ethanol

    PubMed Central

    Rinker, Jennifer A.; Hutchison, Mary Anne; Chen, Scott A.; Thorsell, Annika; Heilig, Markus; Riley, Anthony L.

    2011-01-01

    The majority of smokers begin their habit during adolescence, which often precedes experimentation with alcohol. Interestingly, very little preclinical work has been done examining how exposure to nicotine during periadolescence impacts the affective properties of alcohol in adulthood. Understanding how periadolescent nicotine exposure influences the aversive effects of alcohol might help to explain why it becomes more acceptable to this preexposed population. Thus, Experiment 1 exposed male Sprague Dawley rats to either saline or nicotine (0.4 mg/kg, IP) from postnatal day 34 to 43 (periadolescence) and then examined changes in the aversive effects of alcohol (0, 0.56, 1.0 and 1.8 g/kg, IP) in adulthood using the conditioned taste aversion (CTA) design. Changes in blood alcohol concentration (BAC) as well as alcohol-induced hypothermia and locomotor suppression were also assessed. To determine if changes seen were specific to nicotine exposure during periadolescence, the procedures were replicated in adults (Experiment 2). Preexposure to nicotine during periadolescence attenuated the acquisition of the alcohol-induced CTAs (at 1.0 g/kg) and the hypothermic effects of alcohol (1.0 g/kg). Adult nicotine preexposure produced similar attenuation in alcohol's aversive (at 1.8 g/kg) and hypothermic (1.8 g/kg) effects. Neither adolescent nor adult nicotine preexposure altered BACs or alcohol-induced locomotor suppression. These results suggest that nicotine can alter the aversive and physiological effects of alcohol, regardless of the age at which exposure occurs, possibly increasing its overall reinforcing value and making it more likely to be consumed. PMID:21420998

  3. Moderate prenatal alcohol exposure alters behavior and neuroglial parameters in adolescent rats.

    PubMed

    Brolese, Giovana; Lunardi, Paula; Broetto, Núbia; Engelke, Douglas S; Lírio, Franciane; Batassini, Cristiane; Tramontina, Ana Carolina; Gonçalves, Carlos-Alberto

    2014-08-01

    Alcohol consumption by women during gestation has become increasingly common. Although it is widely accepted that exposure to high doses of ethanol has long-lasting detrimental effects on brain development, the case for moderate doses is underappreciated, and benchmark studies have demonstrated structural and behavioral defects associated with moderate prenatal alcohol exposure in humans and animal models. This study aimed to investigate the influence of in utero exposure to moderate levels of ethanol throughout pregnancy on learning/memory, anxiety parameters and neuroglial parameters in adolescent offspring. Female rats were exposed to an experimental protocol throughout gestation up to weaning. After mating, the dams were divided into three groups and treated with only water (control), non-alcoholic beer (vehicle) or 10% (vv) beer solution (moderate prenatal alcohol exposure - MPAE). Adolescent male offspring were subjected to the plus-maze discriminative avoidance task to evaluate learning/memory and anxiety-like behavior. Hippocampi were dissected and slices were obtained for immunoquantification of GFAP, NeuN, S100B and the NMDA receptor. The MPAE group clearly presented anxiolytic-like behavior, even though they had learned how to avoid the aversive arm. S100B protein was increased in the cerebrospinal fluid (CSF) in the group treated with alcohol, and alterations in GFAP expression were also shown. This study indicates that moderate ethanol doses administered during pregnancy could induce anxiolytic-like effects, suggesting an increase in risk-taking behavior in adolescent male offspring. Furthermore, the data show the possibility that glial cells are involved in the altered behavior present after prenatal ethanol treatment.

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

    SciTech Connect

    Meyer, Armando; Seidler, Frederic J.; Aldridge, Justin E.; Slotkin, Theodore A. . E-mail: t.slotkin@duke.edu

    2005-03-01

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

  5. In utero tobacco smoke exposure alters pulmonary responses of newborn rats to ozone.

    PubMed

    Han, Sung Gu; Bhoopalan, Vanitha; Akinbiyi, Tolulola; Gairola, C Gary; Bhalla, Deepak K

    2011-01-01

    Prenatal tobacco smoke (TS) exposure has been implicated in various adverse health outcomes in the offspring, including poor development of lung and immune system, which in turn can alter the response of neonates to environmental challenges. This study was performed to determine whether in utero exposure to TS influences the pulmonary response of newborn rat pups to ozone (O₃). Timed pregnant Sprague-Dawley (SD) rats were exposed to TS or air for 3 h/d from gestation d 7 through 21. The pulmonary response of pups was assessed following a single 3-h exposure to air or 0.6 ppm O₃ on d 13 after birth. In all, 4 exposure groups were evaluated: (1) Air/Air (in utero air and postnatal air), (2) Air/O₃ (in utero air and postnatal O₃), (3) TS/Air (in utero TS and postnatal air), and (4) TS/O₃ (in utero TS and postnatal O₃). Bronchoalveolar lavage (BAL) was performed, and BAL cells and fluid were analyzed. Data revealed a significant increase in polymorphonuclear leukocytes (PMN) and total BALF protein in the Air/O₃ group compared to the Air/Air control, reflecting the inflammatory and cytotoxic effects of O₃. However, in utero exposure to TS attenuated PMN infiltration into the air spaces for recovery in the BAL of TS/O₃ pups. Lung tissue myeloperoxidase activity significantly increased only in the TS/O₃ group but not in Air/O₃ pups, thus suggesting that PMN are sequestered in the lung tissue and that the in utero TS likely inhibits O₃-mediated influx of PMN into the air spaces. Lung tissue analyses further showed a significant rise in manganese superoxide dismutase (SOD) protein and a decrease in extracellular SOD protein in the Air/O₃ group, suggesting oxidative effects of O₃. Interestingly, in utero TS exposure again suppressed these effects in the TS/O₃ group. Overall, results suggest that in utero exposure to TS alone produced minimal acute pulmonary effects in newborn rats, but modulated adverse effects of postnatal O₃ exposure. The

  6. Mutagenic potential of acute exposure to organophosphorus and organochlorine compounds.

    PubMed

    Vijayaraghavan, M; Nagarajan, B

    1994-04-01

    The cytogenetic and cytotoxic effects of the pesticides methyl parathion, Bayleton and Hinosan were evaluated in mammalian test systems. The frequency of chromosome aberrations and micronuclei in bone marrow cells and the arginase enzyme profile in the liver tend to show the genotoxicity of organophosphorus and organochlorine pesticides in a single-exposure response study. Methyl parathion was the most hazardous among the three, showing definite pathology in the livers of treated rats.

  7. Toxicity of methyl parathion to bats: Mortality and coordination loss

    USGS Publications Warehouse

    Clark, D.R.

    1986-01-01

    The 24-h oral LD50 of methyl parathion (phosphorothioic acid O,O-dimethyl O-(4-nitrophenyl) ester) to little brown bats (Myotis lucifugus) (372 mg/kg) was 8.5 times the LD50 for mice (Mus musculus) (44 mg/kg). However, orally dosed mice either died or appeared behaviorally normal after 2 to 3 h, whereas many dosed bats, although alive at 24 h, could not right themselves when placed on their backs. The oral dose estimated to cause this loss of coordination in 50% of a sample of big brown bats (Eptesicus fuscus) was one-third or less the LD50 of this species. Cholinesterase activity depression in brains of little brown bats was similar whether dosage was oral or dermal. With death as the criterion, bats proved relatively insensitive to methyl parathion in 24-h tests, but considerations of the chemical's potential to cause coordination loss, leading to capture and death by predators, coupled with bats' naturally low reproductive rates, suggest possible injury to exposed bat populations.

  8. Burkholderia jiangsuensis sp. nov., a methyl parathion degrading bacterium, isolated from methyl parathion contaminated soil.

    PubMed

    Liu, Xu-Yun; Li, Chun-Xiu; Luo, Xiao-Jing; Lai, Qi-Liang; Xu, Jian-He

    2014-09-01

    A methyl parathion (MP) degrading bacterial strain, designated MP-1(T), was isolated from a waste land where pesticides were formerly manufactured in Jiangsu province, China. Polyphasic taxonomic studies showed that MP-1(T) is a Gram-stain-negative, non-spore-forming, rod-shaped and motile bacterium. The bacterium could grow at salinities of 0-1 % (w/v) and temperatures of 15-40 °C. Strain MP-1(T) could reduce nitrate to nitrite, utilize d-glucose and l-arabinose, but not produce indole, or hydrolyse gelatin. Phylogenetic analysis based on 16S rRNA gene sequences demonstrated that MP-1(T) belongs to the genus Burkholderia, showing highest sequence similarity to Burkholderia grimmiae DSM 25160(T) (98.5 %), and similar strains including Burkholderia zhejiangensis OP-1(T) (98.2 %), Burkholderia choica LMG 22940(T) (97.5 %), Burkholderia glathei DSM 50014(T) (97.4 %), Burkholderia terrestris LMG 22937(T) (97.2 %) and Burkholderia telluris LMG 22936(T) (97.0 %). In addition, the gyrB and recA gene segments of strain MP-1(T) exhibited less than 89.0 % and 95.1 % similarities with the most highly-related type strains indicated above. The G+C content of strain MP-1(T) was 62.6 mol%. The major isoprenoid quinone was ubiquinone Q-8. The predominant polar lipids comprised phosphatidyl ethanolamine, phosphatidyl glycerol, aminolipid and phospholipid. The principal fatty acids in strain MP-1(T) were C18 : 1ω7c/C18 : 1ω6c (23.3 %), C16 : 0 (16.8 %), cyclo-C17 : 0 (15.0 %), C16 : 1ω7c/C16 : 1ω6 (8.5 %), cyclo-C19 : 0ω8c (8.1 %), C16 : 1 iso I/C14 : 0 3-OH (5.7 %), C16 : 0 3-OH (5.6 %) and C16 : 02-OH (5.1 %). The DNA-DNA relatedness values between strain MP-1(T) and the three type strains (B. grimmiae DSM 25160(T), B. zhejiangensis OP-1(T) and B. glathei DSM 50014(T)) ranged from 24.6 % to 37.4 %. In accordance with phenotypic and genotypic characteristics, strain MP-1(T) represents a novel

  9. Prenatal Exposure to Snus Alters Heart Rate Variability in the Infant.

    PubMed

    Nordenstam, Felicia; Lundell, Bo; Cohen, Gary; Tessma, Mesfin K; Raaschou, Pauline; Wickström, Ronny

    2017-07-01

    Maternal use of smoked tobacco during pregnancy causes significant morbidity and mortality in the human infant including alterations in autonomic control with increased risk of sudden infant death syndrome. We hypothesized that maternal snus (smokeless tobacco) use during pregnancy affects autonomic cardiac regulation in the infant, as measured by heart rate variability (HRV) and the low frequency and high frequency ratio (LF/HF ratio). A prospective observational study of 56 infants of women who used snus (n = 23) or cigarettes (n = 13) during pregnancy versus tobacco- and nicotine-free controls (n = 19). The nicotine dose was estimated by questionnaires at 4 timepoints pre- and post-natally. The infants' urine cotinine concentration and HRV during 2 hours of sleep were studied 1-2 months after birth. LF/HF ratio was higher in snus (mean 3.31; 95% CI 2.78-3.83) and smoke (3.51;2.54-4.47) compared to controls (2.15; 1.76-2.54, p = .002). Early prenatal nicotine exposure "without" any further exposure increased the LF/HF ratio (3.19; 2.55-3.84, p = .02). Continuous prenatal nicotine exposure "without" postnatal exposure was also associated with a residual increase in LF/HF ratio (4.40; 3.38-5.42, p < .001). There was no difference between infants exposed to smokeless versus smoked tobacco, suggesting a common constituent (nicotine) altering autonomic cardiac regulation. Infants to mothers who used snus during pregnancy showed lower vagal activity with an increased LF/HF ratio compared to controls, and similar to infants of smokers. Even early prenatal exposure to snus has a lasting impact on autonomic cardiac regulation suggesting a fetal "re-programing" of the developing autonomic nervous system. The results indicate that smokeless tobacco (Swedish snus) affects the developing autonomic nervous system during gestation. Even if exposure is interrupted during the first or second trimester, effects in autonomic cardiac regulation are seen in the 1-2 month-old infant

  10. Biodegradation of methyl parathion and endosulfan using Pseudomonas aeruginosa and Trichoderma viridae.

    PubMed

    Senthilkumar, S; Anthonisamy, A; Arunkumar, S; Sivakumari, V

    2011-01-01

    Microorganisms play an important role in the bioconversion and total breakdown of pesticides in the environment. This study was conducted to assess the pesticide degradation (endosulfan and methyl parathion) ability of the bacteria and fungi (Pseudomonas aeruginosa and Trichoderma viridae). The screening test conducted to reveal the ability to degrade endosulfan and methyl parathion shows that Trichoderma viridae was effective compared to Pseudomonas aeruginosa. The pesticide degradation was estimated by optical density method. Methyl parathion was highly degraded compared to endosulfan. This study clearly proves that pesticides and their residue degradation can be accelerated by employing microbes which can be effectively utilized both as biocontrol agent and soil cleanser.

  11. Growth of human bronchial epithelial cells at an air-liquid interface alters the response to particle exposure

    EPA Science Inventory

    Abstract: We tested the hypothesis that relative to submerged cells, airway epithelial cells grown at an air-liquid interface would have an altered response to particle exposure. RNA for IL-8, IL-6, heme oxygenase 1 and cyclooxygenase 2 increased following exposure of submer...

  12. Growth of human bronchial epithelial cells at an air-liquid interface alters the response to particle exposure

    EPA Science Inventory

    Abstract: We tested the hypothesis that relative to submerged cells, airway epithelial cells grown at an air-liquid interface would have an altered response to particle exposure. RNA for IL-8, IL-6, heme oxygenase 1 and cyclooxygenase 2 increased following exposure of submer...

  13. Developmental exposure to endocrine disrupting chemicals alters the epigenome: Identification of reprogrammed targets

    PubMed Central

    Prusinski, Lauren; Al-Hendy, Ayman; Yang, Qiwei

    2016-01-01

    Endocrine disruptions induced by environmental toxicants have placed an immense burden on society to properly diagnose, treat and attempt to alleviate symptoms and disease. Environmental exposures during critical periods of development can permanently reprogram normal physiological responses, thereby increasing susceptibility to disease later in life - a process known as developmental reprogramming. During development, organogenesis and tissue differentiation occur through a continuous series of tightly-regulated and precisely-timed molecular, biochemical and cellular events. Humans may encounter endocrine disrupting chemicals (EDCs) daily and during all stages of life, from conception and fetal development through adulthood and senescence. Though puberty and perimenopausal periods may be affected by endocrine disruption due to hormonal effects, prenatal and early postnatal windows are most critical for proper development due to rapid changes in system growth. Developmental reprogramming is shown to be caused by alterations in the epigenome. Development is the time when epigenetic programs are ‘installed’ on the genome by ‘writers’, such as histone methyltransferases (HMTs) and DNA methyltransferases (DNMTs), which add methyl groups to lysine and arginine residues on histone tails and to CpG sites in DNA, respectively. A number of environmental compounds, referred to as estrogenic endocrine disruptors (EEDs), are able to bind to estrogen receptors (ERs) and interfere with the normal cellular development in target tissues including the prostate and uterus. These EEDs, including diethylstilbestrol (DES), bisphenol A (BPA), and genistein (a phytoestrogen derived from soybeans), have been implicated in the malformation of reproductive organs and later development of disease. Due to the lack of fully understanding the underlying mechanisms of how environmental toxicants and their level of exposure affect the human genome, it can be challenging to create clear

  14. Low lead environmental exposure alters semen quality and sperm chromatin condensation in northern Mexico.

    PubMed

    Hernández-Ochoa, Isabel; García-Vargas, Gonzalo; López-Carrillo, Lizbeth; Rubio-Andrade, Marisela; Morán-Martínez, Javier; Cebrián, Mariano E; Quintanilla-Vega, Betzabet

    2005-01-01

    We evaluated environmental-lead (Pb) effects on semen quality and sperm chromatin, considering Pb in seminal fluid (PbSF), spermatozoa (PbSpz), and blood (PbB) as exposure biomarkers in urban men (9.3 microg/dL PbB). Several individuals (44%) showed decreases in sperm quality; sperm concentration, motility, morphology and viability associated negatively with PbSpz, whereas semen volume associated negatively with PbSF. Multiple linear regression estimated PbSF and PbSpz thresholds for alterations in semen quality. Forty-eight percent of samples showed high values of nuclear chromatin condensation (NCD) positively associated with PbSF and zinc in spermatozoa (ZnSpz). ZnSpz values were higher than in fertile men. These results suggest that Pb may affect sperm chromatin by altering sperm Zn availability. PbB was not associated with semen quality or NCD, suggesting that Pb in semen compartments assesses better the amount of Pb in the reproductive tract; therefore, these are better biomarkers to evaluate toxicity at low Pb-exposure levels.

  15. Prenatal exposure to pesticides disrupts testicular histoarchitecture and alters testosterone levels in male Caiman latirostris.

    PubMed

    Rey, Florencia; González, Marianela; Zayas, Marcelo A; Stoker, Cora; Durando, Milena; Luque, Enrique H; Muñoz-de-Toro, Mónica

    2009-07-01

    The increased use of agrochemical pesticides, such as atrazine (ATZ) and endosulfan (END), may have a significant impact on ecosystem health and biodiversity. The aim of this study was to investigate the consequences of in ovum exposure to ATZ and END on Caiman latirostris gonadal histo-functional features. Caiman eggs were collected from environmentally pristine areas and incubated in controlled conditions at male producing temperature (33 degrees C). At stage 20 of embryonic development, the sensitive stage for gonadal sex determination, eggs were exposed to one dose of either END or ATZ. Gonadal histo-morphology was examined in caiman hatchlings and serum levels of testosterone were measured. Regardless of treatment condition, all eggs incubated at 33 degrees C resulted in male hatchlings. Tortuous seminiferous tubules with increased perimeter, disrupted distribution of peritubular myoid cells (desmin positive), and emptied tubular lumens characterized the testes of pesticide-exposed caiman. An imbalance between proliferative activity and cell death was observed in the testes of caiman exposed to the higher doses of END, mainly due to a high frequency of apoptosis in intratubular cells. This altered cell turnover was associated with decreased testosterone levels. Prenatal exposure to only one dose of END and ATZ disrupted neonatal male gonadal histo-functional features. Alterations described here could have detrimental effects on the sexual maturation of the caiman and, ultimately, on the success of male caiman reproduction.

  16. Acute high-intensity sound exposure alters responses of place cells in hippocampus.

    PubMed

    Goble, T J; Møller, A R; Thompson, L T

    2009-07-01

    Overstimulation is known to activate neural plasticity in the auditory nervous system causing changes in function and re-organization. It has been shown earlier that overstimulation using high-intensity noise or tones can induce signs of tinnitus. Here we show in studies in rats that overstimulation causes changes in the way place cells of the hippocampus respond as rats search for rewards in a spatial maze. In familiar environments, a subset of hippocampal pyramidal neurons, known as place cells, respond when the animal moves through specific locations but are relatively silent in others. This place-field activity (i.e. location-specific firing) is stable in a fixed environment. The present study shows that activation of neural plasticity through overstimulation by sound can alter the response of these place cells. Rats implanted with chronic drivable dorsal hippocampal tetrodes (four microelectrodes) were assessed for stable single-unit place-field responses that were extracted from multiunit responses using NeuroExplorer computer spike-sorting software. Rats then underwent either 30 min exposure to a 4 kHz tone at 104 dB SPL or a control period in the same sound chamber. The place-field activity was significantly altered after sound exposure showing that plastic changes induced by overstimulation are not limited to the auditory nervous system but extend to other parts of the CNS, in this case to the hippocampus, a brain region often studied in the context of plasticity.

  17. Long-term exposure to occupational noise alters the cortical organization of sound processing.

    PubMed

    Brattico, Elvira; Kujala, Teija; Tervaniemi, Mari; Alku, Paavo; Ambrosi, Luigi; Monitillo, Vincenzo

    2005-01-01

    Long-term exposure to noise may cause an altered hemispheric lateralization of speech processing even in silent conditions. We examined whether this lateralization shift is speech specific or occurs also for other sounds. Brain responses from 10 healthy noise-exposed workers (>5 years) and 10 matched controls were recorded with a 32-channel electroencephalogram in two conditions, one including standard and deviant speech sounds, the other non-speech sounds, with novel sounds in both. The deviant-sound elicited mismatch negativity (MMN) was larger to non-speech than speech sounds in control subjects, while it did not differ between the sound types in the noise-exposed subjects. Moreover, the MMN to speech sounds was lateralized to the right hemisphere in exposed workers, while it was left-hemisphere predominant in control subjects. No group topography difference was found for non-speech sounds. The deviant sounds that were close in formant space to the standards elicited a longer MMN latency in both speech and non-speech conditions in exposed subjects than controls. No group differences were found for cortical responses to novel sounds. Long-term noise exposure altered the strength and the hemispheric organization of speech-sound discrimination and decreased the speed of sound-change processing. Subpathological changes in cortical responses to sounds may occur even in subjects without a peripheral damage but continuously exposed to noisy auditory environments.

  18. Histopathological findings on Carassius auratus hepatopancreas upon exposure to acrylamide: correlation with genotoxicity and metabolic alterations.

    PubMed

    Larguinho, Miguel; Costa, Pedro M; Sousa, Gonçalo; Costa, Maria H; Diniz, Mário S; Baptista, Pedro V

    2014-12-01

    Acrylamide is an amide used in several industrial applications making it easily discharged to aquatic ecosystems. The toxicity of acrylamide to aquatic organisms is scarcely known, although previous studies with murine models provided evidence for deleterious effects. To assess the effects of acrylamide to freshwater fish, goldfish (Carassius auratus L.) were exposed to several concentrations of waterborne acrylamide and analysed for genotoxic damage, alterations to detoxifying enzymes and histopathology. Results revealed a dose-dependent increase in total DNA strand breakage, the formation of erythrocytic nuclear abnormalities and in the levels of hepatic cytochrome P4501A (CYP1A) and glutathione S-transferase (GST) activity. In addition, acrylamide induced more histopathological changes to pancreatic acini than to the hepatic parenchyma, regardless of exposure concentration, whereas hepatic tissue only endured significant alterations at higher concentrations of exposure. Thus, results confirm the genotoxic potential of acrylamide to fish and its ability to induce CYP1A, probably as a direct primary defence mechanism. This strongly suggests the substance's pro-mutagenic potential in fish, similarly to what is known for rodents. However, the deleterious effects observed in the pancreatic acini, more severe than in the liver, could indicate a specific, albeit unknown toxic mechanism of acrylamide to fish that overran the organism's metabolic defences against a chemical agent rather than causing a general systemic failure. Copyright © 2013 John Wiley & Sons, Ltd.

  19. Morphofunctional Alterations in Zebrafish (Danio rerio) Gills after Exposure to Mercury Chloride

    PubMed Central

    Macirella, Rachele; Brunelli, Elvira

    2017-01-01

    Mercury (Hg) is a global pollutant that may exert its toxic effects on living organisms and is found in both aquatic and terrestrial ecosystems in three chemical forms; elemental, organic, and inorganic. The inorganic form (iHg) tends to predominantly accumulate in aquatic environments. The gill apparatus is a very dynamic organ that plays a fundamental role in gas exchange, osmoregulation, acid-base regulation, detoxification, and excretion, and the gills are the primary route of waterborne iHg entrance in fish. In the present work we investigated the morphofunctional and ultrastructural effects in Danio rerio gills after 96 h exposure to two low HgCl2 concentrations (7.7 and 38.5 µg/L). Our results clearly demonstrated that a short-term exposure to low concentrations of mercury chloride resulted in gill morphology alterations and in the modifications of both Na+/K+-ATPase and metallothioneins (MTs) expression pattern. The main morphological effects recorded in this work were represented by hyperplasia and ectopia of chloride cells (CCs), lamellar fusion, increased mucous secretion, alteration of pavement cells (PVCs), detachment of the secondary epithelium, pillar cell degeneration, degeneration, and apoptosis. Trough immunohistochemistry and real-time PCR analysis also showed a dose-related modulation of Na+/K+-ATPase and MTs. PMID:28406445

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

    PubMed

    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. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2015-06-15

    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

  2. Perinatal Exposure to Bisphenol-A Alters Peripubertal Mammary Gland Development in Mice

    PubMed Central

    Muñoz-de-Toro, Monica; Markey, Caroline M.; Wadia, Perinaaz R.; Luque, Enrique H.; Rubin, Beverly S.; Sonnenschein, Carlos; Soto, Ana M.

