Prenatal Nicotine Alters the Developmental Neurotoxicity of Postnatal Chlorpyrifos Directed Toward Cholinergic Systems: Better, Worse, or Just “Different?”

PubMed Central

Slotkin, Theodore A.; Seidler, Frederic J.

2014-01-01

This study examines whether prenatal nicotine exposure sensitizes the developing brain to subsequent developmental neurotoxicity evoked by chlorpyrifos, a commonly-used insecticide. We gave nicotine to pregnant rats throughout gestation at a dose (3 mg/kg/day) producing plasma levels typical of smokers; offspring were then given chlorpyrifos on postnatal days 1–4, at a dose (1 mg/kg) that produces minimally-detectable inhibition of brain cholinesterase activity. We evaluated indices for acetylcholine (ACh) synaptic function throughout adolescence, young adulthood and later adulthood, in brain regions possessing the majority of ACh projections and cell bodies; we measured nicotinic ACh receptor binding, hemicholinium-3 binding to the presynaptic choline transporter and choline acetyltransferase activity, all known targets for the adverse developmental effects of nicotine and chlorpyrifos given individually. By itself nicotine elicited overall upregulation of the ACh markers, albeit with selective differences by sex, region and age. Likewise, chlorpyrifos alone had highly sex-selective effects. Importantly, all the effects showed temporal progression between adolescence and adulthood, pointing to ongoing synaptic changes rather than just persistence after an initial injury. Prenatal nicotine administration altered the responses to chlorpyrifos in a consistent pattern for all three markers, lowering values relative to those of the individual treatments or to those expected from simple additive effects of nicotine and chlorpyrifos. The combination produced global interference with emergence of the ACh phenotype, an effect not seen with nicotine or chlorpyrifos alone. Given that human exposures to nicotine and chlorpyrifos are widespread, our results point to the creation of a subpopulation with heightened vulnerability. PMID:25510202

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

PubMed Central

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

2014-01-01

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

Chlorpyrifos

Integrated Risk Information System (IRIS)

Chlorpyrifos ; CASRN 2921 - 88 - 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 Eff

How the serotonin story is being rewritten by new gene-based discoveries principally related to SLC6A4, the serotonin transporter gene, which functions to influence all cellular serotonin systems.

PubMed

Murphy, Dennis L; Fox, Meredith A; Timpano, Kiara R; Moya, Pablo R; Ren-Patterson, Renee; Andrews, Anne M; Holmes, Andrew; Lesch, Klaus-Peter; Wendland, Jens R

2008-11-01

Discovered and crystallized over sixty years ago, serotonin's important functions in the brain and body were identified over the ensuing years by neurochemical, physiological and pharmacological investigations. This 2008 M. Rapport Memorial Serotonin Review focuses on some of the most recent discoveries involving serotonin that are based on genetic methodologies. These include examples of the consequences that result from direct serotonergic gene manipulation (gene deletion or overexpression) in mice and other species; an evaluation of some phenotypes related to functional human serotonergic gene variants, particularly in SLC6A4, the serotonin transporter gene; and finally, a consideration of the pharmacogenomics of serotonergic drugs with respect to both their therapeutic actions and side effects. The serotonin transporter (SERT) has been the most comprehensively studied of the serotonin system molecular components, and will be the primary focus of this review. We provide in-depth examples of gene-based discoveries primarily related to SLC6A4 that have clarified serotonin's many important homeostatic functions in humans, non-human primates, mice and other species.

Chlorpyrifos: an unwelcome pesticide in our homes.

PubMed

Lemus, R; Abdelghani, A

2000-01-01

Chlorpyrifos is an extensively used organophosphate insecticide having many urban and agricultural crop pest control uses. Studies conducted in indoor environments after termiticide, crack-and-crevice, broadcast, or fogger applications have shown that chlorpyrifos exposure can occur via inhalation of residual air concentrations, dermal or oral exposure from residues on floors and carpets, children toys, food, and dust. Not long ago the weight of scientific evidence supported safe indoor use, but recent studies support the possibility that when pregnant female rats are given the pesticide, chlorpyrifos causes brain damage in fetal rats. Moreover, the exposure of young rats to chlorpyrifos impairs early nervous system development. After finding that chlorpyrifos is an exposure risk especially to children, in June 2000 the United States Environmental Protection Agency and manufacturers agreed to voluntary measures that will reduce the exposure of children to chlorpyrifos-containing products. This action implies a search for less harmful new products to replace it and/or safer ways to control pests through basic hygiene. Whichever pest control method is selected, one should keep in mind that preventing environmental pesticide exposure in children is always better than treating the resulting disease.

Histopathological and genotoxic effects of chlorpyrifos in rats.

PubMed

Ezzi, Lobna; Belhadj Salah, Imen; Haouas, Zohra; Sakly, Amina; Grissa, Intissar; Chakroun, Sana; Kerkeni, Emna; Hassine, Mohsen; Mehdi, Meriem; Ben Cheikh, Hassen

2016-03-01

This study aims to investigate the effects of chlorpyrifos's sub-acute exposure on male rats. Two groups with six animals each were orally treated, respectively, with 3.1 mg/kg b w and 6.2 mg/kg b w of chlorpyrifos during 4 weeks. The genotoxic effect of chlopyrifos was investigated using the comet assay and the micronucleus test. Some hematological and liver's histopathological changes were also evaluated. Results revealed that chlorpyrifos induced histopathological alterations in liver parenchyma. The lymphoid infiltration observed in liver sections and the increase in white blood cells parameter are signs of inflammation. A significant increase in the platelet' count and in polychromatic erythrocytes/normochromatic erythrocytes (PCE/NCE) ratio was observed in chlorpyrifos-treated groups which could be due to the stimulatory effect of chlorpyrifos on cell formation in the bone marrow at lower doses. In addition, the increase of bone marrow micronucleus percentage and the comet tail length revealed a genotoxic potential of chlorpyrifos in vivo.

An invertebrate model of the developmental neurotoxicity of insecticides: effects of chlorpyrifos and dieldrin in sea urchin embryos and larvae.

PubMed Central

Buznikov, G A; Nikitina, L A; Bezuglov, V V; Lauder, J M; Padilla, S; Slotkin, T A

2001-01-01

Chlorpyrifos targets mammalian brain development through a combination of effects directed at cholinergic receptors and intracellular signaling cascades that are involved in cell differentiation. We used sea urchin embryos as an invertebrate model system to explore the cellular mechanisms underlying the actions of chlorpyrifos and to delineate the critical period of developmental vulnerability. Sea urchin embryos and larvae were exposed to chlorpyrifos at different stages of development ranging from early cell cleavages through the prism stage. Although early cleavages were unaffected even at high chlorpyrifos concentrations, micromolar concentrations added at the mid-blastula stage evoked a prominent change in cell phenotype and overall larval structure, with appearance of pigmented cells followed by their accumulation in an extralarval cap that was extruded from the animal pole. At higher concentrations (20-40 microM), these abnormal cells constituted over 90% of the total cell number. Studies with cholinergic receptor blocking agents and protein kinase C inhibitors indicated two distinct types of effects, one mediated through stimulation of nicotinic cholinergic receptors and the other targeting intracellular signaling. The effects of chlorpyrifos were not mimicked by chlorpyrifos oxon, the active metabolite that inhibits cholinesterase, nor by nonorganophosphate cholinesterase inhibitors. Dieldrin, an organochlorine that targets GABA(A )receptors, was similarly ineffective. The effects of chlorpyrifos and its underlying cholinergic and signaling-related mechanisms parallel prior findings in mammalian embryonic central nervous system. Invertebrate test systems may thus provide both a screening procedure for potential neuroteratogenesis by organophosphate-related compounds, as well as a system with which to uncover novel mechanisms underlying developmental vulnerability. PMID:11485862

IMMUNOASSAY ANALYSIS FOR CHLORPYRIFOS IN FOODS

EPA Science Inventory

Chlorpyrifos is widely used in agriculture on fruits and vegetables. The tolerances for chlorpyrifos on produce range from 0.1-8.0 ppm. Residue detection is commonly performed by gas chromatography following various cleanup procedures. However, the required cleanup can make ...

Biodegradation of chlorpyrifos by bacterial genus Pseudomonas.

PubMed

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

2016-02-01

Chlorpyrifos is an organophosphorus pesticide commonly used in agriculture. It is noxious to a variety of organisms that include living soil biota along with beneficial arthropods, fish, birds, humans, animals, and plants. Exposure to chlorpyrifos may cause detrimental effects as delayed seedling emergence, fruit deformities, and abnormal cell division. Contamination of chlorpyrifos has been found about 24 km from the site of its application. There are many physico-chemical and biological approaches to remove organophosphorus pesticides from the ecosystem, among them most promising is biodegradation. The 3,5,6-trichloro-2-pyridinol (TCP) and diethylthiophosphate (DETP) as primary products are made when chlorpyrifos is degraded by soil microorganisms which further break into nontoxic metabolites as CO(2), H(2)O, and NH(3). Pseudomonas is a diversified genus possessing a series of catabolic pathways and enzymes involved in pesticide degradation. Pseudomonas putida MAS-1 is reported to be more efficient in chlorpyrifos degradation by a rate of 90% in 24 h among Pseudomonas genus. The current review analyzed the comparative potential of bacterial species in Pseudomonas genus for degradation of chlorpyrifos thus, expressing an ecofriendly approach for the treatment of environmental contaminants like pesticides. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Updated Human Health Risk Analyses for Chlorpyrifos

EPA Pesticide Factsheets

EPA has revised the human health hazard assessment and drinking water exposure assessment for chlorpyrifos that supported our October 2015 proposal to revoke all food residue tolerances for chlorpyrifos.

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

PubMed Central

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

2007-01-01

Lower organisms show promise for the screening of neurotoxicants that might target mammalian brain development. Sea urchins use neurotransmitters as embryonic growth regulatory signals, so that adverse effects on neural substrates for mammalian brain development can be studied in this simple organism. We compared the effects of the organophosphate insecticide, chlorpyrifos in sea urchin embryos with those of the monoamine depleter, reserpine, so as to investigate multiple neurotransmitter mechanisms involved in developmental toxicity and to evaluate different therapeutic interventions corresponding to each neurotransmitter system. Whereas reserpine interfered with all stages of embryonic development, the effects of chlorpyrifos did not emerge until the mid-blastula stage. After that point, the effects of the two agents were similar. Treatment with membrane permeable analogs of the monoamine neurotransmitters, serotonin and dopamine, prevented the adverse effects of either chlorpyrifos or reserpine, despite the fact that chlorpyrifos works simultaneously through actions on acetylcholine, monoamines and other neurotransmitter pathways. This suggests that different neurotransmitters, converging on the same downstream signaling events, could work together or in parallel to offset the developmental disruption caused by exposure to disparate agents. We tested this hypothesis by evaluating membrane permeable analogs of acetylcholine and cannabinoids, both of which proved effective against chlorpyrifos- or reserpine-induced teratogenesis. Invertebrate test systems can provide both a screening procedure for mammalian neuroteratogenesis and may uncover novel mechanisms underlying developmental vulnerability as well as possible therapeutic approaches to prevent teratogenesis. PMID:17720543

Revised Human Health Risk Assessment on Chlorpyrifos

EPA Pesticide Factsheets

We have revised our human health risk assessment and drinking water exposure assessment for chlorpyrifos that supported our October 2015 proposal to revoke all food residue tolerances for chlorpyrifos. Learn about the revised analysis.

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

PubMed

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

2016-01-01

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

40 CFR 180.419 - Chlorpyrifos-methyl; tolerances for residues.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Chlorpyrifos-methyl; tolerances for... § 180.419 Chlorpyrifos-methyl; tolerances for residues. (a) General. (1) Tolerances are established for the combined residues of the insecticide chlorpyrifos-methyl [O,-O,-dimethyl O-(3,5,6-trichloro-2...

40 CFR 180.419 - Chlorpyrifos-methyl; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Chlorpyrifos-methyl; tolerances for... § 180.419 Chlorpyrifos-methyl; tolerances for residues. (a) General. (1) Tolerances are established for the combined residues of the insecticide chlorpyrifos-methyl [O,-O,-dimethyl O-(3,5,6-trichloro-2...

40 CFR 180.419 - Chlorpyrifos-methyl; tolerances for residues.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Chlorpyrifos-methyl; tolerances for... § 180.419 Chlorpyrifos-methyl; tolerances for residues. (a) General. (1) Tolerances are established for the combined residues of the insecticide chlorpyrifos-methyl [O,-O,-dimethyl O-(3,5,6-trichloro-2...

40 CFR 180.419 - Chlorpyrifos-methyl; tolerances for residues.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Chlorpyrifos-methyl; tolerances for... § 180.419 Chlorpyrifos-methyl; tolerances for residues. (a) General. (1) Tolerances are established for the combined residues of the insecticide chlorpyrifos-methyl [O,-O,-dimethyl O-(3,5,6-trichloro-2...

Protein tyrosine adduct in humans self-poisoned by chlorpyrifos

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Bin, E-mail: binli@unmc.edu; Eyer, Peter, E-mail: peter.eyer@lrz.uni-muenchen.de; Eddleston, Michael, E-mail: M.Eddleston@ed.ac.uk

2013-06-15

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

Protein tyrosine adduct in humans self-poisoned by chlorpyrifos

PubMed Central

Li, Bin; Eyer, Peter; Eddleston, Michael; Jiang, Wei; Schopfer, Lawrence M.; Lockridge, Oksana

2013-01-01

Studies of human cases of self-inflicted poisoning suggest that chlorpyrifos oxon reacts not only with acetylcholinesterase and butyrylcholinesterase but also with other blood proteins. A favored candidate is albumin because in vitro and animal studies have identified tyrosine 411 of albumin as a site covalently modified by organophosphorus poisons. Our goal was to test this proposal in humans by determining whether plasma from humans poisoned by chlorpyrifos has adducts on tyrosine. Plasma samples from 5 self-poisoned humans were drawn at various time intervals after ingestion of chlorpyrifos for a total of 34 samples. All 34 samples were analyzed for plasma levels of chlorpyrifos and chlorpyrifos oxon (CPO) as a function of time post-ingestion. Eleven samples were analyzed for the presence of diethoxyphosphorylated tyrosine by mass spectrometry. Six samples yielded diethoxyphosphorylated tyrosine in pronase digests. Blood collected as late as 5 days after chlorpyrifos ingestion was positive for CPO-tyrosine, consistent with the 20-day half-life of albumin. High plasma CPO levels did not predict detectable levels of CPO-tyrosine. CPO-tyrosine was identified in pralidoxime treated patients as well as in patients not treated with pralidoxime, indicating that pralidoxime does not reverse CPO binding to tyrosine in humans. Plasma butyrylcholinesterase was a more sensitive biomarker of exposure than adducts on tyrosine. In conclusion, chlorpyrifos oxon makes a stable covalent adduct on the tyrosine residue of blood proteins in humans who ingested chlorpyrifos. PMID:23566956

Transformation of Chlorpyrifos and Chlorpyrifos-Methyl in Prairie Pothole Porewaters

NASA Astrophysics Data System (ADS)

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

2014-12-01

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

Modifying Effects of Vitamin E on Chlorpyrifos Toxicity in Atlantic Salmon

PubMed Central

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

2015-01-01

The aim of this study was to elucidate how vitamin E (alpha tocopherol) may ameliorate the toxicity of the pesticide chlorpyrifos in Atlantic salmon. Freshly isolated hepatocytes were exposed to vitamin E, chlorpyrifos or a combination of vitamin E and chlorpyrifos (all 100 μM). Transcriptomics (RNA-seq) and metabolomics were used to screen for effects of vitamin E and chlorpyrifos. By introducing vitamin E, the number of upregulated transcripts induced by chlorpyrifos exposure was reduced from 941 to 626, while the number of downregulated transcripts was reduced from 901 to 742 compared to the control. Adding only vitamin E had no effect on the transcriptome. Jak-STAT signaling was the most significantly affected pathway by chlorpyrifos treatment according to the transcriptomics data. The metabolomics data showed that accumulation of multiple long chain fatty acids and dipeptides and amino acids in chlorpyrifos treated cells was partially alleviated by vitamin E treatment. Significant interaction effects between chlorpyrifos and vitamin E were seen for 15 metabolites, including 12 dipeptides. The antioxidant had relatively modest effects on chlorpyrifos-induced oxidative stress. By combining the two data sets, the study suggests that vitamin E supplementation prevents uptake and accumulation of fatty acids, and counteracts inhibited carbohydrate metabolism. Overall, this study shows that vitamin E only to a moderate degree modifies chlorpyrifos toxicity in Atlantic salmon liver cells. PMID:25774794

Repeated batch and continuous degradation of chlorpyrifos by Pseudomonas putida.

PubMed

Pradeep, Vijayalakshmi; Subbaiah, Usha Malavalli

2015-01-01

The present study was undertaken with the objective of studying repeated batch and continuous degradation of chlorpyrifos (O,O-diethyl O-3,5,6-trichloropyridin-2-yl phosphorothioate) using Ca-alginate immobilized cells of Pseudomonas putida isolated from an agricultural soil, and to study the genes and enzymes involved in degradation. The study was carried out to reduce the toxicity of chlorpyrifos by degrading it to less toxic metabolites. Long-term stability of pesticide degradation was studied during repeated batch degradation of chlorpyrifos, which was carried out over a period of 50 days. Immobilized cells were able to show 65% degradation of chlorpyrifos at the end of the 50th cycle with a cell leakage of 112 × 10(3) cfu mL(-1). During continuous treatment, 100% degradation was observed at 100 mL h(-1) flow rate with 2% chlorpyrifos, and with 10% concentration of chlorpyrifos 98% and 80% degradation was recorded at 20 mL h(-1) and 100 mL h(-1) flow rate respectively. The products of degradation detected by liquid chromatography-mass spectrometry analysis were 3,5,6-trichloro-2-pyridinol and chlorpyrifos oxon. Plasmid curing experiments with ethidium bromide indicated that genes responsible for the degradation of chlorpyrifos are present on the chromosome and not on the plasmid. The results of Polymerase chain reaction indicate that a ~890-bp product expected for mpd gene was present in Ps. putida. Enzymatic degradation studies indicated that the enzymes involved in the degradation of chlorpyrifos are membrane-bound. The study indicates that immobilized cells of Ps. putida have the potential to be used in bioremediation of water contaminated with chlorpyrifos.

Degradation of chlorpyrifos in tropical rice soils.

PubMed

Das, Subhasis; Adhya, Tapan K

2015-04-01

Chlorpyrifos [O,O-diethyl O-(3,5,6-trichloro-2-pyridinol) phosphorothioate] is used worldwide as an agricultural insecticide against a broad spectrum of insect pests of economically important crops including rice, and soil application to control termites. The insecticide mostly undergoes hydrolysis to diethyl thiophosphoric acid (DETP) and 3,5,6-trichloro-2-pyridinol (TCP), and negligible amounts of other intermediate products. In a laboratory-cum-greenhouse study, chlorpyrifos, applied at a rate of 10 mg kg(-1) soil to five tropical rice soils of wide physico-chemical variability, degraded with a half-life ranging from 27.07 to 3.82 days. TCP was the major metabolite under both non-flooded and flooded conditions. Chlorpyrifos degradation had significant negative relationship with electrical conductivity (EC), cation exchange capacity (CEC), clay and sand contents of the soils under non-flooded conditions. Results indicate that degradation of chlorpyrifos was accelerated with increase in its application frequency, across the representative rice soils. Management regimes including moisture content and presence or absence of rice plants also influenced the process. Biotic factors also play an important role in the degradation of chlorpyrifos as demonstrated by its convincing degradation in mineral salts medium inoculated with non-sterile soil suspension. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Effect of Chlorpyrifos on Isolated Thoracic Aorta in Rats

PubMed Central

Yıldırım, Ebru; Baydan, Emine; Kanbur, Murat; Kul, Oğuz; Çınar, Miyase; Ekici, Hüsamettin; Atmaca, Nurgül

2013-01-01

This study investigated the effect of chlorpyrifos on thoracic aorta and on the level of NO in plasma and aorta. The effect of chlorpyrifos on thoracic aorta in organ bath was determined in 10 rats. Another 45 rats were assigned to 3 groups with 15 rats each: control group 1 received distilled water, control group 2 was given corn oil, and the last group was given 13.5 mg/kg chlorpyrifos dissolved in corn oil every other day for 8 weeks orally. Chlorpyrifos (10−10 M–10−5 M) showed no effect on isolated thoracic aorta. Plasma AChE activity was decreased, while LDH, ALT, GGT, and AST activities were increased in chlorpyrifos group compared to control groups. Plasma NO level was increased in chlorpyrifos group compared to control groups. iNOS expression was present in all groups in the cytoplasm of the endothelia and in the smooth muscle cells of aorta. According to semiquantitative histomorphological analysis, iNOS immunopositive reactions were seen in the decreasing order in chlorpyrifos, control 2, and control 1 groups. eNOS immunopositive reactions were observed in the endothelial cell cytoplasm, rarely in the subintimal layer, and the smooth muscle cells of aorta. There were no differences among the groups in terms of eNOS immunostaining. In conclusion, chlorpyrifos induced NO production in aorta following an increase in NOS expression. PMID:23878805

Serotonin passes through myoendothelial gap junctions to promote pulmonary arterial smooth muscle cell differentiation.

PubMed

Gairhe, Salina; Bauer, Natalie N; Gebb, Sarah A; McMurtry, Ivan F

2012-11-01

Myoendothelial gap junctional signaling mediates pulmonary arterial endothelial cell (PAEC)-induced activation of latent TGF-β and differentiation of cocultured pulmonary arterial smooth muscle cells (PASMCs), but the nature of the signal passing from PAECs to PASMCs through the gap junctions is unknown. Because PAECs but not PASMCs synthesize serotonin, and serotonin can pass through gap junctions, we hypothesized that the monoamine is the intercellular signal. We aimed to determine whether PAEC-derived serotonin mediates PAEC-induced myoendothelial gap junction-dependent activation of TGF-β signaling and differentiation of PASMCs. Rat PAECs and PASMCs were monocultured or cocultured with (touch) or without (no-touch) direct cell-cell contact. In all cases, tryptophan hydroxylase 1 (Tph1) transcripts were expressed predominantly in PAECs. Serotonin was detected by immunostaining in both PAECs and PASMCs in PAEC/PASMC touch coculture but was not found in PASMCs in either PAEC/PASMC no-touch coculture or in PASMC/PASMC touch coculture. Furthermore, inhibition of gap junctions but not of the serotonin transporter in PAEC/PASMC touch coculture prevented serotonin transfer from PAECs to PASMCs. Inhibition of serotonin synthesis pharmacologically or by small interfering RNAs to Tph1 in PAECs inhibited the PAEC-induced activation of TGF-β signaling and differentiation of PASMCs. We concluded that serotonin synthesized by PAECs is transferred through myoendothelial gap junctions into PASMCs, where it activates TGF-β signaling and induces a more differentiated phenotype. This finding suggests a novel role of gap junction-mediated intercellular serotonin signaling in regulation of PASMC phenotype.