    2010-01-01

    Developmental exposure to estrogenic chemicals induces morphological, functional, and behavioral anomalies associated with reproduction. Humans are exposed to bisphenol-A (BPA), an estrogenic compound that leaches from dental materials and plastic food and beverage containers. The aim of the present study was to determine the effects of perinatal exposure to low, environmentally relevant doses of BPA [25 and 250 ng BPA/kg body weight (bw)·d] on the peripubertal development of the mammary gland. BPA exposure enhanced the mammary glands' sensitivity to estradiol in ovariectomized CD-1 mice. In their intact 30-d-old littermates, the area and numbers of terminal end buds relative to the gland ductal area increased whereas their apoptotic activity decreased. There was a positive correlation between ductal length and the age at first proestrus; that was reduced as the BPA dose increased, suggesting that BPA exposure slows down ductal invasion of the stroma. There was also a significant increase of progesterone receptor-positive ductal epithelial cells that were localized in clusters, suggesting future branching points. Indeed, lateral branching was significantly enhanced at 4 months of age in mice exposed to 25 ng BPA /kg bw·d. In conclusion, perinatal exposure to environmentally relevant BPA doses results in persistent alterations in mammary gland morphogenesis. Of special concern is the increased terminal end bud density at puberty as well as the increased number of terminal ends reported previously in adult animals, as these two structures are the sites at which cancer arises in humans and rodents. PMID:15919749

  3. Hypertension Does Not Alter the Increase in Cardiac Baroreflex Sensitivity Caused by Moderate Cold Exposure.

    PubMed

    Hintsala, Heidi E; Kiviniemi, Antti M; Tulppo, Mikko P; Helakari, Heta; Rintamäki, Hannu; Mäntysaari, Matti; Herzig, Karl-Heinz; Keinänen-Kiukaanniemi, Sirkka; Jaakkola, Jouni J K; Ikäheimo, Tiina M

    2016-01-01

    Exposure to cold increases blood pressure and may contribute to higher wintertime cardiovascular morbidity and mortality in hypertensive people, but the mechanisms are not well-established. While hypertension does not alter responses of vagally-mediated heart rate variability to cold, it is not known how hypertension modifies baroreflex sensitivity (BRS) and blood pressure variability during cold exposure. Our study assessed this among untreated hypertensive men during short-term exposure comparable to habitual winter time circumstances in subarctic areas. We conducted a population-based recruitment of 24 untreated hypertensive and 17 men without hypertension (age 55-65 years) who underwent a whole-body cold exposure (-10°C, wind 3 m/s, winter clothes, 15 min, standing). Electrocardiogram and continuous blood pressure were measured to compute spectral powers of systolic blood pressure and heart rate variability at low (0.04-0.15 Hz) and high frequency (0.15-0.4 Hz) and spontaneous BRS at low frequency (LF). Comparable increases in BRS were detected in hypertensive men, from 2.6 (2.0, 4.2) to 3.8 (2.5, 5.1) ms/mmHg [median (interquartile range)], and in control group, from 4.3 (2.7, 5.0) to 4.4 (3.1, 7.1) ms/mmHg. Instead, larger increase (p < 0.05) in LF blood pressure variability was observed in control group; response as median (interquartile range): 8 (2, 14) mmHg(2), compared with hypertensive group [0 (-13, 20) mmHg(2)]. Untreated hypertension does not disturb cardiovascular protective mechanisms during moderate cold exposure commonly occurring in everyday life. Blunted response of the estimate of peripheral sympathetic modulation may indicate higher tonic sympathetic activity and decreased sympathetic responsiveness to cold in hypertension.

  4. Adolescent binge alcohol exposure alters hippocampal progenitor cell proliferation in rats: effects on cell cycle kinetics.

    PubMed

    McClain, Justin A; Hayes, Dayna M; Morris, Stephanie A; Nixon, Kimberly

    2011-09-01

    Binge alcohol exposure in adolescent rats potently inhibits adult hippocampal neurogenesis by altering neural progenitor cell (NPC) proliferation and survival; however, it is not clear whether alcohol results in an increase or decrease in net proliferation. Thus, the effects of alcohol on hippocampal NPC cell cycle phase distribution and kinetics were assessed in an adolescent rat model of an alcohol use disorder. Cell cycle distribution was measured using a combination of markers (Ki-67, bromodeoxyuridine incorporation, and phosphohistone H3) to determine the proportion of NPCs within G1, S, and G2/M phases of the cell cycle. Cell cycle kinetics were calculated using a cumulative bromodeoxyuridine injection protocol to determine the effect of alcohol on cell cycle length and S-phase duration. Binge alcohol exposure reduced the proportion of NPCs in S-phase, but had no effect on G1 or G2/M phases, indicating that alcohol specifically targets S-phase of the cell cycle. Cell cycle kinetics studies revealed that alcohol reduced NPC cell cycle duration by 36% and shortened S-phase by 62%, suggesting that binge alcohol exposure accelerates progression through the cell cycle. This effect would be expected to increase NPC proliferation, which was supported by a slight, but significant increase in the number of Sox-2+ NPCs residing in the hippocampal subgranular zone following binge alcohol exposure. These studies suggest the mechanism of alcohol inhibition of neurogenesis and also reveal the earliest evidence of the compensatory neurogenesis reaction that has been observed a week after binge alcohol exposure.

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

    PubMed Central

    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

  6. Hypertension Does Not Alter the Increase in Cardiac Baroreflex Sensitivity Caused by Moderate Cold Exposure

    PubMed Central

    Hintsala, Heidi E.; Kiviniemi, Antti M.; Tulppo, Mikko P.; Helakari, Heta; Rintamäki, Hannu; Mäntysaari, Matti; Herzig, Karl-Heinz; Keinänen-Kiukaanniemi, Sirkka; Jaakkola, Jouni J. K.; Ikäheimo, Tiina M.

    2016-01-01

    Exposure to cold increases blood pressure and may contribute to higher wintertime cardiovascular morbidity and mortality in hypertensive people, but the mechanisms are not well-established. While hypertension does not alter responses of vagally-mediated heart rate variability to cold, it is not known how hypertension modifies baroreflex sensitivity (BRS) and blood pressure variability during cold exposure. Our study assessed this among untreated hypertensive men during short-term exposure comparable to habitual winter time circumstances in subarctic areas. We conducted a population-based recruitment of 24 untreated hypertensive and 17 men without hypertension (age 55–65 years) who underwent a whole-body cold exposure (−10°C, wind 3 m/s, winter clothes, 15 min, standing). Electrocardiogram and continuous blood pressure were measured to compute spectral powers of systolic blood pressure and heart rate variability at low (0.04–0.15 Hz) and high frequency (0.15–0.4 Hz) and spontaneous BRS at low frequency (LF). Comparable increases in BRS were detected in hypertensive men, from 2.6 (2.0, 4.2) to 3.8 (2.5, 5.1) ms/mmHg [median (interquartile range)], and in control group, from 4.3 (2.7, 5.0) to 4.4 (3.1, 7.1) ms/mmHg. Instead, larger increase (p < 0.05) in LF blood pressure variability was observed in control group; response as median (interquartile range): 8 (2, 14) mmHg2, compared with hypertensive group [0 (−13, 20) mmHg2]. Untreated hypertension does not disturb cardiovascular protective mechanisms during moderate cold exposure commonly occurring in everyday life. Blunted response of the estimate of peripheral sympathetic modulation may indicate higher tonic sympathetic activity and decreased sympathetic responsiveness to cold in hypertension. PMID:27313543

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

    PubMed

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

    2012-02-01

    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. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

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

    PubMed Central

    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

  9. Chronic 835-MHz radiofrequency exposure to mice hippocampus alters the distribution of calbindin and GFAP immunoreactivity.

    PubMed

    Maskey, Dhiraj; Pradhan, Jonu; Aryal, Bijay; Lee, Chang-Min; Choi, In-Young; Park, Ki-Sup; Kim, Seok Bae; Kim, Hyung Gun; Kim, Myeung Ju

    2010-07-30

    Exponential interindividual handling in wireless communication system has raised possible doubts in the biological aspects of radiofrequency (RF) exposure on human brain owing to its close proximity to the mobile phone. In the nervous system, calcium (Ca(2+)) plays a critical role in releasing neurotransmitters, generating action potential and membrane integrity. Alterations in intracellular Ca(2+) concentration trigger aberrant synaptic action or cause neuronal apoptosis, which may exert an influence on the cellular pathology for learning and memory in the hippocampus. Calcium binding proteins like calbindin D28-K (CB) is responsible for the maintaining and controlling Ca(2+) homeostasis. Therefore, in the present study, we investigated the effect of RF exposure on rat hippocampus at 835 MHz with low energy (specific absorption rate: SAR=1.6 W/kg) for 3 months by using both CB and glial fibrillary acidic protein (GFAP) specific antibodies by immunohistochemical method. Decrease in CB immunoreactivity (IR) was noted in exposed (E1.6) group with loss of interneurons and pyramidal cells in CA1 area and loss of granule cells. Also, an overall increase in GFAP IR was observed in the hippocampus of E1.6. By TUNEL assay, apoptotic cells were detected in the CA1, CA3 areas and dentate gyrus of hippocampus, which reflects that chronic RF exposure may affect the cell viability. In addition, the increase of GFAP IR due to RF exposure could be well suited with the feature of reactive astrocytosis, which is an abnormal increase in the number of astrocytes due to the loss of nearby neurons. Chronic RF exposure to the rat brain suggested that the decrease of CB IR accompanying apoptosis and increase of GFAP IR might be morphological parameters in the hippocampus damages.

  10. An intergenerational effect of neuroendocrine metabolic programming alteration induced by prenatal ethanol exposure in rats.

    PubMed

    Kou, Hao; Shen, Lang; Luo, Han-Wen; Chen, Liao-Bin; Wu, Dong-Fang; Wang, Hui

    2017-09-12

    Prenatal ethanol exposure (PEE) induces hypothalamic-pituitary-adrenal (HPA) axis-related neuroendocrine metabolic programming alteration in the first generation (F1) rats. In this study, the HPA hormones and glucose/lipid phenotypes under basal state and stressed condition induced by a fortnight ice-water swimming were examined in F2 to verify the intergenerational effect. Under the basal state, serum corticosterone (CORT) and glucose of some PEE groups were lowered while those of serum triglycerides (TG) were increased comparing with controls. Following chronic stress, the percentage increase in CORT from the basal state tended to be greater for some PEE groups compared with controls while the percentage reduction of glucose and percentage elevation of TG were smaller. These results revealed that the low basal activity and hyper-responsiveness of the HPA axis as well as glucocorticoid-associated glucose and lipid phenotypic alterations were partially retained in F2, which indicates PEE-induced neuroendocrine metabolic programming alteration may have an intergenerational effect. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Opt2 mediates the exposure of phospholipids during cellular adaptation to altered lipid asymmetry.

    PubMed

    Yamauchi, Saori; Obara, Keisuke; Uchibori, Kenya; Kamimura, Akiko; Azumi, Kaoru; Kihara, Akio

    2015-01-01

    Plasma membrane lipid asymmetry is important for various membrane-associated functions and is regulated by membrane proteins termed flippases and floppases. The Rim101 pathway senses altered lipid asymmetry in the yeast plasma membrane. The mutant lem3Δ cells, in which lipid asymmetry is disturbed owing to the inactivation of the plasma membrane flippases, showed a severe growth defect when the Rim101 pathway was impaired. To identify factors involved in the Rim101-pathway-dependent adaptation to altered lipid asymmetry, we performed DNA microarray analysis and found that Opt2 induced by the Rim101 pathway plays an important role in the adaptation to altered lipid asymmetry. Biochemical investigation of Opt2 revealed its localization to the plasma membrane and the Golgi, and provided several lines of evidence for the Opt2-mediated exposure of phospholipids. In addition, Opt2 was found to be required for the maintenance of vacuolar morphology and polarized cell growth. These results suggest that Opt2 is a novel factor involved in cell homeostasis by regulating lipid asymmetry. © 2015. Published by The Company of Biologists Ltd.

  12. Neonatal exposure to amphetamine alters social affiliation and central dopamine activity in adult male prairie voles.

    PubMed

    Fukushiro, D F; Olivera, A; Liu, Y; Wang, Z

    2015-10-29

    The prairie vole (Microtus ochrogaster) is a socially monogamous rodent species that forms pair bonds after mating. Recent data have shown that amphetamine (AMPH) is rewarding to prairie voles as it induces conditioned place preferences. Further, repeated treatment with AMPH impairs social bonding in adult prairie voles through a central dopamine (DA)-dependent mechanism. The present study examined the effects of neonatal exposure to AMPH on behavior and central DA activity in adult male prairie voles. Our data show that neonatal exposure to AMPH makes voles less social in an affiliation test during adulthood, but does not affect animals' locomotor activity and anxiety-like behavior. Neonatal exposure to AMPH also increases the levels of tyrosine hydroxylase (TH) and DA transporter (DAT) mRNA expression in the ventral tegmental area (VTA) in the brain, indicating an increase in central DA activity. As DA has been implicated in AMPH effects on behavioral and cognitive functions, altered DA activity in the vole brain may contribute to the observed changes in social behavior. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Developmental Lead Exposure Alters Synaptogenesis through Inhibiting Canonical Wnt Pathway In Vivo and In Vitro

    PubMed Central

    Hu, Fan; Xu, Li; Liu, Zhi-Hua; Ge, Meng-Meng; Ruan, Di-Yun; Wang, Hui-Li

    2014-01-01

    Lead (Pb) exposure has been implicated in the impairment of synaptic plasticity in the developing hippocampus, but the mechanism remains unclear. Here, we investigated whether developmental lead exposure affects the dendritic spine formation through Wnt signaling pathway in vivo and in vitro. Sprague–Dawley rats were exposed to lead throughout the lactation period and Golgi-Cox staining method was used to examine the spine density of pyramidal neurons in the hippocampal CA1 area of rats. We found that lead exposure significantly decreased the spine density in both 14 and 21 days-old pups, accompanied by a significant age-dependent decline of the Wnt7a expression and stability of its downstream protein (β-catenin). Furthermore, in cultured hippocampal neurons, lead (0.1 and 1 µM lead acetate) significantly decreased the spine density in a dose-dependent manner. Exogenous Wnt7a application attenuated the decrease of spine density and increased the stability of the downstream molecules in Wnt signaling pathway. Together, our results suggest that lead has a negative impact on spine outgrowth in the developing hippocampus through altering the canonical Wnt pathway. PMID:24999626

  14. Alteration of the behavioral effects of nicotine by chronic caffeine exposure.

    PubMed

    Tanda, G; Goldberg, S R

    2000-05-01

    The prevalence of tobacco smoking and coffee drinking place nicotine and caffeine among the most used licit drugs in many societies and their consumption is often characterised by concurrent use. The pharmacological basis for any putative interaction between these drugs remains unclear. Some epidemiological reports support anecdotal evidence, which suggests that smokers consume caffeine to enhance the effects of nicotine. This paper reviews various aspects of the pharmacology of caffeine and nicotine, in humans and experimental animals, important for the understanding of the interactions between these drugs. In particular, recent experiments are reviewed in which chronic exposure to caffeine in the drinking water of rats facilitated acquisition of self-adminstration behavior, enhanced nicotine-induced increases in dopamine levels in the shell of the nucleus accumbens and altered the dopaminergic component of a nicotine discrimination. These studies provide evidence that the rewarding and subjective properties of nicotine can be changed by chronic caffeine exposure and indicate that caffeine exposure may be an important environmental factor in shaping and maintaining tobacco smoking.

  15. Metabolic and histopathological alterations in the marine bivalve Mytilus galloprovincialis induced by chronic exposure to acrylamide.

    PubMed

    Larguinho, Miguel; Cordeiro, Ana; Diniz, Mário S; Costa, Pedro M; Baptista, Pedro V

    2014-11-01

    Although the neurotoxic and genotoxic potential of acrylamide has been established in freshwater fish, the full breadth of the toxicological consequences induced by this xenobiotic has not yet been disclosed, particularly in aquatic invertebrates. To assess the effects of acrylamide on a bivalve model, the Mediterranean mussel (Mytilus galloprovincialis), two different setups were accomplished: 1) acute exposure to several concentrations of waterborne acrylamide to determine lethality thresholds of the substance and 2) chronic exposure to more reduced acrylamide concentrations to survey phases I and II metabolic endpoints and to perform a whole-body screening for histopathological alterations. Acute toxicity was low (LC50≈400mg/L). However, mussels were responsive to prolonged exposure to chronic concentrations of waterborne acrylamide (1-10mg/L), yielding a significant increase in lipid peroxidation plus EROD and GST activities. Still, total anti-oxidant capacity was not exceeded. In addition, no neurotoxic effects could be determined through acetylcholine esterase (AChE) activity. The findings suggest aryl-hydrocarbon receptor (Ahr)-dependent responses in mussels exposed to acrylamide, although reduced comparatively to vertebrates. No significant histological damage was found in digestive gland or gills but female gonads endured severe necrosis and oocyte atresia. Altogether, the results indicate that acrylamide may induce gonadotoxicity in mussels, although the subject should benefit from further research. Altogether, the findings suggest that the risk of acrylamide to aquatic animals, especially molluscs, may be underestimated. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Antenatal betamethasone exposure alters renal responses to angiotensin-(1-7) in uninephrectomized adult male sheep.

    PubMed

    Bi, Jianli; Contag, Stephen A; Carey, Luke C; Tang, Lijun; Valego, Nancy K; Chappell, Mark C; Rose, James C

    2013-12-01

    Antenatal corticosteroid exposure reduces renal function and alters the intrarenal renin-angiotensin system to favor angiotensin activation of angiotensin type 1 receptor (AT1R) mediated responses in ovine offspring. This study aimed to assess whether antenatal steroid exposure would affect renal responses to the direct intrarenal infusion of angiotensin-(1-7) in rams and the angiotensin receptors involved in mediating responses to the peptide. Adult, uninephrectomized rams exposed to either betamethasone or vehicle before birth received intrarenal angiotensin-(1-7) infusions (1 ng/kg/min) alone or in combination with antagonists to angiotensin receptors for 3 h. Basal sodium excretion (UNa) was significantly lower and mean arterial pressure was significantly higher in betamethasone- compared to the vehicle-treated sheep. Angiotensin-(1-7) decreased UNa more in betamethasone- than in vehicle-treated sheep. Candesartan reversed the response to angiotensin-(1-7) but D-Ala(7)-angiotensin-(1-7) did not. Angiotensin-(1-7) infusion decreased effective renal plasma flow in both groups to a similar extent and the response was reversed by candesartan, but was not blocked by D-Ala(7)-angiotensin-(1-7). Glomerular filtration rate increased significantly in both groups after 3 h infusion of angiotensin-(1-7) plus candesartan. These results suggest that antenatal exposure to a clinically relevant dose of betamethasone impairs renal function in rams. Moreover, angiotensin-(1-7) appears capable of activating the AT1R in uninephrectomized rams.

  17. Antenatal Betamethasone Exposure Alters Renal Responses to Angiotensin-(1–7) in Uninephrectomized Adult Male Sheep

    PubMed Central

    Bi, Jianli; Contag, Stephen A.; Carey, Luke C.; Tang, Lijun; Valego, Nancy K.; Chappell, Mark C.; Rose, James C.

    2014-01-01

    Antenatal corticosteroid exposure reduces renal function and alters the intrarenal renin-angiotensin system to favor angiotensin activation of angiotensin type 1 receptor (AT1R) mediated responses in ovine offspring. This study aimed to assess whether antenatal steroid exposure would affect renal responses to the direct intrarenal infusion of angiotensin-(1–7) in rams and the Ang receptors involved in mediating responses to the peptide. Adult, uninephrectomized rams exposed to either betamethasone or vehicle before birth received intrarenal angiotensin-(1–7) infusions (1ng/kg/min) alone or in combination with antagonists to Ang receptors for 3 hours. Basal sodium excretion (UNa) was significantly lower and mean arterial pressure was significantly higher in betamethasone compared to the vehicle treated sheep. Angiotensin-(1–7) decreased UNa more in betamethasone than in vehicle treated sheep. Candesartan reversed the response to Angiotensin-(1–7) but D-Ala7-Angiotensin-(1–7) did not. Angiotensin-(1–7) infusion decreased effective renal plasma flow in both groups to a similar extent and the response was reversed by candesartan, but was not blocked by D-Ala7-Angiotensin-(1–7). Glomerular filtration rate increased significantly in both groups after 3h infusion of Angiotensin-(1–7) plus candesartan. These results suggest that antenatal exposure to a clinically relevant dose of betamethasone impairs renal function in rams. Moreover, Angiotensin-(1–7) appears capable of activating the AT1R in uninephrectomized rams. PMID:23161144

  18. Exposure to 2,4-dichlorophenoxyacetic acid alters glucose metabolism in immature rat Sertoli cells.

    PubMed

    Alves, M G; Neuhaus-Oliveira, A; Moreira, P I; Socorro, S; Oliveira, P F

    2013-07-01

    The purpose of this study was to determine the effects of 2,4-D, an herbicide used worldwide also known as endocrine disruptor, in Sertoli cell (SC) metabolism. Immature rat SCs were maintained 50h under basal conditions or exposed to 2,4-D (100nM, 10μM and 1mM). SCs exposed to 10μM and 1mM of 2,4-D presented lower intracellular glucose and lactate content. Exposure to 10μM of 2,4-D induced a significant decrease in glucose transporter-3 mRNA levels and phosphofructokinase-1 mRNA levels decreased in cells exposed to 100nM and 10μM of 2,4-D. Exposure to 100nM and 10μM also induced a decrease in lactate dehydrogenase (LDH) mRNA levels while the LDH protein levels were only decreased in cells exposed to 1mM of 2,4-D. Exposure to 2,4-D altered glucose uptake and metabolization in SCs, as well as lactate metabolism and export that may result in impaired spermatogenesis. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Acute exposure to methamphetamine alters TLR9-mediated cytokine expression in human macrophage

    PubMed Central

    Burns, Ariel; Ciborowski, Pawel

    2015-01-01

    Recent studies show that methamphetamine (Meth) use leads to higher susceptibility to and progression of infections, which suggests impairment of the immune system. The first line of defense against infections is the innate immune system and the macrophage is a key player in preventing and fighting infections. So we profiled cytokines over time in Meth treated THP-1 cells, as a human macrophage model, at a relevant concentration using high throughput screening to find a signaling target. We showed that after a single exposure, the effect of Meth on macrophage cytokine production was rapid and time dependent and shifted the balance of expression of cytokines to pro-inflammatory. Our results were analogous to previous reports in that Meth up-regulates TNF-α and IL-8 after two hours of exposure. However, global screening led to the novel identification of CXCL16, CXCL1 and many other up-regulated cytokines. We also showed CCL7 as the most down-regulated chemokine due to Meth exposure, which led us to hypothesize that Meth dysregulates the MyD88-dependent Toll-like receptor 9 (TLR9) signaling pathway. In conclusion, altered cytokine expression in macrophages suggests it could lead to a suppressed innate immunity in people who use Meth. PMID:26387832

  20. Prenatal Exposure to Paint Thinner Alters Postnatal Development and Behavior in Mice

    PubMed Central

    Malloul, Hanaa; Mahdani, Ferdaousse M.; Bennis, Mohammed; Ba-M’hamed, Saadia

    2017-01-01

    prenatally treated offspring by 600 ppm of thinner. Based on these results, we can conclude that prenatally exposure to paint thinner causes a long-lasting developmental neurotoxicity and alters a wide range of behavioral functions in mice. This shows the risk that mothers who abuse thinner paint expose their offspring. PMID:28959195

  1. Dietary selenomethionine exposure alters swimming performance, metabolic capacity and energy homeostasis in juvenile fathead minnow.

    PubMed

    McPhee, D Landon; Janz, David M

    2014-10-01

    Selenium (Se) is known to cause chronic toxicity in aquatic species. In particular, dietary exposure of fish to selenomethionine (SeMet), the primary form of Se in the diet, is of concern. Recent studies suggest that chronic exposure to elevated dietary SeMet alters energy and endocrine homeostasis in adult fish. However, little is known about the direct effects of dietary SeMet exposure in juvenile fish. The objective of the present study was to investigate sublethal physiological effects of dietary SeMet exposure in juvenile fathead minnow (Pimephales promelas). Twenty days-post-hatch fathead minnow were exposed for 60 days to different measured concentrations (2.8, 5.4, 9.9, 26.5 μg Se/g dry mass [dm]) of Se in food in the form of SeMet. After exposure, samples were collected for Se analysis and fish were subjected to a swimming performance challenge to assess critical swim speed (Ucrit), tail beat frequency and tail beat amplitude, oxygen consumption (MO2), cost of transport (COT), standard metabolic rate (SMR), active metabolic rate (AMR), and factorial aerobic scope (F-AS). Ucrit was decreased in the 26.5 μg Se/g dm exposure group compared to the control group. Tail beat frequency and tail beat amplitude were significantly reduced in fish fed 9.9 and 26.5 μg Se/g. An increase in MO2 and COT was observed in the 9.9 and 26.5 μg Se/g exposure groups compared to the control group. While the AMR of the high dose group was increased relative to control, there were no significant differences in SMR and F-AS. Energy storage capacity was measured via whole body triglyceride and glycogen concentrations. Triglyceride concentrations in non-swam fish were elevated in the 5.4 μg Se/g group relative to controls. Fatigued (swam) fish had significantly lower whole body triglycerides than non-swam fish. All non-swam SeMet exposure groups had significantly decreased whole body glycogen concentrations compared to controls, while the 5.4 and 26.5 μg Se/g exposure groups had

  2. Spectrofluorimetric study of the interaction of methyl-parathion with fish serum albumin.

    PubMed

    Silva, Dilson; Cortez-Moreira, Madelayne; Bastos, Vera Lúcia Freire Cunha; Bastos, Jayme Cunha; Cortez, Célia Martins

    2010-09-01

    The interaction of methyl-parathion with the albumin of Piaractus mesopotamicus (Holmberg 1887) (= pacu), a fish species typical of Brazilian rivers, was studied and the results compared with known values for human and bovine albumin obtained in an earlier investigation. Methyl-parathion (O,O-dimethyl O-p-nitrophenyl phosphorothioate) is an organophosphorous pesticide still used in agriculture and fish farming in many countries. The fluorescence quenching technique with tryptophan as a natural probe was used to detect for the presence of methyl-parathion. Fluorescence can be mathematically expressed by the Stern-Volmer equation to calculate quenching constants, and changes in the behavior of Stern-Volmer curves at different temperatures indicate the nature of the mechanism causing the quenching. Our results indicate that methyl-parathion forms a complex with fish albumin. The estimated association constant is 9.73 x 103 (+/- 4.9 x 102) M(-1) at 25 degrees C.

  3. 75 FR 43981 - Methyl Parathion; Rescision of Previously Issued Order and Issuance of Revised Cancellation Order...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-27

    ... Methyl Parathion 4 EC 70506-193 PENNCAP-M Microencapsulated Insecticide Table 2 of this unit includes the... provisions for disposition of existing stocks set forth in Unit VI. will be a violation of FIFRA. V. What is...

  4. 77 FR 18813 - Rescission of Previously Issued Cancellation Order for Methyl Parathion Product Registration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-28

    ..., human health, and agricultural advocates; the chemical industry; pesticide users; and members of the... FR 43981), in relation to a Memorandum of Agreement where all methyl parathion products were...

  5. Perinatal Exposure to Oestradiol and Bisphenol A Alters the Prostate Epigenome and Increases Susceptibility to Carcinogenesis

    PubMed Central

    Prins, Gail S.; Tang, Wan-Yee; Belmonte, Jessica; Ho, Shuk-Mei

    2010-01-01

    An important and controversial health concern is whether low-dose exposures to hormonally active environmental oestrogens such as bisphenol A can promote human diseases including prostate cancer. Our studies in rats have shown that pharmacological doses of oestradiol administered during the critical window of prostate development result in marked prostate pathology in adulthood that progress to neoplastic lesions with ageing. Our recent studies have also demonstrated that transient developmental exposure of rats to low, environmentally relevant doses of bisphenol A or oestradiol increases prostate gland susceptibility to adult-onset precancerous lesions and hormonal carcinogenesis. These findings indicate that a wide range of oestrogenic exposures during development can predispose to prostatic neoplasia that suggests a potential developmental basis for this adult disease. To identify a molecular basis for oestrogen imprinting, we screened for DNA methylation changes over time in the exposed prostate glands. We found permanent alterations in DNA methylation patterns of multiple cell signalling genes suggesting an epigenetic mechanism of action. For phosphodiesterase type 4 variant 4 (PDE4D4), an enzyme responsible for intracellular cyclic adenosine monophosphate breakdown, a specific methylation cluster was identified in the 5′-flanking CpG island that was gradually hypermethylated with ageing in normal prostates resulting in loss of gene expression. However, in prostates exposed to neonatal oestradiol or bisphenol A, this region became hypomethylated with ageing resulting in persistent and elevated PDE4D4 expression. In total, these findings indicate that low-dose exposures to ubiquitous environmental oestrogens impact the prostate epigenome during development and in so doing, promote prostate disease with ageing. PMID:18226066

  6. Does Switching to Reduced Ignition Propensity Cigarettes Alter Smoking Behavior or Exposure to Tobacco Smoke Constituents?

    PubMed Central

    Rees, Vaughan W.; Norton, Kaila J.; Cummings, K. Michael; Connolly, Gregory N.; Alpert, Hillel R.; Sjödin, Andreas; Romanoff, Lovisa; Li, Zheng; June, Kristie M.; Giovino, Gary A.

    2010-01-01

    Introduction: Since 2004, several jurisdictions have mandated that cigarettes show reduced ignition propensity (RIP) in laboratory testing. RIP cigarettes may limit fires caused by smoldering cigarettes, reducing fire-related deaths and injury. However, some evidence suggests that RIP cigarettes emit more carbon monoxide and polycyclic aromatic hydrocarbons, and smokers may alter their smoking patterns in response to RIP cigarettes. Both of these could increase smokers’ exposures to harmful constituents in cigarettes. Methods: An 18-day switching study with a comparison group was conducted in Boston, MA (N = 77), and Buffalo, NY (N = 83), in 2006–2007. Current daily smokers completed 4 laboratory visits and two 48-hr field data collections. After a 4-day baseline, Boston participants switched to RIP cigarettes for 14 days, whereas Buffalo participants smoked RIP cigarettes throughout. Outcome measures included cigarettes smoked per day; smoking topography; salivary cotinine; breath CO; and hydroxylated metabolites of pyrene, naphthalene, phenanthrene, and fluorene. Because the groups differed demographically, analyses adjusted for race, age, and sex. Results: We observed no significant changes in smoking topography or CO exposure among participants who switched to RIP cigarettes. Cigarette use decreased significantly in the switched group (37.7 cigarettes/48 hr vs. 32.6 cigarettes/48 hr, p = .031), while hydroxyphenanthrenes increased significantly (555 ng/g creatinine vs. 669 ng/g creatinine, p = .007). No other biomarkers were significantly affected. Discussion: Small increases in exposure to phenanthrene among smokers who switched to RIP versions were observed, while other exposures and smoking topography were not significantly affected. Toxicological implications of these findings are unclear. These findings should be weighed against the potential public health benefits of adopting RIP design standards for cigarette products. PMID:20805292

  7. Exposure to mixtures of solvents among paint workers and biochemical alterations of liver function.

    PubMed Central

    Chen, J D; Wang, J D; Jang, J P; Chen, Y Y

    1991-01-01

    The objective of this study was to determine biochemical alterations of liver function among paint manufacturers and sprayers associated with exposure to organic solvents. Two paint manufacturing factories and 22 various kinds of spray painting factories (16 car painting, two aircraft painting, three video terminal painting; and one trailer painting) were included. Air concentrations of organic solvents were collected by personal samplers and analysed by gas chromatography. A total of 180 workers were given a comprehensive physical examination, a questionnaire, a liver function test, and a test for hepatitis B surface antigen. The questionnaire contained questions regarding detailed personal medical history, intake of alcohol, and use of medicine. Mixtures of solvents were used throughout the factories, and xylene and toluene were the major components found in almost all air samples with average contents of 46% and 29% on a weight basis of 67 air samples. No strong hepatotoxic solvents were detected. Workers were classified according to the different exposure patterns and different air concentrations of breathing zones as: high (eight hour time weighted average (8 h TWA) hygienic effects of solvents 0.25-9.83, median 1.66), short term high (8 h TWA hygienic effects of solvents 0-3.38, median 0.12), and low (8 h TWA hygienic effects of solvents all below 0.38). After applying a multivariate model to control the non-occupational factors (alcohol, medication, age, and hepatitis B viral infection), increase in gamma-glutamyl transferase (GGT) activity was found to be associated with severity of exposure to the mixture of solvents. Because the possible effects on GGT activity of non-occupational factors were controlled for, it is concluded that increased GGT activity among exposed workers may be due to a higher exposure to the mixture of solvents. PMID:1931729

  8. Altered testicular microsomal steroidogenic enzyme activities in rats with lifetime exposure to soy isoflavones.

    PubMed

    McVey, Mark J; Cooke, Gerard M; Curran, Ivan H A

    2004-12-01

    Androgen production in the testis is carried out by the Leydig cells, which convert cholesterol into androgens. Previously, isoflavones have been shown to affect serum androgen levels and steroidogenic enzyme activities. In this study, the effects of lifelong exposure to dietary soy isoflavones on testicular microsomal steroidogenic enzyme activities were examined in the rat. F1 male rats were obtained from a multi-generational study where the parental generation was fed diets containing alcohol-washed soy protein supplemented with increasing amounts of Novasoy, a commercially available isoflavone supplement. A control group was maintained on a soy-free casein protein-based diet (AIN93G). The diets were designed to approximate human consumption levels and ranged from 0 to 1046.6 mg isoflavones/kg pelleted feed, encompassing exposures representative of North American and Asian diets as well as infant fed soy-based formula. Activities of testicular 3beta-hydroxysteroid dehydrogenase (3beta-HSD), P450c17 (CYP17), 17beta-hydroxysteroid dehydrogenase (17beta-HSD) were assayed on post natal day (PND) 28, 70, 120, 240 and 360 while 5alpha-reducatase was assayed on PND 28. At PND 28, 3beta-HSD activity was elevated by approximately 50% in rats receiving 1046.6 mg total isoflavones/kg feed compared to those on the casein only diet. A similar increase in activity was observed for CYP17 in rats receiving 235.6 mg total isoflavones/kg feed, a level representative of infant exposure through formula, compared to those receiving 0mg isoflavones from the casein diet. These results demonstrate that rats fed a mixture of dietary soy isoflavones showed significantly altered enzyme activity profiles during development at PND 28 as a result of early exposure to isoflavones at levels obtainable by humans.

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

    PubMed Central

    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

  10. Prenatal exposure to lambda-cyhalothrin alters brain dopaminergic signaling in developing rats.

    PubMed

    Dhuriya, Yogesh K; Srivastava, Pranay; Shukla, Rajendra K; Gupta, Richa; Singh, Dhirendra; Parmar, Devendra; Pant, Aditya B; Khanna, Vinay K

    2017-07-01

    The present study is focused to decipher the molecular mechanisms associated with dopaminergic alterations in corpus striatum of developing rats exposed prenatally to lambda-cyhalothrin (LCT), a new generation type II synthetic pyrethroid. There was no significant change in the mRNA and protein expression of DA-D1 receptors at any of the doses of LCT (0.5, 1 and 3mg/kg body weight) in corpus striatum of developing rats exposed prenatally to LCT on PD22 and PD45. Prenatal exposure to LCT (1 and 3mg/kg body weight) resulted to decrease the levels of mRNA and protein of DA-D2 receptors in corpus stratum of developing rats on PD22 as compared to controls. Decrease in the binding of 3H-Spiperone in corpus striatum, known to label DA-D2 receptors was also distinct in developing rats on PD22. These rats also exhibited decrease in the expression of proteins - TH, DAT and VMAT2 involved in pre-dopaminergic signaling. Further, decrease in the expression of DARPP-32 and pCREB associated with increased expression of PP1α was evident in developing rats on PD22 as compared to controls. Interestingly, a trend of recovery in the expression of these proteins was observed in developing rats exposed to LCT at moderate dose (1.0mg/kg body weight) while alteration in the expression of these proteins continued to persist in those exposed at high dose (3.0mg/kg body weight) on PD45 as compared to respective controls. No significant change in the expression of any of these proteins was observed in corpus striatum of developing rats prenatally exposed to LCT at low dose (0.5mg/kg body weight) on PD22 and PD45 as compared to respective controls. The results provide interesting evidence that alterations in dopaminergic signaling on LCT exposure are due to selective changes in DA-D2 receptors in corpus striatum of developing rats. Further, these changes could be attributed to impairment in spontaneous motor activity on LCT exposure in developing rats. Copyright © 2017 Elsevier B.V. All

  11. Acute and chronic ethanol exposure differentially alters alcohol dehydrogenase and aldehyde dehydrogenase activity in the zebrafish liver.

    PubMed

    Tran, Steven; Nowicki, Magda; Chatterjee, Diptendu; Gerlai, Robert

    2015-01-02

    Chronic ethanol exposure paradigms have been successfully used in the past to induce behavioral and central nervous system related changes in zebrafish. However, it is currently unknown whether chronic ethanol exposure alters ethanol metabolism in adult zebrafish. In the current study we examine the effect of acute ethanol exposure on adult zebrafish behavioral responses, as well as alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity in the liver. We then examine how two different chronic ethanol exposure paradigms (continuous and repeated ethanol exposure) alter behavioral responses and liver enzyme activity during a subsequent acute ethanol challenge. Acute ethanol exposure increased locomotor activity in a dose-dependent manner. ADH activity was shown to exhibit an inverted U-shaped curve and ALDH activity was decreased by ethanol exposure at all doses. During the acute ethanol challenge, animals that were continuously housed in ethanol exhibited a significantly reduced locomotor response and increased ADH activity, however, ALDH activity did not change. Zebrafish that were repeatedly exposed to ethanol demonstrated a small but significant attenuation of the locomotor response during the acute ethanol challenge but ADH and ALDH activity was similar to controls. Overall, we identified two different chronic ethanol exposure paradigms that differentially alter behavioral and physiological responses in zebrafish. We speculate that these two paradigms may allow dissociation of central nervous system-related and liver enzyme-dependent ethanol induced changes in zebrafish.

  12. Exposure to seismic air gun signals causes physiological harm and alters behavior in the scallop Pecten fumatus.

    PubMed

    Day, Ryan D; McCauley, Robert D; Fitzgibbon, Quinn P; Hartmann, Klaas; Semmens, Jayson M

    2017-09-18

    Seismic surveys map the seabed using intense, low-frequency sound signals that penetrate kilometers into the Earth's crust. Little is known regarding how invertebrates, including economically and ecologically important bivalves, are affected by exposure to seismic signals. In a series of field-based experiments, we investigate the impact of exposure to seismic surveys on scallops, using measurements of physiological and behavioral parameters to determine whether exposure may cause mass mortality or result in other sublethal effects. Exposure to seismic signals was found to significantly increase mortality, particularly over a chronic (months postexposure) time scale, though not beyond naturally occurring rates of mortality. Exposure did not elicit energetically expensive behaviors, but scallops showed significant changes in behavioral patterns during exposure, through a reduction in classic behaviors and demonstration of a nonclassic "flinch" response to air gun signals. Furthermore, scallops showed persistent alterations in recessing reflex behavior following exposure, with the rate of recessing increasing with repeated exposure. Hemolymph (blood analog) physiology showed a compromised capacity for homeostasis and potential immunodeficiency, as a range of hemolymph biochemistry parameters were altered and the density of circulating hemocytes (blood cell analog) was significantly reduced, with effects observed over acute (hours to days) and chronic (months) scales. The size of the air gun had no effect, but repeated exposure intensified responses. We postulate that the observed impacts resulted from high seabed ground accelerations driven by the air gun signal. Given the scope of physiological disruption, we conclude that seismic exposure can harm scallops.

  13. Behavior of parathion in apple juice processed into cider and vinegar.

    PubMed

    Banna, A A; Kawar, N S

    1982-01-01

    Apple juice, fortified with 25 ppm (ug/g) of parathion, was processed into cider and vinegar. After the initial fermentation period of 12 days, the supernatant cider contained 7.4 ppm of parathion while the level in the sedimented lees was 88 ppm. Sorption to the sedimented matter was the main pathway for parathion residue reduction in the cider. Levels of aminoparathion and 4-nitrophenol, the only metabolites of parathion detected as confirmed by thin-layer chromatography, were 0.19 and 1.2 ppm, respectively, in the cider. The 56-day-old finished cider prior to bottling contained 2.2 ppm parathion, 0.15 ppm aminoparathion and 1.3 ppm 4-nitrophenol. Storage of the cider at 24, 12, 4 and -20 degrees C resulted in further reduction in the parathion levels. After one year, samples stored at 24 degrees C contained only 2.5% of the initial level added to the juice. Samples stored at the three other temperatures contained about 5% of the original level. Vinegar formed after 57 days of fermentation contained 5.1 ppm parathion, while the residue level in the lees was 76 ppm. Aminoparathion and 4-nitrophenol levels were 0.23 and 1.2 ppm, respectively in the vinegar. Storage of the vinegar at 24 degrees C for one year resulted in a gradual decline in the parathion level and at the end of the storage period, the remaining residue represented about 6% of the initial 24 ppm added to the juice.

  14. A model for linking the effects of parathion in soil to its degradation and bioavailability kinetics.

    PubMed

    Saffih-Hdadi, K; Bruckler, L; Lafolie, F; Barriuso, E

    2006-01-01

    Parathion is an insecticide of a group of highly toxic organophosphorus compounds. To investigate the dissipation and toxicological impact of parathion [O,O-diethyl O-(4-nitrophenyl) phosphorothioate] and its highly toxic metabolite, paraoxon, soil laboratory experiments were conducted in columns during a 19-d experiment under variably saturated conditions. Water and pesticide transport, sorption, and biodegradation of parathion were measured in three soil pools (soluble phase, weakly and strongly sorbed phases) using C-labeled pesticide. The effects of parathion and its metabolite on the mobility of soil nematodes were observed and then modeled with an effective variable, which combined pesticide concentration and time of application. Results showed that parathion was highly sorbed and slowly degraded to a mixture of metabolites. The parent compound and its metabolites remained located in the top 0.06-m soil layer. A kinetic model describing the sorption, biodegradation, and allocation into different soil pools of parathion and its metabolites was coupled with heat and water transport equations to predict the fate of parathion in soil. Simulated results were in agreement with experimental data, showing that the products remained in the upper soil layers even in the case of long-term (11-mo) simulation. The strongly sorbed fraction may be regarded as a pesticide reservoir that regularly provides pesticide to the weakly sorbed phase, and then, liquid phase, respectively. From both modeling and observations, no major toxicological damage of parathion and paraoxon to soil nematodes was found, although some effects on nematodes were possible, but at the soil surface only (0.01- and 0.02-m depth).

  15. Neonatal exposure to a glyphosate based herbicide alters the development of the rat uterus.

    PubMed

    Guerrero Schimpf, Marlise; Milesi, María M; Ingaramo, Paola I; Luque, Enrique H; Varayoud, Jorgelina

    2017-02-01

    Glyphosate-based herbicides (GBHs) are extensively used to control weeds on both cropland and non-cropland areas. No reports are available regarding the effects of GBHs exposure on uterine development. We evaluated if neonatal exposure to a GBH affects uterine morphology, proliferation and expression of proteins that regulate uterine organogenetic differentiation in rats. Female Wistar pups received saline solution (control, C) or a commercial formulation of glyphosate (GBH, 2mg/kg) by sc injection every 48h from postnatal day (PND) 1 to PND7. Rats were sacrificed on PND8 (neonatal period) and PND21 (prepubertal period) to evaluate acute and short-term effects, respectively. The uterine morphology was evaluated in hematoxylin and eosin stained sections. The epithelial and stromal immunophenotypes were established by assessing the expression of luminal epithelial protein (cytokeratin 8; CK8), basal epithelial proteins (p63 and pan cytokeratin CK1, 5, 10 and 14); and vimentin by immunohistochemistry (IHC). To investigate changes on proteins that regulate uterine organogenetic differentiation we evaluated the expression of estrogen receptor alpha (ERα), progesterone receptor (PR), Hoxa10 and Wnt7a by IHC. The GBH-exposed uteri showed morphological changes, characterized by an increase in the incidence of luminal epithelial hyperplasia (LEH) and an increase in the stromal and myometrial thickness. The epithelial cells showed a positive immunostaining for CK8, while the stromal cells for vimentin. GBH treatment increased cell proliferation in the luminal and stromal compartment on PND8, without changes on PND21. GBH treatment also altered the expression of proteins involved in uterine organogenetic differentiation. PR and Hoxa10 were deregulated both immediately and two weeks after the exposure. ERα was induced in the stromal compartment on PND8, and was downregulated in the luminal epithelial cells of gyphosate-exposed animals on PND21. GBH treatment also increased

  16. Nighttime dim light exposure alters the responses of the circadian system.

    PubMed

    Shuboni, D; Yan, L

    2010-11-10

    The daily light dark cycle is the most salient entraining factor for the circadian system. However, in modern society, darkness at night is vanishing as light pollution steadily increases. The impact of brighter nights on wild life ecology and human physiology is just now being recognized. In the present study, we tested the possible detrimental effects of dim light exposure on the regulation of circadian rhythms, using CD1 mice housed in light/dim light (LdimL, 300 lux:20 lux) or light/dark (LD, 300 lux:1 lux) conditions. We first examined the expression of clock genes in the suprachiasmatic nucleus (SCN), the locus of the principal brain clock, in the animals of the LD and LdimL groups. Under the entrained condition, there was no difference in PER1 peak expression between the two groups, but at the trough of the PER 1 rhythm, there was an increase in PER1 in the LdimL group, indicating a decrease in the amplitude of the PER1 rhythm. After a brief light exposure (30 min, 300 lux) at night, the light-induced expression of mPer1 and mPer2 genes was attenuated in the SCN of LdimL group. Next, we examined the behavioral rhythms by monitoring wheel-running activity to determine whether the altered responses in the SCN of LdimL group have behavioral consequence. Compared to the LD controls, the LdimL group showed increased daytime activity. After being released into constant darkness, the LdimL group displayed shorter free-running periods. Furthermore, following the light exposure, the phase shifting responses were smaller in the LdimL group. The results indicate that nighttime dim light exposure can cause functional changes of the circadian system, and suggest that altered circadian function could be one of the mechanisms underlying the adverse effects of light pollution on wild life ecology and human physiology. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Subchronic Arsenic Exposure Through Drinking Water Alters Lipid Profile and Electrolyte Status in Rats.

    PubMed

    Waghe, Prashantkumar; Sarkar, Souvendra Nath; Sarath, Thengumpallil Sasindran; Kandasamy, Kannan; Choudhury, Soumen; Gupta, Priyanka; Harikumar, Sankarankutty; Mishra, Santosh Kumar

    2017-04-01

    Arsenic is a groundwater pollutant and can cause various cardiovascular disorders in the exposed population. The aim of the present study was to assess whether subchronic arsenic exposure through drinking water can induce vascular dysfunction associated with alteration in plasma electrolytes and lipid profile. Rats were exposed to arsenic as 25, 50, and 100 ppm of sodium arsenite through drinking water for 90 consecutive days. On the 91st day, rats were sacrificed and blood was collected. Lipid profile and the levels of electrolytes (sodium, potassium, and chloride) were assessed in plasma. Arsenic reduced high-density lipoprotein cholesterol (HDL-C) and HDL-C/LDL-C ratio, but increased the levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and electrolytes. The results suggest that the arsenic-mediated dyslipidemia and electrolyte retention could be important mechanisms in the arsenic-induced vascular disorder.