Distribution of chlorpyrifos in rice paddy environment and its potential dietary risk.

PubMed

Fu, Yan; Liu, Feifei; Zhao, Chenglin; Zhao, Ying; Liu, Yihua; Zhu, Guonian

2015-09-01

Chlorpyrifos is one of the most extensively used insecticides in China. The distribution and residues of chlorpyrifos in a paddy environment were characterized under field and laboratory conditions. The half-lives of chlorpyrifos in the two conditions were 0.9-3.8days (field) and 2.8-10.3days (laboratory), respectively. The initial distribution of chlorpyrifos followed the increasing order of waterchlorpyrifos was rather low compared to the acceptable daily intake (ADI=0.01mg/kg bw) due to rice consumption. The chronic exposure risk from chlorpyrifos in rice grain was 5.90% and 1.30% ADI from field and laboratory results respectively. Concerning the acute dietary exposure, intake estimated for the highest chlorpyrifos level did not exceed the acute reference dose (ARfD=0.1mg/kg bw). The estimated short-term intakes (ESTIs) were 0.78% and 0.25% of the ARfD for chlorpyrifos. The results showed that the use of chlorpyrifos in rice paddies was fairly safe for consumption of rice grain by consumers. Copyright © 2015. Published by Elsevier B.V.

Environmental fate of chlorpyrifos.

PubMed

Racke, K D

1993-01-01

Chlorpyrifos is an organophosphorus compound that displays broad-spectrum insecticidal activity against a number of important arthropod pests. As a result, it is employed in a wide variety of agricultural and specialty pest control scenarios. Various formulations of chlorpyrifos have been developed to maximize stability and contact with pests and minimize human exposure. From corn agriculture in the United States to termite control in Japan to cotton agriculture in Egypt to citrus horticulture in Spain, chloropyrifos has been successfully employed to combat insect and other arthropod pests threatening the production of food and fiber and maintenance of human health. Due to the nonpolar nature of the chlorpyrifos molecule, it possesses a low water solubility (< 2 ppm) and great tendency to partition from aqueous into organic phases in the environment (log P of 4.7-5.3). It is characterized by an average soil and sediment sorption coefficient (Koc) of 8498 and aquatic bioconcentration factor of 100-5100 in fish. As a result of its high propensity for sorption, its movement through and over the soil profile is limited. It has been found to be relatively immobile vertically in soil and has not proved to be a groundwater contaminant. Surface runoff and erosion mobility are also low, and, in general, less than 0.3% of soil surface application has been observed to move even under the heaviest simulated precipitation conditions. Chlorpyrifos has an intermediate vapor pressure (2 x 10(-5) mm Hg, 25 degrees C), and under some conditions volatility is a significant mechanism of dissipation. This is especially true for plant foliage, from which it is the major means of loss, to some extent from water surfaces, and to a lesser degree from moist soil surfaces. Chlorpyrifos is a degradable compound, and both abiotic and biotic transformation processes effect its degradation within environmental compartments (Fig. 1). In all cases, the major pathway of transformation involves

[The rabbit experimental study for toxicokinetics of chlorpyrifos impacted by hemoperfusion].

PubMed

Guo, Xiang; Chen, Xiao; Zhang, Hongshun; Long, Xin; He, Qian; Sun, Chengye; Huang, Xianqing; He, Jian

2015-11-01

To investigate toxicokinetic parameters impacted by hemoperfusion after oral chlorpyrifos exposure, to investigate the adsorption effect of hemoperhusion for chlorpyrifos poisoning. 12 rabbits were divided into two groups after oral exposure with chlorpyrifos 300 mg/kg body weight. Control group: without hemoperfusion; hemoperfusion group: hemoperfusion starts 0.5 h after chlorpyrifos exposure and lasts for 2h. Blood samples were collected at different times, concentrations of chlorpyrifos were tested by GC, then, toxicokinetic parameterswere calculated and analysis by DAS3.0. In hemoperfusion group, peak time was (7.19±3.74) h, peak concentrations was (1.37±0.56) mg/L, clearance rate was (13.93±10.27) L/h/kg, apparent volume of distribution was (418.18±147.15) L/kg The difference of these parameter were statistically significant compared with control group (P<0.05). Hmoperfusion will decrease the inner exposure and load dose of rabbits with chlorpyrifos poisoning.

Serotonin-related pathways and developmental plasticity: relevance for psychiatric disorders

PubMed Central

Dayer, Alexandre

2014-01-01

Risk for adult psychiatric disorders is partially determined by early-life alterations occurring during neural circuit formation and maturation. In this perspective, recent data show that the serotonin system regulates key cellular processes involved in the construction of cortical circuits. Translational data for rodents indicate that early-life serotonin dysregulation leads to a wide range of behavioral alterations, ranging from stress-related phenotypes to social deficits. Studies in humans have revealed that serotonin-related genetic variants interact with early-life stress to regulate stress-induced cortisol responsiveness and activate the neural circuits involved in mood and anxiety disorders. Emerging data demonstrate that early-life adversity induces epigenetic modifications in serotonin-related genes. Finally, recent findings reveal that selective serotonin reuptake inhibitors can reinstate juvenile-like forms of neural plasticity, thus allowing the erasure of long-lasting fear memories. These approaches are providing new insights on the biological mechanisms and clinical application of antidepressants. PMID:24733969

Chlorpyrifos chronic toxicity in broilers and effect of vitamin C.

PubMed

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

2011-01-01

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

Persistence of chlorpyrifos in a mineral and an organic soil.

PubMed

Chapman, R A; Harris, C R

1980-01-01

Chlorpyrifos (Lorsban emulsifiable concentrate) was applied at 3.4 kg AI/ha and incorporated into sand and muck soil contained in small field plots. Soil samples were taken at intervals over 2 yr. Radishes and carrots, seeded yearly, served as indicator crops for absorption of insecticide residues. Samples were extracted and analyzed, by gas-liquid chromatography, for chlorpyrifos, oxychlorpyrifos, and 3,5,6-trichloro-2-pyridinol. Chlorpyrifos residues declined rapidly, with 50% of the initial application remaining after 2 and 8 wk in sand and muck, respectively, and 4 and 9% after 1 yr. Pyridinol residues increased to 13 and 39% of the initial chlorpyrifos application in sand and muck after 1 and 8 wk, respectively, and declined thereafter. Oxychlorpyrifos was detected in the 2 soils at very low levels only in immediate posttreatment samples. In the first year of the study low levels (less than 0.1 ppm) of chlorpyrifos and the pyridinol were detected in radishes and carrots.

Chronic toxicity of commercial chlorpyrifos to earthworm Pheretima peguana.

PubMed

Muangphra, Ptumporn; Tharapoom, Kampanat; Euawong, Nongnuch; Namchote, Suluck; Gooneratne, Ravi

2016-11-01

A chronic toxicity study was conducted in earthworms (Pheretima peguana) exposed to soil spiked with chlorpyrifos at concentrations of 0, 0.1, 1, 10, and 100 mg/kg soil dry matter for 7, 14, and 28 days. The integrity of the coelomocyte lysosomal membrane, nervous system, and male reproductive tissue was monitored using, respectively, the neutral-red retention assay, acetylcholinesterase (AChE) enzyme assay, and histomorphology of spermatogenic cells in the seminal vesicles and cocoon production (at 28 days after 28 days' exposure). Chlorpyrifos decreased the coelomocyte neutral-red retention time (NRRT) significantly (p < 0.05) at concentrations > 0.1 mg/kg soil as early as day 7 of exposure and was dose- and time-dependent. Chlorpyrifos inhibition of AChE activity was greater at day 7 than at day14 (p < 0.05) indicating possibly nerve recovery. Chlorpyrifos induced concentration-dependent damage to spermatogenic cells and cytophores in premature stages. The number and size of premature, maturing, and fully mature spermatogenic stages were increased at low concentrations (<1 mg/kg) but a number of these maturation stages declined at higher concentrations (10 and100 mg/kg) on day 28. The most severe effects were observed in the maturing and fully mature stages at the highest chlorpyrifos concentration, and this had an adverse impact on cocoon production and cocoon viability. Collectively, the results suggest induction of widespread effects on multiple organ systems in P. peguana exposed to chlorpyrifos. Although NRRT and AChE activity were the most sensitive of the biomarkers, cocoon production and cocoon viability could still be considered as diagnostic tools for monitoring effects from low-dose long-term chlorpyrifos toxicity and for evaluating population effects. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1450-1459, 2016. © 2015 Wiley Periodicals, Inc.

Effect of chlorpyrifos and enrofloxacin on selected enzymes in rats.

PubMed

Barski, D; Spodniewska, A

2018-03-01

This study examined the effect of chlorpyrifos and/or enrofloxacin on the activity of acetylcholinesterase (AChE) in the blood and brain, and the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum. The experiment was conducted on Wistar strain rats. Chlorpyrifos was administered with a stomach tube at a dose of 0.04 LD50 for 28 days and enrofloxacin at a dose of 5 mg/kg bw for 5 consecutive days. The experiment found that enrofloxacin changed the activity of the enzymes under study only to a small extent. At the dose applied in the experiment, chlorpyrifos decreased the activity of AChE significantly, both in blood and in the brain, and increased the activity of ALT and AST in rat serum. The administration of chlorpyrifos in combination with enrofloxacin changed the activity of the enzymes under study only slightly. A weaker, but longer, inhibition of AChE activity in both blood and the brain was observed in this group compared to the animals exposed only to chlorpyrifos. However, although enrofloxacin, like chlorpyrifos, increases the activity of ALT and AST in serum, their combined administration did not increase the hepatotoxic effect. Copyright© by the Polish Academy of Sciences.

Effects of storage and processing on residue levels of chlorpyrifos in soybeans.

PubMed

Zhao, Liuwei; Ge, Jing; Liu, Fengmao; Jiang, Naiwen

2014-05-01

The residue levels of chlorpyrifos in soybeans during storage and processing were investigated. Soybeans were treated with chlorpyrifos aqueous solution and placed in a sealed plastic container. The residue of chlorpyrifos was determined in soybeans at six time points within 0 and 112days during storage and oil processing of the soybeans was conducted. The analysis of the residues of chlorpyrifos was carried out by gas chromatography-mass spectrometry (GC-MS). Results show that the dissipation of chlorpyrifos in soybeans is about 62% during the storage period. Moreover, the carryover of the residues from soybeans into oil is found to be related to the processing methods. Processing factor, which is defined as the ratio of chlorpyrifos residue concentration in oil sample to that in the soybean samples, was 11 and 0.25 after cold and hot pressing, respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

Peripheral Serotonin Regulates Maternal Calcium Trafficking in Mammary Epithelial Cells during Lactation in Mice

PubMed Central

Laporta, Jimena; Keil, Kimberly P.; Vezina, Chad M.; Hernandez, Laura L.

2014-01-01

Lactation is characterized by massive transcellular flux of calcium, from the basolateral side of the mammary alveolar epithelium (blood) into the ductal lumen (milk). Regulation of calcium transport during lactation is critical for maternal and neonatal health. The monoamine serotonin (5-HT) is synthesized by the mammary gland and functions as a homeostatic regulation of lactation. Genetic ablation of tryptophan hydroxylase 1 (Tph1), which encodes the rate-limiting enzyme in non-neuronal serotonin synthesis, causes a deficiency in circulating serotonin. As a consequence maternal calcium concentrations decrease, mammary epithelial cell morphology is altered, and cell proliferation is decreased during lactation. Here we demonstrate that serotonin deficiency decreases the expression and disrupts the normal localization of calcium transporters located in the apical (PMCA2) and basolateral (CaSR, ORAI-1) membranes of the lactating mammary gland. In addition, serotonin deficiency decreases the mRNA expression of calcium transporters located in intracellular compartments (SERCA2, SPCA1 and 2). Mammary expression of serotonin receptor isoform 2b and its downstream pathways (PLCβ3, PKC and MAP-ERK1/2) are also decreased by serotonin deficiency, which might explain the numerous phenotypic alterations described above. In most cases, addition of exogenous 5-hydroxy-L-tryptophan to the Tph1 deficient mice rescued the phenotype. Our data supports the hypothesis that serotonin is necessary for proper mammary gland structure and function, to regulate blood and mammary epithelial cell transport of calcium during lactation. These findings can be applicable to the treatment of lactation-induced hypocalcemia in dairy cows and can have profound implications in humans, given the wide-spread use of selective serotonin reuptake inhibitors as antidepressants during pregnancy and lactation. PMID:25299122

Paraoxonase Enzyme Protects Retinal Pigment Epithelium from Chlorpyrifos Insult

PubMed Central

Jasna, Jagan Mohan; Anandbabu, Kannadasan; Bharathi, Subramaniam Rajesh; Angayarkanni, Narayanasamy

2014-01-01

Retinal pigment epithelium (RPE) provides nourishment and protection to the eye. RPE dysfunction due to oxidative stress and inflammation is one of the major reason for many of the retinal disorders. Organophosphorus pesticides are widely used in the agricultural, industrial and household activities in India. However, their effects on the eye in the context of RPE has not been studied. In this study the defense of the ARPE19 cells exposed to Chlorpyrifos (1 nM to 100 µM) in terms of the enzyme paraoxonase (PON) was studied at 24 hr and 9 days of treatment. Chlorpyrifos was found to induce oxidative stress in the ARPE19 cells as seen by significant increase in ROS and decrease in glutathione (GSH) levels without causing cell death. Tissue resident Paraoxonase 2 (PON2) mRNA expression was elevated with chlorpyrifos exposure. The three enzymatic activities of PON namely, paraoxonase (PONase), arylesterase (PON AREase) and thiolactonase (PON HCTLase) were also found to be significantly altered to detoxify and as an antioxidant defense. Among the transcription factors regulating PON2 expression, SP1 was significantly increased with chlorpyrifos exposure. PON2 expression was found to be crucial as ARPE19 cells showed a significant loss in their ability to withstand oxidative stress when the cells were subjected to chlorpyrifos after silencing PON2 expression. Treatment with N-acetyl cysteine positively regulated the PON 2 expression, thus promoting the antioxidant defense put up by the cells in response to chlorpyrifos. PMID:24979751

Feasibility of using drinking water treatment residuals as a novel chlorpyrifos adsorbent.

PubMed

Zhao, Yuanyuan; Wang, Changhui; Wendling, Laura A; Pei, Yuansheng

2013-08-07

Recent efforts have increasingly focused on the development of low-cost adsorbents for pesticide retention. In this work, the novel reuse of drinking water treatment residuals (WTRs), a nonhazardous ubiquitous byproduct, as an adsorbent for chlorpyrifos was investigated. Results showed that the kinetics and isothermal processes of chlorpyrifos sorption to WTRs were better described by a pseudo-second-order model and by the Freundlich equation, respectively. Moreover, compared with paddy soil and other documented absorbents, the WTRs exhibited a greater affinity for chlorpyrifos (log Koc = 4.76-4.90) and a higher chlorpyrifos sorption capacity (KF = 5967 mg(1-n)·L·kg(-1)) owing to the character and high content of organic matter. Further investigation demonstrated that the pH had a slight but statistically insignificant effect on chlorpyrifos sorption to WTRs; solution ionic strength and the presence of low molecular weight organic acids both resulted in concentration-dependent inhibition effects. Overall, these results confirmed the feasibility of using WTRs as a novel chlorpyrifos adsorbent.

Competitive immunochromatographic assay for the detection of the organophosphorus pesticide chlorpyrifos

PubMed Central

Kim, Young Ah; Lee, Eun-Hye; Kim, Kwang-Ok; Lee, Yong Tae; Hammock, Bruce D.; Lee, Hye-Sung

2014-01-01

An immunochromatographic assay (ICA) based on competitive antigen-coated format using colloidal gold as the label was developed for the detection of the organophosphorus insecticide chlorpyrifos. The ICA test strip consisted of a membrane with a detection zone, a sample pad and an absorbent pad. The membrane was separately coated with chlorpyrifos hapten-OVA conjugate (test line) and anti-mouse IgG (control line). Based on the fact that the competition is between the migrating analyte in the sample and the analyte hapten immobilized on the test strip for the binding sites of the antibody-colloidal gold (Ab-CG) conjugate migrating on the test strip, this study suggests that the relative migration speed between the two migrating substances is a critically important factor for the sensitive detection by competitive ICA. This criterion was utilized for the confirmation of appropriateness of a nitrocellulose (NC) membrane for chlorpyrifos ICA. The detection limit of the ICA for chlorpyrifos standard and chlorpyrifos spiked into agricultural samples were 10 and 50 ng mL−1, respectively. The assay time for the ICA test was less than 10 min, suitable for rapid on-site testing of chlorpyrifos. PMID:21504817

Preparation of Magnetic Molecularly Imprinted Polymer for Chlorpyrifos Adsorption and Enrichment

NASA Astrophysics Data System (ADS)

Chen, M.; Ma, X.; Sheng, J.

2017-11-01

Magnetic molecularly imprinted polymer (MMIP) for chlorpyrifos was prepared and characterized. The adsorption performance of MMIP for chlorpyrifos was evaluated under various conditions. The results showed that the adsorption equilibrium was achieved within 1 h, the adsorption capacity was 16.8 mg/g, and the adsorption process could be well described by Langmuir isotherm model and pseudo-second-order kinetic model. The MMIP was used as the selective sorbent for solid-phase extraction of chlorpyrifos from environmental water and vegetable samples. Combined with gas chromatography-mass spectrometry, a LOD of 30 ng/L, spiked recovery of 89.6%-107.3% and RSD of 1.9%-3.8% for chlorpyrifos were obtained.

An integrated vegetated ditch system reduces chlorpyrifos loading in agricultural runoff.

PubMed

Phillips, Bryn M; Anderson, Brian S; Cahn, Michael; Rego, Jessa L; Voorhees, Jennifer P; Siegler, Katie; Zhang, Xuyang; Budd, Robert; Goh, Kean; Tjeerdema, Ron S

2017-03-01

Agricultural runoff containing toxic concentrations of the organophosphate pesticide chlorpyrifos has led to impaired water body listings and total maximum daily load restrictions in California's central coast watersheds. Chlorpyrifos use is now tightly regulated by the Central Coast Regional Water Quality Control Board. This study evaluated treatments designed to reduce chlorpyrifos in agricultural runoff. Initial trials evaluated the efficacy of 3 different drainage ditch installations individually: compost filters, granulated activated carbon (GAC) filters, and native grasses in a vegetated ditch. Treatments were compared to bare ditch controls, and experiments were conducted with simulated runoff spiked with chlorpyrifos at a 1.9 L/s flow rate. Chlorpyrifos concentrations and toxicity to Ceriodaphnia dubia were measured at the input and output of the system. Input concentrations of chlorpyrifos ranged from 858 ng/L to 2840 ng/L. Carbon filters and vegetation provided the greatest load reduction of chlorpyrifos (99% and 90%, respectively). Toxicity was completely removed in only one of the carbon filter trials. A second set of trials evaluated an integrated approach combining all 3 treatments. Three trials were conducted each at 3.2 L/s and 6.3 L/s flow rates at input concentrations ranging from 282 ng/L to 973 ng/L. Chlorpyrifos loadings were reduced by an average of 98% at the low flow rate and 94% at the high flow rate. Final chlorpyrifos concentrations ranged from nondetect (<50 ng/L) to 82 ng/L. Toxicity to C. dubia was eliminated in 3 of 6 integrated trials. Modeling of the ditch and its components informed design alterations that are intended to eventually remove up to 100% of pesticides and sediment. Future work includes investigating the adsorption capacity of GAC, costs associated with GAC disposal, and real-world field trials to further reduce model uncertainties and confirm design optimization. Trials with more water-soluble pesticides

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

PubMed

Akbar, Shamsa; Sultan, Sikander

2016-01-01

Since 1960s, the organophosphate pesticide chlorpyrifos has been widely used for the purpose of pest control. However, given its persistence and toxicity towards life forms, the elimination of chlorpyrifos from contaminated sites has become an urgent issue. For this process bioremediation is the method of choice. Two bacterial strains, JCp4 and FCp1, exhibiting chlorpyrifos-degradation potential were isolated from pesticide contaminated agricultural fields. These isolates were able to degrade 84.4% and 78.6% of the initial concentration of chlorpyrifos (100mgL(-1)) within a period of only 10 days. Based on 16S rRNA sequence analysis, these strains were identified as Achromobacter xylosoxidans (JCp4) and Ochrobactrum sp. (FCp1). These strains exhibited the ability to degrade chlorpyrifos in sterilized as well as non-sterilized soils, and were able to degrade 93-100% of the input concentration (200mgkg(-1)) within 42 days. The rate of degradation in inoculated soils ranged from 4.40 to 4.76mg(-1)kg(-1)d(-1) with rate constants varying between 0.047 and 0.069d(-1). These strains also displayed substantial plant growth promoting traits such as phosphate solubilization, indole acetic acid production and ammonia production both in absence as well as in the presence of chlorpyrifos. However, presence of chlorpyrifos (100 and 200mgL(-1)) was found to have a negative effect on indole acetic acid production and phosphate solubilization with percentage reduction values ranging between 2.65-10.6% and 4.5-17.6%, respectively. Plant growth experiment demonstrated that chlorpyrifos has a negative effect on plant growth and causes a decrease in parameters such as percentage germination, plant height and biomass. Inoculation of soil with chlorpyrifos-degrading strains was found to enhance plant growth significantly in terms of plant length and weight. Moreover, it was noted that these strains degraded chlorpyrifos at an increased rate (5.69mg(-1)kg(-1)d(-1)) in planted soil. The

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

PubMed

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

2016-08-01

The long-term abuse use of chlorpyrifos-like pesticides in agriculture and horticulture has resulted in significant soil or water contamination and a worldwide ecosystem threat. In this study, the ability of a solvent-tolerant bacterium, Pseudomonas putida MB285, with surface-displayed bacterial laccase, to biodegrade chlorpyrifos was investigated. The results of compositional analyses of the degraded products demonstrate that the engineered MB285 was capable of completely eliminating chlorpyrifos via direct biodegradation, as determined by high-performance liquid chromatography and gas chromatography-mass spectrometry assays. Two intermediate metabolites, namely 3,5,6-trichloro-2-pyridinol (TCP) and diethyl phosphate, were temporarily detectable, verifying the joint and stepwise degradation of chlorpyrifos by surface laccases and certain cellular enzymes, whereas the purified free laccase incompletely degraded chlorpyrifos into TCP. The degradation reaction can be conducted over a wide range of pH values (2-7) and temperatures (5-55 °C) without the need for Cu(2+). Bioassays using Caenorhabditis elegans as an indicator organism demonstrated that the medium was completely detoxified of chlorpyrifos by degradation. Moreover, the engineered cells exhibited a high capacity of repeated degradation and good performance in continuous degradation cycles, as well as a high capacity to degrade real effluents containing chlorpyrifos. Therefore, the developed system exhibited a high degradation capacity and performance and constitutes an improved approach to address chlorpyrifos contamination in chlorpyrifos-remediation practice. Copyright © 2016 Elsevier Ltd. All rights reserved.