  18. Altered behavioral development in Nrf2 knockout mice following early postnatal exposure to valproic acid

    PubMed Central

    Furnari, Melody A.; Saw, Constance Lay-Lay; Kong, Ah-Ng; Wagner, George C

    2015-01-01

    Early exposure to valproic acid results in autism-like neural and behavioral deficits in humans and other animals through oxidative stress-induced neural damage. In the present study, valproic acid was administered to genetically altered mice lacking the Nrf2 (nuclear factor-erythroid 2 related factor 2) gene on postnatal day 14 (P14). Nrf2 is a transcription factor that induces genes that protect against oxidative stress. It was found that valproic acid-treated Nrf2 knockout mice were less active in open field activity chambers, less successful on the rotorod, and had deficits in learning and memory in the Morris water maze compared to the valproic acid-treated wild type mice. Given these results, it appears that Nrf2 knockout mice were more sensitive to the neural damage caused by valproic acid administered during early development. PMID:25454122

  19. Altered behavioral development in Nrf2 knockout mice following early postnatal exposure to valproic acid.

    PubMed

    Furnari, Melody A; Saw, Constance Lay-Lay; Kong, Ah-Ng; Wagner, George C

    2014-10-01

    Early exposure to valproic acid results in autism-like neural and behavioral deficits in humans and other animals through oxidative stress-induced neural damage. In the present study, valproic acid was administered to genetically altered mice lacking the Nrf2 (nuclear factor-erythroid 2 related factor 2) gene on postnatal day 14 (P14). Nrf2 is a transcription factor that induces genes that protect against oxidative stress. It was found that valproic acid-treated Nrf2 knockout mice were less active in open field activity chambers, less successful on the rotorod, and had deficits in learning and memory in the Morris water maze compared to the valproic acid-treated wild type mice. Given these results, it appears that Nrf2 knockout mice were more sensitive to the neural damage caused by valproic acid administered during early development. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Graphene modified screen printed immunosensor for highly sensitive detection of parathion.

    PubMed

    Mehta, Jyotsana; Vinayak, Priya; Tuteja, Satish K; Chhabra, Varun A; Bhardwaj, Neha; Paul, A K; Kim, Ki-Hyun; Deep, Akash

    2016-09-15

    Due to indiscriminate use of pesticides, there is a growing need to develop sensors that can sensitively detect the trace amount of pesticides in food and water samples. Parathion, identified as an acetylcholinesterase inhibitor, had been one of the most widely used pesticides throughout the world. Symptoms of its poisoning are found to be diverse enough to include nausea, vomiting, diarrhea, muscle cramping/twitching, and shortness of breath. In this work, a graphene based impedimetric immunosensor has been fabricated and employed for highly sensitive and specific detection of parathion. The fabrication proceeded through the modification of the screen-printed carbon electrodes (SPE) with graphene sheets, followed by their functionalization with 2-aminobenzyl amine (2-ABA) via an electrochemical reaction. These amine functionalized graphene electrodes were then bio-interfaced with the anti-parathion antibodies. In the impedimetric mode, this biosensor detected parathion in a broad linear range, i.e. 0.1-1000ng/L with a very low limit of detection (52pg/L). It also showed high selectivity towards parathion in the presence of malathion, paraoxon, and fenitrothion. The viability of this biosensor was demonstrated by detecting parathion in real samples (e.g., tomato and carrot) and through cross-calibration against HPLC.

  1. Simultaneous detection of imidacloprid and parathion by the dual-labeled time-resolved fluoroimmunoassay.

    PubMed

    Shi, Haiyan; Sheng, Enze; Feng, Lu; Zhou, Liangliang; Hua, Xiude; Wang, Minghua

    2015-10-01

    A highly sensitive direct dual-labeled time-resolved fluoroimmunoassay (TRFIA) to detect parathion and imidacloprid simultaneously in food and environmental matrices was developed. Europium (Eu(3+)) and samarium (Sm(3+)) were used as fluorescent labels by coupling separately with L1-Ab and A1P1-Ab. Under optimal assay conditions, the half-maximal inhibition concentration (IC50) and limit of detection (LOD, IC10) were 10.87 and 0.025 μg/L for parathion and 7.08 and 0.028 μg/L for imidacloprid, respectively. The cross-reactivities (CR) were negligible except for methyl-parathion (42.4 %) and imidaclothiz (103.4 %). The average recoveries of imidacloprid ranged from 78.9 to 104.2 % in water, soil, rice, tomato, and Chinese cabbage with a relative standard deviation (RSD) of 2.4 to 11.6 %, and those of parathion were from 81.5 to 110.9 % with the RSD of 3.2 to 10.5 %. The results of TRFIA for the authentic samples were validated by comparison with gas chromatography (GC) analyses, and satisfactory correlations (parathion: R (2) = 0.9918; imidacloprid: R (2) = 0.9908) were obtained. The results indicate that the dual-labeled TRFIA is convenient and reliable to detect parathion and imidacloprid simultaneously in food and environmental matrices.

  2. Reduced glutathione attenuates liver injury induced by methyl parathion in rats.

    PubMed

    Jiang, Na; Lu, Lina; Wang, Tian; Zhang, Leiming; Xin, Wenyu; Fu, Fenghua

    2010-02-01

    The aim of this study was to investigate whether exogenous reduced glutathione (GSH) could protect liver injury induced by methyl parathion. Rats were allocated into four groups named as control, MP (methyl parathion poisoning), MP+GSH1 (methyl parathion poisoning treated with GSH 600 mg/kg), and MP+GSH2 (methyl parathion poisoning treated with GSH 1200 mg/kg). Each one of the last three groups was assigned into 6 h, 24 h, and 72 h sub-groups. The activities of acetylcholinesterase (AChE), glutamate pyruvate transaminase (GPT), and glutamic oxalacetic transaminase (GOT) in plasma, and superoxide dismutase (SOD) and glutathione peroxidase (GPx) in liver were assayed. The malondialdehyde (MDA) in liver was also determined. Histopathological changes in liver were observed. Results showed that AChE activity was significantly inhibited by methyl parathion and attenuated after GSH administered. GSH could relieve hepatocellular edema and fatty degeneration, and attenuate the increased activities of GPT and GOT. GSH treatment increased the SOD and GPx activities, but had no effect on the MDA level. These results indicated that GSH could attenuate liver injury induced by methyl parathion.

  3. Degradation of parathion and the reduction of acute toxicity in TiO2 photocatalysis.

    PubMed

    Zoh, K D; Kim, T S; Kim, J G; Choi, K H

    2005-01-01

    Photocatalytic degradation of methyl parathion was done using a circulating TiO2/UV and TiO2/solar reactor. Indoor experimental results showed that, under the photocatalysis conditions, parathion was more effectively degraded than under the photolysis and TiO2 only conditions. Parathion (38 microM) was completely degraded under photocatalysis within 90 min, and more than 80% TOC decrease after 150 minutes. The main ionic byproducts during the photocatalysis were measured, and almost complete nitrogen recovery was achieved as mainly NO3- NO2-, and NH4+, and 80% of sulfur as recovered as SO4(2)-. Organic intermediates such as nitrophenol and methyl paraoxon were also identified during the photocatalysis of parathion, and these were further degraded after 90 minutes. Microtox bioassay using Vibrio fischeri was used in evaluating the toxicity of solutions treated by photocatalysis and photolysis of parathion. The results showed that the acute toxicity expressed as EC50 almost reduced after 90 min under the photocatalysis condition whereas only 40% reduction of toxicity as EC50 was achieved in photolysis condition. The outdoor results using a TiO2/solar system were similar to the TiO2 indoor system, indicating the possibility of applying TiO2/solar system for the treatment of parathion-contaminated water.

  4. Studies on the metabolism of diethyl 4-nitrophenyl phosphorothionate (parathion) in vitro.

    PubMed

    Neal, R A

    1967-04-01

    1. The metabolism of the phosphorothionate parathion in vitro was examined by using [(32)P]parathion and microsomes isolated from the livers of various animal species. 2. The major metabolic products of parathion in this system in vitro were identified as diethyl 4-nitrophenyl phosphate (paraoxon), diethyl hydrogen phosphate, diethyl hydrogen phosphorothionate and p-nitrophenol. 3. The reaction leading to the formation of diethyl hydrogen phosphorothionate and p-nitrophenol requires the same cofactors (NADPH and oxygen) required for metabolism of parathion to its active anti-acetylcholinesterase paraoxon. 4. The enzyme activity towards parathion per unit weight of liver is increased some 65-130% by pretreatment of male rats with phenobarbital and 3,4-benzopyrene. 5. The metabolism of parathion is inhibited by incubation in a nitrogen atmosphere and in an atmosphere containing carbon monoxide. Pure oxygen is also inhibitory. These results are discussed in terms of a deficiency of oxygen for maximal activity as well as the lability of some component of the system to oxidation.

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

    SciTech Connect

    Sunil, Vasanthi R.; Patel, Kinal J.; Shen, Jianliang; Reimer, David; Gow, Andrew J.; Laskin, Jeffrey D.; Laskin, Debra L.

    2011-01-01

    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.

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

    PubMed Central

    Sunil, Vasanthi R.; Patel, Kinal J.; Shen, Jianliang; Reimer, David; Gow, Andrew J.; Laskin, Jeffrey D.; Laskin, Debra L.

    2013-01-01

    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. PMID:20883710

  7. Chronic lead exposure alters transthyretin concentration in rat cerebrospinal fluid: the role of the choroid plexus.

    PubMed

    Zheng, W; Shen, H; Blaner, W S; Zhao, Q; Ren, X; Graziano, J H

    1996-08-01

    The choroid plexus, which is responsible for the maintenance of the biochemical milieu of the cerebrospinal fluid (CSF), avidly sequesters Pb. In order to test the hypothesis that chronic Pb exposure may impair choroid plexus function, male weanling Sprague-Dawley rats were exposed to Pb in drinking water at doses of 0, 50, or 250 micrograms Pb/ml (as Pb acetate) for 30, 60, or 90 days. The function of the choroid plexus was assessed as reflected by CSF concentrations of transthyretin (TTR, a major CSF protein manufactured by brain choroid plexus) and CSF essential metal ions (Ca2+, Mg2+, K+, and Na+). TTR concentrations were determined by radioimmunoassay using a monospecific rabbit anti-rat TTR polyclonal antibody, and CSF metal ions analyzed by flame atomic absorption spectrophotometry. Two-way ANOVA of CSF TTR concentrations revealed highly significant dose (p < 0.0001), time (p < 0.0223), and dose-by-time effects (p < 0.0379). Moreover, the percentage of reduction of CSF TTR was directly correlated with Pb concentrations in the choroid plexus (r = 0.703, p < 0.05). Pb exposure significantly increased CSF concentrations of Mg2+, but did not markedly altered CSF concentrations of Ca2+, K+, and Na+. Histopathologic examination under the light microscope did not show distinct alterations of plexus structure in Pb-treated rats. Since TTR is responsible for transport of thyroid hormones to the developing brain, we postulate that the depression of choroid plexus TTR production (and/or secretion) by Pb may impair brain development in young animals by depriving the CNS of thyroid hormones.

  8. Perinatal Nicotine Exposure Increases Obesity Susceptibility in Adult Male Rat Offspring by Altering Early Adipogenesis.

    PubMed

    Fan, Jie; Zhang, Wan-Xia; Rao, Yi-Song; Xue, Jing-Ling; Wang, Fei-Fei; Zhang, Li; Yan, You-E

    2016-11-01

    The present study aims to evaluate whether perinatal nicotine (NIC) exposure increases obesity susceptibility in adult male rat offspring by altering early adipogenesis. NIC was sc administered (2.0 mg/kg per day) to pregnant rats from gestational day 9 to the time of weaning (postnatal day 28). At weaning, NIC-exposed male pups had an increased body weight and inguinal sc fat mass and a decreased average cell area of adipocyte, which was accompanied by an overexpression of adipogenic and lipogenic genes in the epididymal white adipose tissue. Additionally, the hepatic lipogenic gene levels from NIC-exposed male pups were also affected. At 12 and 26 weeks of age, body weight and fat mass were increased, whereas there was no change in food intake in NIC-exposed male offspring. Adipogenic and lipogenic genes, glucose transporter 4, and leptin mRNA levels were increased, whereas adiponectin mRNA levels were decreased in the epididymal white adipose tissue of NIC-exposed males. The hepatic lipogenic gene expression of NIC-exposed males was increased. NIC-exposed male offspring showed normal glycemia and a higher serum insulin level, homeostasis model assessment of insulin resistance, and homeostasis model assessment of β-cell function. Furthermore, the NIC-exposed male offspring showed higher serum lipids and Castelli index I and lower nonesterified fatty acid. At 26 weeks, in the ip glucose and insulin tolerance tests, the glucose clearance was delayed, and the area under the curve was higher in the NIC-exposed male offspring. In conclusion, perinatal NIC exposure increased obesity susceptibility in adult male rat offspring by altering early adipogenesis.

  9. Steroid levels in crinoid echinoderms are altered by exposure to model endocrine disruptors.

    PubMed

    Lavado, Ramón; Barbaglio, Alice; Carnevali, M Daniela Candia; Porte, Cinta

    2006-06-01

    Sexual steroids (testosterone and estradiol) were measured in the whole body of wild specimens of the crinoid Antedon mediterranea collected from the Tyrrhenian Sea (Italy). Testosterone levels (274-1,488 pg/g wet weight (w.w.)) were higher than those of estradiol (60-442 pg/g w.w.) and no significant differences between males and females were observed. No clear seasonal trend was either detected - individuals from February, June and October 2004 analyzed - apart from a peak of estradiol in males in autumn. Nonetheless, dramatic changes on tissue steroid levels were observed when individuals were exposed to model androgenic and anti-androgenic compounds for 2 and 4 weeks. The selected compounds were 17 alpha-methyltestosterone (17 alpha-MT), triphenyltin (TPT), fenarimol (FEN), cyproterone acetate (CPA), and p,p'-DDE. Endogenous testosterone levels were significantly increased after exposure to 17 alpha-MT, TPT and FEN, while different responses were observed for estradiol; 17 alpha-MT and FEN increased endogenous estradiol (up to seven-fold), and TPT lead to a significant decrease. Concerning the anti-androgenic compounds, CPA significantly reduced testosterone in a dose-dependent manner without altering estradiol levels, whereas specimens exposed to p,p'-DDE at a low dose (24 ng/L) for 4 weeks showed a four-fold increase in T levels. Overall, the data show the ability of the selected compounds to alter endogenous steroid concentrations in A. mediterranea, and suggest the existence in this echinoderm species of vertebrate-like mechanisms that can be affected by exposure to androgenic and anti-androgenic chemicals.

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

    PubMed

    Davis, David A; Bortolato, Marco; Godar, Sean C; Sander, Thomas K; Iwata, Nahoko; Pakbin, Payam; Shih, Jean C; Berhane, Kiros; McConnell, Rob; Sioutas, Constantinos; Finch, Caleb E; Morgan, Todd E

    2013-01-01

    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.

  11. Chronic scream sound exposure alters memory and monoamine levels in female rat brain.

    PubMed

    Hu, Lili; Zhao, Xiaoge; Yang, Juan; Wang, Lumin; Yang, Yang; Song, Tusheng; Huang, Chen

    2014-10-01

    Chronic scream sound alters the cognitive performance of male rats and their brain monoamine levels, these stress-induced alterations are sexually dimorphic. To determine the effects of sound stress on female rats, we examined their serum corticosterone levels and their adrenal, splenic, and thymic weights, their cognitive performance and the levels of monoamine neurotransmitters and their metabolites in the brain. Adult female Sprague-Dawley rats, with and without exposure to scream sound (4h/day for 21 day) were tested for spatial learning and memory using a Morris water maze. Stress decreased serum corticosterone levels, as well as splenic and adrenal weight. It also impaired spatial memory but did not affect the learning ability. Monoamines and metabolites were measured in the prefrontal cortex (PFC), striatum, hypothalamus, and hippocampus. The dopamine (DA) levels in the PFC decreased but the homovanillic acid/DA ratio increased. The decreased DA and the increased 5-hydroxyindoleacetic acid (5-HIAA) levels were observed in the striatum. Only the 5-HIAA level increased in the hypothalamus. In the hippocampus, stress did not affect the levels of monoamines and metabolites. The results suggest that scream sound stress influences most physiologic parameters, memory, and the levels of monoamine neurotransmitter and their metabolites in female rats. Copyright © 2014. Published by Elsevier Inc.

  12. Maternal caffeine exposure alters neuromotor development and hippocampus acetylcholinesterase activity in rat offspring.

    PubMed

    Souza, Ana Claudia; Souza, Andressa; Medeiros, Liciane Fernandes; De Oliveira, Carla; Scarabelot, Vanessa Leal; Da Silva, Rosane Souza; Bogo, Mauricio Reis; Capiotti, Katiucia Marques; Kist, Luiza Wilges; Bonan, Carla D; Caumo, Wolnei; Torres, Iraci L S

    2015-01-21

    The objective of this study was to evaluate the effects of maternal caffeine intake on the neuromotor development of rat offspring and on acetylcholine degradation and acetylcholinesterase (AChE) expression in the hippocampus of 14-day-old infant rats. Rat dams were treated with caffeine (0.3g/L) throughout gestation and lactation until the pups were 14 days old. The pups were divided into three groups: (1) control, (2) caffeine, and (3) washout caffeine. The washout group received a caffeine solution until the seventh postnatal day (P7). Righting reflex (RR) and negative geotaxis (NG) were assessed to evaluate postural parameters as an index of neuromotor reflexes. An open-field (OF) test was conducted to assess locomotor and exploratory activities as well as anxiety-like behaviors. Caffeine treatment increased both RR and NG latency times. In the OF test, the caffeine group had fewer outer crossings and reduced locomotion compared to control, while the washout group showed increased inner crossings in relation to the other groups and fewer rearings only in comparison to the control group. We found decreased AChE activity in the caffeine group compared to the other groups, with no alteration in AChE transcriptional regulation. Chronic maternal exposure to caffeine promotes important alterations in neuromotor development. These results highlight the ability of maternal caffeine intake to interfere with cholinergic neurotransmission during brain development.

  13. In utero exposure to chloroquine alters sexual development in the male fetal rat

    SciTech Connect

    Clewell, Rebecca A. Pluta, Linda; Thomas, Russell S.; Andersen, Melvin E.

    2009-06-15

    Chloroquine (CQ), a drug that has been used extensively for the prevention and treatment of malaria, is currently considered safe for use during pregnancy. However, CQ has been shown to disrupt steroid homeostasis in adult rats and similar compounds, such as quinacrine, inhibit steroid production in the Leydig cell in vitro. To explore the effect of in utero CQ exposure on fetal male sexual development, pregnant Sprague-Dawley rats were given a daily dose of either water or chloroquine diphosphate from GD 16-18 by oral gavage. Chloroquine was administered as 200 mg/kg CQ base on GD 16, followed by two maintenance doses of 100 mg/kg CQ base on GD 16 and 18. Three days of CQ treatment resulted in reduced maternal and fetal weight on GD 19 and increased necrosis and steatosis in the maternal liver. Fetal livers also displayed mild lipid accumulation. Maternal serum progesterone was increased after CQ administration. Fetal testes testosterone, however, was significantly decreased. Examination of the fetal testes revealed significant alterations in vascularization and seminiferous tubule development after short-term CQ treatment. Anogenital distance was not altered. Microarray and RT-PCR showed down-regulation of several genes associated with cholesterol transport and steroid synthesis in the fetal testes. This study indicates that CQ inhibits testosterone synthesis and normal testis development in the rat fetus at human relevant doses.

  14. Adolescent exposure to nicotine alters the aversive effects of cocaine in adult rats.

    PubMed

    Hutchison, Mary Anne; Riley, Anthony L

    2008-01-01

    Nicotine is one of the most commonly used drugs in adolescence and has been shown to alter the rewarding effects of cocaine when administered in adulthood. Although the abuse potential of a drug has been suggested to be a balance between its rewarding and aversive effects, the long-term effects of nicotine on the aversive properties of other drugs had not been studied. To that end, in the present study rats exposed to nicotine (0.4 mg/kg) during adolescence (postnatal days 35-44) were tested for the acquisition and extinction of a cocaine-induced conditioned taste aversion (10, 18 or 32 mg/kg) in adulthood. Conditioning consisted of four saccharin-drug pairings followed by six extinction trials. Although cocaine-induced aversions at all doses, no effect of nicotine preexposure was seen during acquisition. During extinction, the nicotine-preexposed groups conditioned with 10 and 18 mg/kg cocaine displayed a decreased rate of extinction compared to their respective controls. These results suggest that while adolescent nicotine exposure does not appear to directly alter the aversive properties of cocaine it may affect other processes related to the response to drugs given in adulthood.

  15. Altered lung function at mid-adulthood in mice following neonatal exposure to hyperoxia.

    PubMed

    Sozo, Foula; Horvat, Jay C; Essilfie, Ama-Tawiah; O'Reilly, Megan; Hansbro, Philip M; Harding, Richard

    2015-11-01

    Infants born very preterm are usually exposed to high oxygen concentrations but this may impair lung function in survivors in later life. However, the precise changes involved are poorly understood. We determined how neonatal hyperoxia alters lung function at mid-adulthood in mice. Neonatal C57BL/6J mice inhaled 65% oxygen (HE group) from birth for 7 days. They then breathed room air until 11 months of age (P11mo); these mice experienced growth restriction. Controls breathed only room air. To exclude the effects of growth restriction, a group of dams was rotated between hyperoxia and normoxia during the exposure period (HE+DR group). Lung function was measured at P11mo. HE mice had increased inspiratory capacity, work of breathing and tissue damping. HE+DR mice had further increases in inspiratory capacity and work of breathing, and reduced FEV100/FVC. Total lung capacity was increased in HE+DR males. HE males had elevated responses to methacholine. Neonatal hyperoxia alters lung function at mid-adulthood, especially in males. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Acute exposure to a high-fat diet alters meal patterns and body composition

    PubMed Central

    Melhorn, Susan J; Krause, Eric G; Scott, Karen A; Mooney, Marie R; Johnson, Jeffrey D; Woods, Stephen C; Sakai, Randall R

    2009-01-01

    Weight gain and adiposity are often attributed to the overconsumption of unbalanced, high-fat diets however, the pattern of consumption can also contribute to associated body weight and compositional changes. The present study explored the rapid alterations in meal patterns of normal-weight rats given continuous access to high-fat diet and examined body weight and composition changes compared to chow fed controls. Ten Long-Evans rats were implanted with subcutaneous microchips for meal pattern analysis. Animals were body weight-matched and separated into two groups: high-fat or chow fed. Each group was maintained on their assigned diet for nine days and monitored for 22-hours each day for meal pattern behavior. Body weight was evaluated every other day, and body composition measures were taken prior and following diet exposure. High-fat fed animals gained more weight and adipose tissue than chow fed controls and displayed a reduced meal frequency and increased meal size. Furthermore, meal size was significantly correlated with the gain of adipose tissue. Together, these results suggest that consumption of a high-fat diet can rapidly alter meal patterns, which in turn contribute to the development of adiposity. PMID:19835896

  17. Ecological implications of altered fish foraging after exposure to an antidepressant pharmaceutical.

    PubMed

    Hedgespeth, Melanie L; Nilsson, P Anders; Berglund, Olof

    2014-06-01

    Pharmaceutical residues are increasingly detected in environmental and biological samples, some at levels known to adversely affect non-target organisms; however, less is known of how these organism-level effects relate to the ecology of aquatic systems. Foraging processes may be used as behavioral endpoints that link effects on individuals to the population and community levels, enabling risk assessment of environmental contaminants at larger ecological scales. In this study, we performed feeding trials using juvenile Eurasian perch (Perca fluviatilis) exposed to the selective serotonin reuptake inhibitor (SSRI) sertraline to test the hypothesis that sertraline alters foraging ecology of the fish in terms of their functional response. We found an exposure-dependent decrease in feeding with increasing sertraline concentrations. Further experiments revealed that feeding rates decrease at both low and high prey densities, indicating effects on both attack rate and handling time, respectively. Because the functional response can shape consumer-resource dynamics, such effects may alter the stability of predator-prey systems and consequently, community structure. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Ethanol exposure during gastrulation alters neuronal morphology and behavior in zebrafish.

    PubMed

    Shan, Shubham D; Boutin, Savanna; Ferdous, Jannatul; Ali, Declan W

    2015-01-01

    Ethanol (EtOH) exposure during development has been shown to lead to deficits in fine and gross motor control. In this study we used zebrafish embryos to determine the effects of EtOH treatment during gastrulation. We treated embryos in the gastrulation stage (5.25 hours post fertilization (hpf) to 10.75 hpf) with 10 mM, 50 mM or 100 mM EtOH and examined the effects on general animal morphology, the c-start reflex behavior, Mauthner cell (M-cell) morphology and motor neuron morphology. EtOH treated fish exhibited a minor but significant increase in gross morphological deformities compared with untreated fish. Behavioral studies showed that EtOH treatment resulted in an increase in the peak speed of the tail during the escape response. Furthermore, there was a marked increase in abnormally directed c-starts, with treated fish showing greater incidences of c-starts in inappropriate directions. Immunolabeling of the M-cells, which are born during gastrulation, revealed that they were significantly smaller in fish treated with 100 mM EtOH compared with controls. Immunolabeling of primary motor neurons using anti-znp1, showed no significant effect on axonal branching, whereas secondary motor axons had a greater number of branches in ethanol treated fish compared with controls. Together these findings indicate that ethanol exposure during gastrulation can lead to alterations in behavior, neuronal morphology and possibly function.

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

    PubMed Central

    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

  20. Developmental exposure to methylmercury alters learning and induces depression-like behavior in male mice.

    PubMed

    Onishchenko, Natalia; Tamm, Christoffer; Vahter, Marie; Hökfelt, Tomas; Johnson, Jeffrey A; Johnson, Delinda A; Ceccatelli, Sandra

    2007-06-01

    To investigate the long-term effects of developmental exposure to methylmercury (MeHg), pregnant mice were exposed to at 0.5 mg MeHg/kg/day via drinking water from gestational day 7 until day 7 after delivery. The behavior of offspring was monitored at 5-15 and 26-36 weeks of age using an automated system (IntelliCage) designed for continuous long-term recording of the home cage behavior in social groups and complex analysis of basic activities and learning. In addition, spontaneous locomotion, motor coordination on the accelerating rotarod, spatial learning in Morris water maze, and depression-like behavior in forced swimming test were also studied. The analysis of behavior performed in the IntelliCage without social deprivation occurred to be more sensitive in detecting alterations in activity and learning paradigms. We found normal motor function but decreased exploratory activity in MeHg-exposed male mice, especially at young age. Learning disturbances observed in MeHg-exposed male animals suggest reference memory impairment. Interestingly, the forced swimming test revealed a predisposition to depressive-like behavior in the MeHg-exposed male offspring. This study provides novel evidence that the developmental exposure to MeHg can affect not only cognitive functions but also motivation-driven behaviors.

  1. Maternal nicotine exposure during lactation alters hypothalamic neuropeptides expression in the adult rat progeny.

    PubMed

    Younes-Rapozo, Viviane; Moura, Egberto G; Manhães, Alex C; Pinheiro, Cintia R; Santos-Silva, Ana Paula; de Oliveira, Elaine; Lisboa, Patricia C

    2013-08-01

    Maternal exposure to nicotine during lactation causes hyperleptinemia in the pups and, at adulthood, these animals are overweight and hyperleptinemic, while, in their hypothalamus, the leptin signaling pathway is reduced, evidencing a central leptin resistance. Then, we evaluated the expression of pro-opiomelanocortin (POMC), alpha-melanocyte stimulating hormone (α-MSH), cocaine and amphetamine-regulated transcript (CART), neuropeptide Y (NPY), agouti-related peptide (AgRP) and others in different hypothalamic nuclei in order to better understand the mechanisms underlying the obese phenotype observed in these animals at adulthood. On the 2nd postnatal day (P2), dams were subcutaneously implanted with osmotic minipumps releasing nicotine (NIC-6 mg/kg/day) or saline for 14 days. Offspring were killed in P180 and immunohistochemistry and Western blot analysis were carried out. Significance data had p<0.05. Adult NIC offspring showed more intense NPY staining in the paraventricular nucleus (PVN) (+21%) and increased number of POMC-positive cells in the: arcuate nucleus (+33%), as an increase in fiber density of α-MSH in PVN (+85%). However, the number of CART-positive cells was reduced in the PVN (-25%). CRH staining was more intense in NIC offspring (+136%). Orexins and AgRP were not altered. Thus, maternal nicotine exposure changes hypothalamic neuropeptides in the adult progeny that is partially compatible with leptin resistance.

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

    PubMed

    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.

  3. Prenatal cocaine exposure alters emotional arousal regulation and its effects on working memory

    PubMed Central

    Li, Zhihao; Coles, Claire D.; Lynch, Mary Ellen; Hamann, Stephan; Peltier, Scott; LaConte, Stephen; Hu, Xiaoping

    2009-01-01

    While prenatal cocaine exposure (PCE) has been associated with arousal dysregulation and attentional impairments in both human and animal studies, the neurobiological bases of these teratogenic effects have not been well characterized. In the current study, we report functional neuroimaging observations of these effects in exposed youth. Using functional magnetic resonance imaging (fMRI), we embedded task-irrelevant emotional distracters in a working memory task to examine the interaction of emotional arousal and memory in 33 PCE and 23 non-exposed adolescents. Though with similar behavioral performance, the two groups exhibited different activation patterns associated with emotion-memory interactions. On the one hand, higher memory load attenuated emotion-related amygdala activation in controls but not in the exposed adolescents; on the other hand, prefrontal activation associated with memory load decreased in the presence of emotional distraction in the controls but increased in the exposed group. These group interaction differences suggest neurobiological substrates for arousal-associated neuronal alterations related to prenatal cocaine exposure. Consistent with previous findings in behavioral and physiological studies, the present neuroimaging data provided more in-depth evidence supporting the view that PCE has significant long-term teratogenic effect on arousal regulation system. PMID:19699795

  4. Larval environmental temperature and insecticide exposure alter Aedes aegypti competence for arboviruses.

    PubMed

    Muturi, Ephantus J; Alto, Barry W

    2011-08-01

    Temperature is a key factor influencing mosquito growth and development and is also known to affect insecticide efficacy. We evaluated the effects of larval rearing temperature and exposure to insecticides on adult mosquito fitness and competence for arboviral infection using Sindbis virus (SINV). We exposed newly hatched larvae of Aedes aegypti to an environmentally realistic level of insecticide malathion at 20°C and 30°C and allowed the resulting adults to feed on SINV-infected blood meal. Exposure to malathion significantly reduced survival to adulthood. Statistically significant interactions between temperature and malathion were observed for body size, estimated population growth, and SINV infection and dissemination. Malathion-exposed Ae. aegypti cohorts had significantly higher population growth at 20°C than at 30°C. Body size decreased with higher temperature and malathion-exposed females were larger than unexposed females at 20°C but not at 30°C. Viral infection and dissemination increased with larval rearing temperature and were higher in malathion-exposed than unexposed females at 30°C but not at 20°C. These results show that environmental factors, including those factors used in controlling mosquitoes, experienced by immature stages have latent effects that continue to adulthood and alter vector competence to arboviruses.

  5. Brief Exposure to Turbulence Permanently Alters Development of Sand Dollar Larvae

    NASA Astrophysics Data System (ADS)

    Ferner, M. C.; Hodin, J.; Ng, G.; Lowe, C. J.; Gaylord, B.

    2016-02-01

    Fluid motion underlies interactions between animals and their environment through effects on locomotion, food capture, respiration, information transfer, and other processes. Recent studies of marine invertebrates indicate that metamorphosis and settlement can be altered when swimming larvae experience a change in turbulence intensity, possibly increasing the likelihood that larvae will settle in appropriate habitat. For example, brief exposure to levels of turbulence characteristic of wave-swept coasts causes echinoderm larvae to quickly transition from a non-responsive "pre-competent" stage into a "competent" stage, thereby allowing the larvae to respond to local cues and settle. However, responding to one's entry into the nearshore environment isn't enough, as many such species live as adults in a narrower range of highly specific benthic habitat that is even more rarely encountered. Here we provide an account for this apparent mismatch between larval responses to broadly distributed cues and their need for more specialized settlement locations: turbulence exposure seems to cause larval sand dollars (Dendraster excentricus) to permanently shift from pre-competence to competence. This observation suggests a scenario where turbulence can activate a temporally extensive search image in larvae over a broad habitat range, a seemingly adaptive feature for larvae entering dynamic coastal environments.

  6. Prenatal cocaine exposure alters emotional arousal regulation and its effects on working memory.

    PubMed

    Li, Zhihao; Coles, Claire D; Lynch, Mary Ellen; Hamann, Stephan; Peltier, Scott; LaConte, Stephen; Hu, Xiaoping

    2009-01-01

    While prenatal cocaine exposure (PCE) has been associated with arousal dysregulation and attentional impairments in both human and animal studies, the neurobiological bases of these teratogenic effects have not been well characterized. In the current study, we report functional neuroimaging observations of these effects in exposed youth. Using functional magnetic resonance imaging (fMRI), we embedded task-irrelevant emotional distracters in a working memory task to examine the interaction of emotional arousal and memory in 33 PCE and 23 non-exposed adolescents. Though with similar behavioral performance, the two groups exhibited different activation patterns associated with emotion-memory interactions. On the one hand, higher memory load attenuated emotion-related amygdala activation in controls but not in the exposed adolescents; on the other hand, prefrontal activation associated with memory load decreased in the presence of emotional distraction in the controls but increased in the exposed group. These group interaction differences suggest neurobiological substrates for arousal-associated neuronal alterations related to prenatal cocaine exposure. Consistent with previous findings in behavioral and physiological studies, the present neuroimaging data provided more in-depth evidence supporting the view that PCE has significant long-term teratogenic effect on arousal regulation system.

  7. Exposure of cardiac fibroblasts to the herbicide nitrofen causes altered interactions with the extracellular matrix.

    PubMed

    Borck, A; Massey, E; Loftis, M J; Carver, W

    2004-02-01

    A large proportion of congenital heart defects result from dysmorphogenesis of valvuloseptal precursors, the endocardial cushions. Intrinsic to formation and maturation of these tissues are developmental changes in cell-cell and cell-extracellular matrix interactions. Interactions between cells and the extracellular matrix play critical roles in modulating cellular processes including proliferation, migration, differentiation and even survival. While significant progress is being made in the elucidation of the cellular events involved in valvuloseptal development, little is known regarding how environmental factors may affect this process. Embryonic exposure to the herbicide nitrofen has been shown to result in congenital heart defects associated with altered endocardial cushion formation or maturation. The present studies were performed to begin to address the cellular mechanisms of these nitrofen-induced effects. Heart fibroblasts were isolated and treated with varying doses of nitrofen in vitro. Experiments were performed to determine the effects of this herbicide on important cellular processes including migration, proliferation and apoptosis. These studies illustrated a dose-dependent decrease in collagen gel contraction and proliferation in response to nitrofen. Assays were also performed to determine the effects of nitrofen on fibroblast gene expression. Increased expression of collagen type I and specific integrins were seen following nitrofen exposure. These studies illustrate that nitrofen has direct effects on cardiac fibroblast proliferation and extracellular matrix remodeling, cellular events important in valvuloseptal development.

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

    PubMed

    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.

  9. Exposure to sorbitol during lactation causes metabolic alterations and genotoxic effects in rat offspring.

    PubMed

    Cardoso, Felipe S; Araujo-Lima, Carlos F; Aiub, Claudia A F; Felzenszwalb, Israel

    2016-10-17

    Sorbitol is a polyol used by the food industry as a sweetener. Women are consuming diet and light products containing sorbitol during pregnancy and in the postnatal period to prevent themselves from excessive weight gain and maintain a slim body. Although there is no evidence for the genotoxicity of sorbitol in the perinatal period, this study focused on evaluating the effects of the maternal intake of sorbitol on the biochemical and toxicological parameters of lactating Wistar rat offspring after 14days of mother-to-offspring exposure. A dose-dependent reduction of offspring length was observed. An increase in sorbitol levels determined in the milk was also observed. However, we detected an inverse relationship between the exposition dose in milk fructose and triacylglycerols concentrations. There was an increase in the plasmatic levels of ALT, AST and LDLc and a decrease in proteins, cholesterol and glucose levels in the offspring. Sorbitol exposure caused hepatocyte genotoxicity, including micronuclei induction. Maternal sorbitol intake induced myelotoxicity and myelosuppression in their offspring. The Comet assay of the blood cells detected a dose-dependent genotoxic response within the sorbitol-exposed offspring. According to our results, sorbitol is able to induce important metabolic alterations and genotoxic responses in the exposed offspring. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Histological and morphological alterations induced by copper exposure in Laeonereis acuta (Polychaeta, Nereididae).

    PubMed

    Geracitano, L A; Luquet, C; Monserrat, J M; Bianchini, A

    2004-01-01

    Laeonereis acuta (Polychaeta, Nereididae) was collected in an unpolluted (UP) and an polluted (P) site at the Patos Lagoon estuary (Southern Brazil) and maintained under control conditions (UPC and PC, respectively) or exposed to waterborne copper (UPCu and PCu; 500 microg Cu/l), for 48 h. Four groups (aaUPC, aaPC, aaUPCu, and aaPCu) were also pre-exposed for 48 h to ascorbic acid (aa; 0.1 mM) before copper exposure. Histological and morphological alterations, as well as oxygen consumption changes were evaluated. Independently of the sampling site and the pre-exposure to the ascorbic acid, morphological abnormalities were evident in more than 80% of worms exposed to copper. Conspicuous histological changes (coeloma obliteration, cuticle separation from the epidermis, and absence of dorsal vessel) were also observed. In addition, PCu worms showed loss of the digestive epithelium and coiling behavior. Similar oxygen consumption values were observed in control and copper exposed worms.

  11. Prenatal neuroleptic exposure alters postnatal striatal cholinergic activity in the rat.

    PubMed

    Miller, J C; Friedhoff, A J

    1986-01-01

    Previous studies in our laboratory have shown that prenatal exposure to a neuroleptic during a critical period of gestation in the rat results in a marked deficit in the number of striatal dopamine-binding sites and in a diminution of dopamine agonist-induced stereotyped behavior. In the present studies, we examined the effect of prenatal neuroleptic exposure on biochemical parameters of cholinergic activity to determine whether the balance between striatal dopaminergic and cholinergic activity might be altered. The number of muscarinic cholinergic-binding sites and the specific activity of choline acetyltransferase were found to be significantly increased by prenatal treatment with the neuroleptics haloperidol or (+)-butaclamol. From the present studies and previous observations made in our laboratory, it is concluded that the ability of a neuroleptic to affect the number of muscarinic cholinergic receptors in postnatal life may be a result of the phenotypically undifferentiated state of the developing dopamine-binding site. Our findings of increased striatal cholinergic activity accompanied by a marked decrease in dopaminergic activity may have implications for an increased vulnerability to extrapyramidal motor disturbances during postnatal development.

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

    PubMed

    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. Copyright © 2014 Elsevier B.V. All

  13. Activation and degradation of the phosphorothionate insecticides parathion and EPN by rat brain.

    PubMed

    Forsyth, C S; Chambers, J E

    1989-05-15

    Cytochrome P-450-dependent monooxygenases are known to activate phosphorothionate insecticides to their oxon (phosphate) analogs by oxidative desulfuration. These activations produced potent anticholinesterases, decreasing the I50 values to rat brain acetylcholinesterase almost 1000-fold (from the 10(-5) M range to the 10(-8) M range). Since the usual cause of death in mammals from organophosphorus insecticide poisoning is respiratory failure resulting, in part, from a failure of the respiratory control center of the brain, we investigated the ability of rat brain to activate and subsequently degrade two phosphorothionate insecticides, parathion (diethyl 4-nitrophenyl phosphorothioate) and EPN (ethyl 4-nitrophenyl phenylphosphonothioate). Microsomes from specific regions (cerebral cortex, corpus striatum, cerebellum, and medulla/pons) of the brains of male and female rats and from liver were incubated with the phosphorothionate and an NADPH-generating system. Oxon production was quantified indirectly by the amount of inhibition resulting in an exogenous source of acetylcholinesterase added to the incubation mixture as an oxon trap. The microsomal activation specific activity was low for brain when compared to liver [0.23 to 0.44 and 5.1 to 12.0 nmol.min-1.(g tissue)-1 respectively]. The mitochondrial fraction of the brain possessed an activation activity for parathion similar to that of microsomes [about 0.35 nmol.min-1.(g tissue)-1 for each fraction], but mitochondrial activity was slightly greater than microsomal activity for EPN activation [0.53 to 0.58 and 0.23 to 0.47 nmole.min-1.(g tissue)-1]. Whole homogenates were tested for their ability to degrade paraoxon and EPN-oxon (ethyl 4-nitrophenyl phenylphosphonate), quantitated by 4-nitrophenol production. Specific activity for oxon degradation in liver was greater than that in brain [31 to 74 and 1.1 to 10.7 nmole.min-1.(g tissue)-1 respectively]. Overall, the brain and liver had about 1.5- to 12-fold higher

  14. Alteration of iron homeostasis following chronic exposure to manganese in rats1

    PubMed Central

    Zheng, Wei; Zhao, Qiuqu; Slavkovich, Vesna; Aschner, Michael; Graziano, Joseph H.

    2014-01-01

    Recent studies suggest that manganese-induced neurodegenerative toxicity may be partly due to its action on aconitase, which participates in cellular iron regulation and mitochondrial energy production. This study was performed to investigate whether chronic manganese exposure in rats influenced the homeostasis of iron in blood and cerebrospinal fluid (CSF). Groups of 8–10 rats received intraperitoneal injections of MnCl2 at the dose of 6 mg Mn/kg/day or equal volume of saline for 30 days. Concentrations of manganese and iron in plasma and CSF were determined by atomic absorption spectrophotometry. Rats exposed to manganese showed a greatly elevated manganese concentration in both plasma and CSF. The magnitude of increase in CSF manganese (11-fold) was equivalent to that of plasma (10-fold). Chronic manganese exposure resulted in a 32% decrease in plasma iron (p < 0.01) and no changes in plasma total iron binding capacity (TIBC). However, it increased CSF iron by 3-fold as compared to the controls (p < 0.01). Northern blot analyses of whole brain homogenates revealed a 34% increase in the expression of glutamine synthetase (p < 0.05) with unchanged metallothionein-I in manganese-intoxicated rats. When the cultured choroidal epithelial cells derived from rat choroid plexus were incubated with MnCl2 (100 µM) for four days, the expression of transferrin receptor mRNA appeared to exceed by 50% that of control (p < 0.002). The results indicate that chronic manganese exposure alters iron homeostasis possibly by expediting unidirectional influx of iron from the systemic circulation to cerebral compartment. The action appears likely to be mediated by manganese-facilitated iron transport at brain barrier systems. PMID:10375687

  15. Antenatal exposure to antidepressants is associated with altered brain development in very preterm-born neonates.

    PubMed

    Podrebarac, Samantha K; Duerden, Emma G; Chau, Vann; Grunau, Ruth E; Synnes, Anne; Oberlander, Tim F; Miller, Steven P

    2017-02-07

    Antenatal exposure to selective serotonin reuptake inhibitors (SSRIs) is associated with an enhanced risk of preterm birth. Very preterm-born neonates (<32weeks' gestation) antenatally-exposed to SSRIs may show altered brain development. To examine whether antenatal-SSRI exposure was associated with adverse neonatal brain microstructural and metabolic development using diffusion tensor and magnetic resonance spectroscopic imaging. Of 177 neonates enrolled, 14 (8%) were antenatally exposed to SSRIs. Neonates were scanned twice (median week 32; interquartile range [IQR]: 30.4-33.6) and again at term-equivalent age (40.1, IQR: 38.6-42.1). Using a region-of-interest approach, N-acetylaspartate to choline ratios (NAA/Cho), lactate to choline ratios, white and gray matter fractional anisotropy (FA), mean, axial, radial diffusivity (MD, AD, RD) values were extracted from white and gray matter subcortical regions. Neurodevelopment was assessed at 18 months, corrected age. SSRI-exposed neonates exhibited increased FA and decreased MD, AD and RD values in the superior white matter (p<0.05). FA values in the basal ganglia and thalamus were significantly lower in neonates antenatally exposed to SSRIs, compared to non-exposed (p=0.004). Lower NAA/Cho values (p=0.04) and higher Lactate/Cho values (p=0.004) in posterior gray matter were evident in neonates exposed to SSRIs. No association with antenatal-SSRI exposure and neurodevelopment was evident. Given the importance of treating depression in mothers at risk for preterm delivery, the impact of antenatal-SSRIs on early brain development requires further attention. Future research is directed at determining the mechanism of this relationship and the contribution of maternal mood. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Fetal hematopoietic alterations after maternal exposure to benzo[a]pyrene: A cytometric evaluation

    SciTech Connect

    Holladay, S.D.; Smith, B.J.

    1994-12-31

    In utero exposure to the environmental contaminant benzo[a]pyrene (BaP) was found to alter expression of murine thymocyte and liver fetal cell-surface markers. Pregnant mice were treated (via gavage) with 0, 50, 100, or 150 mg BaP/kg/d on gestational days (gd) 13-17, and offspring were examined on gd 18. Severe thymic atrophy and cellular depletion were found in BaP-exposed fetal mice. Flow cytometric analysis indicated that the BaP treatment resulted in a significant decrease in the percentage of CD4{sup +}8{sup +} fetal thymocytes, as well as significantly increased CD4{sup {minus}}8{sup {minus}} and CD4{sup {minus}}8{sup +} thymocytes. Staining of thymocytes with anti-mouse heat-stable antigen (HSA) and CD8 monoclonal antibodies produced similar results. These data suggest that BaP, in addition to producing thymic hypocellularity, inhibits normal thymocyte maturation processes. The BaP treatment was also found to decrease total fetal liver cellularity including numbers of cells within resident hematopoietic subpopulations. In particular, prolymphocytic cells, identified by CD44 and CD45R antigen expression and by presence of nuclear terminal deoxynucleotidyl transferase (TdT), were significantly decreased in animals gestationally exposed to BaP. These data, taken together, indicate that postnatal suppression of cell and humoral-mediated immune function following in utero exposure to BaP may result from multiple targeting of immune function following in utero exposure to BaP may result from multiple targeting of immune cells at different hematopoietic levels. Furthermore, results of the present study identify both qualitative and quantitative changes in fetal immune cell antigen expression that correlate well with the postnatal immunosuppression that occurs in experimental animals exposed to this carcinogenic polycyclic aromatic hydrocarbon. 41 refs., 4 figs., 3 tabs.

  17. Adolescent cannabis exposure alters opiate intake and opioid limbic neuronal populations in adult rats.

    PubMed

    Ellgren, Maria; Spano, Sabrina M; Hurd, Yasmin L

    2007-03-01

    Cannabis use is a hypothesized gateway to subsequent abuse of other drugs such as heroin. We currently assessed whether Delta-9-tetrahydrocannabinol (THC) exposure during adolescence modulates opiate reinforcement and opioid neural systems in adulthood. Long-Evan male rats received THC (1.5 mg/kg intraperitoneally (i.p.)) or vehicle every third day during postnatal days (PNDs) 28-49. Heroin self-administration behavior (fixed ratio-1; 3-h sessions) was studied from young adulthood (PND 57) into full adults (PND 102). THC-pretreated rats showed an upward shift throughout the heroin self-administration acquisition (30 microg/kg/infusion) phase, whereas control animals maintained the same pattern once stable intake was obtained. Heightened opiate sensitivity in THC animals was also evidenced by higher heroin consumption during the maintenance phase (30 and 60 microg/kg/infusion) and greater responding for moderate-low heroin doses (dose-response curve: 7.5, 15, 30, 60, and 100 microg/kg/injection). Specific disturbance of the endogenous opioid system was also apparent in the brain of adults with adolescent THC exposure. Striatal preproenkephalin mRNA expression was exclusively increased in the nucleus accumbens (NAc) shell; the relative elevation of preproenkephalin mRNA in the THC rats was maintained even after heroin self-administration. Moreover, mu opioid receptor (muOR) GTP-coupling was potentiated in mesolimbic and nigrostriatal brainstem regions in THC-pretreated animals. muOR function in the NAc shell was specifically correlated to heroin intake. The current findings support the gateway hypothesis demonstrating that adolescence cannabis exposure has an enduring impact on hedonic processing resulting in enhanced opiate intake, possibly as a consequence of alterations in limbic opioid neuronal populations.