78 FR 14540 - Chlorpyrifos Registration Review; Preliminary Volatilization Assessment; Extension of Comment Period

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-06

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPP-2008-0850; FRL-9380-7] Chlorpyrifos Registration... Federal Register issue of February 6, 2013, concerning Chlorpyrifos Registration Review; Preliminary... volatilization assessment for the registration review of chlorpyrifos. EPA received requests from several...

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

PubMed

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

2016-03-01

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

Effects of chlorpyrifos on soil carboxylesterase activity at an aggregate-size scale.

PubMed

Sanchez-Hernandez, Juan C; Sandoval, Marco

2017-08-01

The impact of pesticides on extracellular enzyme activity has been mostly studied on the bulk soil scale, and our understanding of the impact on an aggregate-size scale remains limited. Because microbial processes, and their extracellular enzyme production, are dependent on the size of soil aggregates, we hypothesized that the effect of pesticides on enzyme activities is aggregate-size specific. We performed three experiments using an Andisol to test the interaction between carboxylesterase (CbE) activity and the organophosphorus (OP) chlorpyrifos. First, we compared esterase activity among aggregates of different size spiked with chlorpyrifos (10mgkg -1 wet soil). Next, we examined the inhibition of CbE activity by chlorpyrifos and its metabolite chlorpyrifos-oxon in vitro to explore the aggregate size-dependent affinity of the pesticides for the active site of the enzyme. Lastly, we assessed the capability of CbEs to alleviate chlorpyrifos toxicity upon soil microorganisms. Our principal findings were: 1) CbE activity was significantly inhibited (30-67% of controls) in the microaggregates (<0.25mm size) and smallest macroaggregates (<1.0 - 0.25mm), but did not change in the largest macroaggregates (>1.0mm) compared with the corresponding controls (i.e., pesticide-free aggregates), 2) chlorpyrifos-oxon was a more potent CbE inhibitor than chlorpyrifos; however, no significant differences in the CbE inhibition were found between micro- and macroaggregates, and 3) dose-response relationships between CbE activity and chlorpyrifos concentrations revealed the capability of the enzyme to bind chlorpyrifos-oxon, which was dependent on the time of exposure. This chemical interaction resulted in a safeguarding mechanism against chlorpyrifos-oxon toxicity on soil microbial activity, as evidenced by the unchanged activity of dehydrogenase and related extracellular enzymes in the pesticide-treated aggregates. Taken together, these results suggest that environmental risk

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

PubMed

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

2016-06-01

Long-term use of chlorpyrifos poses a potential threat to the environment that cannot be ignored, yet little is known about the succession of substrate microbial communities in constructed wetlands (CWs) under chlorpyrifos stress. Six pilot-scale CW systems receiving artificial wastewater containing 1mg/L chlorpyrifos were established to investigate the effects of chlorpyrifos and wetland vegetation on the microbial metabolism pattern of carbon sources and community structure, using BIOLOG and denaturing gradient gel electrophoresis (DGGE) approaches. Based on our samples, BIOLOG showed that Shannon diversity (H') and richness (S) values distinctly increased after 30days when chlorpyrifos was added. At the same time, differences between the vegetated and the non-vegetated systems disappeared. DGGE profiles indicated that H' and S had no significant differences among four different treatments. The effect of chlorpyrifos on the microbial community was mainly reflected at the physiological level. Principal component analysis (PCA) of both BIOLOG and DGGE showed that added chlorpyrifos made a difference on test results. Meanwhile, there was no difference between the vegetation and no-vegetation treatments after addition of chlorpyrifos at the physiological level. Moreover, the vegetation had no significant effect on the microbial community at the genetic level. Comparisons were made between bacteria in this experiment and other known chlorpyrifos-degrading bacteria. The potential chlorpyrifos-degrading ability of bacteria in situ may be considerable. Copyright © 2016. Published by Elsevier B.V.

Retention and Migration of Chlorpyrifos in Aquatic Sediments and Soils

NASA Astrophysics Data System (ADS)

Gebremariam, S. Y.; Beutel, M.; Yonge, D.; Flury, M.; Harsh, J. B.

2010-12-01

The accurate description of the fate and transport of potentially toxic agricultural pesticides in sediments and soils is of great interest to environmental scientists and regulators. Of particular concern is the widely documented detection of agricultural pesticides and their byproducts in drinking water wells. This presentation discusses results of a study of the fate and transport of chlorpyrifos, a strongly hydrophobic organophosphate-pesticide, in sediments and soils collected from a range of aquatic environments. Using radio-labeled chlorpyrifos, this study is unique in its comprehensive nature and focus on aquatic sediments, for which studies involving pesticide fate and transport are limited. Study components include: (1) batch equilibrium experiments to evaluate sorption/desorption parameters; (2) kinetic and non-equilibrium sorption experiments using miniaturized flow-cells; (3) column experiments to understand patterns of pesticide break through; and (4) numerical modeling of chlorpyrifos transport through aquatic sediments and soils. Initial results show that chlorpyrifos sorption, when corrected for reversible sorption to container walls, exhibited two component sorption, a large irreversible fraction and a smaller reversible fraction that can act as a secondary source. In addition, of a wide range of soil parameters measured, organic carbon content exhibited the highest correlation with chlorpyrifos retention in cranberry field soils. Simulation models developed in this study, which account for hysteretic and nonlinear sorption, will help to better predict the fate of chlorpyrifos and other hydrophobic chemicals in sediments and soils.

EVALUATION OF CHLORPYRIFOS UPTAKE IN STERILIZED AND NON-STERILIZED SEDIMENT

EPA Science Inventory

In order to evaluate chemical interactions in sediment, initial experiments were designed to assess the role of microbial activitiy on chemical fate of chlorpyrifos. In these initial experiments, sediment uptake of chlorpyrifos was evaluated using Enzyme Linked Immunosorbent Assa...

Degradation of chlorpyrifos residues in apple under temperate conditions of Kashmir Valley.

PubMed

Mukhtar, Malik; Sherwani, Asma; Wani, Ashraf Alam; Ahmed, Sheikh Bilal; Sofi, Javid Ahmad; Bano, Parveena

2015-08-01

The present studies were carried out to observe the dissipation pattern of chlorpyrifos on apple in Kashmir Valley. Persistence of chlorpyrifos in apple was studied following two applications rates of chlorpyrifos (Dursban 20 EC) at 200 g a.i. ha(-1) (single dose T 1) and 400 g a.i. ha(-1) (double dose T 2). The average initial deposit of chlorpyrifos was found to be 1.61 and 1.98 μg g(-1) for T 1 and T 2 application rates respectively on apple. The residues dissipated to 0.09 and 0.06 μg g(-1) after 15- and 30-day post treatment with half-life periods of 3.34 and 5.47 days in T 1 and T 2 application rates, respectively. The residues of chlorpyrifos dissipated to below limit of quantification (LOQ) of 0.04 μg g(-1) after 30 day at T 1 application rate. A waiting period of 6 days must be observed for chlorpyrifos on apple at recommended application rate for the safety of consumers. Theoretical maximum residue contribution (TMRC) values were found to be far less than maximum permissible intake (MPI) at 0 day in both the dosages suggesting chlorpyrifos on apple in Kashmir is unlikely to cause health risks.

A human life-stage physiologically based pharmacokinetic and pharmacodynamic model for chlorpyrifos: development and validation.

PubMed

Smith, Jordan Ned; Hinderliter, Paul M; Timchalk, Charles; Bartels, Michael J; Poet, Torka S

2014-08-01

Sensitivity to some chemicals in animals and humans are known to vary with age. Age-related changes in sensitivity to chlorpyrifos have been reported in animal models. A life-stage physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed to predict disposition of chlorpyrifos and its metabolites, chlorpyrifos-oxon (the ultimate toxicant) and 3,5,6-trichloro-2-pyridinol (TCPy), as well as B-esterase inhibition by chlorpyrifos-oxon in humans. In this model, previously measured age-dependent metabolism of chlorpyrifos and chlorpyrifos-oxon were integrated into age-related descriptions of human anatomy and physiology. The life-stage PBPK/PD model was calibrated and tested against controlled adult human exposure studies. Simulations suggest age-dependent pharmacokinetics and response may exist. At oral doses ⩾0.6mg/kg of chlorpyrifos (100- to 1000-fold higher than environmental exposure levels), 6months old children are predicted to have higher levels of chlorpyrifos-oxon in blood and higher levels of red blood cell cholinesterase inhibition compared to adults from equivalent doses. At lower doses more relevant to environmental exposures, simulations predict that adults will have slightly higher levels of chlorpyrifos-oxon in blood and greater cholinesterase inhibition. This model provides a computational framework for age-comparative simulations that can be utilized to predict chlorpyrifos disposition and biological response over various postnatal life stages. Copyright © 2013 Elsevier Inc. All rights reserved.

Serotonin rebalances cortical tuning and behavior linked to autism symptoms in 15q11-13 CNV mice

PubMed Central

Nakai, Nobuhiro; Nagano, Masatoshi; Saitow, Fumihito; Watanabe, Yasuhito; Kawamura, Yoshinobu; Kawamoto, Akiko; Tamada, Kota; Mizuma, Hiroshi; Onoe, Hirotaka; Watanabe, Yasuyoshi; Monai, Hiromu; Hirase, Hajime; Nakatani, Jin; Inagaki, Hirofumi; Kawada, Tomoyuki; Miyazaki, Taisuke; Watanabe, Masahiko; Sato, Yuka; Okabe, Shigeo; Kitamura, Kazuo; Kano, Masanobu; Hashimoto, Kouichi; Suzuki, Hidenori; Takumi, Toru

2017-01-01

Serotonin is a critical modulator of cortical function, and its metabolism is defective in autism spectrum disorder (ASD) brain. How serotonin metabolism regulates cortical physiology and contributes to the pathological and behavioral symptoms of ASD remains unknown. We show that normal serotonin levels are essential for the maintenance of neocortical excitation/inhibition balance, correct sensory stimulus tuning, and social behavior. Conversely, low serotonin levels in 15q dup mice (a model for ASD with the human 15q11-13 duplication) result in impairment of the same phenotypes. Restoration of normal serotonin levels in 15q dup mice revealed the reversibility of a subset of ASD-related symptoms in the adult. These findings suggest that serotonin may have therapeutic potential for discrete ASD symptoms. PMID:28691086

[Enzymatic degradation of organophosphorus insecticide chlorpyrifos by fungus WZ-I].

PubMed

Xie, Hui; Zhu, Lu-sheng; Wang, Jun; Wang, Xiu-guo; Liu, Wei; Qian, Bo; Wang, Qian

2005-11-01

Degradation characteristics of chlorpyrifos insecticides was determined by the crude enzyme extracted from the isolated strain WZ-I ( Fusarium LK. ex Fx). The best separating condition and the degrading characteristic of chlorpyrifos were studied. Rate of degradation for chlorpyrifos by its intracellular enzyme, extracellular enzyme and cell fragment was 60.8%, 11.3% and 48%, respectively. The degrading enzyme was extracted after this fungus was incubated for 8 generations in the condition of noninducement, and its enzymic activity lost less, the results show that this enzyme is an intracellular and connatural enzyme. The solubility protein of the crude enzyme was determined with Albumin (bovine serum) as standard protein and the solubility protein of the crude enzyme was 3.36 mg x mL(-1). The pH optimum for crude enzyme was 6.8 for enzymatic degradation of chlorpyrifos, and it had comparatively high activity in the range of pH 6.0 - 9.0. The optimum temperature for enzymatic activity was at 40 degrees C, it still had comparatively high activity in the range of temperature 20-50 degrees C, the activity of enzyme rapidly reduced at 55 degrees C, its activity was 41% of the maximal activity. The crude enzyme showed Km value for chlorpyrifos of 1.049 26 mmol x L(-1), and the maximal enzymatic degradation rate was 0.253 5 micromol x (mg x min)(-1). Additional experimental evidence suggests that the enzyme had the stability of endure for temperature and pH, the crude enzyme of fungus WZ-I could effectively degrade chlorpyrifos.

Chlorpyrifos degradation in a biomixture of biobed at different maturity stages.

PubMed

Tortella, G R; Rubilar, O; Castillo, M d P; Cea, M; Mella-Herrera, R; Diez, M C

2012-06-01

The biomixture is a principal element controlling the degradation efficacy of the biobed. The maturity of the biomixture used in the biobed affects its overall performance of the biobed, but this is not well studied yet. The aim of this research was to evaluate the effect of using a typical composition of Swedish biomixture at different maturity stages on the degradation of chlorpyrifos. Tests were made using biomixture at three maturity stages: 0 d (BC0), 15 d (BC15) and 30 d (BC30); chlorpyrifos was added to the biobeds at final concentration of 200, 320 and 480 mg kg(-1). Chlorpyrifos degradation in the biomixture was monitored over time. Formation of TCP (3,5,6-trichloro-2-pyrinidol) was also quantified, and hydrolytic and phenoloxidase activities measured. The biomixture efficiently degraded chlorpyrifos (degradation efficiency >50%) in all the evaluated maturity stages. However, chlorpyrifos degradation decreased with increasing concentrations of the pesticide. TCP formation occurred in all biomixtures, but a major accumulation was observed in BC30. Significant differences were found in both phenoloxidase and hydrolytic activities in the three maturity stages of biomixture evaluated. Also, these two biological activities were affected by the increase in pesticide concentration. In conclusion, our results demonstrated that chlorpyrifos can be degraded efficiently in all the evaluated maturity stages. Copyright © 2012 Elsevier Ltd. All rights reserved.

Chlorpyrifos Exposures in Egyptian Cotton Field Workers

PubMed Central

Farahat, Fayssal M.; Fenske, Richard A.; Olson, James R.; Galvin, Kit; Bonner, Matthew R.; Rohlman, Diane S.; Lein, Pamela J.; Anger, W. Kent

2013-01-01

Neurobehavioral deficits have been reported in Egyptian pesticide application teams using organophosphorus (OP) pesticides, but whether these effects are related to OP pesticide exposures has yet to be established. In preparation for a comprehensive study of the relationship between OP pesticide dose and neurobehavioral deficits, we assessed exposure within this population. We conducted occupational surveys and workplace observations, and collected air, dermal patch and biological samples from applicators, technicians and engineers involved in chlorpyrifos applications during cotton production to test the hypotheses that: 1) dermal exposure was an important contributor to internal dose and varied across body regions; and 2) substantial differences would be seen across the three job categories. Applicators were substantially younger and had shorter exposure histories than did technicians and engineers. Applicators and technicians were observed to have relatively high levels of skin or clothing contact with pesticide-treated foliage as they walked through the fields. Both dermal patch loadings of chlorpyrifos and measurements of a chlorpyrifos-specific metabolite (TCPy) in urine confirmed substantial exposure to and skin absorption of chlorpyrifos that varied according to job category; and dermal patch loading was significantly higher on the thighs than on the forearms. These findings support our hypotheses and support the need for research to examine neurobehavioral performance and exposures in this population. More importantly, the exposures reported here are sufficiently high to recommend urgent changes in work practices amongst these workers. PMID:20193710

Chlorpyrifos exposures in Egyptian cotton field workers.

PubMed

Farahat, Fayssal M; Fenske, Richard A; Olson, James R; Galvin, Kit; Bonner, Matthew R; Rohlman, Diane S; Farahat, Taghreed M; Lein, Pamela J; Anger, W Kent

2010-06-01

Neurobehavioral deficits have been reported in Egyptian pesticide application teams using organophosphorus (OP) pesticides, but whether these effects are related to OP pesticide exposures has yet to be established. In preparation for a comprehensive study of the relationship between OP pesticide dose and neurobehavioral deficits, we assessed exposure within this population. We conducted occupational surveys and workplace observations, and collected air, dermal patch and biological samples from applicators, technicians and engineers involved in chlorpyrifos applications during cotton production to test the hypotheses that: (1) dermal exposure was an important contributor to internal dose and varied across body regions; and (2) substantial differences would be seen across the three job categories. Applicators were substantially younger and had shorter exposure histories than did technicians and engineers. Applicators and technicians were observed to have relatively high levels of skin or clothing contact with pesticide-treated foliage as they walked through the fields. Both dermal patch loadings of chlorpyrifos and measurements of a chlorpyrifos-specific metabolite (TCPy) in urine confirmed substantial exposure to and skin absorption of chlorpyrifos that varied according to job category; and dermal patch loading was significantly higher on the thighs than on the forearms. These findings support our hypotheses and support the need for research to examine neurobehavioral performance and exposures in this population. More importantly, the exposures reported here are sufficiently high to recommend urgent changes in work practices amongst these workers. Copyright 2010 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-01-01

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

Assessment of biochemical mechanisms of tolerance to chlorpyrifos in ancient and contemporary Daphnia pulicaria genotypes.

PubMed

Simpson, Adam M; Jeyasingh, Punidan D; Belden, Jason B

2017-12-01

The evolution of tolerance to environmental contaminants in non-target taxa has been largely studied by comparing extant populations experiencing contrasting exposure. Previous research has demonstrated that "resurrected" genotypes from a population of Daphnia pulicaria express temporal variation in sensitivity to the insecticide chlorpyrifos. Ancient genotypes (1301-1646AD.) were on average more sensitive to this chemical compared to the contemporary genotypes (1967-1977AD.). To determine the physiological mechanisms of tolerance, a series of biochemical assays was performed on three ancient and three contemporary genotypes; these six genotypes exhibited the most sensitive and most tolerant phenotypes within the population, respectively. Metabolic tolerance mechanisms were evaluated using acute toxicity testing, while target-site tolerance was assessed via in vitro acetylcholinesterase (AChE) assays. Acute toxicity tests were conducted using i) the toxic metabolite chlorpyrifos-oxon (CPF-oxon) and ii) CPF-oxon co-applied with piperonyl butoxide (PBO), a known Phase-I metabolic inhibitor. Both series of toxicity tests reduced the mean variation in sensitivity between tolerant and sensitive genotypes. Exposure to CPF-O reduced the disparity from a 4.7-fold to 1.6-fold difference in sensitivity. The addition of PBO further reduced the variation to a 1.2-fold difference in sensitivity. In vitro acetylcholinesterase assays yielded no significant differences in constitutive activity or target-site sensitivity. These findings suggest that pathways involving Phase-I detoxification and/or bioactivation of chlorpyrifos play a significant role in dictating the microevolutionary trajectories of tolerance in this population. Copyright © 2017 Elsevier B.V. All rights reserved.

Purification and Characterization of a Novel Chlorpyrifos Hydrolase from Cladosporium cladosporioides Hu-01

PubMed Central

Chen, Shaohua; Hu, Meiying; Luo, Jianjun; Li, Yanan

2012-01-01

Chlorpyrifos is of great environmental concern due to its widespread use in the past several decades and its potential toxic effects on human health. Thus, the degradation study of chlorpyrifos has become increasing important in recent years. A fungus capable of using chlorpyrifos as the sole carbon source was isolated from organophosphate-contaminated soil and characterized as Cladosporium cladosporioides Hu-01 (collection number: CCTCC M 20711). A novel chlorpyrifos hydrolase from cell extract was purified 35.6-fold to apparent homogeneity with 38.5% overall recovery by ammoniumsulfate precipitation, gel filtration chromatography and anion-exchange chromatography. It is a monomeric structure with a molecular mass of 38.3 kDa. The pI value was estimated to be 5.2. The optimal pH and temperature of the purified enzyme were 6.5 and 40°C, respectively. No cofactors were required for the chlorpyrifos-hydrolysis activity. The enzyme was strongly inhibited by Hg2+, Fe3+, DTT, β-mercaptoethanol and SDS, whereas slight inhibitory effects (5–10% inhibition) were observed in the presence of Mn2+, Zn2+, Cu2+, Mg2+, and EDTA. The purified enzyme hydrolyzed various organophosphorus insecticides with P-O and P-S bond. Chlorpyrifos was the preferred substrate. The Km and Vmax values of the enzyme for chlorpyrifos were 6.7974 μM and 2.6473 μmol·min−1, respectively. Both NH2-terminal sequencing and matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometer (MALDI-TOF-MS) identified an amino acid sequence MEPDGELSALTQGANS, which shared no similarity with any reported organophosphate-hydrolyzing enzymes. These results suggested that the purified enzyme was a novel hydrolase and might conceivably be developed to fulfill the practical requirements to enable its use in situ for detoxification of chlorpyrifos. Finally, this is the first described chlorpyrifos hydrolase from fungus. PMID:22693630

Order Denying Petition to Revoke All Tolerances for the Pesticide Chlorpyrifos

EPA Pesticide Factsheets

In this Order, EPA denies a petition requesting that EPA revoke all tolerances for the pesticide chlorpyrifos under section 408(d) of the Federal Food, Drug, and Cosmetic Act and cancel all chlorpyrifos registrations under FIFRA.

Acute toxicity of chlorpyrifos to embryo and larvae of banded gourami Trichogaster fasciata.

PubMed

Sumon, Kizar Ahmed; Saha, Sampa; van den Brink, Paul J; Peeters, Edwin T H M; Bosma, Roel H; Rashid, Harunur

2017-02-01

This study elucidated the acute toxicity of chlorpyrifos on the early life stages of banded gourami (Trichogaster fasciata). To determine the acute effects of chlorpyrifos on their survival and development, we exposedthe embryos and two-day-old larvae to six concentrations (0, 0.01, 0.10, 1.0, 10 and 100 µg L -1 ) of chlorpyrifos in plastic bowls. Log-logistic regression was used to calculate LC10 and LC50 values. Results showed that embryo mortality significantly increased with increasing chlorpyrifos concentrations. The 24-h LC10 and LC50 values (with 95% confidence limits) of chlorpyrifos for embryos were 0.89 (0.50-1.58) and 11.8 (9.12-15.4) µg L -1 , respectively. Hatching success decreased and mortality of larvae significantly increased with increasing concentrations of chlorpyrifos. The 24-h LC10 and LC50 values (with 95% confidence limits) of chlorpyrifos for larvae were 0.53 (0.27-1.06) and 21.7 (15.9-29.4) µg L -1 , respectively; the 48-h LC10 and LC50 for larvae were 0.04 (0.02-0.09) and 5.47 (3.77-7.94) µg L -1 , respectively. The results of this study suggest that 1 µg L -1 of chlorpyrifos in the aquatic environment may adversely affect the development and the reproduction of banded gourami. Our study also suggests that banded gourami fish can serve as an ideal model species for evaluating developmental toxicity of environmental contaminants.

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

PubMed

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

2016-08-01

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

Mice lacking the serotonin 5-HT2B receptor as an animal model of resistance to selective serotonin reuptake inhibitors antidepressants.