  18. Neonatal exposure to sucralose does not alter biochemical markers of neuronal development or adult behavior.

    PubMed

    Viberg, Henrik; Fredriksson, Anders

    2011-01-01

    Sucralose, a high-intensity sweetener, has been approved as a general-purpose sweetener in all food since the late 1990s. Due to its good taste and physiochemical profile, its use has increased and sucralose is considered a way of managing health and an option to improve the quality of life in the diabetic population. Recently high concentrations of sucralose have been found in the environment. Other environmental pollutants have been shown to induce neurotoxic effects when administered during a period of rapid brain growth and development. This period of rapid brain growth and development is postnatal in mice and rats, spanning the first 3-4 wk of life, reaching its peak around postnatal day 10, whereas in humans, brain growth and development is perinatal. The proteins calcium/calmodulin-dependent protein kinase II, growth-associated protein-43, synaptophysin, and tau play important roles during brain growth and development. In the present study, mice were orally exposed to 5-125 mg of sucralose per kilogram of body weight per day during postnatal days 8-12. Twenty-four hours after last exposure, brains were analyzed for calcium/calmodulin-dependent protein kinase II, growth-associated protein-43, synaptophysin, and tau, and at the age of 2 mo the animals were tested for spontaneous behavior. The protein analysis showed no alterations in calcium/calmodulin-dependent protein kinase II, growth-associated protein-43, synaptophysin, or tau. Furthermore, there were no disturbances in adult behavior or habituation after neonatal sucralose exposure. The present study shows that repeated neonatal exposure to the artificial sweetener sucralose does not result in neurotoxicity, which supports that sucralose seems to be a safe alternative for people who want or need to reduce or substitute glucose in their diet. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Cellular alterations upon IR-laser (890 nm) exposures, in vivo.

    PubMed

    Kolesnikova, A I; Kubasova, T; Konoplyannikov, A G; Köteles, G J

    1998-01-01

    Exposure of cultured cells and small animals to ionizing radiation as well as irradiation of cultured cells with He-Ne laser can cause changes in the functional condition of plasma membranes. The ionizing radiation-induced cell membrane alterations have been determined after either partial or local exposures. The aim of the present study was to reveal whether the local laser treatments cause a general, distant, so called abscopal" effect measured at cellular level, when the laser treatment is intended as a stimulatory procedure. The biological effect of infrared laser (mean power of 5 Watts, 150 Hz frequency, 890 nm wavelength) was demonstrated through 3H-concanavalin A binding by blood cells of daily irradiated (altogether 10 exposures) oncological and non-oncological patients as well as by changes in the proliferation of bone marrow cells of whole body gamma-irradiated (4 Gy) rats, partially laser-treated. The lectin binding of lymphocytes of oncological, as well as ischaemic heart disease patients was increased immediately after the first laser treatment. However, it was decreased after completion of the full course. In cases of inflammatory diseases the test parameters were either unchanged or decreased as compared to their self-control values. The platelets and erythrocytes did not react in any group. Gamma irradiation caused a deep inhibition of proliferation of rat bone marrow cells. The number of fibroblast colony-forming units (CFU-F) could be increased again if the animals were partially exposed to laser. Laser irradiation of one of the femurs led to some recovery of CFU-F values in the exposed as well as unexposed femur. Thus, local infrared laser treatment induces abscopal effects on the cell membrane and cell proliferation characteristics.

  20. Exposure to Acetylcholinesterase Inhibitors Alters the Physiology and Motor Function of Honeybees

    PubMed Central

    Williamson, Sally M.; Moffat, Christopher; Gomersall, Martha A. E.; Saranzewa, Nastja; Connolly, Christopher N.; Wright, Geraldine A.

    2013-01-01

    Cholinergic signaling is fundamental to neuromuscular function in most organisms. Sub-lethal doses of neurotoxic pesticides that target cholinergic signaling can alter the behavior of insects in subtle ways; their influence on non-target organisms may not be readily apparent in simple mortality studies. Beneficial arthropods such as honeybees perform sophisticated behavioral sequences during foraging that, if influenced by pesticides, could impair foraging success and reduce colony health. Here, we investigate the behavioral effects on honeybees of exposure to a selection of pesticides that target cholinergic signaling by inhibiting acetylcholinesterase (AChE). To examine how continued exposure to AChE inhibitors affected motor function, we fed adult foraging worker honeybees sub-lethal concentrations of these compounds in sucrose solution for 24 h. Using an assay for locomotion in bees, we scored walking, stopped, grooming, and upside down behavior continuously for 15 min. At a 10 nM concentration, all the AChE inhibitors caused similar effects on behavior, notably increased grooming activity and changes in the frequency of bouts of behavior such as head grooming. Coumaphos caused dose-dependent effects on locomotion as well as grooming behavior, and a 1 μM concentration of coumaphos induced symptoms of malaise such as abdomen grooming and defecation. Biochemical assays confirmed that the four compounds we assayed (coumaphos, aldicarb, chlorpyrifos, and donepezil) or their metabolites acted as AChE inhibitors in bees. Furthermore, we show that transcript expression levels of two honeybee AChE inhibitors were selectively upregulated in the brain and in gut tissues in response to AChE inhibitor exposure. The results of our study imply that the effects of pesticides that rely on this mode of action have subtle yet profound effects on physiological effects on behavior that could lead to reduced survival. PMID:23386834

  1. Exposure to the endocrine disruptor nonylphenol alters structure and function of thyroid gland in rats.

    PubMed

    Xi, Yue; Li, Dehua; San, Wei

    2013-08-10

    Nonylphenol (NP) is an estrogenic-like compound which can induce vitellogenin synthesis in males and immature teleostean species. Known as an endocrine disruptor, it has been reported to affect endocrine glands; however, little is known about its effects on thyroid function. The present study aimed to evaluate whether exposure to NP alters the structure and function of the thyroid gland of rats and/or the underlying mechanisms. Rats were gavaged with NP (40, 80 and 200 mg/kg/d) for 15 days. Serum levels of thyroid-stimulating hormone were determined by radioimmunoassay. Ultramicroscopic structure of follicular cells was examined by a transmission electron microscope. Histopathology was conducted with hematoxylin-eosin (HE) staining. We found that NP exposure induced a decrease in serum levels of free tetraiodothyronine (FT) 3 and FT4 while it induced an increase in serum levels of thyroid-stimulating hormone (TSH) in a dose-dependent manner. There was a negative correlation between different doses of NP with serum levels of FT3 and FT4 (FT4 r=-0.932; FT3 r=-0.926) and a positive correlation with serum levels of TSH (r=0.967). Histological and morphometric study in the NP-exposed group revealed dilation of endoplasmic reticulum into cystic in thyroid follicular cells. Mitochondrion was damaged in the 80 and 200 mg/kg/d groups. Exposure to NP may lead to thyroid dysfunction. It may be a potential contributor to thyroid disruption. © 2013 Elsevier B.V. All rights reserved.

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

    PubMed Central

    2009-01-01

    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. PMID:19331648

  3. Kinetics and mechanism of the degradation of methyl parathion in aqueous hydrogen sulfide solution: investigation of natural organic matter effects.

    PubMed

    Guo, Xiaofen; Jans, Urs

    2006-02-01

    The kinetics of the transformation of methyl parathion have been investigated in aqueous solution containing reduced sulfur species and small concentrations of natural organic matter (NOM) from different sources such as soil, river, and peat. It was shown that NOM mediates the degradation of methyl parathion in aqueous solutions containing hydrogen sulfide. After evaluating and quantifying the effect of the NOM concentration on the degradation kinetics of methyl parathion in the presence of hydrogen sulfide, it was found that the observed pseudo-first-order reaction rate constants (k(obs)) were proportional to NOM concentrations. The influence of pH on the degradation of methyl parathion in the aqueous solutions containing hydrogen sulfide and NOM has been studied. The rate of degradation of methyl parathion was strongly pH dependent. The results indicate k(obs) with a commercially available humic acid has a maximum value at approximately pH 8.3. Two main reaction mechanisms are identified to dominate the degradation of methyl parathion in aqueous solution containing hydrogen sulfide and NOM based on the products aminomethyl parathion and desmethyl methyl parathion. The two mechanisms are nitro-group reduction and nucleophilic attack at the methoxy-carbon. The reduction of the nitro-group is only observed in the presence of NOM. The results of this study form an important base for the evaluation and interpretation of transformation processes of methyl parathion in the environment.

  4. Association between lead exposure from electronic waste recycling and child temperament alterations.

    PubMed

    Liu, Junxiao; Xu, Xijin; Wu, Kusheng; Piao, Zhongxian; Huang, Jinrong; Guo, Yongyong; Li, Weiqiu; Zhang, Yuling; Chen, Aimin; Huo, Xia

    2011-08-01

    We aimed to evaluate the dose-dependent effects of lead exposure on temperament alterations in children from a primitive e-waste (obsolete electrical and electronic devices) recycling area in Guiyu of China and a control area (Chendian, China). Blood lead levels (BLL) might be correlated with temperament, health, and relevant factors that were evaluated through Parent Temperament Questionnaire (PTQ), physical examination, and residential questionnaires. We collected venipuncture blood samples from 303 children (aged 3-7 years old) between January and February 2008. Child BLL were higher in Guiyu than in Chendian (median 13.2 μg/dL, range 4.0-48.5 μg/dL vs. 8.2 μg/dL, 0-21.3 μg/dL) (P<0.01). Significant differences of mean scores in activity level (4.53±0.83 vs. 4.18±0.81), approach-withdrawal (4.62±0.85 vs. 4.31±0.89), and adaptability (4.96±0.73 vs. 4.67±0.83) were found between Guiyu and Chendian children (all P<0.01). High BLL (BLL≥10μg/dL) child had higher mean scores of approach-withdrawal when compared with those children with low BLL (BLL<10 μg/dL) (4.61±0.87 vs. 4.30±0.88, P<0.01). Location of child residence in Guiyu, and parents engagement in work related to e-waste were the risk factors related to child BLL, activity level, approach-withdrawal, adaptability, and mood. Child hand washing prior to food consumption was a protected factor for BLL and several dimensions. There are close relationships between BLL elevation, temperament alteration and the e-waste recycling activities in Guiyu. Primitive e-waste recycling may threaten the health of children by increasing BLL and altering children temperament, although the exposure to other toxicants needs to be examined in future studies.

  5. Altered neuron-glia interactions in a low, chronic prenatal ethanol exposure.

    PubMed

    Evrard, Sergio Gustavo; Vega, Maite Duhalde; Ramos, Alberto Javier; Tagliaferro, Patricia; Brusco, Alicia

    2003-12-30

    Serotoninergic neurons, astrocytes and nitrergic system play an important role in central nervous system (CNS) development. These systems are altered in prenatal ethanol exposure (PEE) but ethanol (EtOH) effects may be very diverse under different conditions. In this study, we analyzed morphologically two serotoninergic mesencephalic nuclei and three prosencephalic areas of serotoninergic innervation in a model of pre- and postnatal low-ethanol exposure. Female Wistar rats were orally exposed to EtOH 6.6% (v/v), ad libitum, for 6 weeks before mating and during gestation and lactation while control group received water ad libitum. Twenty-day-old offspring (P21) brains were processed and immunoreactivity (IR) using antibodies against tryptophan hydroxylase (TPH), 5-HT, 5-HT transporter (5HTT), glial fibrillary acidic protein (GFAP), S-100B protein, 200-kDa neurofilaments (Nf-200) and neuronal nitric oxide synthase (nNOS) was evaluated. Dorsal and median raphe nucleus (DRN and MRN), hippocampus (Hipp), striatum (Strt) and frontal cortex (FCx) were studied by computer-assisted image analysis. Relative optical density (ROD) of TPH-IR, 5-HT-IR and nNOS-IR neurons; cell area of GFAP-IR astrocytes; relative area of 5HTT-IR fibers and Nf-200-IR were evaluated. TPH-IR was increased in DRN and MRN and 5-HT-IR was increased only in MRN. 5-HTT-IR fibers and ROD of S-100B-IR astrocytes were increased in the three prosencephalic areas while GFAP-IR astrocytes were hypertrophied only in Hipp and FCx. Nf-200 expression was increased in Hipp and Strt and morphologically altered in the FCx. ROD of nNOS-IR neurons was increased in Strt and FCx but was not detected in Hipp. We have also detected morphological changes resembling accelerated development and maturation, and early aging. Considering the evidences of a close 5-HT-astroglial-NO relationship during CNS development the differential response of the studied regions is an interesting result that could be due to different

  6. Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation.

    PubMed

    Liu, Yunlong; Balaraman, Yokesh; Wang, Guohua; Nephew, Kenneth P; Zhou, Feng C

    2009-10-01

    Alcohol exposure during development can cause variable neurofacial deficit and growth retardation known as fetal alcohol spectrum disorders (FASD). The mechanism underlying FASD is not fully understood. However, alcohol, which is known to affect methyl donor metabolism, may induce aberrant epigenetic changes contributing to FASD. Using a tightly controlled whole-embryo culture, we investigated the effect of alcohol exposure (88mM) at early embryonic neurulation on genome-wide DNA methylation and gene expression in the C57BL/6 mouse. The DNA methylation landscape around promoter CpG islands at early mouse development was analyzed using MeDIP (methylated DNA immunoprecipitation) coupled with microarray (MeDIP-chip). At early neurulation, genes associated with high CpG promoters (HCP) had a lower ratio of methylation but a greater ratio of expression. Alcohol-induced alterations in DNA methylation were observed, particularly in genes on chromosomes 7, 10, and X; remarkably, a >10 fold increase in the number of genes with increased methylation on chromosomes 10 and X was observed in alcohol-exposed embryos with a neural tube defect phenotype compared to embryos without a neural tube defect. Significant changes in methylation were seen in imprinted genes, genes known to play roles in cell cycle, growth, apoptosis, cancer, and in a large number of genes associated with olfaction. Altered methylation was associated with significant (p<0.01) changes in expression for 84 genes. Sequenom EpiTYPER DNA methylation analysis was used for validation of the MeDIP-chip data. Increased methylation of genes known to play a role in metabolism (Cyp4f13) and decreased methylation of genes associated with development (Nlgn3, Elavl2, Sox21 and Sim1), imprinting (Igf2r) and chromatin (Hist1h3d) was confirmed. In a mouse model for FASD, we show for the first time that alcohol exposure during early neurulation can induce aberrant changes in DNA methylation patterns with associated changes in

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

    PubMed

    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

  8. Chronic lead exposure alters presynaptic calcium regulation and synaptic facilitation in Drosophila larvae

    PubMed Central

    He, T.; Hirsch, H.V.B.; Ruden, D. M.; Lnenicka, G. A.

    2009-01-01

    Prolonged exposure to inorganic lead (Pb2+) during development has been shown to influence activity-dependent synaptic plasticity in the mammalian brain, possibly by altering the regulation of intracellular Ca2+ concentration ([Ca2+]i). To explore this possibility, we studied the effect of Pb2+ exposure on [Ca2+]i regulation and synaptic facilitation at the neuromuscular junction of larval Drosophila. Wild-type Drosophila (CS) were raised from egg stages through the third larval instar in media containing either 0, 100 μM or 250 μM Pb2+ and identified motor terminals were examined in late third-instar larvae. To compare resting [Ca2+]i and the changes in [Ca2+]i produced by impulse activity, the motor terminals were loaded with a Ca2+ indicator, either Oregon Green 488 BAPTA-1 (OGB-1) or fura-2 conjugated to a dextran. We found that rearing in Pb2+ did not significantly change the resting [Ca2+]i nor the Ca2+ transient produced in synaptic boutons by single action potentials (APs); however, the Ca2+ transients produced by 10 and 20 Hz AP trains were larger in Pb2+-exposed boutons and decayed more slowly. For larvae raised in 250 μM Pb2+, the increase in [Ca2+]i during an AP train (20 Hz) was 29% greater than in control larvae and the [Ca2+]i decay τ was 69% greater. These differences appear to result from reduced activity of the plasma membrane Ca2+ ATPase (PMCA), which extrudes Ca2+ from these synaptic terminals. These findings are consistent with studies in mammals showing a Pb2+-dependent reduction in PMCA activity. We also observed a Pb2+-dependent enhancement of synaptic facilitation at these larval neuromuscular synapses. Facilitation of EPSP amplitude during AP trains (20 Hz) was 55% greater in Pb2+-reared larvae than in controls. These results showed that Pb2+ exposure produced changes in the regulation of [Ca2+]i during impulse activity, which could affect various aspects of nervous system development. At the mature synapse, this altered [Ca2+]i

  9. Adult Hippocampal Neurogenesis and mRNA Expression are Altered by Perinatal Arsenic Exposure in Mice and Restored by Brief Exposure to Enrichment

    PubMed Central

    Tyler, Christina R.; Allan, Andrea M.

    2013-01-01

    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 progenitor

  10. Developmental lead exposure alters methamphetamine self-administration in the male rat: acquisition and reinstatement.

    PubMed

    Rocha, Angelica; Valles, Rodrigo; Bratton, Gerald R; Nation, Jack R

    2008-05-01

    control group. These results suggest perinatal lead exposure alters patterns of methamphetamine self-administration during the adult cycle.

  11. In vitro dermal absorption of methyl salicylate, ethyl parathion, and malathion: first responder safety.

    PubMed

    Moody, Richard P; Akram, Mohammed; Dickson, Eva; Chu, Ih

    2007-06-01

    In vitro tests with fresh dermatomed (0.3 to 0.4 mm thick) female breast skin and one leg skin specimen were conducted in Bronaugh flow-through Teflon diffusion cells with three chemicals used to simulate chemical warfare agents: 14C-radiolabeled methyl salicylate (MES), ethyl parathion (PT), and malathion (MT), at three dose levels (2, 20, and 200 mM). Tests were conducted at a skin temperature of 29 degrees C using a brief 30-min exposure to the chemical and a 6.5-h receivor collection period. Rapid absorption of all three chemicals was observed, with MES absorbed about 10-fold faster than PT and MT. For MES, PT, and MT, respectively, there was 32%, 7%, and 12% absorption into the receivor solution (Hank's HEPES buffered saline with 4% bovine serum albumin [BSA], pH 7.4) at the low dose (2 mM), 17%, 2%, and 3% at the medium dose (20 mM), and 11%, 1%, and 1% at the high dose (200 mM) levels. Including the skin depot for MES, PT, and MT, respectively, there was 40%, 41%, and 21% (low dose), 26%, 16%, and 8% (medium dose), and 13%, 19%, and 10% (high does) absorption. Efficacy of skin soap washing conducted at the 30 min exposure time ranged from 31% to 86%, varying by chemical and dose level. Skin depot levels were highest for the relatively lipophilic PT. "Pseudo" skin permeability coefficient (K(p)) data declined with dose level, suggesting skin saturation had occurred. An in-depth comparison with literature data was conducted and risk assessment of first responder exposure was briefly considered.

  12. Repeated exposures of the male Sprague Dawley rat reproductive tract to environmental toxicants: Do earlier exposures to di-(2-ethylhexyl)phthalate (DEHP) alter the effects of later exposures?

    PubMed

    Traore, Kassim; Martinez-Arguelles, Daniel B; Papadopoulos, Vassilios; Chen, Haolin; Zirkin, Barry R

    2016-06-01

    Although exposures to environmental toxicants occur throughout life, little attention has been paid to the possible effects of exposures early in life on later exposure effects. We asked whether DEHP administered in utero (GD14-parturition) affects how male rats respond to later exposures. Neither in utero nor juvenile (PND21-35) exposures to 100mg/kg/day DEHP affected testis weight or histology as assessed on PND35. However, after in utero DEHP, subsequent juvenile exposure resulted in significantly reduced testis weight and altered testicular histology. Both in utero and juvenile exposures resulted in significant reductions in serum testosterone, but there was no effect of earlier on later exposure. Whether or not there had been in utero DEHP exposure, juvenile DEHP exposure had no effect on body, kidney or liver weights. These observations indicate that in utero exposure can, but will not necessarily, alter later exposure effects, with outcomes dependent upon endpoints measured and dose. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Exposure to the insecticide endosulfan induces liver morphology alterations and oxidative stress in fruit-eating bats (Artibeus lituratus).

    PubMed

    Oliveira, Jerusa Maria; Brinati, Alessandro; Miranda, Liany Divina Lima; Morais, Danielle Barbosa; Zanuncio, José Cola; Gonçalves, Reggiani Vilela; Peluzio, Maria do Carmo Gouveia; Freitas, Mariella Bontempo

    2017-02-01

    Exposure to pesticides may increase the generation of reactive oxygen species (ROS), leading to oxidation of cell membrane lipids and proteins. Although fruit bats are potentially exposed to pesticides during their entire lifespan, the impacts of this exposure are still poorly investigated. We examined the effects of low, commercially recommended concentrations (0, 1.05 and 2.1 g/l) of an organochlorine insecticide endosulfan (EDS) formulation on oxidative responses in the liver and kidneys of Neotropical fruit bats (Artibeus lituratus), as well as possible liver morphological alterations following a 35-day oral exposure. Superoxide dismutase activity was significantly decreased upon exposure to 1.05 g/l of EDS in the liver and kidneys, catalase was decreased in the liver of 2.1 g/l EDS-exposed bats, while glutathione S-transferase was increased in the liver of 2.1 g/l EDS-exposed bats. Protein carbonyls increased following the exposure to the highest EDS dose tested. Endosulfan-induced morphological alterations in the liver included cell degeneration and cell death, with apparent cytoplasm lipid accumulation (steatosis) and pyknotic nuclei, karyolysis and deposit of collagen fibres. Our findings suggest that exposure to low concentrations of EDS induced a certain extent of oxidative damage in fruit bats, which may have led to liver morphological alterations. © 2017 The Authors. International Journal of Experimental Pathology © 2017 International Journal of Experimental Pathology.

  14. The timing of embryonic exposure to elevated temperature alters stress endocrinology in domestic chickens (Gallus domesticus).

    PubMed

    Wilsterman, Kathryn; Mast, Andrew D; Luu, Thuyvan H; Haussmann, Mark F

    2015-02-01

    Patterns of glucocorticoid (GC) release in response to stimuli vary both among individuals and within individuals across their lifetime. While much work has focused on how the prenatal steroid environment can affect GC release, relatively little is known about how environmental parameters, such as incubation temperature affect GCs. We tested the hypothesis that variation and timing of elevated incubation temperature within the thermoneutral zone can alter the pattern of GC release. We incubated domestic chicken eggs (Gallus domesticus) at the optimal incubation temperature (37.5 °C) or at a slightly higher temperature (+1.1 °C) either early, late, or throughout incubation. At three weeks post-hatch, all birds were (i) exposed to a capture-restraint stress to measure stress-induced GC release (naïve). Three days following the naïve stressor, birds were (ii) exposed to a heat challenge, which was followed the next day by a second capture-restraint stress (post-heat challenge). Regardless of treatment, birds had similar patterns of GC release following the naïve stress series. However, during the post-heat challenge stress series, birds incubated at optimal temperatures increased their peak GC release. In contrast, birds exposed to slightly elevated temperatures for any period of development failed to increase peak GC release, and their specific response varied with timing of exposure to the elevated incubation temperature. Our results demonstrate that subtle variation in the embryonic environment, such as elevated incubation temperature within the thermoneutral zone, can impact the pattern of GC release of offspring. Further work is needed to understand the mechanisms underlying these changes and the relationship between fitness and environmentally-altered phenotypes.

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

    PubMed Central

    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

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

    PubMed

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

    2015-09-01

    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.

  17. Neoplastic alterations induced in mammalian skin following mancozeb exposure using in vivo and in vitro models.

    PubMed

    Tyagi, Shilpa; George, Jasmine; Singh, Richa; Bhui, Kulpreet; Shukla, Yogeshwer

    2011-03-01

    Mancozeb, ethylene(bis)dithiocarbamate fungicides, has been well documented in the literature as a multipotent carcinogen, but the underlying mechanism remains unrevealed. Thus, mancozeb has been selected in this study with the objective to decipher the molecular mechanism that culminates in carcinogenesis. We employed two-dimensional gel electrophoresis and mass spectrometry to generate a comparative proteome profile of control and mancozeb (200 mg/kg body weight) exposed mouse skin. Although many differentially expressed proteins were found, among them, two significantly upregulated proteins, namely, S100A6 (Calcyclin) and S100A9 (Calgranulin-B), are known markers of keratinocyte differentiation and proliferation, which suggested their role in mancozeb-induced neoplastic alterations. Therefore, we verified these alterations in the human system by using HaCaT cells as an in vitro model for human skin keratinocyte carcinogenesis. Upregulation of these two proteins upon mancozeb (0.5 μg/mL) exposure in HaCaT cells indicated its neoplastic potential in human skin also. This potential was confirmed by increase in number of colonies in colony formation and anchorage-independent growth assays. Modulation of S100A6/S100A9 targets, elevated phosphorylation of extracellular signal regulated kinase (ERK1/2), Elk1, nuclear factor- kappa B and cell division cycle 25 C phosphatase, and cyclin D1 and cyclooxygenase-2 upregulation was seen. In addition, PD98059 (ERK1/2 inhibitor) reduced cell proliferation induced by mancozeb, confirming the involvement of ERK1/2 signaling. Conclusively, we herein present the first report asserting that the mechanism involving S100A6 and S100A9 regulated ERK1/2 signaling underlies the mancozeb-induced neoplastic potential in human skin.