PubMed

Diaz, Silvina Laura; Narboux-Nême, Nicolas; Boutourlinsky, Katia; Doly, Stéphane; Maroteaux, Luc

2016-02-01

Depressive disorders are among the most prevalent neuropsychiatric dysfunctions worldwide, with high rates of resistance to antidepressant treatment. Genetic factors clearly contribute to the manifestation of depression as well as to the response to antidepressants. Transgenic mouse models appear as seminal tools to disentangle this complex disorder. Here, we analyzed new key aspects of the phenotype of knock-out mice for the gene encoding the serotonin 2B receptor (Htr(2B)(-/-)), including basal phenotype, ability to develop a depressive-like phenotype upon chronic isolation, and effect of chronic exposure to fluoxetine on chronically stressed Htr(2B)(-/-) mice. We find, here, that Htr(2B)(-/-) mice display an antidepressant-like phenotype, which includes reduced latency to feed in the novelty suppressed feeding test, basal increase in hippocampal BDNF levels, no change in TrkB and p75 protein levels, and an increased preference for sucrose consumption compared to wild type (Htr(2B)(+/+)) mice. Nevertheless, we show that these mice can develop depressive-like behaviors when socially isolated during four weeks. Selective serotonin reuptake inhibitors (SSRI) have been previously shown to be ineffective in non-stressed Htr(2B)(-/-) mice. We evaluated, here, the effects of the SSRI fluoxetine in chronically stressed Htr(2B)(-/-) mice and similarly no behavioral or plastic effect was induced by this antidepressant. All together, these results highlight the suitability to study resistance to SSRI antidepressants of this mouse model displaying panoply of conditions among which behavioral, neurotrophic and plastic causative factors can be analyzed. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Type I Interferon-Mediated Skewing of the Serotonin Synthesis Is Associated with Severe Disease in Systemic Lupus Erythematosus

PubMed Central

Lood, Christian; Tydén, Helena; Gullstrand, Birgitta; Klint, Cecilia; Wenglén, Christina; Nielsen, Christoffer T.; Heegaard, Niels H. H.; Jönsen, Andreas; Kahn, Robin; Bengtsson, Anders A.

2015-01-01

Serotonin, a highly pro-inflammatory molecule released by activated platelets, is formed by tryptophan. Tryptophan is also needed in the production of kynurenine, a process mediated by the type I interferon (IFN)-regulated rate-limiting enzyme indoleamine 2,3-dioxygenase (IDO). The aim of this study was to investigate levels of serotonin in patients with the autoimmune disease systemic lupus erythematosus (SLE), association to clinical phenotype and possible involvement of IDO in regulation of serotonin synthesis. Serotonin levels were measured in serum and plasma from patients with SLE (n=148) and healthy volunteers (n=79) by liquid chromatography and ELISA, as well as intracellularly in platelets by flow cytometry. We found that SLE patients had decreased serotonin levels in serum (p=0.01) and platelets (p<0.0001) as compared to healthy individuals. SLE patients with ongoing type I IFN activity, as determined by an in-house reporter assay, had decreased serum levels of serotonin (p=0.0008) as well as increased IDO activity (p<0.0001), as determined by the kynurenine/tryptophan ratio measured by liquid chromatography. Furthermore, SLE sera induced IDO expression in WISH cells in a type I IFN-dependent manner (p=0.008). Also platelet activation contributed to reduce overall availability of serotonin levels in platelets and serum (p<0.05). Decreased serum serotonin levels were associated with severe SLE with presence of anti-dsDNA antibodies and nephritis. In all, reduced serum serotonin levels in SLE patients were related to severe disease phenotype, including nephritis, suggesting involvement of important immunopathological processes. Further, our data suggest that type I IFNs, present in SLE sera, are able to up-regulate IDO expression, which may lead to decreased serum serotonin levels. PMID:25897671

Increased Expression of P-Glycoprotein Is Associated With Chlorpyrifos Resistance in the German Cockroach (Blattodea: Blattellidae).

PubMed

Hou, Weiyuan; Jiang, Chu; Zhou, Xiaojie; Qian, Kun; Wang, Lei; Shen, Yanhui; Zhao, Yan

2016-12-01

A principal method for control of the German cockroach, Blattella germanica (L.), is the broad-spectrum organophosphorus insecticide, chlorpyrifos (O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate); however, extensive and repeated application has resulted in the development of resistance to chlorpyrifos in this insect. Evidence suggests that ATP-binding cassette protein transporters, including P-glycoprotein, are involved in insecticide resistance. However, little is known of the role of P-glycoprotein in insecticide resistance in the German cockroach. Here, we developed a chlorpyrifos-resistant strain of German cockroach and investigated the relationship between P-glycoprotein and chlorpyrifos resistance using toxicity assays; inhibition studies with two P-glycoprotein inhibitors, verapamil and quinine; P-glycoprotein-ATPase activity assays; and western blotting analysis. After 23 generations of selection from susceptible strain cockroaches, we obtained animals with high resistance to chlorpyrifos. When P-glycoprotein-ATPase activity was inhibited by verapamil and quinine, we observed enhanced susceptibility to chlorpyrifos in both control and chlorpyrifos-resistant cockroaches. No significant alterations of P-glycoprotein expression or ATPase activity were observed in cockroaches acutely exposed to LD50 doses of chlorpyrifos for 24 h, while P-glycoprotein expression and ATPase activity were clearly elevated in the chlorpyrifos-resistant cockroach strain. Thus, we conclude that P-glycoprotein is associated with chlorpyrifos resistance in the German cockroach and that elevated levels of P-glycoprotein expression and ATPase activity may be an important mechanism of chlorpyrifos resistance in the German cockroach. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiao, Dan; Seidler, Frederic J.; Slotkin, Theodore A.

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

Placenta-derived hypo-serotonin situations in the developing forebrain cause autism.

PubMed

Sato, Kohji

2013-04-01

Autism is a pervasive developmental disorder that is characterized by the behavioral traits of impaired social cognition and communication, and repetitive and/or obsessive behavior and interests. Although there are many theories and speculations about the pathogenetic causes of autism, the disruption of the serotonergic system is one of the most consistent and well-replicated findings. Recently, it has been reported that placenta-derived serotonin is the main source in embryonic day (E) 10-15 mouse forebrain, after that period, the serotonergic fibers start to supply serotonin into the forebrain. E 10-15 is the very important developing period, when cortical neurogenesis, migration and initial axon targeting are processed. Since all these events have been considered to be involved in the pathogenesis of autism and they are highly controlled by serotonin signals, the paucity of placenta-derived serotonin should have potential importance when the pathogenesis of autism is considered. I, thus, postulate a hypothesis that placenta-derived hypo-serotonin situations in the developing forebrain cause autism. The hypothesis is as follows. Various factors, such as inflammation, dysfunction of the placenta, together with genetic predispositions cause a decrease of placenta-derived serotonin levels. The decrease of placenta-derived serotonin levels leads to hypo-serotonergic situations in the forebrain of the fetus. The paucity of serotonin in the forebrain leads to mis-wiring in important regions which are responsible for the theory of mind. The paucity of serotonin in the forebrain also causes over-growth of serotonergic fibers. These disturbances result in network deficiency and aberration of the serotonergic system, leading to the autistic phenotypes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Taurine ameliorated thyroid function in rats co-administered with chlorpyrifos and lead.

PubMed

Akande, Motunrayo Ganiyat; Shittu, Muftau; Uchendu, Chidiebere; Yaqub, Lukuman Surakat

2016-12-01

Chlorpyrifos is a widely used organophosphate insecticide for domestic, agricultural and industrial purposes. Lead is a toxic heavy metal and it is used for domestic and industrial purposes. Taurine is a semi essential amino acid with bioprotective properties. The aim of this study was to investigate the effects of taurine on thyroid function in Wistar rats co-administered with chlorpyrifos and lead. The rats were divided into 5 groups of 10 rats each. The first two groups were administered with distilled water and soya oil (1 ml/kg) respectively. The other groups received taurine (50 mg/kg), chlorpyrifos + lead [chlorpyrifos (4.25 mg/kg, 1/20 median lethal dose] and lead (233.25 mg/kg, 1/20 median lethal dose) and taurine + chlorpyrifos + lead respectively. The treatments were administered once daily by oral gavage for 16 weeks. The rats were euthanized after the completion of the study and the thyroid function and thyroid histoarchitecture were evaluated. The results revealed that co-administration of chlorpyrifos and lead to the rats induced perturbations in thyroid function and this was manifested by reductions in the concentrations of triiodothyronine and thyroxine, increased thyroid stimulating hormone concentration and degeneration of the follicular epithelia of the thyroid gland. Taurine alleviated the perturbations in thyroid function and improved thyroid gland histoarchitecture. The beneficial effects of taurine may be attributed to its ability to protect the body from toxicity and oxidative stress. Taurine may be useful for prophylaxis against disruptions in thyroid function in animals that are exposed to environmental chlorpyrifos and lead.

Nanoimages show disruption of tubulin polymerization by chlorpyrifos oxon; implications for neurotoxicity

PubMed Central

Grigoryan, Hasmik; Lockridge, Oksana

2009-01-01

Organophosphorus agents cause cognitive deficits and depression in some people. We hypothesize that the mechanism by which organophosphorus agents cause these disorders is by modification of proteins in the brain. One such protein could be tubulin. Tubulin polymerizes to make the microtubules that transport cell components to nerve axons. The goal of the present work was to measure the effect of the organophosphorus agent chlorpyrifos oxon on tubulin polymerization. An additional goal was to identify the amino acids covalently modified by chlorpyrifos oxon in microtubule polymers and to compare them to the amino acids modified in unpolymerized tubulin dimers. Purified bovine tubulin (0.1 mM) was treated with 0.005-0.1 mM chlorpyrifos oxon for 30 min at room temperature and then polymerized by addition of 1 mM GTP to generate microtubules. Microtubules were visualized by atomic force microscopy. Chlorpyrifos oxon-modified residues were identified by tandem ion trap electrospray ionization and matrix-assisted laser desorption/ionization mass spectrometry of tryptic peptides. Nanoimaging showed that low concentrations (0.005 and 0.01 mM) of chlorpyrifos oxon yielded short, thin microtubules. A concentration of 0.025 mM stimulated polymerization, while high concentrations (0.05 and 0.1 mM) caused aggregation. Of the 17 tyrosines covalently modified by chlorpyrifos oxon in unpolymerized tubulin dimers, only 2 tyrosines were labeled in polymerized microtubules. The two labeled tyrosines in polymerized tubulin were Tyr 103 in EDAANNY*R of alpha tubulin, and Tyr 281 in GSQQY*R of beta tubulin. In conclusion, chlorpyrifos oxon binding to tubulin disrupts tubulin polymerization. These results may lead to an understanding of the neurotoxicity of organophosphorus agents. PMID:19631231

Toxicity of environmentally realistic concentrations of chlorpyrifos and terbuthylazine in indoor microcosms.

PubMed

Pereira, Ana Santos; Cerejeira, Maria José; Daam, Michiel A

2017-09-01

Few studies have been conducted into the evaluation of environmentally realistic pesticide mixtures using model ecosystems. In the present study, the effects of single and combined environmentally realistic concentrations of the herbicide terbuthylazine and the insecticide chlorpyrifos were evaluated using laboratory microcosms. Direct toxic effects of chlorpyrifos were noted on copepod nauplii and cladocerans and the recovery of the latter was likely related with the decrease observed in rotifer abundances. Terbuthylazine potentiated the effect of chlorpyrifos on feeding rates of Daphnia magna, presumably by triggering the transformation of chlorpyrifos to more toxic oxon-analogs. Possible food-web interactions resulting from multiple chemical (and other) stressors likely to be present in edge-of-field water bodies need to be further evaluated. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2016-05-25

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

TOXICOLOGICAL INTERACTIONS OF CHLORPYRIFOS AND METHYL MERCURY IN THE AMPHIPOD, HYALELLA AZTECA

EPA Science Inventory

The mechanism of interaction between chlorpyrifos, an organo-phosphate insecticide, and methyl mercury, an organometal, was assessed utilizing the amphipod, Hyalella azteca. Previous studies have demonstrated that chlorpyrifos and methyl mercury interact additively, with survival...

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

PubMed

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

2016-08-01

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

Chlorpyrifos induces anxiety-like behavior in offspring rats exposed during pregnancy.

PubMed

Silva, Jonas G; Boareto, Ana C; Schreiber, Anne K; Redivo, Daiany D B; Gambeta, Eder; Vergara, Fernanda; Morais, Helen; Zanoveli, Janaína M; Dalsenter, Paulo R

2017-02-22

Chlorpyrifos is a pesticide, member of the organophosphate class, widely used in several countries to manage insect pests on many agricultural crops. Currently, chlorpyrifos health risks are being reevaluated due to possible adverse effects, especially on the central nervous system. The aim of this study was to investigate the possible action of this pesticide on the behaviors related to anxiety and depression of offspring rats exposed during pregnancy. Wistar rats were treated orally with chlorpyrifos (0.01, 0.1, 1 and 10mg/kg/day) on gestational days 14-20. Male offspring behavior was evaluated on post-natal days 21 and 70 by the elevated plus-maze test, open field test and forced swimming test. The results demonstrated that exposure to 0.1, 1 or 10mg/kg/day of chlorpyrifos could induce anxiogenic-like, but not depressive-like behavior at post-natal day 21, without causing fetal toxicity. This effect was reversed on post-natal day 70. Copyright © 2017 Elsevier B.V. All rights reserved.

Degradation behavior and products of malathion and chlorpyrifos spiked in apple juice by ultrasonic treatment.

PubMed

Zhang, Yuanyuan; Xiao, Zhiyong; Chen, Fang; Ge, Yiqiang; Wu, Jihong; Hu, Xiaosong

2010-01-01

Apple juice (13 degrees Brix) spiked with malathion and chlorpyrifos (2-3 mg l(-1) of each compound) was treated under different ultrasonic irradiations. Results showed that ultrasonic treatment was effective for the degradation of malathion and chlorpyrifos in apple juice, and the output power and treatment time significantly influenced the degradation of both pesticides (p<0.05). The maximum degradations were achieved for malathion (41.7%) and chlorpyrifos (82.0%) after the ultrasonic treatment at 500 W for 120 min. The degradation kinetics of both pesticides were fitted to the first-order kinetics model well (R(2)>or=0.90). The kinetics parameters indicated that chlorpyrifos was much more labile to ultrasonic treatment than malathion. Furthermore, malaoxon and chlorpyrifos oxon were identified as the degradation products of malathion and chlorpyrifos by gas chromatography-mass spectrometry (GC-MS), respectively. The oxidation pathway through the hydroxyl radical attack on the P=S bond of pesticide molecules was proposed.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grigoryan, Hasmik; Lockridge, Oksana

2009-10-15

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

Role of serotonin in the regulation of renal proximal tubular epithelial cells.

PubMed

Erikci, Acelya; Ucar, Gulberk; Yabanoglu-Ciftci, Samiye

2016-08-01

In various renal injuries, tissue damage occurs and platelet activation is observed. Recent studies suggest that some factors, such as serotonin, are released into microenvironment upon platelet activation following renal injury. In the present study, we aimed to investigate whether platelets and platelet-released serotonin are involved in the functional regulation of renal proximal tubular epithelial cells (PTECs). PTECs were obtained by primary cell culture and treated with platelet lysate (PL) (2 × 10(6)/mL, 4 × 10(6)/mL, 8 × 10(6)/mL) or serotonin (1 μM or 5 μM) for 12 or 24 h. Phenotypic transdifferentiation of epithelial cells into myofibroblasts were demonstrated under light microscope and confirmed by the determination of α-smooth muscle actin gene expression. Serotonin and PL were shown to induce epithelial-mesenchymal transdifferentiation of PTECs. After stimulation of PTECs with serotonin or PL, matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-1, and collagen-α1 gene expressions, which were reported to be elevated in renal injury, were determined by real-time PCR and found to be upregulated. Expressions of some inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and transforming growth factor-β1 were found to be increased in both protein and gene levels. Recently there is no published report on the effect of serotonin on renal PTECs. Results obtained in this study have lightened the role of serotonin and platelet-mediated effects of serotonin on fibrotic and inflammatory processes in PTECs.

Exogenous salicylic acid alleviates the toxicity of chlorpyrifos in wheat plants (Triticum aestivum).

PubMed

Wang, Caixia; Zhang, Qingming

2017-03-01

The role of exogenous salicylic acid (SA) in protecting wheat plants (Triticum aestivum) from contamination by the insecticide chlorpyrifos was investigated in this study. The wheat plants were grown in soils with different concentrations (5, 10, 20, and 40mgkg -1 ) of chlorpyrifos. When the third leaf emerged, the wheat leaves were sprayed with 1, 2, 4, 8, and 16mgL -1 of SA once a day for 6 days. The results showed that wheat exposed to higher concentrations of chlorpyrifos (≥20mgkg -1 ) caused declines in growth and chlorophyll content and altered the activities of a series of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX). Interestingly, treatments with different concentrations of SA mitigated the stress generated by chlorpyrifos and improved the measured parameters to varying degrees. Furthermore, a reverse transcription and quantitative PCR experiment revealed that the activities of SOD and CAT can be regulated by their target gene in wheat when treated with SA. We also found that SA is able to block the accumulation of chlorpyrifos in wheat. However, the effect of SA was related to its concentration. In this study, the application of 2mgL -1 of SA had the greatest ameliorating effect on chlorpyrifos toxicity in wheat plants. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2014-07-01

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

Concentration of hepatic vitamins A and E in rats exposed to chlorpyrifos and/or enrofloxacin.

PubMed

Spodniewska, A; Barski, D

2016-01-01

The aim of the study was to determine the level of antioxidant vitamins A and E in the liver of rats exposed to chlorpyrifos and/or enrofloxacin. Chlorpyrifos (Group I) was administered at a dose of 0.04 LD50 (6 mg/kg b.w.) for 28 days, and enrofloxacin (Group II) at a dose of 5 mg/kg b.w. for 5 consecutive days. The animals of group III were given both of the mentioned above compounds at the same manner as groups I and II, but enrofloxacin was applied to rats for the last 5 days of chlorpyrifos exposure (i.e. on day 24, 25, 26, 27 and 28). Chlorpyrifos and enrofloxacin were administered to rats intragastrically via a gastric tube. The quantitative determination of vitamins was made by the HPLC method. The results of this study indicated a reduction in the hepatic concentrations of vitamins A and E, compared to the control, which sustained for the entire period of the experiment. The four-week administration of chlorpyrifos to rats resulted in a significant decrease of vitamins in the initial period of the experiment, i.e. up to 24 hours after exposure. For vitamin A the maximum drop was observed after 24 hours (19.24%) and for vitamin E after 6 hours (23.19%). Enrofloxacin caused a slight (3-9%) reduction in the level of the analysed vitamins. In the chlorpyrifos-enrofloxacin co-exposure group reduced vitamins A and E levels were also noted, but changes in this group were less pronounced in comparison to the animals intoxicated with chlorpyrifos only. The decrease in the antioxidant vitamin levels, particularly noticeable in the chlorpyrifos- and the chlorpyrifos combined with enrofloxacin-treated groups, may result not only from the increase in the concentration of free radicals, but also from the intensification of the secondary stages of lipid peroxidation.

Effects of chlorpyrifos on enzymatic systems of Cydia pomonella (Lepidoptera: Tortricidae) adults.

PubMed

Parra Morales, Laura Beatriz; Alzogaray, Raúl Adolfo; Cichón, Liliana; Garrido, Silvina; Soleño, Jimena; Montagna, Cristina Mónica

2017-06-01

The control program of codling moth (Cydia pomonella L.) in the Río Negro and Neuquén Valley is intended to neonate larvae. However, adults may be subjected to sublethal pesticide concentrations generating stress which might enhance both mutation rates and activity of the detoxification system. This study assessed the exposure effects of chlorpyrifos on target enzyme and, both detoxifying and antioxidant systems of surviving adults from both a laboratory susceptible strain (LSS) and a field population (FP). The results showed that the FP was as susceptible to chlorpyrifos as the LSS and, both exhibited a similar chlorpyrifos-inhibitory concentration 50 (IC 50 ) of acetylcholinesterase (AChE). The FP displayed higher carboxylesterase (CarE) and 7-ethoxycoumarine O-deethylase (ECOD) activities than LSS. Both LSS and FP showed an increase on CarE activity after the exposure to low-chlorpyrifos concentrations, followed by enzyme inhibition at higher concentrations. There were no significant differences neither in the activities of glutathione S-transferases (GST), catalase (CAT) and superoxide dismutase (SOD) nor in the reduced glutathione (GSH) content between LSS and FP. Moreover, these enzymes were unaffected by chlorpyrifos. In conclusion, control adults from the FP exhibited higher CarE and ECOD activities than control adults from the LSS. AChE and CarE activities were the most affected by chlorpyrifos. Control strategies used for C. pomonella, such as rotations of insecticides with different modes of action, will probably delay the evolution of insecticide resistance in FPs from the study area. © 2015 Institute of Zoology, Chinese Academy of Sciences.

Development of a Freeze-Dried Fungal Wettable Powder Preparation Able to Biodegrade Chlorpyrifos on Vegetables

PubMed Central

Chen, Shaohua; Xiao, Ying; Hu, Meiying; Zhong, Guohua

2014-01-01

Continuous use of the pesticide chlorpyrifos has resulted in harmful contaminations in environment and species. Based on a chlorpyrifos-degrading fungus Cladosporium cladosporioides strain Hu-01 (collection number: CCTCC M 20711), a fungal wettable powder preparation was developed aiming to efficiently remove chlorpyrifos residues from vegetables. The formula was determined to be 11.0% of carboxymethyl cellulose-Na, 9.0% of polyethylene glycol 6000, 5.0% of primary alcohol ethoxylate, 2.5% of glycine, 5.0% of fucose, 27.5% of kaolin and 40% of freeze dried fungi by response surface methodology (RSM). The results of quality inspection indicated that the fungal preparation could reach manufacturing standards. Finally, the degradation of chlorpyrifos by this fungal preparation was determined on pre-harvest cabbage. Compared to the controls without fungal preparation, the degradation of chlorpyrifos on cabbages, which was sprayed with the fungal preparation, was up to 91% after 7 d. These results suggested this freeze-dried fungal wettable powder may possess potential for biodegradation of chlorpyrifos residues on vegetables and provide a potential strategy for food and environment safety against pesticide residues. PMID:25061758

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

PubMed

Liu, Jie; He, Yue; Chen, Shaohua; Xiao, Ying; Hu, Meiying; Zhong, Guohua

2014-01-01

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

INTERACTIONS OF CHLORPYRIFOS AND METHYL MERCURY: A MECHANISTIC APPROACH TO ASSESS CHEMICAL MIXTURES

EPA Science Inventory

The mechanism of interaction between chlorpyrifos, an organophosphate insecticide, and methyl mercury was assessed utilizing the amphipod, Hyalella azteca. Previous studies have demonstrated that chlorpyrifos and methl mercury interact additively with survival as the endpoint. I...

Rhamnolipid mediated enhanced degradation of chlorpyrifos by bacterial consortium in soil-water system.

PubMed

Singh, Partapbir; Saini, Harvinder Singh; Raj, Mayil

2016-12-01

The study was conducted with the aim to develop an environmentally compatible bio-based system which may rapidly detoxify soil and water polluted by inordinate use of organophosphate (OP) pesticides. Chlorpyrifos was used as model pesticide as it degrade slowly due to its low aqueous phase solubility (2ppm) and formation of antibacterial intermediate 3,5,6, trichloropyridinol (TCP). Five potential bacteria used in this study belonging to genus Pseudomonas, Klebsiella, Stenotrophomonas, Ochrobactrum and Bacillus and their mixed culture system efficiently degraded chlorpyrifos and its toxic intermediates TCP and diethylthiophosphate (DETP) in aqueous medium. However, degradation rate in soil-water based slurry system was slow as it took 10 days to degrade 82% of added chlorpyrifos (50mg/kg) by a potential mixed culture CS2 comprised of isolates F-3 and CH-y. This might be due to strong sorption affinity of chlorpyrifos to soil components which limits its bioavailability. Hence, a crude rhamnolipid biosurfactant produced by ChlD was used which improved the aqueous phase solubility of chlorpyrifos by 2-15 folds. This supported CS2 to attain 30% higher degradation within short period of 6 days as compared to biotic control without surfactant. Thus, this combination of mixed bacterial population with biosurfactant significantly improved the rate of chlorpyrifos degradation in soil without accumulation of toxic intermediates. This environmentally benign biosurfactant may be produced "in situ" and can replace commonly used toxic synthetic surfactants for bioremediation purposes. Copyright © 2016 Elsevier Inc. All rights reserved.

Plasma serotonin in autism.

PubMed

Connors, Susan L; Matteson, Karla J; Sega, Gary A; Lozzio, Carmen B; Carroll, Roger C; Zimmerman, Andrew W

2006-09-01

Serotonin is necessary for normal fetal brain development. Administration of serotonin inhibitors to pregnant rats results in offspring with abnormal behaviors, brain morphology, and serotonin receptor numbers. Low maternal plasma serotonin may contribute to abnormal brain development in autism. In this study, plasma serotonin levels in autism mothers and control mothers of typically developing children were compared, and plasma serotonin levels in children with autism (n = 17) and their family members were measured. Plasma serotonin levels in autism mothers were significantly lower than in mothers of normal children (P = 0.002). Plasma serotonin levels correlated between autism mothers and their children, but differed between autistic children and their fathers (P = 0.028) and siblings (P = 0.063). Low maternal plasma serotonin may be a risk factor for autism through effects on fetal brain development.

Effects of EGCG and Chlorpyrifos on the Mortality, AChE and GSH of Adult Zebrafish: Independent and Combination

NASA Astrophysics Data System (ADS)

Zhang, Rong; Zhang, Jian; Gao, Qian; Guo, Nichun

2018-01-01

Chlorpyrifos is a neurotoxic agent and also causes oxidative stress in the body. EGCG is a typical strong antioxidant and has been reported to be neuroprotective. Our study investigated the mortality, the activity of acetylcholinesterase (AChE) in the brain and glutathione (GSH) in the liver of the adult Zebrafish in present of Chlorpyrifos and EGCG independent and combination. The results indicated that after the addition of EGCG, the mortality of zebrafish induced by Chlorpyrifos was reduced and the activity of AChE and glutathione (GSH) inhibited by Chlorpyrifos in zebrafish was significantly increased, which demonstrated that EGCG inhibited the toxicity Chlorpyrifos to zebrafish. The inhibition was dependent on the concentration of EGCG and Chlorpyrifos, which was not shown a gradual change trend but a complex situation.

Serotonin mediated immunoregulation and neural functions: Complicity in the aetiology of autism spectrum disorders.

PubMed

Jaiswal, Preeti; Mohanakumar, Kochupurackal P; Rajamma, Usha

2015-08-01

Serotonergic system has long been implicated in the aetiology of autism spectrum disorders (ASD), since platelet hyperserotonemia is consistently observed in a subset of autistic patients, who respond well to selective serotonin reuptake inhibitors. Apart from being a neurotransmitter, serotonin functions as a neurotrophic factor directing brain development and as an immunoregulator modulating immune responses. Serotonin transporter (SERT) regulates serotonin level in lymphoid tissues to ensure its proper functioning in innate and adaptive responses. Immunological molecules such as cytokines in turn regulate the transcription and activity of SERT. Dysregulation of serotonergic system could trigger signalling cascades that affect normal neural-immune interactions culminating in neurodevelopmental and neural connectivity defects precipitating behavioural abnormalities, or the disease phenotypes. Therefore, we suggest that a better understanding of the cross talk between serotonergic genes, immune systems and serotonergic neurotransmission will open wider avenues to develop pharmacological leads for addressing the core ASD behavioural deficits. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tolerance of ARPE 19 cells to organophosphorus pesticide chlorpyrifos is limited to concentration and time of exposure.

PubMed

Gomathy, Narayanan; Sumantran, Venil N; Shabna, A; Sulochana, K N

2015-01-01

Age related macular degeneration is a blinding disease common in elder adults. The prevalence of age related macular degeneration has been found to be 1.8% in the Indian population. Organophosphates are widely used insecticides with well documented neurological effects, and the persistent nature of these compounds in the body results in long term health effects. Farmers exposed to organophosphorus pesticides in USA had an earlier onset of age related macular degeneration when compared to unexposed controls. A recent study found significant levels of an organophosphate, termed chlorpyrifos, in the blood samples of Indian farmers. Therefore, in understanding the link between age related macular degeneration and chlorpyrifos, the need for investigation is important. Our data show that ARPE-19 (retinal pigment epithelial cells) exhibit a cytoprotective response to chlorpyrifos as measured by viability, mitochondrial membrane potential, superoxide dismutase activity, and increased levels of glutathione peroxidase and reduced glutathione, after 24 h exposure to chlorpyrifos. However, this cytoprotective response was absent in ARPE-19 cells exposed to the same range of concentrations of chlorpyrifos for 48 h. These results have physiological significance, since HPLC analysis showed that effects of chlorpyrifos were mediated through its entry into ARPE-19 cells. HPLC analysis also showed that chlorpyrifos remained stable, as we recovered up to 80% of the chlorpyrifos added to 6 different ocular tissues. Copyright © 2014. Published by Elsevier Inc.

Prenatal Drug Exposures Sensitize Noradrenergic Circuits to Subsequent Disruption by Chlorpyrifos

PubMed Central

Slotkin, Theodore A.; Skavicus, Samantha; Seidler, Frederic J.

2015-01-01

We examined whether nicotine or dexamethasone, common prenatal drug exposures, sensitize the developing brain to chlorpyrifos. We gave nicotine to pregnant rats throughout gestation at a dose (3 mg/kg/day) producing plasma levels typical of smokers; offspring were then given chlorpyrifos on postnatal days 1–4, at a dose (1 mg/kg) that produces minimally-detectable inhibition of brain cholinesterase activity. In a parallel study, we administered dexamethasone to pregnant rats on gestational days 17–19 at a standard therapeutic dose (0.2 mg/kg) used in the management of preterm labor, followed by postnatal chlorpyrifos. We evaluated cerebellar noradrenergic projections, a known target for each agent, and contrasted the effects with those in the cerebral cortex. Either drug augmented the effect of chlorpyrifos, evidenced by deficits in cerebellar β-adrenergic receptors; the receptor effects were not due to increased systemic toxicity or cholinesterase inhibition, nor to altered chlorpyrifos pharmacokinetics. Further, the deficits were not secondary adaptations to presynaptic hyperinnervation/hyperactivity, as there were significant deficits in presynaptic norepinephrine levels that would serve to augment the functional consequence of receptor deficits. The pretreatments also altered development of cerebrocortical noradrenergic circuits, but with a different overall pattern, reflecting the dissimilar developmental stages of the regions at the time of exposure. However, in each case the net effects represented a change in the developmental trajectory of noradrenergic circuits, rather than simply a continuation of an initial injury. Our results point to the ability of prenatal drug exposure to create a subpopulation with heightened vulnerability to environmental neurotoxicants. PMID:26419632

From the Cover: AstrocytesAre Protective Against Chlorpyrifos Developmental Neurotoxicity in Human Pluripotent Stem Cell-Derived Astrocyte-Neuron Cocultures.

PubMed

Wu, Xian; Yang, Xiangkun; Majumder, Anirban; Swetenburg, Raymond; Goodfellow, Forrest T; Bartlett, Michael G; Stice, Steven L

2017-06-01

Human neural progenitor cells are capable of independent, directed differentiation into astrocytes, oligodendrocytes and neurons and thus offer a potential cell source for developmental neurotoxicity (DNT) systems. Human neural progenitor-derived astrocyte-neuron cocultured at defined ratios mimic cellular heterogeneity and interaction in the central nervous system. Cytochrome P450 enzymes are expressed at a relatively high level in astrocytes and may play a critical role in the biotransformation of endogenous or exogenous compounds, including chlorpyrifos, an organophosphate insecticide that affects the central nervous system. P450 enzymes metabolize chlorpyrifos to chlorpyrifos-oxon, which is then metabolized primarily to 3, 5, 6-trichloropyridinol in addition to diethylphosphate and diethylthiophosphate. These end metabolites are less neurotoxic than chlorpyrifos and chlorpyrifos-oxon. Our objective was to identify the interactive role of astrocytes and neurons in chlorpyrifos-induced human DNT. In neuron-only cultures, chlorpyrifos inhibited neurite length, neurite number and branch points per neuron in a dose-dependent manner during a 48 h exposure, starting at 10 μM. However, in astrocyte-neuron cocultures, astrocytes protected neurons from the effects of chlorpyrifos at higher concentrations, up to and including 30 μM chlorpyrifos and endogenous astrocyte P450 enzymes effectively metabolized chlorpyrifos. The P450 inhibitor SKF525A partly negated the protective effect of astrocytes, allowing reduction in branch points with chlorpyrifos (10 μM). Thus, the scalable and defined astrocyte-neuron cocultures model that we established here has potentially identified a role for P450 enzymes in astrocytic neuroprotection against chlorpyrifos and provides a novel model for addressing DNT in a more accurate multicellular environment. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For

The enzyme toxicity and genotoxicity of chlorpyrifos and its toxic metabolite TCP to zebrafish Danio rerio.

PubMed

Wang, Jun; Wang, Jinhua; Zhu, Lusheng; Xie, Hui; Shao, Bo; Hou, Xinxin

2014-12-01

Chlorpyrifos is a broad-spectrum organophosphorus insecticide (O,O-diethyl -O-3,5,6-trichloro-2-pyridyl phosphorothioate) that is used in numerous agricultural and urban pest controls. The primary metabolite of chlorpyrifos is 3,5,6-trichloro pyridine-2-phenol (TCP). Because of its strong water solubility and mobility, this harmful metabolite exists in the environment in a large amount. Although TCP has potentially harmful effects on organisms in the environment, few studies have addressed TCP pollution. Therefore, this study was undertaken to investigate the effect of chlorpyrifos and TCP on the microsomal cytochrome P450 content in the liver, on the activity of NADPH-P450 reductase and antioxidative enzymes [catalase (CAT) and superoxide dismutase (SOD)], and on reactive oxygen species (ROS) generation and DNA damage in zebrafish. Male and female zebrafish were separated and exposed to a control solution and three concentrations of chlorpyrifos (0.01, 0.1, 1 mg L(-1)) and TCP (0.01, 0.1, 0.5 mg L(-1)), respectively, sampled after 5, 10, 15, 20 and 25 days. The results indicated that the P450 content and the NADPH-P450 reductase and antioxidative enzyme (CAT and SOD) activities could be induced by chlorpyrifos and TCP. DNA damage of zebrafish was enhanced with increasing chlorpyrifos and TCP concentrations. Meanwhile, chlorpyrifos and TCP induced a significant increase of ROS generation in the zebrafish hepatopancreas. In conclusion, this study proved that chlorpyrifos (0.01-1 mg L(-1)) and TCP (0.01-0.5 mg L(-1)) are both highly toxic to zebrafish.

Chlorpyrifos residual behaviors in field crops and transfers during duck pellet feed processing.

PubMed

Li, Rui; Wei, Wei; He, Liang; Hao, Lili; Ji, Xiaofeng; Zhou, Yu; Wang, Qiang

2014-10-22

Chlorpyrifos is a widely used organophosphorus pesticide in agricultural crops (including food) and animal feeds in China, resulting in heavy contamination. Many studies have focused on the food-processing effects on chlorpyrifos removal, but sufficient information is not observed for feed-processing steps. Here, chlorpyrifos residual behaviors in field crops and its transfers in duck pellet feed-processing steps were evaluated. In field trials, the highest residues for rice grain, shelled corn, and soybean seed were 12.0, 0.605, and 0.220 mg/kg, respectively. Residues of all rice grain and about half of shelled corn exceeded the maximum residue limits (MRLs) of China, and five soybean seeds exceeded the MRL of China. Chlorpyrifos residue was reduced 38.2% in brown rice after the raw rice grain was hulled. The residue in bran increased 71.2% after milling from brown rice. During the squashing step, the residue reduced 73.8% in soybean meal. The residues reduced significantly (23.7-36.8%) during the process of granulating for rice, maize, and soybean products. Comparatively, the grinding process showed only limited influence on chlorpyrifos removal (<10%). The residues of duck pellet feeds produced from highly contaminated raw materials of this study were 1.01 mg/kg (maize-soybean feed) and 3.20 mg/kg (rice-soybean feed), which were much higher than the generally accepted value (>0.1 mg/kg) for animal feeding. Chlorpyrifos residues were removed significantly by processing steps of pellet feeds, but the residue of raw materials was the determining factor for the safety of duck feeding.

Developmental sub-chronic exposure to chlorpyrifos reduces anxiety-related behavior in zebrafish larvae

PubMed Central

Richendrfer, Holly; Pelkowski, Sean D.; Colwill, Ruth M.; Créton, Robbert

2013-01-01

Neurobehavioral disorders such as anxiety, autism, and attention deficit hyperactivity disorders are typically influenced by genetic and environmental factors. Although several genetic risk factors have been identified in recent years, little is known about the environmental factors that either cause neurobehavioral disorders or contribute to their progression in genetically predisposed individuals. One environmental factor that has raised concerns is chlorpyrifos, an organophosphate pesticide that is widely used in agriculture and is found ubiquitously in the environment. In the present study, we examined the effects of sub-chronic chlorpyrifos exposure on anxiety-related behavior during development using zebrafish larvae. We found that sub-chronic exposure to 0.01 or 0.1 μM chlorpyrifos during development induces specific behavioral defects in 7-day-old zebrafish larvae. The larvae displayed decreases in swim speed and thigmotaxis, yet no changes in avoidance behavior were seen. Exposure to 0.001 μM chlorpyrifos did not affect swimming, thigmotaxis, or avoidance behavior and exposure to 1 μM chlorpyrifos induced behavioral defects, but also induced defects in larval morphology. Since thigmotaxis, a preference for the edge, is an anxiety-related behavior in zebrafish larvae, we propose that sub-chronic chlorpyrifos exposure interferes with the development of anxiety-related behaviors. The results of this study provide a good starting point for examination of the molecular, cellular, developmental, and neural mechanisms that are affected by environmentally relevant concentrations of organophosphate pesticides. A more detailed understanding of these mechanisms is important for the development of predictive models and refined health policies to prevent toxicant-induced neurobehavioral disorders. PMID:22579535

BDE99 (2,2',4,4',5-pentabromodiphenyl ether) suppresses differentiation into neurotransmitter phenotypes in PC12 cells.

PubMed

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

2013-01-01

Early-life exposures to brominated diphenyl ethers (BDEs) lead to neurobehavioral abnormalities later in life. Although these agents are thyroid disruptors, it is not clear whether this mechanism alone accounts for the adverse effects. We evaluated the impact of 2,2',4,4',5-pentabromodiphenyl ether (BDE99) on PC12 cells undergoing neurodifferentiation, contrasting the effects with chlorpyrifos, a known developmental neurotoxicant. BDE99 elicited decrements in the number of cells, evidenced by a reduction in DNA levels, to a lesser extent than did chlorpyrifos. This did not reflect cytotoxicity from oxidative stress, since cell enlargement, monitored by the total protein/DNA ratio, was not only unimpaired by BDE99, but was actually enhanced. Importantly, BDE99 impaired neurodifferentiation into both the dopamine and acetylcholine neurotransmitter phenotypes. The cholinergic phenotype was affected to a greater extent, so that neurotransmitter fate was diverted away from acetylcholine and toward dopamine. Chlorpyrifos produced the same imbalance, but through a different underlying mechanism, promoting dopaminergic development at the expense of cholinergic development. In our earlier work, we did not find these effects with BDE47, a BDE that has greater endocrine disrupting and cytotoxic effects than BDE99. Thus, our results point to interference with neurodifferentiation by specific BDE congeners, distinct from cytotoxic or endocrine mechanisms. Copyright © 2013 Elsevier Inc. All rights reserved.

Sleep and rhythm consequences of a genetically induced loss of serotonin.

PubMed

Leu-Semenescu, Smaranda; Arnulf, Isabelle; Decaix, Caroline; Moussa, Fathi; Clot, Fabienne; Boniol, Camille; Touitou, Yvan; Levy, Richard; Vidailhet, Marie; Roze, Emmanuel

2010-03-01

A genetic deficiency in sepiapterin reductase leads to a combined deficit of serotonin and dopamine. The motor phenotype is characterized by a dopa-responsive fluctuating generalized dystonia-parkinsonism. The non-motor symptoms are poorly recognized. In particular, the effects of brain serotonin deficiency on sleep have not been thoroughly studied. We examine the sleep, sleep-wake rhythms, CSF neurotransmitters, and melatonin profile in a patient with sepiapterin reductase deficiency. The patient was a 28-year-old man with fluctuating generalized dystonia-parkinsonism caused by sepiapterin reductase deficiency. A sleep interview, wrist actigraphy, sleep log over 14 days, 48-h continuous sleep and core temperature monitoring, and measurement of CSF neurotransmitters and circadian serum melatonin and cortisol levels before and after treatment with 5-hydroxytryptophan (the precursor of serotonin) and levodopa were performed. Before treatment, the patient had mild hypersomnia with long sleep time (704 min), ultradian sleep-wake rhythm (sleep occurred every 11.8 +/- 5.3 h), organic hyperphagia, attentionlexecutive dysfunction, and no depression. The serotonin metabolism in the CSF was reduced, and the serum melatonin profile was flat, while cortisol and core temperature profiles were normal. Supplementation with 5-hydroxytryptophan, but not with levodopa, normalized serotonin metabolism in the CSF, reduced sleep time to 540 min, normalized the eating disorder and the melatonin profile, restored a circadian sleep-wake rhythm (sleep occurred every 24 +/- 1.7 h, P < 0.0001), and improved cognition. In this unique genetic paradigm, the melatonin deficiency (caused by a lack of its substrate, serotonin) may cause the ultradian sleep-wake rhythm.

A tachykinin-like neuroendocrine signalling axis couples central serotonin action and nutrient sensing with peripheral lipid metabolism

PubMed Central

Palamiuc, Lavinia; Noble, Tallie; Witham, Emily; Ratanpal, Harkaranveer; Vaughan, Megan; Srinivasan, Supriya

2017-01-01

Serotonin, a central neuromodulator with ancient ties to feeding and metabolism, is a major driver of body fat loss. However, mechanisms by which central serotonin action leads to fat loss remain unknown. Here, we report that the FLP-7 neuropeptide and its cognate receptor, NPR-22, function as the ligand-receptor pair that defines the neuroendocrine axis of serotonergic body fat loss in Caenorhabditis elegans. FLP-7 is secreted as a neuroendocrine peptide in proportion to fluctuations in neural serotonin circuit functions, and its release is regulated from secretory neurons via the nutrient sensor AMPK. FLP-7 acts via the NPR-22/Tachykinin2 receptor in the intestine and drives fat loss via the adipocyte triglyceride lipase ATGL-1. Importantly, this ligand-receptor pair does not alter other serotonin-dependent behaviours including food intake. For global modulators such as serotonin, the use of distinct neuroendocrine peptides for each output may be one means to achieve phenotypic selectivity. PMID:28128367

Interpretation and estimation for dynamic mobility of chlorpyrifos in soils containing different organic matters.

PubMed

Hwang, Jeong-In; Lee, Sung-Eun; Kim, Jang-Eok

2015-12-01

The adsorption and removal behaviors of the organophosphate insecticide chlorpyrifos in two soils (AS and GW soils) with different organic matter contents were investigated to predict the dynamic residues in the soil environment. The adsorption test showed that the chlorpyrifos adsorptive power for the AS soil containing high organic matter content was greater than that for the GW soil. The extent of the time-dependent removal of chlorpyrifos in the tested soils was not significantly different except at 90 days after the treatment. The availability of a chemical-specific residue model developed in this study was statistically assessed to estimate the chlorpyrifos residue in soil solutions that could be absorbed into plants. The values modeled using the soil experimental data were satisfactory, having a mean deviation of 32% from the measured data. The correlation between the modeled and measured data was acceptable, with mean coefficients of correlation (R(2)) of 0.89. Furthermore, the average of the residual error was low at 0.43, which corresponded to a mean factor of -1.9. The developed model could be used as a critical tool to predict the subsequent plant uptake of chlorpyrifos.

Prenatal drug exposures sensitize noradrenergic circuits to subsequent disruption by chlorpyrifos.

PubMed

Slotkin, Theodore A; Skavicus, Samantha; Seidler, Frederic J

2015-12-02

We examined whether nicotine or dexamethasone, common prenatal drug exposures, sensitize the developing brain to chlorpyrifos. We gave nicotine to pregnant rats throughout gestation at a dose (3mg/kg/day) producing plasma levels typical of smokers; offspring were then given chlorpyrifos on postnatal days 1-4, at a dose (1mg/kg) that produces minimally-detectable inhibition of brain cholinesterase activity. In a parallel study, we administered dexamethasone to pregnant rats on gestational days 17-19 at a standard therapeutic dose (0.2mg/kg) used in the management of preterm labor, followed by postnatal chlorpyrifos. We evaluated cerebellar noradrenergic projections, a known target for each agent, and contrasted the effects with those in the cerebral cortex. Either drug augmented the effect of chlorpyrifos, evidenced by deficits in cerebellar β-adrenergic receptors; the receptor effects were not due to increased systemic toxicity or cholinesterase inhibition, nor to altered chlorpyrifos pharmacokinetics. Further, the deficits were not secondary adaptations to presynaptic hyperinnervation/hyperactivity, as there were significant deficits in presynaptic norepinephrine levels that would serve to augment the functional consequence of receptor deficits. The pretreatments also altered development of cerebrocortical noradrenergic circuits, but with a different overall pattern, reflecting the dissimilar developmental stages of the regions at the time of exposure. However, in each case the net effects represented a change in the developmental trajectory of noradrenergic circuits, rather than simply a continuation of an initial injury. Our results point to the ability of prenatal drug exposure to create a subpopulation with heightened vulnerability to environmental neurotoxicants. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kacham, R.; Karanth, S.; Baireddy, P.