  18. Exposure of Persian sturgeon (Acipenser persicus) to cadmium results in biochemical, histological and transcriptional alterations.

    PubMed

    Miandare, Hamed Kolangi; Niknejad, Mahtab; Shabani, Ali; Safari, Roghieh

    2016-01-01

    Sturgeon is one of the endangered families of fish in the Caspian Sea region, where there is up to 80% of their global caching. Unfortunately, in recent years, increase of pollutants has been resulted in their total population reduction. Due to their benthic nature, sturgeons are at great risk of exposing to contaminants such as cadmium. Despite their endangered status in the Caspian Sea, there are only a few studies on characterizing the relative sensitivity of sturgeons to cadmium. Adverse effects associated with pollution on angiogenesis are mediated by hypoxia inducing factor-1 (HIF-1) and vascular endothelial growth factor (VEGF). In this investigation, gene expression of two distinct HIFs-1, HIF-1α and HIF-2α, and VEGF was investigated at the mRNA transcript levels after exposure of Persian sturgeon (Acipenser persicus) to cadmium. VEGF, HIF-1α and HIF-2α expressions in treated Persian sturgeon were greater than controls. Significant increases (P<0.05) were also observed in cortisol and glucose levels compared to the control group especially in the fish exposed to higher cadmium concentration (800 μg/L). Plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactic acid dehydrogenase (LDH) levels were increased in the cadmium-exposed fish, although the observed increases were not significant between the control and 200 μg/L cadmium treatment at some sampling time points. Gill tissues also showed histopathological changes in the cadmium treatments. Overall, results indicated that cadmium resulted in some alterations in biochemical parameters, mRNA transcript level expression of two important angiogenesis related genes as well as histological alterations in Persian sturgeon.

  19. Functional changes after prenatal opiate exposure related to opiate receptors' regulated alterations in cholinergic innervation.

    PubMed

    Yanai, Joseph; Huleihel, Rabab; Izrael, Michal; Metsuyanim, Sally; Shahak, Halit; Vatury, Ori; Yaniv, Shiri P

    2003-09-01

    Opioid drugs act primarily on the opiate receptors; they also exert their effect on other innervations resulting in non-opioidergic behavioural deficits. Similarly, opioid neurobehavioural teratogenicity is attested in numerous behaviours and neural processes which hinder the research on the mechanisms involved. Therefore, in order to be able to ascertain the mechanism we have established an animal (mouse) model for the teratogenicity induced by opioid abuse, which focused on behaviours related to specific brain area and innervation. Diacetylmorphine (heroin) and not morphine was applied because heroin exerts a unique action, distinguished from that of morphine. Pregnant mice were exposed to heroin (10 mg/kg per day) and the offspring were tested for behavioural deficits and biochemical alterations related to the septohippocampal cholinergic innervation. Some studies employing the chick embryo were concomitantly added as a control for the confounding indirect variables. Prenatal exposure to heroin in mice induced global hyperactivation both pre- and post-synaptic along the septohippocampal cholinergic innervation, including basal protein kinase C (PKC) activity accompanied by a desensitization of PKC activity in response to cholinergic agonist. Functionally, the heroin-exposed offspring displayed deficits in hippocampus-related behaviours, suggesting deficits in the net output of the septohippocampal cholinergic innervation. Grafting of cholinergic cells to the impaired hippocampus reversed both pre- and post-synaptic hyperactivity, resensitized PKC activity, and restored the associated behaviours to normality. Consistently, correlation studies point to the relative importance of PKC to the behavioural deficits. The chick model, which dealt with imprinting related to a different brain region, confirmed that the effect of heroin is direct. Taken together with studies by others on the effect of prenatal exposure to opioids on the opioidergic innervation and with what

  20. Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation

    PubMed Central

    Rodgers, Ali B.; Morgan, Christopher P.; Bronson, Stefanie L.; Revello, Sonia; Bale, Tracy L.

    2013-01-01

    Neuropsychiatric disease frequently presents with an underlying hypo- or hyper- reactivity of the HPA stress axis, suggesting an exceptional vulnerability of this circuitry to external perturbations. Parental lifetime exposures to environmental challenges are associated with increased offspring neuropsychiatric disease risk, and likely contribute to stress dysregulation. While maternal influences have been extensively examined, much less is known regarding the specific role of paternal factors. To investigate the potential mechanisms by which paternal stress may contribute to offspring hypothalamic-pituitary-adrenal (HPA) axis dysregulation, we exposed mice to six weeks of chronic stress prior to breeding. As epidemiological studies support variation in paternal germ cell susceptibility to reprogramming across the lifespan, male stress exposure occurred either throughout puberty or in adulthood. Remarkably, offspring of sires from both paternal stress groups displayed significantly reduced HPA axis stress responsivity. Gene set enrichment analyses in offspring stress regulating brain regions, the paraventricular nucleus (PVN) and the bed nucleus of stria terminalis (BNST), revealed global pattern changes in transcription suggestive of epigenetic reprogramming and consistent with altered offspring stress responsivity, including increased expression of glucocorticoid-responsive genes in the PVN. In examining potential epigenetic mechanisms of germ cell transmission, we found robust changes in sperm miRNA (miR) content, where nine specific miRs were significantly increased in both paternal stress groups. Overall, these results demonstrate that paternal experience across the lifespan can induce germ cell epigenetic reprogramming and impact offspring HPA stress axis regulation, and may therefore offer novel insight into factors influencing neuropsychiatric disease risk. PMID:23699511

  1. Prenatal Oxycodone Exposure Alters CNS Endothelin Receptor Expression in Neonatal Rats.

    PubMed

    Devarapalli, M; Leonard, M; Briyal, S; Stefanov, G; Puppala, B L; Schweig, L; Gulati, A

    2016-05-01

    Prenatal opioid exposure such as oxycodone is linked to significant adverse effects on the developing brain. Endothelin (ET) and its receptors are involved in normal development of the central nervous system. Opioid tolerance and withdrawal are mediated through ET receptors. It is possible that adverse effect of oxycodone on the developing brain is mediated through ET receptors. We evaluated brain ETA and ETB receptor expression during postnatal development in rats with prenatal oxycodone exposure. Timed pregnant Sprague-Dawley rats received either oxycodone or placebo throughout gestation. After birth, male rat pups were sacrificed on postnatal day (PND) 1, 7, 14 or 28. Brain ETA and ETB receptor expression was determined by Western blot analysis. Oxycodone pups compared to placebo demonstrated congenital malformations of the face, mouth, and vertebrae at the time of birth [4/69 (5.7%) vs. 0/60 (0%); respectively] and intrauterine growth retardation [10/69 (15%) vs. 2/60 (3.3%); respectively]. On PND 28, oxycodone pups compared to placebo had lower body and kidney weight. ETA receptor expression in the oxycodone group was significantly higher compared to placebo on PND 1 (p=0.035), but was similar on PND 7, 14, or 28. ETB receptor expression decreased in oxycodone compared to placebo on PND 1 and 7 (p=0.001); and increased on PND 28 (p=0.002), but was similar on PND 14. Oxycodone-exposed rat pups had lower birth weight and postnatal weight gain and greater congenital malformations. ETB receptor expression is altered in the brain of oxycodone-treated rat pups indicating a possible delay in CNS development.

  2. CO-occurring exposure to perchlorate, nitrate and thiocyanate alters thyroid function in healthy pregnant women.

    PubMed

    Horton, Megan K; Blount, Benjamin C; Valentin-Blasini, Liza; Wapner, Ronald; Whyatt, Robin; Gennings, Chris; Factor-Litvak, Pam

    2015-11-01

    Adequate maternal thyroid function during pregnancy is necessary for normal fetal brain development, making pregnancy a critical window of vulnerability to thyroid disrupting insults. Sodium/iodide symporter (NIS) inhibitors, namely perchlorate, nitrate, and thiocyanate, have been shown individually to competitively inhibit uptake of iodine by the thyroid. Several epidemiologic studies examined the association between these individual exposures and thyroid function. Few studies have examined the effect of this chemical mixture on thyroid function during pregnancy We examined the cross sectional association between urinary perchlorate, thiocyanate and nitrate concentrations and thyroid function among healthy pregnant women living in New York City using weighted quantile sum (WQS) regression. We measured thyroid stimulating hormone (TSH) and free thyroxine (FreeT4) in blood samples; perchlorate, thiocyanate, nitrate and iodide in urine samples collected from 284 pregnant women at 12 (±2.8) weeks gestation. We examined associations between urinary analyte concentrations and TSH or FreeT4 using linear regression or WQS adjusting for gestational age, urinary iodide and creatinine. Individual analyte concentrations in urine were significantly correlated (Spearman's r 0.4-0.5, p<0.001). Linear regression analyses did not suggest associations between individual concentrations and thyroid function. The WQS revealed a significant positive association between the weighted sum of urinary concentrations of the three analytes and increased TSH. Perchlorate had the largest weight in the index, indicating the largest contribution to the WQS. Co-exposure to perchlorate, nitrate and thiocyanate may alter maternal thyroid function, specifically TSH, during pregnancy. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Co-occurring exposure to perchlorate, nitrate and thiocyanate alters thyroid function in healthy pregnant women

    PubMed Central

    Horton, Megan K.; Blount, Benjamin C.; Valentin-Blasini, Liza; Wapner, Ronald; Whyatt, Robin; Gennings, Chris; Factor-Litvak, Pam

    2015-01-01

    Background Adequate maternal thyroid function during pregnancy is necessary for normal fetal brain development, making pregnancy a critical window of vulnerability to thyroid disrupting insults. Sodium/iodide symporter (NIS) inhibitors, namely perchlorate, nitrate, and thiocyanate, have been shown individually to competitively inhibit uptake of iodine by the thyroid. Several epidemiologic studies examined the association between these individual exposures and thyroid function. Few studies have examined the effect of this chemical mixture on thyroid function during pregnancy. Objectives We examined the cross sectional association between urinary perchlorate, thiocyanate and nitrate concentrations and thyroid function among healthy pregnant women living in New York City using weighted quantile sum (WQS) regression. Methods We measured thyroid stimulating hormone (TSH) and free thyroxine (FreeT4) in blood samples; perchlorate, thiocyanate, nitrate and iodide in urine samples collected from 284 pregnant women at 12 (± 2.8) weeks gestation. We examined associations between urinary analyte concentrations and TSH or FreeT4 using linear regression or WQS adjusting for gestational age, urinary iodide and creatinine. Results Individual analyte concentrations in urine were significantly correlated (Spearman’s r 0.4–0.5, p < 0.001). Linear regression analyses did not suggest associations between individual concentrations and thyroid function. The WQS revealed a significant positive association between the weighted sum of urinary concentrations of the three analytes and increased TSH. Perchlorate had the largest weight in the index, indicating the largest contribution to the WQS. Conclusions Co-exposure to perchlorate, nitrate and thiocyanate may alter maternal thyroid function, specifically TSH, during pregnancy. PMID:26408806

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

    PubMed

    Frazier, Cristianne R M; Mason, Peggy; Zhuang, Xiaoxi; Beeler, Jeff A

    2008-09-17

    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.

  5. Pesticide Exposure Alters Follicle-Stimulating Hormone Levels in Mexican Agricultural Workers

    PubMed Central

    Recio, Rogelio; Ocampo-Gómez, Guadalupe; Morán-Martínez, Javier; Borja-Aburto, Victor; López-Cervantes, Malaquías; Uribe, Marisela; Torres-Sánchez, Luisa; Cebrián, Mariano E.

    2005-01-01

    Organophosphorous pesticides (OPs) are suspected of altering reproductive function by reducing brain acetylcholinesterase activity and monoamine levels, thus impairing hypothalamic and/or pituitary endocrine functions and gonadal processes. Our objective was to evaluate in a longitudinal study the association between OP exposure and serum levels of pituitary and sex hormones. Urinary OP metabolite levels were measured by gas–liquid chromatography, and serum pituitary and sex hormone levels by enzymatic immunoassay and radioimmunoassay in 64 men. A total of 147 urine and blood samples were analyzed for each parameter. More than 80% of the participants had at least one OP metabolite in their urine samples. The most frequent metabolite found was diethylthiophosphate (DETP; 55%), followed by diethylphosphate (DEP; 46%), dimethylthiophosphate (DMTP; 32%), and dimethyldithiophosphate (DMDTP; 31%). However, the metabolites detected at higher concentrations were DMTP, DEP, DMDTP, and dimethylphosphate. There was a high proportion of individuals with follicle-stimulating hormone (FSH) concentrations outside the range of normality (48%). The average FSH serum levels were higher during the heavy pesticide spraying season. However, a multivariate analysis of data collected in all periods showed that serum FSH levels were negatively associated with urinary concentrations of both DMTP and DMDTP, whereas luteinizing hormone (LH) was negatively associated with DMTP. We observed no significant associations between estradiol or testosterone serum levels with OP metabolites. The hormonal disruption in agricultural workers presented here, together with results from experimental animal studies, suggests that OP exposure disrupts the hypothalamic–pituitary endocrine function and also indicates that FSH and LH are the hormones most affected. PMID:16140621

  6. Exposure of Soil Microbial Communities to Chromium and Arsenic Alters Their Diversity and Structure

    PubMed Central

    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

  7. Functional alterations in immature cultured rat hippocampal neurons after sustained exposure to static magnetic fields.

    PubMed

    Hirai, Takao; Yoneda, Yukio

    2004-01-15

    In cultured rat hippocampal neurons, gradual increases were seen in the expression of microtubule-associated protein-2 (MAP-2), neuronal nuclei (NeuN) and growth-associated protein-43 (GAP-43), in proportion to increased duration, up to 9 days in vitro (DIV). Sustained exposure to static magnetic fields at 100 mT for up to 9 DIV significantly decreased expression of MAP-2 and NeuN in cultured rat hippocampal neurons without markedly affecting GAP-43 expression. Although a significant increase was seen in the expression of glial fibrillary acidic protein (GFAP) in hippocampal neuronal preparations cultured for 6-9 DIV under sustained magnetism, GFAP and proliferating cell nuclear antigen expression were not affected markedly in cultured astrocytes prepared from rat hippocampus and neocortex, irrespective of cellular maturity. No significant alteration was seen in cell survivability of hippocampal neurons or astrocytes cultured under sustained magnetism. In hippocampal neurons cultured for 3 DIV under sustained magnetism, marked mRNA expression was seen for N-methyl-D-aspartate (NMDA) receptor subunits, NR1, NR2A-2C, NR2D, and NR3A. In addition, significant potentiation of the ability of NMDA to increase intracellular free Ca(2+) ions was observed. Differential display analysis revealed a significant decrease in mRNA expression for the transcription factor ALF1 in response to sustained magnetism for 3 DIV. These results suggest that sustained exposure to static magnetic fields may affect cellular functionality and maturity in immature cultured rat hippocampal neurons through modulation of expression of particular NMDA receptor subunits.

  8. Exposure to Synthetic Gray Water Inhibits Amoeba Encystation and Alters Expression of Legionella pneumophila Virulence Genes

    PubMed Central

    Lu, Jingrang; Ashbolt, Nicholas J.

    2014-01-01

    Water conservation efforts have focused on gray water (GW) usage, especially for applications that do not require potable water quality. However, there is a need to better understand environmental pathogens and their free-living amoeba (FLA) hosts within GW, given their growth potential in stored gray water. Using synthetic gray water (sGW) we examined three strains of the water-based pathogen Legionella pneumophila and its FLA hosts Acanthamoeba polyphaga, A. castellanii, and Vermamoeba vermiformis. Exposure to sGW for 72 h resulted in significant inhibition (P < 0.0001) of amoebal encystation versus control-treated cells, with the following percentages of cysts in sGW versus controls: A. polyphaga (0.6 versus 6%), A. castellanii (2 versus 62%), and V. vermiformis (1 versus 92%), suggesting sGW induced maintenance of the actively feeding trophozoite form. During sGW exposure, L. pneumophila culturability decreased as early as 5 h (1.3 to 2.9 log10 CFU, P < 0.001) compared to controls (Δ0 to 0.1 log10 CFU) with flow cytometric analysis revealing immediate changes in membrane permeability. Furthermore, reverse transcription-quantitative PCR was performed on total RNA isolated from L. pneumophila cells at 0 to 48 h after sGW incubation, and genes associated with virulence (gacA, lirR, csrA, pla, and sidF), the type IV secretion system (lvrB and lvrE), and metabolism (ccmF and lolA) were all shown to be differentially expressed. These results suggest that conditions within GW may promote interactions between water-based pathogens and FLA hosts, through amoebal encystment inhibition and alteration of bacterial gene expression, thus warranting further exploration into FLA and L. pneumophila behavior in GW systems. PMID:25381242

  9. Chronic exposure to a neonicotinoid pesticide alters the interactions between bumblebees and wild plants.

    PubMed

    Stanley, Dara A; Raine, Nigel E

    2016-07-01

    Insect pollinators are essential for both the production of a large proportion of world crops and the health of natural ecosystems. As important pollinators, bumblebees must learn to forage on flowers to feed both themselves and provision their colonies.Increased use of pesticides has caused concern over sublethal effects on bees, such as impacts on reproduction or learning ability. However, little is known about how sublethal exposure to field-realistic levels of pesticide might affect the ability of bees to visit and manipulate flowers.We observed the behaviour of individual bumblebees from colonies chronically exposed to a neonicotinoid pesticide (10 ppb thiamethoxam) or control solutions foraging for the first time on an array of morphologically complex wildflowers (Lotus corniculatus and Trifolium repens) in an outdoor flight arena.We found that more bees released from pesticide-treated colonies became foragers, and that they visited more L. corniculatus flowers than controls. Interestingly, bees exposed to pesticide collected pollen more often than controls, but control bees learnt to handle flowers efficiently after fewer learning visits than bees exposed to pesticide. There were also different initial floral preferences of our treatment groups; control bees visited a higher proportion of T. repens flowers, and bees exposed to pesticide were more likely to choose L. corniculatus on their first visit.Our results suggest that the foraging behaviour of bumblebees on real flowers can be altered by sublethal exposure to field-realistic levels of pesticide. This has implications for the foraging success and persistence of bumblebee colonies, but perhaps more importantly for the interactions between wild plants and flower-visiting insects and ability of bees to deliver the crucial pollination services to plants necessary for ecosystem functioning.

  10. Sucrose Exposure in Early Life Alters Adult Motivation and Weight Gain

    PubMed Central

    Frazier, Cristianne R. M.; Mason, Peggy; Zhuang, Xiaoxi; Beeler, Jeff A.

    2008-01-01

    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. PMID:18797507

  11. Exposure to synthetic gray water inhibits amoeba encystation and alters expression of Legionella pneumophila virulence genes.

    PubMed

    Buse, Helen Y; Lu, Jingrang; Ashbolt, Nicholas J

    2015-01-01

    Water conservation efforts have focused on gray water (GW) usage, especially for applications that do not require potable water quality. However, there is a need to better understand environmental pathogens and their free-living amoeba (FLA) hosts within GW, given their growth potential in stored gray water. Using synthetic gray water (sGW) we examined three strains of the water-based pathogen Legionella pneumophila and its FLA hosts Acanthamoeba polyphaga, A. castellanii, and Vermamoeba vermiformis. Exposure to sGW for 72 h resulted in significant inhibition (P < 0.0001) of amoebal encystation versus control-treated cells, with the following percentages of cysts in sGW versus controls: A. polyphaga (0.6 versus 6%), A. castellanii (2 versus 62%), and V. vermiformis (1 versus 92%), suggesting sGW induced maintenance of the actively feeding trophozoite form. During sGW exposure, L. pneumophila culturability decreased as early as 5 h (1.3 to 2.9 log10 CFU, P < 0.001) compared to controls (Δ0 to 0.1 log10 CFU) with flow cytometric analysis revealing immediate changes in membrane permeability. Furthermore, reverse transcription-quantitative PCR was performed on total RNA isolated from L. pneumophila cells at 0 to 48 h after sGW incubation, and genes associated with virulence (gacA, lirR, csrA, pla, and sidF), the type IV secretion system (lvrB and lvrE), and metabolism (ccmF and lolA) were all shown to be differentially expressed. These results suggest that conditions within GW may promote interactions between water-based pathogens and FLA hosts, through amoebal encystment inhibition and alteration of bacterial gene expression, thus warranting further exploration into FLA and L. pneumophila behavior in GW systems.

  12. GDF-15 gene expression alterations in human lymphoblastoid cells and peripheral blood lymphocytes following exposure to ionizing radiation

    PubMed Central

    Li, Shuang; Zhang, Qing-Zhao; Zhang, De-Qin; Feng, Jiang-Bin; Luo, Qun; Lu, Xue; Wang, Xin-Ru; Li, Kun-Peng; Chen, De-Qing; Mu, Xiao-Feng; Gao, Ling; Liu, Qing-Jie

    2017-01-01

    The identification of rapid, sensitive and high-throughput biomarkers is imperative in order to identify individuals harmed by radiation accidents, and accurately evaluate the absorbed doses of radiation. DNA microarrays have previously been used to evaluate the alterations in growth/differentiation factor 15 (GDF15) gene expression in AHH-1 human lymphoblastoid cells, following exposure to γ-rays. The present study aimed to characterize the relationship between the dose of ionizing radiation and the produced effects in GDF-15 gene expression in AHH-1 cells and human peripheral blood lymphocytes (HPBLs). GDF-15 mRNA and protein expression levels following exposure to γ-rays and neutron radiation were assessed by reverse transcription-quantitative polymerase chain reaction and western blot analysis in AHH-1 cells. In addition, alterations in GDF-15 gene expression in HPBLs following ex vivo irradiation were evaluated. The present results demonstrated that GDF-15 mRNA and protein expression levels in AHH-1 cells were significantly upregulated following exposure to γ-ray doses ranging between 1 and 10 Gy, regardless of the dose rate. A total of 48 h following exposure to neutron radiation, a dose-response relationship was identified in AHH-1 cells at γ-ray doses between 0.4 and 1.6 Gy. GDF-15 mRNA levels in HPBLs were significantly upregulated following exposure to γ-ray doses between 1 and 8 Gy, within 4–48 h following irradiation. These results suggested that significant time- and dose-dependent alterations in GDF-15 mRNA and protein expression occur in AHH-1 cells and HPBLs in the early phases following exposure to ionizing radiation. In conclusion, alterations in GDF-15 gene expression may have potential as a biomarker to evaluate radiation exposure. PMID:28440431

  13. Chromatin Modifications during Repair of Environmental Exposure-Induced DNA Damage: A Potential Mechanism for Stable Epigenetic Alterations

    PubMed Central

    O’Hagan, Heather M.