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 sequentialmore » 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

CHLORPYRIFOS TRANSFORMATION BY AQUEOUS CHLORINE IN THE PRESENCE OF BROMIDE AND NATURAL ORGANIC MATTER

EPA Science Inventory

The aqueous chlorination of chlorpyrifos (CP) was investigated in the presence of bromide and natural organic matter (NOM), which were identified as naturally occurring aqueous constituents that could impact CP transformation rates to the toxic product chlorpyrifos oxon (CPO). Br...

BEHAVIORAL AND NEUROCHEMICAL OUTCOMES OF REPEATED ORAL ADMINISTRATION OF CHLORPYRIFOS IN POSTNATAL/JUVENILE RATS.

EPA Science Inventory

Concern has been raised regarding potential adverse effects on the nervous system following childhood exposure to chlorpyrifos (O,O-diethyl-O-3,5,6-trichloro-2-pyridyl-phosphorothioate). This study examined the outcomes of daily oral dosing with chlorpyrifos, from early postnata...

An Amperometric Immunosensor Based on Multi-Walled Carbon Nanotubes-Thionine-Chitosan Nanocomposite Film for Chlorpyrifos Detection

PubMed Central

Sun, Xia; Cao, Yaoyao; Gong, Zhili; Wang, Xiangyou; Zhang, Yan; Gao, Jinmei

2012-01-01

In this work, a novel amperometric immunosensor based on multi-walled carbon nanotubes-thionine-chitosan (MWCNTs-THI-CHIT) nanocomposite film as electrode modified material was developed for the detection of chlorpyrifos residues. The nanocomposite film was dropped onto a glassy carbon electrode (GCE), and then the anti-chlorpyrifos monoclonal antibody was covalently immobilized onto the surface of MWCNTs-THI-CHIT/GCE using the crosslinking agent glutaraldehyde (GA). The modification procedure was characterized by using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Under the optimized conditions, a linear relationship between the relative change in peak current of different pulse voltammetry (DPV) and the logarithm of chlorpyrifos solution concentration was obtained in the range from 0.1 to 1.0 × 105 ng/mL with a detection limit of 0.046 ng/mL. The proposed chlorpyrifos immunosensor exhibited high reproducibility, stability, and good selectivity and regeneration, making it a potential alternative tool for ultrasensitive detection of chlorpyrifos residues in vegetables and fruits. PMID:23443396

Triptans, serotonin agonists, and serotonin syndrome (serotonin toxicity): a review.

PubMed

Gillman, P Ken

2010-02-01

The US Food and Drug Administration (FDA) have suggested that fatal serotonin syndrome (SS) is possible with selective serotonin reuptake inhibitors (SSRIs) and triptans: this warning affects millions of patients as these drugs are frequently given simultaneously. SS is a complex topic about which there is much misinformation. The misconception that 5-HT1A receptors can cause serious SS is still widely perpetuated, despite quality evidence that it is activation of the 5-HT2A receptor that is required for serious SS. This review considers SS involving serotonin agonists: ergotamine, lysergic acid diethylamide, bromocriptine, and buspirone, as well as triptans, and reviews the experimental foundation underpinning the latest understanding of SS. It is concluded that there is neither significant clinical evidence, nor theoretical reason, to entertain speculation about serious SS from triptans and SSRIs. The misunderstandings about SS exhibited by the FDA, and shared by the UK Medicines and Healthcare products Regulatory Agency (in relation to methylene blue), are an important issue with wide ramifications.

Use of Fe-Impregnated Biochar To Efficiently Sorb Chlorpyrifos, Reduce Uptake by Allium fistulosum L., and Enhance Microbial Community Diversity.

PubMed

Tang, Xiao-Yan; Huang, Wen-Da; Guo, Jing-Jing; Yang, Yang; Tao, Ran; Feng, Xu

2017-07-05

Fe-impregnated biochar was assessed as a method to remove the pesticide pollutant chlorpyrifos, utilizing biochar/FeO x composite synthesized via chemical coprecipitation of Fe 3+ /Fe 2+ onto Cyperus alternifolius biochar. Fe-impregnated biochar exhibited a higher sorption capacity than pristine biochar, resulting in more efficient removal of chlorpyrifos from water. Soil was dosed with pristine or Fe-impregnated biochar at 0.1 or 1.0% w/w, to evaluate chlorpyrifos uptake in Allium fistulosum L. (Welsh onion). The results showed that the average concentration of chlorpyrifos and its degradation product, 3,5,6-trichloro-2-pyridinol (TCP), decreased in A. fistulosum L. with increased levels of pristine biochar and Fe-biochar. Fe-biochar was found to be more effective in reducing the uptake of chlorpyrifos by improving the sorption ability and increasing plant root iron plaque. Bioavailability of chlorpyrifos is reduced with both biochar and Fe-biochar soil dosing; however, the greatest persistence of chlorpyrifos residues was observed with 1.0% pristine biochar. Microbial community analysis showed Fe-biochar to have a positive impact on the efficiency of chlorpyrifos degradation in soils, possibly by altering microbial communities.

Heterogeneous reaction of particulate chlorpyrifos with NO3 radicals: Products, pathways, and kinetics

NASA Astrophysics Data System (ADS)

Li, Nana; Zhang, Peng; Yang, Bo; Shu, Jinian; Wang, Youfeng; Sun, Wanqi

2014-08-01

Chlorpyrifos is a typical chlorinated organophosphorus pesticide. The heterogeneous reaction of chlorpyrifos particles with NO3 radicals was investigated using a vacuum ultraviolet photoionization aerosol time-of-flight mass spectrometer (VUV-ATOFMS) and a real-time atmospheric gas analysis mass spectrometer. Chlorpyrifos oxon, 3,5,6-trichloro-2-pyridinol, O,O-diethyl O-hydrogen phosphorothioate, O,O-diethyl ester thiophosphoric acid, diethyl hydrogen phosphate and a phosphinyl disulfide compound were identified as the main degradation products. The heterogeneous reaction pathways were proposed and their kinetic processes were investigated via a mixed-phase relative rate method. The observed effective rate constant is 3.4 ± 0.2 × 10-12 cm3 molecule-1 s-1.

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

PubMed

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

2016-07-01

This paper aims to acquire the experimental data on the eco-toxicological effects of agricultural pollutants on the aquatic plants and the data can support the assessment of toxicity on the phytoplankton. The pesticide of Chlorpyrifos used as a good model to investigate its eco-toxicological effect on the different microalgae in freshwater. In order to address the pollutants derived from forestry and agricultural applications, freshwater microalgae were considered as a good sample to investigate the impact of pesticides such as Chlorpyrifos on aquatic life species. Two microalgae of Chlorella pyrenoidosa and Merismopedia sp. were employed to evaluate toxicity of Chlorpyrifos in short time and long time by means of measuring the growth inhibition rate, the redox system and the content of chlorophyll a, respectively. In this study, the results showed that EC50 values ranging from 7.63 to 19.64mg/L, indicating the Chlorpyrifos had a relatively limited to the growth of algae during the period of the acute toxicity experiment. Moreover, when two kinds of algae were exposed to a medium level of Chlorpyrifos, SOD and CAT activities were importantly advanced. Therefore, the growth rate and SOD and CAT activities can be highly recommended for the eco-toxicological assessment. In addition, chlorophyll a also could be used as a targeted parameter for assessing the eco-toxicity of Chlorpyrifos on both Chlorella pyrenoidosa and Merismopedia sp. Copyright © 2016 Elsevier B.V. All rights reserved.

Urinary serotonin level is associated with serotonin syndrome after moclobemide, sertraline, and citalopram overdose.

PubMed

Brvar, Miran; Stajer, Dusan; Kozelj, Gordana; Osredkar, Josko; Mozina, Martin; Bunc, Matjaz

2007-01-01

Altered mental status, autonomic dysfunction, and neuromuscular abnormalities are a characteristic triad of serotonin syndrome. No laboratory tests confirm the diagnosis of serotonin syndrome. A 35-year-old woman took moclobemide, sertraline, and citalopram in a suicide attempt. She was conscious with mild tachycardia, hypertension, and tachypnea one hour after ingestion. In the second hour after ingestion diaphoresis, mydriasis, horizontal nystagmus, trismus, hyperreflexia, clonus, and tremor appeared. She became agitated and unresponsive. In the third hour after ingestion she became comatose and hyperthermic. She was anesthetized, paralyzed, intubated, and ventilated for 24 hours. Serum moclobemide, sertraline, and citalopram levels were above therapeutic levels. The serum serotonin level was within normal limits and the urinary 5-hydroxyindoleacetic acid:creatinine ratio was below the average daily value. The urinary serotonin:creatinine ratio was increased on arrival (1 mg/g). The urinary serotonin level is increased in serotonin syndrome due to a monoamine oxidase inhibitor and selective serotonin-reuptake inhibitors overdose. It is possible that urinary serotonin concentration could be used as a biochemical marker of serotonin syndrome.

Roles of uptake, biotransformation, and target site sensitivity in determining the differential toxicity of chlorpyrifos to second to fourth instar Chironomous riparius (Meigen)

USGS Publications Warehouse

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

2004-01-01

Early life stages of aquatic organisms tend to be more sensitive to various chemical contaminants than later life stages. This research attempted to identify the key biological factors that determined sensitivity differences among life stages of the aquatic insect Chironomous riparius. Specifically, second to fourth instar larvae were exposed in vivo to both low and high waterborne concentrations of chlorpyrifos to examine differences in accumulation rates, chlorpyrifos biotransformation, and overall sensitivity among instars. In vitro acetylcholinesterase (AChE) assays were performed with chlorpyrifos and the metabolite, chlorpyrifos-oxon, to investigate potential target site sensitivity differences among instars. Earlier instars accumulated chlorpyrifos more rapidly than later instars. There were no major differences among instars in the biotransformation rates of chlorpyrifos to the more polar metabolites, chlorpyrifos-oxon, and chlorpyridinol (TCP). Homogenate AChE activities from second to fourth instar larvae were refractory to chlorpyrifos, even at high concentrations. In contrast, homogenate AChE activities were responsive in a dose-dependent manner to chlorpyrifos-oxon. In general, it appeared that chlorpyrifos sensitivity differences among second to fourth instar C. riparius were largely determined by differences in uptake rates. In terms of AChE depression, fourth instar homogenates were more sensitive to chlorpyrifos and chlorpyrifos-oxon than earlier instars. However, basal AChE activity in fourth instar larvae was significantly higher than basal AChE activity in second to third instar larvae, which could potentially offset the apparent increased sensitivity to the oxon. ?? 2003 Elsevier B.V. All rights reserved.

Effects of acute and repeated oral exposure to the organophosphate insecticide chlorpyrifos on open-field activity in chicks.

PubMed

Al-Badrany, Y M A; Mohammad, F K

2007-11-01

The effects of the organophosphate insecticide chlorpyrifos on 5min open-field activity were examined in a 7-15 days old chick model. Chlorpyrifos was acutely administered taking into account cholinesterase inhibition and determination of the acute (24h) median lethal dose (LD50). The oral LD50 value of chlorpyrifos in chicks was 18.14mg/kg, with cholinergic toxicosis observed on intoxicated chicks. Chlorpyrifos at the dose rates of 5,10 and 20mg/kg orally produced within 2h signs of cholinergic toxicosis in the chicks and significantly inhibited plasma (40-70%), whole brain (43-69%) and liver (31-46%) cholinesterase activities in a dose-dependent manner. Chlorpyrifos at 2 and 4mg/kg, orally did not produce overt signs of cholinergic toxicosis, but decreased (30, 60 and 90min after dosing) the general locomotor activity of the chicks as seen by a significant increase in the latency to move from the central square of the open-field arena, decreases in the numbers of lines crossed and vocalization score. Repeated daily chlorpyrifos treatments (2 and 4mg/kg, orally) for seven consecutive days also caused hypoactivity in chicks in the open-field behavioral paradigm. Only the high dose of chlorpyrifos (4mg/kg, orally) given repeatedly for 7 days caused significant cholinesterase inhibition in the whole brain (37%) and the liver (22%). In conclusion, chlorpyrifos at single or short-term repeated doses-induced behavioral changes in 7-15 days old chicks, in a model that could be used for further neurobehavioral studies involving subtle effects of organophosphates on chicks.

Persistence and Dissipation of Chlorpyrifos in Brassica Chinensis, Lettuce, Celery, Asparagus Lettuce, Eggplant, and Pepper in a Greenhouse

PubMed Central

Lu, Meng-Xiao; Jiang, Wayne W.; Wang, Jia-Lei; Jian, Qiu; Shen, Yan; Liu, Xian-Jin; Yu, Xiang-Yang

2014-01-01

The residue behavior of chlorpyrifos, which is one of the extensively used insecticides all around the world, in six vegetable crops was assessed under greenhouse conditions. Each of the vegetables was subjected to a foliar treatment with chlorpyrifos. Two analytical methods were developed using gas chromatography equipped with a micro-ECD detector (LOQ = 0.05 mg kg−1) and liquid chromatography with a tandem mass spectrometry (LOQ = 0.01 mg kg−1). The initial foliar deposited concentration of chlorpyrifos (mg kg−1) on the six vegetables followed the increasing order of brassica chinensischlorpyrifos showed differences among the six selected vegetable plants, ranging from 16.5±0.9 mg kg−1 (brassica chinensis) to 74.0±5.9 mg kg−1 (pepper plant). At pre-harvest interval 21 days, the chlorpyrifos residues in edible parts of the crops were <0.01 (eggplant fruit), <0.01 (pepper fruit), 0.56 (lettuce), 0.97 (brassica chinensis), 1.47 (asparagus lettuce), and 3.50 mg kg−1 (celery), respectively. The half-lives of chlorpyrifos were found to be 7.79 (soil), 2.64 (pepper plants), 3.90 (asparagus lettuce), 3.92 (lettuce), 5.81 (brassica chinensis), 3.00 (eggplant plant), and 5.45 days (celery), respectively. The dissipation of chlorpyrifos in soil and the six selected plants was different, indicating that the persistence of chlorpyrifos residues strongly depends upon leaf characteristics of the selected vegetables. PMID:24967589

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cole, Toby B.; Walter, Betsy J.; Shih, Diana M.

2005-08-01

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

Molecular characterisation of two α-esterase genes involving chlorpyrifos detoxification in the diamondback moth, Plutella xylostella.

PubMed

Xie, Miao; Ren, Na-Na; You, Yan-Chun; Chen, Wei-Jun; Song, Qi-Sheng; You, Min-Sheng

2017-06-01

Carboxylesterases (CarEs) are involved in metabolic detoxification of dietary and environmental xenobiotics in insects. However, owing to the complexity of the protein family, the involvement of CarEs in insecticide metabolism in Plutella xylostella has not been fully elucidated. This study aimed to characterise two CarE genes and assess their potential roles in response to chlorpyrifos in P. xylostella. Synergistic tests showed that triphenyl phosphate decreased the resistance of the third-instar larvae to chlorpyrifos. The treatment of the third-instar larvae with chlorpyrifos at the LC 30 dose led to a significant increase in CarE activity. Two CarE cDNAs (Pxae18 and Pxae28) were subsequently sequenced and characterised. Both genes were expressed predominantly in the larval midgut. Most importantly, two CarE genes showed significantly higher expression in the chlorpyrifos-resistant strain than in the susceptible strain. RNAi knockdown of Pxae18 and Pxae28 significantly increased the mortality to chlorpyrifos from 40% in the control to 73.8 and 63.3% respectively. RNAi knockdown of Pxae18 and Pxae28 significantly inhibited detoxification ability and increased the mortality in P. xylostella. The results indicate that these two CarE genes play important roles in the detoxification of chlorpyrifos in P. xylostella. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Toxicity of Cypermethrin and Chlorpyrifos Against German Cockroach [ Blattella germanica (Blattaria: Blattellidae)] Strains from Hamadan, Iran.

PubMed

Nazari, Mansour; Motlagh, Behrouz Alipourian; Nasirian, Hassan

German cockroach has relatively short life cycle and reproduce rapidly. It is the most common medically and public health pest. As a result, it is essential to combat this pest. Cypermethrin and chlorpyrifos are used by private companies in Hamadan to control Blattella germanica. It seems necessary to determine its susceptibility levels to these insecticides. The aim of this study was to determine the susceptibility levels of B. germanica strains to cypermethrin and chlorpyrifos in Hamadan. In this study, the German cockroach strains were collected from two hospitals (Fatemiyeh and Atiyeh) in Hamadan and transfered to the insectarium. The cockroach strains were reared under the same laboratory condition. Then their sensitivity levels were considered to 1, 2, 4, 8 and 16 mg m -2 for cypermethrin and 0.82, 1.65, 3.31, 6.63, 9.945 and 13.26 mg m -2 for chlorpyrifos using surface contact method. Results based on insecticide treated doses, B. germanica strains showed different percent mortality to the insecticides ranged from 13.3-100. The LD 50 and LD 90 and regression lines of the treated insecticides against German cockroach strains indicate that Fatemiyeh Hospital strain is more susceptible to the treated insecticides than Atiyeh Hospital strain. The LD 50 and LD 90 of chlorpyrifos are also lower than cypermethrin, indicated that chlorpyrifos is more effective than cypermethrin against German cockroach. As the slopes of the regression lines are observed mild in this study indicate that the population of the cockroach strains is very heterogeneous. It can be a symbol of insecticides resistance to cypermethrin and chlorpyrifos. As chlorpyrifos and cypermethrin insecticides are also used for residual spraying by private companies and the doses which provide more than 90% mortality are below the WHO recommended insecticide doses. Therefore, chlorpyrifos and cypermethrin insecticides can be used for B. germanica control in Hamadan within regular monitoring and preventive

NEUROBEHAVIORAL EFFECTS OF CHRONIC DIETARY AND REPEATED HIGH-LEVEL SPIKE EXPOSURE TO CHLORPYRIFOS IN RATS.

EPA Science Inventory

This study aimed to model long-term subtoxic human exposure to an organophosphorus pesticide, chlorpyrifos, and to examine the influence of that exposure on the response to intermittent high-dose acute challenges. Adult rats were maintained on a chlorpyrifos-containing diet to p...

Characterization and functional analysis of a carboxylesterase gene associated with chlorpyrifos resistance in Nilaparvata lugens (Stål).

PubMed

Lu, Kai; Wang, Ying; Chen, Xia; Zhang, Zhichao; Li, Yue; Li, Wenru; Zhou, Qiang

2017-12-01

The widespread and extensive application of insecticides have promoted the development of resistance in the brown planthopper Nilaparvata lugens (Stål), one of the most important rice pests in Asia. To better understand the underlying molecular mechanisms of metabolic resistance to insecticides, a chlorpyrifos-resistant (CR) strain of N. lugens was selected and its possible resistance mechanism was investigated. Synergistic tests using carboxylesterases (CarEs) inhibitor triphenyl phosphate (TPP) decreased the resistance of N. lugens to chlorpyrifos, and CarE activities could be induced by low concentrations of chlorpyrifos. Subsequently, a gene putatively encoding CarE, namely NlCarE, predominant in the midgut and ovary was isolated and characterized. The expression levels of NlCarE were detected and compared between the CR and a susceptible (SS) strain of N. lugens. Consistent with the increased CarE activity, this gene was overexpressed in the CR strain compared to the SS strain. The transcript levels of NlCarE were up-regulated by chlorpyrifos exposure, showing dose- and time-dependent expression patterns. Furthermore, RNA interference (RNAi)-mediated knockdown of NlCarE followed by insecticide application significantly increased the susceptibility of N. lugens to chlorpyrifos. These results demonstrate that NlCarE plays an important role in chlorpyrifos detoxification and its overexpression may be involved in chlorpyrifos resistance in N. lugens. Copyright © 2017 Elsevier Inc. All rights reserved.

Laboratory selection of chlorpyrifos resistance in an Invasive Pest, Phenacoccus solenopsis (Homoptera: Pseudococcidae): Cross-resistance, stability and fitness cost.

PubMed

Ejaz, Masood; Afzal, Muhammad Babar Shahzad; Shabbir, Ghulam; Serrão, José Eduardo; Shad, Sarfraz Ali; Muhammad, Wali

2017-04-01

The cotton mealybug, Phenacoccus solenopsis is an important polyphagous sucking pest of ornamentals, horticultural and fiber crops worldwide. Some P. solenopsis populations have developed insecticide resistance. This study evaluated cross-resistance, stability of insecticide resistance and life history traits affected by chlorpyrifos resistance in P. solenopsis. After nine generations selected with chlorpyrifos, P. solenopsis exhibited a 539.76-fold resistance level compared to an unselected population (UNSEL Pop). Chlorpyrifos selected population (Chlor-SEL Pop) displayed moderate cross-resistance to profenofos, nitenpyram and high cross-resistance to lambda-cyhalothrin. Biological parameters of P. Solenopsis were affected by chlorpyrifos resistance. The Chlor-SEL Pop had a significant reduction in fitness (relative fitness=0.10), along with significant decreases in pupal weight, fecundity, egg hatching %, intrinsic rate of natural population increase, biotic potential, and mean relative growth rate. It is concluded that selection with chlorpyrifos had marked effect on resistance development in P. solenopsis and upon removal of selection pressure chlorpyrifos resistance declined significantly indicating unstable resistance. Development of resistance led to high fitness costs for the chlorpyrifos-selected strain. These findings should be helpful for better and more successful resistance management of P. solenopsis. Copyright © 2016 Elsevier B.V. All rights reserved.

Potential Uses of Biomonitoring Data: A Case Study Using the Organophosphorus Pesticides Chlorpyrifos and Malathion

PubMed Central

Barr, Dana B.; Angerer, Jürgen

2006-01-01

Background Organophosphorus pesticides such as chlorpyrifos and malathion are widely used insecticides. They do not bioaccumulate appreciably in humans and are rapidly metabolized and excreted in the urine. In nonoccupational settings, exposures to these pesticides are typically sporadic and short-lived because the pesticides tend to degrade in the environment over time; however, dietary exposures may be more chronic. Biologic monitoring has been widely used to assess exposures, susceptibility, and effects of chlorpyrifos and malathion; thus, the information base on these compounds is data rich. For biomonitoring of exposure, chlorpyrifos and malathion have been measured in blood, but most typically their urinary metabolites have been measured. For assessing early effects and susceptibility, cholinesterase and microsomal esterase activities, respectively, have been measured. Objectives Although many biologic monitoring data have been generated and published on these chemicals, their interpretation is not straightforward. For example, exposure to environmental degradates of chlorpyrifos and malathion may potentially increase f urinary metabolite levels, thus leading to overestimation of exposure. Also, the temporal nature of the exposures makes the evaluation of both exposure and effects difficult. We present an overview of the current biomonitoring and other relevant data available on exposure to chlorpyrifos and malathion and the use of these data in various environmental public health applications. PMID:17107865

Differences in response of two model estuarine crustaceans after lethal and sublethal exposures to chlorpyrifos.

PubMed

Key, Peter B; Simonik, Elizabeth; Kish, Nicole; Chung, Katy W; Fulton, Michael H

2013-01-01

This study assessed the in vitro and in vivo effects of an acetylcholinesterase enzyme inhibitor (chlorpyrifos) in two estuarine crustaceans: grass shrimp (Palaemonetes pugio) and mysid (Americamysis bahia). The differences in response were quantified after lethal and sublethal exposures to chlorpyrifos and in vitro assays with chlorpyrifos-oxon. Results from the in vitro experiments indicated that the target enzyme, acetylcholinesterase (AChE), in the two species was similar in sensitivity to chlorpyrifos inhibition with IC50s of 0.98 nM and 0.89 nM for grass shrimp and mysids, respectively. In vivo experiments showed that mysids were significantly more sensitive to chlorpyrifos-induced AChE inhibition after 24 h of exposure. The in vivo EC50s for AChE inhibition were 1.23 μg L(-1) for grass shrimp and 0.027 μg L(-1) for mysids. Median lethal concentrations (24h LC50 values) were 1.06 μg L(-1) for grass shrimp and 0.068 μg L(-1) for mysids. The results suggest that differences in the response of these two crustaceans are likely related to differences in uptake and metabolism rather than target site sensitivity.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Jeong Eun; Hanyang Biomedical Research Institute, Seoul; Park, Jae Hyeon

2012-09-01

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

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

PubMed

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

2015-10-01

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

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

PubMed Central

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

2015-01-01

The objectives of this study were to determine the effects of food processing on field incurred residues levels of chlorpyrifos and its metabolite 3,5,6-Trichloro-2-pyridinol (TCP) in rice. The chlorpyrifos and TCP were found to be 1.27 and 0.093 mg kg-1 in straw and 0.41 and 0.073 mg kg-1 in grain, respectively. It is observed that the sunlight for 2 hours does not decrease the chlorpyrifos and TCP residues in grain significantly. Their residues in rice were reduced by up to 50% by hulling. The cooking reduced the chlorpyrifos and TCP in rice to undetectable level (below 0.01 mg kg-1). Processing factors (PFs) of chlorpyrifos and TCP residues in rice during food processing were similar. Various factors have impacts on the fates of chlorpyrifos and TCP residues and the important steps to reduce their residues in rice were hulling and cooking. The results can contribute to assure the consumer of a safe wholesome food supply. PMID:25608031

Dissipation, half-lives, and mass spectrometric identification of chlorpyrifos and its two metabolites on field-grown collard and kale.

PubMed

Antonious, George F; Turley, Eric T; Abubakari, Mutari; Snyder, John C

2017-04-03

The persistence and fate of chlorpyrifos and its two metabolites, chlorpyrifos-oxon and the 3, 5, 6-trichloro-2-pyridinol (TCP) break-down product were investigated on kale and collard leaves under field conditions. A simultaneous extraction and quantification procedure was developed for chrorpyrifos and its two main metabolites. Residues of chlorpyrifos, chlorpyrifos oxon, and TCP were determined using a gas chromatograph (GC) equipped with an electron capture detector (GC/ECD). Chlorpyrifos metabolites were detectable up to 23 days following application. Residues were confirmed using a GC equipped with a mass selective detector (GC/MSD) in total ion mode. Initial residues of chlorpyrifos were greater on collard (14.5 µg g -1 ) than kale (8.2 µg g -1 ) corresponding to half-lives (T 1/2 ) values of 7.4 and 2.2 days, respectively. TCP, the hydrolysis product, was more persistent on collards with an estimated T 1/2 of 6.5 days compared to kale (T 1/2 of 1.9 days).

Electrochemical Determination of Chlorpyrifos on a Nano-TiO₂Cellulose Acetate Composite Modified Glassy Carbon Electrode.

PubMed

Kumaravel, Ammasai; Chandrasekaran, Maruthai

2015-07-15

A rapid and simple method of determination of chlorpyrifos is important in environmental monitoring and quality control. Electrochemical methods for the determination of pesticides are fast, sensitive, reproducible, and cost-effective. The key factor in electrochemical methods is the choice of suitable electrode materials. The electrode materials should have good stability, reproducibility, more sensitivity, and easy method of preparation. Mercury-based electrodes have been widely used for the determination of chlorpyrifos. From an environmental point of view mercury cannot be used. In this study a biocompatible nano-TiO2/cellulose acetate modified glassy carbon electrode was prepared by a simple method and used for the electrochemical sensing of chlorpyrifos in aqueous methanolic solution. Electroanalytical techniques such as cyclic voltammetry, differential pulse voltammetry, and amperometry were used in this work. This electrode showed very good stability, reproducibility, and sensitivity. A well-defined peak was obtained for the reduction of chlorpyrifos in cyclic voltammetry and differential pulse voltammetry. A smooth noise-free current response was obtained in amperometric analysis. The peak current obtained was proportional to the concentration of chlorpyrifos and was used to determine the unknown concentration of chlorpyrifos in the samples. Analytical parameters such as LOD, LOQ, and linear range were estimated. Analysis of real samples was also carried out. The results were validated through HPLC. This composite electrode can be used as an alternative to mercury electrodes reported in the literature.

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

PubMed

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

2015-01-01

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

CHARACTERIZATION OF RESIDENTIAL EXPOSURE TO CHLORPYRIFOS AND DIAZINON

EPA Science Inventory

Exposures to chlorpyrifos and diazinon in residential microenvironment in AZ were estimated using the indirect method of exposure calculation by combining measured concentrations in multiple media with time subjects spent indoors, dietary and non-dietary items they consumed, an...

Diazinon and chlorpyrifos loads in the San Joaquin River basin, California, January and February 2000

USGS Publications Warehouse

Kratzer, Charles R.; Zamora, Celia; Knifong, Donna L.

2002-01-01

The application of diazinon and chlorpyrifos on dormant orchards in 2000 in the San Joaquin River Basin was less than 21 percent of application in 1993 and 1994. A total of 13 sites were sampled weekly during nonstorm periods and more frequently during two storm periods. The sites included five major river and eight minor tributary sites. The highest concentrations of diazinon and chlorpyrifos occurred during the storm periods. Four samples from major river sites (Tuolumne River and two San Joaquin River sites) had diazinon concentrations greater than 0.08 microgram per liter, the concentration being considered by the state of California as its criterion maximum concentration for the protection of aquatic habitat. One sample from a major river site (San Joaquin River) exceeded the equivalent State guideline of 0.02 microgram per liter for chlorpyrifos. At the eight minor tributary sites, 24 samples exceeded the diazinon guideline and four samples exceeded the chlorpyrifos guideline. The total diazinon load in the San Joaquin River near Vernalis during January and February 2000 was 19.6 pounds active ingredient; of this, 8.17 pounds active ingredient was transported during two storms. In 1994, 27.4 pounds active ingredient was transported during two storms. The total chlorpyrifos load in the San Joaquin River near Vernalis during January and February 2000 was 5.68 pounds active ingredient; of this, 2.17 pounds active ingredient was transported during the two storms. During the frequently sampled February 2000 storm, the main sources of diazinon in the San Joaquin River Basin were the San Joaquin River near Stevinson Basin (25 percent), Tuolumne River Basin (14 percent), and the Stanislaus River Basin (10 percent). The main sources of chlorpyrifos in the San Joaquin River Basin were the San Joaquin River near Stevinson Basin (17 percent), Tuolumne River Basin (13 percent), and the Merced River Basin (11 percent). The total January and February diazinon load in the

Evaluation of abamectin, diazinon and chlorpyrifos pesticide residues in apple product of Mahabad region gardens: Iran in 2014.

PubMed

Pirsaheb, Meghdad; Fattahi, Nazir; Rahimi, Rahim; Sharafi, Kiomars; Ghaffari, Hamid Reza

2017-09-15

The purpose of this study was to investigate abamectin, diazinon and chlorpyrifos in apple from the Mahabad of Iran. The influences of several parameters including shadow and sun, geographical directions and varieties of apples, whether they are golden or red type, was also taken into account on the residuals of the pesticides in the samples. The results indicated that sun considerably decreased the concentrations of diazinon and chlorpyrifos in samples exposed to it. Geographical directions are showed to be non-influential on diazinon while they are influential on chlorpyrifos ones. This can be attributed to pesticide spraying time and prevailing wind direction in Mahabad. The pesticides in golden and red varieties showed no significant relations. The apple samples from Mahabad did not contain any abamectin while they contained residuals of diazinon and chlorpyrifos. In some samples the diazinon and chlorpyrifos were above allowed limit according to World Health Organization (WHO) standard. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dissipation and distribution of chlorpyrifos in selected vegetables through foliage and root uptake.

PubMed

Ge, Jing; Lu, Mengxiao; Wang, Donglan; Zhang, Zhiyong; Liu, Xianjin; Yu, Xiangyang

2016-02-01

Dissipation, distribution and uptake pathways of chlorpyrifos were investigated in pakchoi (Brassica chinensis L.) and lettuce (Lactuca sativa) with foliage treatments under a greenhouse trial and root treatments under a hydroponic experiment. The dissipation trends were similar for chlorpyrifos in pakchoi and lettuce with different treatments. More than 94% of chlorpyrifos was degraded in the samples for both of the vegetables 21 days after the foliage treatments. For the root treatment, the dissipation rate of chlorpyrifos in pakchoi and lettuce at the low concentration was greater than 93%, however, for the high concentrations, the dissipation rates were all under 90%. Both shoots and roots of the vegetables were able to absorb chlorpyrifos from the environment and distribute it inside the plants. Root concentration factor (RCF) values at different concentrations with the hydroponic experiment ranged from 5 to 39 for pakchoi, and from 14 to 35 for lettuce. The translocation factor (TF) representing the capability of the vegetables to translocate contaminants was significantly different for pakchoi and lettuce with foliage and root treatments. The values of TF with foliage treatments ranged from 0.003 to 0.22 for pakchoi, and from 0.032 to 1.63 for lettuce. The values of TF with root treatments ranged from 0.01 to 0.17 for pakchoi, and from 0.003 to 0.23 for lettuce. Significant difference of TF was found between pakchoi and lettuce with foliage treatments, and at high concentrations (10 and 50 mg L(-1)) with root treatments as well. However, there was no significant difference of TF between pakchoi and lettuce at 1 mg L(-1) with root treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chlorpyrifos Exposure and Urban Residential Environment Characteristics as Determinants of Early Childhood Neurodevelopment

PubMed Central

Quinn, James W.; Rauh, Virginia A.; Perera, Frederica P.; Andrews, Howard F.; Garfinkel, Robin; Hoepner, Lori; Whyatt, Robin; Rundle, Andrew

2011-01-01

Objectives. We evaluated whether neighborhood characteristics correlated with early neurodevelopment and whether these characteristics confounded the previously reported association between exposure to chlorpyrifos (an organophosphate insecticide) and neurodevelopment. Methods. We obtained prenatal addresses, chlorpyrifos exposure data, and 36-month Psychomotor Development Index (PDI) and Mental Development Index (MDI) scores for a birth cohort in New York City (born 1998–2002). We used data from the 2000 US Census to estimate measures of physical infrastructure, socioeconomic status, crowding, demographic composition, and linguistic isolation for 1-kilometer network areas around each child's prenatal address. Generalized estimating equations were adjusted for demographics, maternal education and IQ, prenatal exposure to tobacco smoke, caretaking environment quality, and building dilapidation. Results. Of 266 children included as participants, 47% were male, 59% were Dominican, and 41% were African American. For each standard deviation higher in neighborhood percent poverty, the PDI score was 2.6 points lower (95% confidence interval [CI] = −3.7, −1.5), and the MDI score was 1.7 points lower (95% CI = −2.6, −0.8). Neighborhood-level confounding of the chlorpyrifos-neurodevelopment association was not apparent. Conclusions. Neighborhood context and chlorpyrifos exposure were independently associated with neurodevelopment, thus providing distinct opportunities for health promotion. PMID:20299657

Temperature influences on water permeability and chlorpyrifos uptake in aquatic insects with differing respiratory strategies.

PubMed

Buchwalter, David B; Jenkins, Jeffrey J; Curtis, Lawrence R

2003-11-01

Aquatic insects have evolved diverse respiratory strategies that range from breathing atmospheric air to breathing dissolved oxygen. These strategies result in vast morphological differences among taxa in terms of exchange epithelial surface areas that are in direct contact with the surrounding water that, in turn, affect physiological processes. This paper examines the effects of acute temperature shifts on water permeability and chlorpyrifos uptake in aquatic insects with different respiratory strategies. While considerable differences existed in water permeability among the species tested, acute temperature shifts raised water influx rates similarly in air-breathing and gill-bearing taxa. This contrasts significantly with temperature-shift effects on chlorpyrifos uptake. Temperature shifts of 4.5 degrees C increased 14C-chlorpyrifos accumulation rates in the gill-bearing mayfly Cinygma sp. and in the air-breathing hemipteran Sigara washingtonensis. However, the temperature-induced increase in 14C-chlorpyrifos uptake after 8 h of exposure was 2.75-fold higher in Cinygma than in Sigara. Uptake of 14C-chlorpyrifos was uniformly higher in Cinygma than in Sigara in all experiments. These findings suggest that organisms with relatively large exchange epithelial surface areas are potentially more vulnerable to both osmoregulatory distress as well as contaminant accumulation. Temperature increases appear more likely to impact organisms that have relatively large exchange epithelial surface areas, both as an individual stressor and in combination with additional stressors such as contaminants.

Temperature influences on water permeability and chlorpyrifos uptake in aquatic insects with differing respiratory strategies

USGS Publications Warehouse

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

2003-01-01

Aquatic insects have evolved diverse respiratory strategies that range from breathing atmospheric air to breathing dissolved oxygen. These strategies result in vast morphological differences among taxa in terms of exchange epithelial surface areas that are in direct contact with the surrounding water that, in turn, affect physiological processes. This paper examines the effects of acute temperature shifts on water permeability and chlorpyrifos uptake in aquatic insects with different respiratory strategies. While considerable differences existed in water permeability among the species tested, acute temperature shifts raised water influx rates similarly in air-breathing and gill-bearing taxa. This contrasts significantly with temperature-shift effects on chlorpyrifos uptake. Temperature shifts of 4.5??C increased 14C-chlorpyrifos accumulation rates in the gill-bearing mayfly Cinygma sp. and in the air-breathing hemipteran Sigara washingtonensis. However, the temperature-induced increase in 14C-chlorpyrifos uptake after 8 h of exposure was 2.75-fold higher in Cinygma than in Sigara. Uptake of 14C-chlorpyrifos was uniformly higher in Cinygma than in Sigara in all experiments. These findings suggest that organisms with relatively large exchange epithelial surface areas are potentially more vulnerable to both osmoregulatory distress as well as contaminant accumulation. Temperature increases appear more likely to impact organisms that have relatively large exchange epithelial surface areas, both as an individual stressor and in combination with additional stressors such as contaminants.

Enzyme induction and cytotoxicity in human hepatocytes by chlorpyrifos and N,N-diethyl-m-toluamide (DEET).

PubMed

Das, Parikshit C; Cao, Yan; Rose, Randy L; Cherrington, Nathan; Hodgson, Ernest

2008-01-01

Xenobiotics, including drugs and environmental chemicals, can influence cytochrome P450 (CYP) levels by altering the transcription of CYP genes. To minimize potential drug-pesticide and pesticide-pesticide interactions it is important to evaluate the potential of pesticides to induce CYP isoforms and to cause cytotoxicity in humans. The present study was designed to examine chlorpyrifos and DEET mediated induction of CYP isoforms and also to characterize their potential cytotoxic effects on primary human hepatocytes. DEET significantly induced CYP3A4, CYP2B6, CYP2A6 and CYP1A2 mRNA expression while chlorpyrifos induced CYP1A1, CYP1A2 and CYP3A4 mRNA, and to a lesser extent, CYP1B1 and CYP2B6 mRNA in primary human hepatocytes. Chlorpyrifos and DEET also mediated the expression of CYP isoforms, particularly CYP3A4, CYP2B6 and CYP1A1, as shown by CYP3A4-specific protein expression, testosterone metabolism and CYP1Al-specific activity assays. DEET is a mild, while chlorpyrifos is a relatively potent, inducer of adenylate kinase and caspase-3/7, an indicator of apoptosis, while inducing 15-20% and 25-30% cell death, respectively. Therefore, DEET and chlorpyrifos mediated induction of CYP mRNA and functional CYP isoforms together with their cytotoxic potential in human hepatocytes suggests that exposure to chlorpyrifos and/or DEET should be considered in human health impact analysis.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

van der Wel, H.; Welling, W.

1989-04-01

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

Simultaneous gas chromatographic determination of chlorpyrifos and its impurity sulfotep in liquid pesticide formulations.

PubMed

Płonka, Marlena; Walorczyk, Stanisław; Miszczyk, Marek; Kronenbach-Dylong, Dorota

2016-11-01

An analytical method for simultaneous determination of the active substance (chlorpyrifos) and its relevant impurity (sulfotep) in commercial pesticide formulations has been developed and validated. The proposed method entails extraction of the analytes from samples by sonication with acetone and analysis by gas chromatography-flame ionization detection (GC-FID). The proposed method was characterized by satisfactory accuracy and precision. The repeatability expressed as relative standard deviation (RSD) was lower than the acceptable values calculated from the modified Horwitz equation whereas individual recoveries were in the range of 98-102% and 80-120% for chlorpyrifos and sulfotep, respectively. The limit of quantification (LOQ) for the impurity (sulfotep) was 0.003 mg mL(-1) corresponding to the maximum permitted level according to Food and Agricultural Organization of the United Nations (FAO) specifications for the active substance (chlorpyrifos) being 3 g kg(-1) of the chlorpyrifos content found. The main advantage of the proposed method was a considerable reduction in the analysis time since both analytes were determined based on a single injection into the GC-FID. Analysis of real samples of commercial pesticide formulations confirmed fitness-for-purpose of the proposed method.

Evaluation of chlorpyrifos transferred from contaminated feed to duck commodities and dietary risks to Chinese consumers.

PubMed

Li, Rui; Ji, Xiaofeng; He, Liang; Liu, Zhiqiang; Wei, Wei; Qiang, Mingrong; Wang, Qiang; Yuan, Yuwei

2015-06-03

The present study describes chlorpyrifos residues in duck commodities through the duck food chain, transfer factors, and dietary risks to Chinese consumers. After duck feeding experiments with pellet feed that lasted for 42 days, chlorpyrifos residues found in all samples collected from the ducks on maximum estimated dose group (3.20 mg/kg level) were from <0.0005 to 0.019 mg/kg. The residue levels of the fat, intestine, and tongue were obviously higher than those of the meat and other edible tissues. The transfer factors of all duck commodities were from 0.0001 to 0.0049 among different contamination levels, which indicated that chlorpyrifos had a low persistency in duck meat and metabolism organs. The chronic exposure assessment revealed that only 0.034-0.150% of the acceptable daily intake (ADI; 0-0.01 mg/kg/bw/day) of chlorpyrifos was consumed via the duck commodities for different age and gender groups in China. The acute exposure assessments of different age and gender groups were only 0.019-0.082% of the acute reference dose (ARfD; 0-0.1 mg/kg/bw). The results show that the single dietary exposure risk of chlorpyrifos raised by the intake of duck commodities was quite low in China.

Serotonin blood test

MedlinePlus

5-HT level; 5-hydroxytryptamine level; Serotonin test ... Chernecky CC, Berger BJ. Serotonin (5-hydroxytryptamine) - serum or blood. In: Chernecky CC, Berger BJ, eds. Laboratory Tests and Diagnostic Procedures . 6th ed. St Louis, MO: Elsevier ...

MODELING AGGREGATE CHLORPYRIFOS EXPOSURE AND DOSE TO CHILDREN

EPA Science Inventory

To help address the aggregate exposure assessment needs of the Food Quality Protection Act, a physically-based probabilistic model (SHEDS-Pesticides, version 3) has been applied to estimate aggregate chlorpyrifos exposure and dose to children. Two age groups (0-4, 5-9 years) a...

Selection for chlorpyrifos resistance in Liriomyza sativae Blanchard: Cross-resistance patterns, stability and biochemical mechanisms.

PubMed

Askari-Saryazdi, Ghasem; Hejazi, Mir Jalil; Ferguson, J Scott; Rashidi, Mohammad-Reza

2015-10-01

The vegetable leafminer (VLM), Liriomyza sativae (Diptera: Agromyzidae) is a serious pest of vegetable crops and ornamentals worldwide. In cropping systems with inappropriate management strategies, development of resistance to insecticides in leafminers is probable. Chlorpyrifos is a commonly used pesticide for controlling leafminers in Iran, but resistance to this insecticide in leafminers has not been characterized. In order to develop strategies to minimize resistance in the field and greenhouse, a laboratory selected chlorpyrifos resistant strain of L. sativae was used to characterize resistance and determine the rate of development and stability of resistance. Selecting for resistance in the laboratory after 23 generations yielded a chlorpyrifos resistant selected strain (CRSS) with a resistance ratio of 40.34, determined on the larval stage. CRSS exhibited no cross-resistance to other tested insecticides except for diazinon. Synergism and biochemical assays indicated that esterases (EST) had a key role in metabolic resistance to chlorpyrifos, but glutathione S-transferase (GST) and mixed function oxidase (MFO) were not mediators in this resistance. In CRSS acetylcholinesterase (AChE) was more active than the susceptible strain, Sharif (SH). AChE in CRSS was also less sensitive to inhibition by propoxur. The kinetics parameters (Km and Vmax) of AChE indicated that affinities and hydrolyzing efficiencies of this enzyme in CRSS were higher than SH. Susceptibility to chlorpyrifos in L. sativae was re-gained in the absence of insecticide pressure. Synergism, biochemical and cross-resistance assays revealed that overactivity of metabolic enzymes and reduction in target site sensitivity are probably joint factors in chlorpyrifos resistance. An effective insecticide resistance management program is necessary to prevent fast resistance development in crop systems. Copyright © 2015 Elsevier Inc. All rights reserved.

Use of Bacillus thuringiensis supernatant from a fermentation process to improve bioremediation of chlorpyrifos in contaminated soils.

PubMed

Aceves-Diez, Angel E; Estrada-Castañeda, Kelly J; Castañeda-Sandoval, Laura M

2015-07-01

The aim of this research was to investigate the potential of a nutrient-rich organic waste, namely the cell-free supernatant of Bacillus thuringiensis (BtS) gathered from fermentation, as a biostimulating agent to improve and sustain microbial populations and their enzymatic activities, thereby assisting in the bioremediation of chlorpyrifos-contaminated soil at a high dose (70 mg kg(-1)). Experiments were performed for up to 80 d. Chlorpyrifos degradation and its major metabolic product, 3,5,6-trichloro-2-pyridinol (TCP), were quantified by high-performance liquid chromatography (HPLC); total microbial populations were enumerated by direct counts in specific medium; and fluorescein diacetate (FDA) hydrolysis was measured as an index of soil microbial activity. Throughout the experiment, there was higher chlorpyrifos degradation in soil supplemented with BtS (83.1%) as compared to non-supplemented soil. TCP formation and degradation occurred in all soils, but the greatest degradation (30.34%) was observed in soil supplemented with BtS. The total microbial populations were significantly improved by supplementation with BtS. The application of chlorpyrifos to soil inhibited the enzymatic activity; however, this negative effect was counteracted by BtS, inducing an increase of approximately 16% in FDA hydrolysis. These results demonstrate the potential of B. thuringiensis supernatant as a suitable biostimulation agent for enhancing chlorpyrifos and TCP biodegradation in chlorpyrifos-contaminated soils. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crow, J. Allen; Bittles, Victoria; Herring, Katye L.