    2014-01-01

    Exposures to environmental toxicants and toxins cause epigenetic changes that likely play a role in the development of diseases associated with exposure. The mechanism behind these exposure-induced epigenetic changes is currently unknown. One commonality between most environmental exposures is that they cause DNA damage either directly or through causing an increase in reactive oxygen species, which can damage DNA. Like transcription, DNA damage repair must occur in the context of chromatin requiring both histone modifications and ATP-dependent chromatin remodeling. These chromatin changes aid in DNA damage accessibility and signaling. Several proteins and complexes involved in epigenetic silencing during both development and cancer have been found to be localized to sites of DNA damage. The chromatin-based response to DNA damage is considered a transient event, with chromatin being restored to normal as DNA damage repair is completed. However, in individuals chronically exposed to environmental toxicants or with chronic inflammatory disease, repeated DNA damage-induced chromatin rearrangement may ultimately lead to permanent epigenetic alterations. Understanding the mechanism behind exposure-induced epigenetic changes will allow us to develop strategies to prevent or reverse these changes. This review focuses on epigenetic changes and DNA damage induced by environmental exposures, the chromatin changes that occur around sites of DNA damage, and how these transient chromatin changes may lead to heritable epigenetic alterations at sites of chronic exposure. PMID:24259318

  14. Perinatal exposure to lead (Pb) induces ultrastructural and molecular alterations in synapses of rat offspring.

    PubMed

    Gąssowska, Magdalena; Baranowska-Bosiacka, Irena; Moczydłowska, Joanna; Frontczak-Baniewicz, Małgorzata; Gewartowska, Magdalena; Strużyńska, Lidia; Gutowska, Izabela; Chlubek, Dariusz; Adamczyk, Agata

    2016-12-12

    noticed in the cerebellum, while the expression of postsynaptic PSD-95 was significantly decreased in forebrain cortex and cerebellum, and raised in hippocampus. Additionally, we observed the lower level of BDNF in all brain structures in comparison to control animals. In conclusion, perinatal exposure to low doses of Pb caused pathological changes in nerve endings associated with the alterations in the level of key synaptic proteins. All these changes can lead to synaptic dysfunction, expressed by the impairment of the secretory mechanism and thereby to the abnormalities in neurotransmission as well as to the neuronal dysfunction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Altered reward processing in adolescents with prenatal exposure to maternal cigarette smoking.

    PubMed

    Müller, Kathrin U; Mennigen, Eva; Ripke, Stephan; Banaschewski, Tobias; Barker, Gareth J; Büchel, Christian; Conrod, Patricia; Fauth-Bühler, Mira; Flor, Herta; Garavan, Hugh; Heinz, Andreas; Lawrence, Claire; Loth, Eva; Mann, Karl; Martinot, Jean-Luc; Pausova, Zdenka; Rietschel, Marcella; Ströhle, Andreas; Struve, Maren; Walaszek, Bernadeta; Schumann, Gunter; Paus, Tomáš; Smolka, Michael N

    2013-08-01

    Higher rates of substance use and dependence have been observed in the offspring of mothers who smoked during pregnancy. Animal studies indicate that prenatal exposure to nicotine alters the development of brain areas related to reward processing, which might be a risk factor for substance use and addiction later in life. However, no study has examined the effect of maternal smoking on the offspring's brain response during reward processing. To determine whether adolescents with prenatal exposure to maternal cigarette smoking differ from their nonexposed peers in the response of the ventral striatum to the anticipation or the receipt of a reward. An observational case-control study. Data were obtained from the IMAGEN Study, a European multicenter study of impulsivity, reinforcement sensitivity, and emotional reactivity in adolescents. The IMAGEN sample consists of 2078 healthy adolescents (age range, 13-15 years) recruited from March 1, 2008, through December 31, 2011, in local schools. We assessed an IMAGEN subsample of 177 adolescents with prenatal exposure to maternal cigarette smoking and 177 nonexposed peers (age range, 13-15 years) matched by sex, maternal educational level, and imaging site. Response to reward in the ventral striatum measured with functional magnetic resonance imaging. In prenatally exposed adolescents, we observed a weaker response in the ventral striatum during reward anticipation (left side, F = 14.98 [P < .001]; right side, F = 15.95 [P < .001]) compared with their nonexposed peers. No differences were found regarding the responsivity of the ventral striatum to the receipt of a reward (left side, F = 0.21 [P = .65]; right side, F = 0.47 [P = .49]). The weaker responsivity of the ventral striatum to reward anticipation in prenatally exposed adolescents may represent a risk factor for substance use and development of addiction later in life. This result highlights the need for education and preventive

  16. Adaptations of the vestibular system to short and long-term exposures to altered gravity

    NASA Astrophysics Data System (ADS)

    Bruce, L.

    Long-term space flight creates unique environmental conditions to which the vestibular system must adapt for optimal survival. We are studying two aspects of this vestibular adaptation: (1) How does long-term exposure to microgravity and hypergravity affect the development of vestibular afferents? (2) How does short- term exposure to extremely rapid changes in gravity, such as those that occur during launch and landing, affect the vestibular system. During space flight the gravistatic receptors in the otolith organs are effectively unloaded. In hypergravity conditions they are overloaded. However, the angular acceleration receptors of the semicircular canals receive relatively normal stimulation in both micro- and hypergravity.Rat embryos exposed to microgravity from gestation day 10 (prior to vestibular function) until gestation day 20 (vestibular system is somewhat functional) showed that afferents from the posterior vertical canal projecting to the medial vestibular nucleus developed similarly in microgravity, hypergravity, and in controls . However, afferents from the saccule showed delayed development in microgravity as compared to development in hypergravity and in controls. Cerebellar plasticity is crucial for modification of sensory-motor control and learning. Thus we explored the possibility that strong vestibular stimuli would modify cerebellar motor control (i.e., eye movement, postural control, gut motility) by altering the morphology of cerebellar Purkinje cells. To study the effects of short-term exposures to strong vestibular stimuli we focused on structural changes in the vestibulo-cerebellum that are caused by strong vestibular stimuli. Adult mice were exposed to various combinations of constant and/or rapidly changing angular and linear accelerations for 8.5 min (the time length of shuttle launch). Our data shows that these stimuli cause intense excitation of cerebellar Purkinje cells, inducing up-regulation of clathrin-mediated endocytosis

  17. Maternal bisphenol A exposure alters rat offspring hepatic and skeletal muscle insulin signaling protein abundance.

    PubMed

    Galyon, Kristina D; Farshidi, Farnoosh; Han, Guang; Ross, Michael G; Desai, Mina; Jellyman, Juanita K

    2017-03-01

    skeletal muscle. In adult female bisphenol A offspring, the skeletal muscle protein abundance of glucose transporter 4 was 0.4-fold of the control. Maternal bisphenol A had sex- and tissue-specific effects on insulin signaling components, which may contribute to increased risk of glucose intolerance in offspring. Glucose transporters were consistently altered at both ages as well as in both sexes and may contribute to glucose intolerance. These data suggest that maternal bisphenol A exposure should be limited during pregnancy and lactation. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Perinatal exposure to lead (Pb) induces ultrastructural and molecular alterations in synapses of rat offspring.

    PubMed

    Gąssowska, Magdalena; Baranowska-Bosiacka, Irena; Moczydłowska, Joanna; Frontczak-Baniewicz, Małgorzata; Gewartowska, Magdalena; Strużyńska, Lidia; Gutowska, Izabela; Chlubek, Dariusz; Adamczyk, Agata

    2016-10-29

    noticed in the cerebellum, while the expression of postsynaptic PSD-95 was significantly decreased in forebrain cortex and cerebellum, and raised in hippocampus. Additionally, we observed the lower level of BDNF in all brain structures in comparison to control animals. In conclusion, perinatal exposure to low doses of Pb caused pathological changes in nerve endings associated with the alterations in the level of key synaptic proteins. All these changes can lead to synaptic dysfunction, expressed by the impairment of the secretory mechanism and thereby to the abnormalities in neurotransmission as well as to the neuronal dysfunction.

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

    EPA Science Inventory

    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, ...

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

    EPA Science Inventory

    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, ...

  1. POSTWEANING EXPOSURE TO A HIGH FAT DIET IS ASSOCIATED WITH ALTERATIONS TO THE HEPATIC HISTONE CODE IN JAPANESE MACAQUES

    PubMed Central

    Suter, Melissa A.; Takahashi, Diana; Grove, Kevin L.; Aagaard, Kjersti M.

    2013-01-01

    Background Expression of the circadian gene, Npas2, is altered in fetal life with maternal high fat diet exposure by virtue of alterations in the fetal histone code. We postulated that these disruptions would persist postnatally. Methods Pregnant macaques were fed a control (CTR) or high fat (HF) diet and delivered at term. When offspring were weaned, they were placed on either CTR or HF diet for a period of 5 months to yield four exposure models (in utero diet/postweaning diet: CTR/CTR n = 5; CTR/HF n = 4; HF/CTR n = 4; HF/HF n = 5). Liver specimens were obtained at necropsy at one year of age. Results Hepatic trimethylation of lysine 4 of histone H3 is decreased, (CTR/HF 0.87-fold, P = 0.038; HF/CTR 0.84-fold, P = 0.038) while hepatic methyltransferase activity increased by virtue of diet exposure (HF/HF 1.3-fold, P = 0.019). Using chromatin immunoprecipitation to determine Npas2 promoter occupancy, we found alterations of both repressive and permissive histone modifications specifically with postweaning high fat diet exposure. Conclusion We find altered Npas2 expression corresponds with a change in the histone code within the Npas2 promoter. PMID:23788059

  2. Arginine exposure alters ectonucleotidase activities and morphology of zebrafish larvae (Danio rerio).

    PubMed

    Capiotti, Katiucia Marques; Fazenda, Lidiane; Nazario, Luiza Reali; Menezes, Fabiano Peres; Kist, Luiza Wilges; Bogo, Maurício Reis; Da Silva, Rosane Souza; Wyse, Angela Terezinha; Bonan, Carla Denise

    2013-02-01

    Hyperargininemia is an inborn error of metabolism (IEM) characterized by tissue accumulation of arginine (Arg). Mental retardation and other neurological features are common symptoms in hyperargininemic patients. Considering purinergic signaling has a crucial role from the early stages of development and underlying mechanisms of this disease are poorly established, we investigated the effect of Arg administration on locomotor activity, morphological alterations, and extracellular nucleotide hydrolysis in larvae and adult zebrafish. We showed that 0.1 mM Arg was unable to promote changes in locomotor activity. In addition, 7-day-post-fertilization (dpf) larvae treated with Arg demonstrated a decreased body size. Arg exposure (0.1 mM) promoted an increase in ATP, ADP, and AMP hydrolysis when compared to control group. These findings demonstrated that Arg might affect morphological parameters and ectonucleotidase activities in zebrafish larvae, suggesting that purinergic system is a target for neurotoxic effects induced by Arg. Copyright © 2012 ISDN. Published by Elsevier Ltd. All rights reserved.

  3. Prenatal nicotine exposure alters respiratory long term facilitation in neonatal rats

    PubMed Central

    Fuller, DD; Dougherty, BJ; Sandhu, MS; Doperalski, NJ; Reynolds, CR; Hayward, LF

    2009-01-01

    Intermittent hypoxia can evoke persistent increases in ventilation (ν̇ E) in neonates (i.e. long-term facilitation, LTF) (Julien et al. Am J Physiol Regul Integr Comp Physiol 294: R1356–R1366, 2008). Since prenatal nicotine (PN) exposure alters neonatal respiratory control (Fregosi & Pilarski. Respir. Physiol. Neurobiol. 164: 80–86, 2008), we hypothesized that PN would influence LTF of ventilation (ν̇ E) in neonatal rats. An osmotic minipump delivered nicotine (6 mg/kg/day) or saline to pregnant dams. ν̇ E was assessed in unanesthetized pups via whole body plethysmography at post-natal (P) days 9–11 or 15–17 during baseline (BL, 21% O2), hypoxia (10 × 5 min, 5% O2) and 30 min post-hypoxia. PN pups had reduced BL ν̇ E (p<0.05) but greater increases in ν̇ E during hypoxia (p<0.05). Post-hypoxia ν̇ E (i.e. LTF) showed an age × treatment interaction (p<0.01) with similar values at P9-11 but enhanced LTF in saline (30±8 %BL) vs. PN pups (6±5 %BL; p=0.01) at P15-17. We conclude that the post-natal developmental time course of hypoxia-induced LTF is influenced by PN. PMID:19818419

  4. Exposure to caregiver maltreatment alters expression levels of epigenetic regulators in the medial prefrontal cortex

    PubMed Central

    Blaze, Jennifer; Roth, Tania L

    2013-01-01

    Quality of maternal care experienced during infancy is a key factor that can confer vulnerability or resilience to psychiatric disorders later in life. Research continues to indicate that early-life experiences can affect developmental trajectories through epigenetic alterations capable of affecting gene regulation and neural plasticity. Previously, our lab has shown that experiences within an adverse caregiving environment (i.e. maltreatment) produce aberrant DNA methylation patterns at various gene loci in the medial prefrontal cortex (mPFC) of developing and adult rats. This study aimed to determine whether caregiver maltreatment likewise affects expression levels of several genes important in regulating DNA methylation patterns (Dnmt1, Dnmt3a, MeCP2, Gadd45b, and Hdac1). While we observed minimal changes in gene expression within the mPFC of developing rats, we observed expression changes for all genes in adult animals. Specifically, exposure to maltreatment produced a significant decrease in mRNA levels of all epigenetic regulators in adult males and a significant decrease in Gadd45b in adult females. Our results here provide further empirical support for the long-term and sex-specific epigenetic consequences of caregiver maltreatment on the mPFC. PMID:24120634

  5. Reduction of copper-induced histopathological alterations by calcium exposure in Nile tilapia (Oreochromis niloticus).

    PubMed

    Kosai, Piya; Jiraungkoorskul, Wannee; Thammasunthorn, Tawan; Jiraungkoorskul, Kanitta

    2009-09-01

    This study was undertaken to determine whether calcium could render any protection against copper (Cu) toxicity in Nile tilapia with emphasis on histopathological and histochemical analysis. The copper LC(50) values for 24, 48, 72, and 96 h to tilapia in the laboratory were 210.27, 213.34, 193.30, and 185. 75 mg/L, respectively. Prior to Cu exposure, fish were exposed to 0 (G1 and G3) and 30 mg/L calcium carbonate (G2 and G4) for 4 days. After that, fish were exposed to 46 mg/L copper, which corresponds to 25% of the 96 h LC(50) (G3 and G4) for 96 h and 7 days. In the gills of the copper treatment group, primary filament cell hyperplasia, epithelial lifting, or edema, secondary lamellar fusion, and aneurysm were observed. Swollen hepatocytes showing vacuoles and congestion in sinusoids were observed. Necrosis was observed in some areas. In the kidney, glomerulus's atrophy, tubular swelling, and also necrosis were seen. Fish that were pre-exposed to calcium showed slight alteration when compared to copper alone-treatment groups. Histochemical staining for calcium and copper by alizarin red S and rhodanine staining, respectively, indicated no accumulation of calcium and copper in kidney, liver, gills, and muscle. In conclusion, calcium appears to be beneficial in reducing the effects of heavy metal contaminations in aquatic organisms.

  6. Brood patches of American kestrels altered by experimental exposure to PCBs.

    PubMed

    Fisher, Sheri A; Bortolotti, Gary R; Fernie, Kim J; Bird, David M; Smits, Judit E

    2006-09-01

    Captive breeding (n = 25 pairs) and nonbreeding (n = 25) American kestrels were exposed to a mixture of polychlorinated biphenyls (PCBs) (Aroclor 1248:1254:1260) through their diet of day-old cockerels. Kestrels ingested approximately 7 mg/kg body weight each day of PCBs, and this dosage resulted in environmentally relevant total PCB residues in eggs (geometric mean of 34.1 microg/g). An equal number of unexposed birds served as controls. Bare areas of skin known as brood patches function during incubation to warm eggs; therefore, brood patch size could potentially influence hatching success, or patches may be a confounding factor in the relationship between poor incubation behavior and hatching failure observed in birds in toxicological studies. Exposure to PCBs altered the size of brood patches in American kestrels. PCB-exposed male and female nonbreeders had two of three brood patches that were larger than those of control nonbreeders. Breeding males exposed to PCBs had smaller patches than controls, whereas PCB-exposed female kestrels had one larger and one smaller patch than controls. Patch sizes were not related to total PCB residue levels in eggs of exposed birds. Brood patches were not related to various incubation behaviors or hatching success in either control or PCB-exposed kestrels.

  7. Repeated ethanol exposure alters social behavior and oxidative stress parameters of zebrafish.

    PubMed

    Müller, Talise Ellwanger; Nunes, Stenio Zimermann; Silveira, Ariane; Loro, Vania Lucia; Rosemberg, Denis Broock

    2017-06-07

    Repeated ethanol (EtOH) consumption induces neurological disorders in humans and is considered an important public health problem. The physiological effects of EtOH are dose- and time-dependent, causing relevant changes in the social behavior. In addition, alcohol-induced oxidative stress has been proposed as a key mechanism involved in EtOH neurotoxicity. Here we investigate for the first time whether repeated EtOH exposure (REE) alters the social behavior of zebrafish and influences brain oxidation processes. Animals were exposed to water (control group) or 1% (v/v) EtOH (EtOH group) for 8 consecutive days (20min per day). EtOH was added directly to the tank water. At day 9, the social behavior and biochemical parameters were assessed. REE increased shoal cohesion by reducing inter-fish and farthest neighbor distances. SOD and CAT activities, as well as NPSH levels decreased in brain tissue. Moreover, REE increased lipid peroxidation suggesting oxidative damage. In summary, changes in oxidation processes may play a role in the CNS effects of EtOH, influencing the social behavior of zebrafish. Furthermore, in a translational neuroscience perspective, our data reinforces the utility of zebrafish to clarify the biochemical and behavioral effects of intermittent EtOH administration. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Embryonic alcohol exposure leading to social avoidance and altered anxiety responses in adult zebrafish.

    PubMed

    Baggio, Suelen; Mussulini, Ben Hur; de Oliveira, Diogo Losch; Gerlai, Robert; Rico, Eduardo Pacheco

    2017-09-04

    Fetal Alcohol Spectrum Disorders (FASD) is a syndrome characterized by neurological and behavioral impairments. A recently discovered hallmark of FASD is impaired social behavior. Avoidance of social interaction typical of FASD may be the result of increased anxiety. Previously, the zebrafish was successfully used to model embryonic alcohol induced social abnormalities. Here, we analyzed both anxiety and social responses using a zebrafish FASD model, in adult fish. We exposed zebrafish embryos to low concentrations of ethanol (0.1%; 0.25%; 0.5% and 1% v/v) for 2h at, 24h post-fertilization, to mimic the most prevalent milder FASD cases, and investigated the ensuing alterations in adult, 4-month-old, zebrafish. We studied social interaction in the social preference task and anxiety in the novel tank task. We observed an ethanol dose dependent reduction of time spend in the conspecific zone compared to control, corroborating prior findings. We also found significant changes in the novel tank (e.g. increased bottom dwell time, increased distance to top) suggesting elevated anxiety to control, but we also found, using an anxiolytic drug buspirone, that reduction of anxiety is associated with reduced shoaling. Our results confirm that embryonic alcohol exposure disrupts social behavior, and also show that its effects on anxiety related phenotypes may be genotype, alcohol administration method, experimental procedure and test-context dependent. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    SciTech Connect

    Di Cicco, D.; Antal, S.; Ammassari-Teule, M. )

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

    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 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. PMID:27292372

  12. Developmental exposure to the pesticide dieldrin alters the dopamine system and increases neurotoxicity in an animal model of Parkinson's disease.

    PubMed

    Richardson, Jason R; Caudle, W Michael; Wang, Minzheng; Dean, E Danielle; Pennell, Kurt D; Miller, Gary W

    2006-08-01

    Exposure to pesticides has been suggested to increase the risk of Parkinson's disease (PD), but the mechanisms responsible for this association are not clear. Here, we report that perinatal exposure of mice during gestation and lactation to low levels of dieldrin (0.3, 1, or 3 mg/kg every 3 days) alters dopaminergic neurochemistry in their offspring and exacerbates MPTP toxicity. At 12 wk of age, protein and mRNA levels of the dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) were increased by perinatal dieldrin exposure in a dose-related manner. We then administered MPTP (2 x 10 mg/kg s.c) at 12 wk of age and observed a greater reduction of striatal dopamine in dieldrin-exposed offspring, which was associated with a greater DAT:VMAT2 ratio. Additionally, dieldrin exposure during development potentiated the increase in GFAP and alpha-synuclein levels induced by MPTP, indicating increased neurotoxicity. In all cases there were greater effects observed in the male offspring than the female, similar to that observed in human cases of PD. These data suggest that developmental exposure to dieldrin leads to persistent alterations of the developing dopaminergic system and that these alterations induce a "silent" state of dopamine dysfunction, thereby rendering dopamine neurons more vulnerable later in life.

  13. Exposure to acute electromagnetic radiation of mobile phone exposure range alters transiently skin homeostasis of a model of pigmented reconstructed epidermis.

    PubMed

    Simon, D; Daubos, A; Pain, C; Fitoussi, R; Vié, K; Taieb, A; de Benetti, L; Cario-André, M

    2013-02-01

    Exposure to electromagnetic radiations (EMR) produced by mobile phone concerns half the world's population and raises the problem of their impact on human health. In this study, we looked at the effects of mobile phone exposure (GSM basic, 900 MHz, SAR 2 mW g(-1) , 6 h) on a model of pigmented skin. We have analysed the expression and localization of various markers of keratinocyte and melanocyte differentiation 2, 6, 18 and 24 h after EMR exposure of reconstructed epidermis containing either only keratinocytes or a combination of keratinocytes and melanocytes grown on dead de-epidermized dermis, using histology, immunohistochemistry and Western blot. No changes were found in epidermal architecture, localization of epidermal markers, presence of apoptotic cells and the induction of p53 in both types of epidermis (with or without melanocytes) after exposure to EMR. In pigmented reconstructs, no change in the location and dendricity of melanocytes and in melanin transfer to neighbouring keratinocytes was detected after EMR exposure. Loricrin, cytokeratin 14 were significantly decreased at 6 h. The level of all markers increased at 24 h as compared to 6 h post-EMR exposure, associated with a significant decrease of the 20S proteasome activity. Our data indicate that exposure to 900 MHz frequency induces a transient alteration of epidermal homoeostasis, which may alter the protective capacity of the skin against external factors. Presence or absence of melanocytes did not modify the behaviour of reconstructs after EMR exposure.

  14. Effect of methyl parathion on nitrous oxide production: a laboratory study.

    PubMed

    Rojas-Oropeza, Marcelo; Fernández, Francisco J; Dendooven, Luc; Cabirol, Nathalie

    2012-03-01

    We investigated the diversity of a denitrifying gene (nirK) and the emission of CO(2) and N(2)O, in a "chinampa" soil contaminated with methyl parathion. Soil at 40% of water holding capacity was spiked with methyl parathion at four concentrations (i.e. 0, 0.7, 1.47 and 4.27 g kg(-1) dry soil), while emission of N(2)O and CO(2) and nirK diversity was determined after 0, 1, 14, 30, 60 and 90 days. The emission of N(2)O on a daily base and the cumulative emission of CO(2) was not affected by the different concentrations of methyl parathion applied to soil. The diversity of the nirK gene, determined by using temperature gradient gel electrophoresis (TGGE), decreased with increased methyl parathion application. It was found that methyl parathion had effect on the emissions of N(2)O and CO(2), and reduced the diversity of the nirK gene. Consequently, the reduced diversity of the nirK gene could affect the emission of N(2)O.

  15. Degradation mechanism and the toxicity assessment in TiO2 photocatalysis and photolysis of parathion.

    PubMed

    Kim, Tak-Soo; Kim, Jung-Kon; Choi, Kyungho; Stenstrom, Michael K; Zoh, Kyung-Duk

    2006-02-01

    The photocatalytic degradation of methyl parathion was carried out using a circulating TiO2/UV reactor. The experimental results showed that parathion was more effectively degraded in the photocatalytic condition than the photolysis and TiO2-only condition. With photocatalysis, 10mg/l parathion was completely degraded within 60 min with a TOC decrease exceeding 90% after 150 min. The main ionic byproducts during photocatalysis were measured. The nitrogen from parathion was recovered mainly as NO3-, NO2- and NH4+, 80% of the sulfur as SO4(2-), and less than 5% of the phosphorus as PO4(3-). The organic intermediates 4-nitrophenol and paraoxon were also identified, and these were further degraded. Two different bioassays (Vibrio fischeri and Daphnia magna) were used to test the acute toxicity of solutions treated by photocatalysis and photolysis. A Microtox test using V. fischeri showed that the toxicity, expressed as the relative toxicity (%), was reduced almost completely after 90 min under photocatalysis, whereas only an 83% reduction was achieved with photolysis alone. Another toxicity test using D. magna also showed that the relative toxicity disappeared after 90 min under photocatalysis, whereas there was a 65% reduction in relative toxicity with photolysis alone. The pattern of toxicity reduction parallels the decrease in parathion and TOC concentrations.

  16. Modeling impact of parathion and its metabolite paraoxon on the nematode Caenorhabditis elegans