2012-01-01

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

The effect of stress on the acute neurotoxicity of the organophosphate insecticide chlorpyrifos

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hancock, Sandra; Ehrich, Marion; Hinckley, Jonathan

2007-03-15

A study was conducted to determine if multiple exposures to several stress paradigms might affect the anticholinesterase effect of subsequently administered organophosphate insecticide chlorpyrifos. Male Sprague-Dawley rats were subject to daily periods of restraint, swimming, a combination of the two, or neither of the two (controls) (n = 8/group) for 5 days per week over a six-week period. The most profound stress, as measured by reduced body weight gain and elevated levels of plasma corticosterone, was swimming. On day 39 of the study, shortly after the daily stress episode, one half of the rats in each group was dosed withmore » 60 mg/kg chlorpyrifos subcutaneously. This had no effect on subsequent levels of plasma corticosterone. There were no stress-related differences in the degree of chlorpyrifos-induced inhibition of brain acetylcholinesterase in animals sacrificed on day 43.« less

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

USGS Publications Warehouse

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

2001-01-01

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

Effects of chlorpyrifos on the growth and ultrastructure of green algae, Ankistrodesmus gracilis.

PubMed

Asselborn, Viviana; Fernández, Carolina; Zalocar, Yolanda; Parodi, Elisa R

2015-10-01

The effect of the organophosphorus insecticide chlorpyrifos on the growth, biovolume, and ultrastructure of the green microalga Ankistrodesmus gracilis was evaluated. Concentrations of 9.37, 18.75, 37.5, 75 and 150mgL(-1) of chlorpyrifos were assayed along with a control culture. At the end of the bioassay the ultrastructure of algal cells from control culture and from cultures exposed to 37.5 and 150mgL(-1) was observed under transmission (TEM) and scanning electron microscopy (SEM). After 24 and 48h, treatments with 75 and 150mgL(-1) inhibited the growth of A. gracilis; whereas after 72 and 96h, all the treatments except at 9.37mgL(-1) significantly affected the algae growth. The effective concentration 50 (EC50) after 96h was 22.44mgL(-1) of chlorpyrifos. After the exposure to the insecticide, an increase in the biovolume was observed, with a larger increase in cells exposed to 75 and 150mgL(-1). Radical changes were observed in the ultrastructure of cells exposed to chlorpyrifos. The insecticide affected the cell shape and the distribution of the crests in the wall. At 37.5mgL(-1) electodense bodies were observed along with an increase in the size and number of starch granules. At 150mgL(-1) such bodies occupied almost the whole cytoplasm together with lipids and remains of thylakoids. Autospores formation occurred normally at 37.5mgL(-1) while at 150mgL(-1) karyokinesis occurred, but cell-separation-phase was inhibited. The present study demonstrates that the exposure of phytoplankton to the insecticide chlorpyrifos leads to effects observed at both cellular and population level. Copyright © 2015 Elsevier Inc. All rights reserved.

Attenuating effects of caffeic acid phenethyl ester with intralipid on hepatotoxicity of chlorpyrifos in the case of rats.

PubMed

Dokuyucu, Recep; Bilgili, Ali; Hanedan, Basak; Dogan, Hatice; Dokuyucu, Ahmet; Celik, Muhammed Murat

2016-12-22

Chlorpyrifos (CPF), insecticide widely used in agriculture, may cause poisonings in the case of humans. As a result, there is a large amount of treatment research underway to focus on the possibility of chlorpyrifos induced poisonings. The aim of this study has been to evaluate the effects of caffeic acid phenethyl ester (CAPE) and intralipid (IL) on hepatotoxicity induced by chlorpyrifos in the case of rats. The rats in this study were treated with CPF (10 mg/kg body weight (b.w.), orally), CAPE (10 μmol/kg b.w., intraperitoneally), IL (18.6 ml/kg b.w., orally), CPF+CAPE, CPF+IL, and CPF+CAPE+IL. The plasma total oxidant capacity (TOC), total antioxidant capacity (TAC) were measured and the oxidative stress index (OSI) was calculated. Liver histopathology and immunohistochemical staining were performed. Chlorpyrifos statistically significantly decreased the TAC levels in the rats' plasma and increased the apoptosis and the TOC and OSI levels. In the chlorpyrifos induced liver injury, CAPE and CAPE+IL significantly decreased the plasma OSI levels and the apoptosis, and significantly increased the plasma TAC levels. This study revealed that CAPE and CAPE+IL attenuate chlorpyrifos induced liver injuries by decreasing oxidative stress and apoptosis. Med Pr 2016;67(6):743-749. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Photodegradation of chlorpyrifos with humic acid-bound suspended matter.

PubMed

Amarathunga, A A D; Kazama, F

2014-09-15

Land exploitation in several developing countries, including tropical areas, has caused a rapid change of the landscape, from forest to farms. This has led to an increase of pesticide use and concentration of suspended matter in river waters, which may cause soil erosion of these areas. Humic acid (HA), one of the main components in the soil particulate organic matter, has a positive effect on the photodegradation of organic matter in water; however, the efficiency of HA-bound suspended matter (HABSM) for pesticide photodegradation is not known. The aim of this study is to clarify the effect of HABSM on the photodegradation of chlorpyrifos employed in artificial soil particulate covered with HA. Experiments were carried out in liquid HA phase, with/without HABSM phase and HABSM with additional LHA phase under light. The adsorption procedure of the pesticide on HABSM was also studied. Our results reveal that adsorption takes place within a short time period on HABSM and that photodegradation is successfully achieved. The additional LHA+HABSM phase have not demonstrated any significant effect of HA concentration to photodegradation of chlorpyrifos. For instance, when 2.0mg/L chlorpyrifos was used in the experiments, concentration reductions caused by adsorption, photodegradation under suspended matter and HABSM were found to be 19.3, 17.7, and 61.7% respectively. This finding suggests that HABSM can be considered as a potential catalyst for pesticide photodegradation under sunlight. Copyright © 2014 Elsevier B.V. All rights reserved.

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

PubMed

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

2016-06-01

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

A point mutation in the acetylcholinesterase-1 gene is associated with chlorpyrifos resistance in the plant bug Apolygus lucorum.

PubMed

Wu, Shuwen; Zuo, Kairan; Kang, Zhaokui; Yang, Yihua; Oakeshott, John G; Wu, Yidong

2015-10-01

Control of Chinese Apolygus lucorum relies heavily on organophosphate insecticides. Here we describe resistance to the organophosphate chlorpyrifos in an A. lucorum strain, BZ-R, which was developed from a field-collected strain (BZ) by selection with chlorpyrifos in the laboratory. BZ-R showed 21-58 fold resistance to chlorpyrifos compared with the laboratory reference strain LSF and another susceptible strain, BZ-S, derived from BZ. BZ-R also showed several fold resistance to two other organophosphates and a carbamate. No synergism of chlorpyrifos by metabolic enzyme inhibitors nor any increase in detoxifying enzyme activities were observed in BZ-R. No sequence differences in acetylcholinesterase-2 were found to be associated with the resistance but the frequency of an alanine to serine substitution at position 216 of acetylcholinesterase-1 was 100% in BZ-R, ∼21-23% in SLF and BZ, and 0% in BZ-S. A single generation treatment of chlorpyrifos on the BZ strain also increased its frequency of the serine substitution to 64%. Recombinantly expressed acetylcholinesterase-1 carrying the serine substitution was about five fold less sensitive to inhibition by chlorpyrifos oxon than the wild-type enzyme. Quantitative real-time PCR found no differences in ace1 or ace2 expression levels among the strains tested. Thus the chlorpyrifos resistance is strongly associated with the serine substituted acetylcholinesterase-1. An equivalent substitution has been found to confer resistance to many organophosphate and carbamate insecticides in four other insect species. Copyright © 2015 Elsevier Ltd. All rights reserved.

Degradation of Chlorpyrifos by an alkaline phosphatase from the cyanobacterium Spirulina platensis.

PubMed

Thengodkar, Rutwik Ravindra Mandakini; Sivakami, S

2010-07-01

Spirulina is a photosynthetic, filamentous, spiral-shaped, multicellular, blue-green microalga. The two most important species are Spirulina maxima and Spirulina platensis. Spirulina is considered an excellent food, lacking toxicity and having corrective properties against viral attacks, anemia, tumor growth and malnutrition. We have observed that cultures of Spirulina platensis grow in media containing up to 80 ppm of the organophosphorous pesticide, Chlorpyrifos. It was found to be due to an alkaline phosphatase (ALP) activity that was detected in cell free extracts of Spirulina platensis. This activity was purified from the cell free extracts using ammonium sulphate precipitation and gel filtration and shown to belong to the class of EC 3.1.3.1 ALP. The purified enzyme degrades 100 ppm Chlorpyrifos to 20 ppm in 1 h transforming it into its primary metabolite 3, 5, 6-trichloro-2-pyridinol. This is the first report of degradation of Chlorpyrifos by Spirulina platensis whose enzymic mechanism has been clearly identified. These findings have immense potential for harnessing Spirulina platensis in bioremediation of polluted ecosystems.

Molecular fMRI of Serotonin Transport.

PubMed

Hai, Aviad; Cai, Lili X; Lee, Taekwan; Lelyveld, Victor S; Jasanoff, Alan

2016-11-23

Reuptake of neurotransmitters from the brain interstitium shapes chemical signaling processes and is disrupted in several pathologies. Serotonin reuptake in particular is important for mood regulation and is inhibited by first-line drugs for treatment of depression. Here we introduce a molecular-level fMRI technique for micron-scale mapping of serotonin transport in live animals. Intracranial injection of an MRI-detectable serotonin sensor complexed with serotonin, together with serial imaging and compartmental analysis, permits neurotransmitter transport to be quantified as serotonin dissociates from the probe. Application of this strategy to much of the striatum and surrounding areas reveals widespread nonsaturating serotonin removal with maximal rates in the lateral septum. The serotonin reuptake inhibitor fluoxetine selectively suppresses serotonin removal in septal subregions, whereas both fluoxetine and a dopamine transporter blocker depress reuptake in striatum. These results highlight promiscuous pharmacological influences on the serotonergic system and demonstrate the utility of molecular fMRI for characterization of neurochemical dynamics. Copyright © 2016 Elsevier Inc. All rights reserved.

Serotonin release varies with brain tryptophan levels

NASA Technical Reports Server (NTRS)

Schaechter, Judith D.; Wurtman, Richard J.

1990-01-01

This study examines directly the effects on serotonin release of varying brain tryptophan levels within the physiologic range. It also addresses possible interactions between tryptophan availability and the frequency of membrane depolarization in controlling serotonin release. We demonstrate that reducing tryptophan levels in rat hypothalamic slices (by superfusing them with medium supplemented with 100 microM leucine) decreases tissue serotonin levels as well as both the spontaneous and the electrically-evoked serotonin release. Conversely, elevating tissue tryptophan levels (by superfusing slices with medium supplemented with 2 microM tryptophan) increases both the tissue serotonin levels and the serotonin release. Serotonin release was found to be affected independently by the tryptophan availability and the frequency of electrical field-stimulation (1-5 Hz), since increasing both variables produced nearly additive increases in release. These observations demonstrate for the first time that both precursor-dependent elevations and reductions in brain serotonin levels produce proportionate changes in serotonin release, and that the magnitude of the tryptophan effect is unrelated to neuronal firing frequency. The data support the hypothesis that serotonin release is proportionate to intracellular serotonin levels.

Passive Sampling for Indoor and Outdoor Exposures to Chlorpyrifos, Azinphos-Methyl, and Oxygen Analogs in a Rural Agricultural Community

PubMed Central

Gibbs, Jenna L.; Yost, Michael G.; Negrete, Maria; Fenske, Richard A.

2016-01-01

Background: Recent studies have highlighted the increased potency of oxygen analogs of organophosphorus pesticides. These pesticides and oxygen analogs have previously been identified in the atmosphere following spray applications in the states of California and Washington. Objectives: We used two passive sampling methods to measure levels of the ollowing organophosphorus pesticides: chlorpyrifos, azinphos-methyl, and their oxygen analogs at 14 farmworker and 9 non-farmworker households in an agricultural region of central Washington State in 2011. Methods: The passive methods included polyurethane foam passive air samplers deployed outdoors and indoors and polypropylene deposition plates deployed indoors. We collected cumulative monthly samples during the pesticide application seasons and during the winter season as a control. Results: Monthly outdoor air concentrations ranged from 9.2 to 199 ng/m3 for chlorpyrifos, 0.03 to 20 ng/m3 for chlorpyrifos-oxon, < LOD (limit of detection) to 7.3 ng/m3 for azinphos-methyl, and < LOD to 0.8 ng/m3 for azinphos-methyl-oxon. Samples from proximal households (≤ 250 m) had significantly higher outdoor air concentrations of chlorpyrifos, chlorpyrifos-oxon, and azinphos-methyl than did samples from nonproximal households (p ≤ 0.02). Overall, indoor air concentrations were lower than outdoors. For example, all outdoor air samples for chlorpyrifos and 97% of samples for azinphos-methyl were > LOD. Indoors, only 78% of air samples for chlorpyrifos and 35% of samples for azinphos-methyl were > LOD. Samples from farmworker households had higher indoor air concentrations of both pesticides than did samples from non-farmworker households. Mean indoor and outdoor air concentration ratios for chlorpyrifos and azinphos-methyl were 0.17 and 0.44, respectively. Conclusions: We identified higher levels in air and on surfaces at both proximal and farmworker households. Our findings further confirm the presence of pesticides and their

Passive Sampling for Indoor and Outdoor Exposures to Chlorpyrifos, Azinphos-Methyl, and Oxygen Analogs in a Rural Agricultural Community.

PubMed

Gibbs, Jenna L; Yost, Michael G; Negrete, Maria; Fenske, Richard A

2017-03-01

Recent studies have highlighted the increased potency of oxygen analogs of organophosphorus pesticides. These pesticides and oxygen analogs have previously been identified in the atmosphere following spray applications in the states of California and Washington. We used two passive sampling methods to measure levels of the ollowing organophosphorus pesticides: chlorpyrifos, azinphos-methyl, and their oxygen analogs at 14 farmworker and 9 non-farmworker households in an agricultural region of central Washington State in 2011. The passive methods included polyurethane foam passive air samplers deployed outdoors and indoors and polypropylene deposition plates deployed indoors. We collected cumulative monthly samples during the pesticide application seasons and during the winter season as a control. Monthly outdoor air concentrations ranged from 9.2 to 199 ng/m 3 for chlorpyrifos, 0.03 to 20 ng/m 3 for chlorpyrifos-oxon, < LOD (limit of detection) to 7.3 ng/m 3 for azinphos-methyl, and < LOD to 0.8 ng/m 3 for azinphos-methyl-oxon. Samples from proximal households (≤ 250 m) had significantly higher outdoor air concentrations of chlorpyrifos, chlorpyrifos-oxon, and azinphos-methyl than did samples from nonproximal households ( p ≤ 0.02). Overall, indoor air concentrations were lower than outdoors. For example, all outdoor air samples for chlorpyrifos and 97% of samples for azinphos-methyl were > LOD. Indoors, only 78% of air samples for chlorpyrifos and 35% of samples for azinphos-methyl were > LOD. Samples from farmworker households had higher indoor air concentrations of both pesticides than did samples from non-farmworker households. Mean indoor and outdoor air concentration ratios for chlorpyrifos and azinphos-methyl were 0.17 and 0.44, respectively. We identified higher levels in air and on surfaces at both proximal and farmworker households. Our findings further confirm the presence of pesticides and their oxygen analogs in air and highlight their potential for

Clemizole and modulators of serotonin signalling suppress seizures in Dravet syndrome.

PubMed

Griffin, Aliesha; Hamling, Kyla R; Knupp, Kelly; Hong, SoonGweon; Lee, Luke P; Baraban, Scott C

2017-03-01

Dravet syndrome is a catastrophic childhood epilepsy with early-onset seizures, delayed language and motor development, sleep disturbances, anxiety-like behaviour, severe cognitive deficit and an increased risk of fatality. It is primarily caused by de novo mutations of the SCN1A gene encoding a neuronal voltage-activated sodium channel. Zebrafish with a mutation in the SCN1A homologue recapitulate spontaneous seizure activity and mimic the convulsive behavioural movements observed in Dravet syndrome. Here, we show that phenotypic screening of drug libraries in zebrafish scn1 mutants rapidly and successfully identifies new therapeutics. We demonstrate that clemizole binds to serotonin receptors and its antiepileptic activity can be mimicked by drugs acting on serotonin signalling pathways e.g. trazodone and lorcaserin. Coincident with these zebrafish findings, we treated five medically intractable Dravet syndrome patients with a clinically-approved serotonin receptor agonist (lorcaserin, Belviq®) and observed some promising results in terms of reductions in seizure frequency and/or severity. Our findings demonstrate a rapid path from preclinical discovery in zebrafish, through target identification, to potential clinical treatments for Dravet syndrome. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Biodegradation of Chlorpyrifos and Its Hydrolysis Product 3,5,6-Trichloro-2-Pyridinol by a New Fungal Strain Cladosporium cladosporioides Hu-01

PubMed Central

Peng, Chuyan; Liu, Hongmei; Hu, Meiying; Zhong, Guohua

2012-01-01

Intensive use of chlorpyrifos has resulted in its ubiquitous presence as a contaminant in surface streams and soils. It is thus critically essential to develop bioremediation methods to degrade and eliminate this pollutant from environments. We present here that a new fungal strain Hu-01 with high chlorpyrifos-degradation activity was isolated and identified as Cladosporium cladosporioides based on the morphology and 5.8S rDNA gene analysis. Strain Hu-01 utilized 50 mg·L−1 of chlorpyrifos as the sole carbon of source, and tolerated high concentration of chlorpyrifos up to 500 mg·L−1. The optimum degradation conditions were determined to be 26.8°C and pH 6.5 based on the response surface methodology (RSM). Under these conditions, strain Hu-01 completely metabolized the supplemented chlorpyrifos (50 mg·L−1) within 5 d. During the biodegradation process, transient accumulation of 3,5,6-trichloro-2-pyridinol (TCP) was observed. However, this intermediate product did not accumulate in the medium and disappeared quickly. No persistent accumulative metabolite was detected by gas chromatopraphy-mass spectrometry (GC-MS) analysis at the end of experiment. Furthermore, degradation kinetics of chlorpyrifos and TCP followed the first-order model. Compared to the non-inoculated controls, the half-lives (t 1/2) of chlorpyrifos and TCP significantly reduced by 688.0 and 986.9 h with the inoculum, respectively. The isolate harbors the metabolic pathway for the complete detoxification of chlorpyrifos and its hydrolysis product TCP, thus suggesting the fungus may be a promising candidate for bioremediation of chlorpyrifos-contaminated water, soil or crop. PMID:23056611

Determination of Residues of Diazinon and Chlorpyrifos in Lavender and Rosemary Leaves by Gas Chromatography.

PubMed

Rezk, Mamdouh R; Abd El-Aleem, Abd El-Aziz B; Khalile, Shaban M; El-Naggar, Omneya K

2018-03-01

A sensitive gas chromatographic (GC) GC method has been developed for the determination of diazinon and chlorpyrifos residues in lavender and rosemary leaves. The developed method consists of blending weighed samples of chopped leaves with sodium sulfate as the dehydrating agent, extraction with ethyl acetate, filtration, evaporation with a rotary evaporator, and, finally, capillary GC determination of the pesticides. The recoveries of the method were greater than 90%, and the LOQ was less than 0.1 µg/mL. The method was applied to determine the rate of disappearance of diazinon and chlorpyrifos from lavender and rosemary leaves pretreated with the studied pesticides. The half-life values (t1/2) of diazinon were found to be 5.93 and 6.35 days for lavender and rosemary leaves, respectively, whereas the t1/2 values of chlorpyrifos were calculated to be 7.86 and 9.52 days for lavender and rosemary leaves, respectively. The safe harvest interval (preharvest interval; PHI) was suggested to be after 21 and 24 days for diazinon and chlorpyrifos, respectively. The PHI refers to the amount of time that must lapse (in days) after a pesticide application before a crop can be cut.

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

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. Copyright © 2015 Elsevier Inc. All rights reserved.

Sublethal toxicity of chlorpyrifos to salmonid olfaction after hypersaline acclimation.

PubMed

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

2015-04-01

Salmonid habitats can be impacted by several environmental factors, such as salinization, which can also affect salmonid tolerance to anthropogenic stressors, such as pesticides. Previous studies have shown that hypersaline acclimation enhances the acute toxicity of certain organophosphate and carbamate pesticides to euryhaline fish; however, sublethal impacts have been far less studied. The current study aims to determine how hypersaline acclimation and exposure to the organophosphate chlorpyrifos (CPF) impact salmonid olfaction. Combined acclimation and exposure to CPF was shown to impact rainbow trout olfaction at the molecular, physiological, and behavioral levels. Concurrent exposure to hypersalinity and 0.5μg/L CPF upregulated four genes (chloride intracellular channel 4, G protein zgc:101761, calcium calmodulin dependent protein kinase II delta, and adrenergic alpha 2C receptor) that inhibit olfactory signal transduction. At the physiological level, hypersalinity and chlorpyrifos caused a decrease in sensory response to the amino acid l-serine and the bile salt taurocholic acid. Combined acclimation and exposure also negatively impacted behavior and reduced the avoidance of a predator cue (l-serine). Thus, acclimation to hypersaline conditions and exposure to environmentally relevant concentrations of chlorpyrifos caused an inhibition of olfactory signal transduction leading to a decreased response to odorants and impairment of olfactory mediated behaviors. Copyright © 2015 Elsevier B.V. All rights reserved.

USE OF PHARMACOKINETIC MODEL TO ASSESS CHLORPYRIFOS EXPOSURE AND DOSE IN CHILDREN BASED ON URINARY BIOMARKER MEASUREMENTS

EPA Science Inventory

Chlorpyrifos is a common agricultural insecticide and has been used residentially in the United States until 2000 when this use was restricted by the U.S. Environmental Protection Agency (U.S. EPA). A chlorpyrifos metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) has been found i...

Effect of enrofloxacin and chlorpyrifos on the levels of vitamins A and E in Wistar rats.

PubMed

Spodniewska, Anna; Barski, Dariusz; Giżejewska, Aleksandra

2015-09-01

This study investigates the effects of enrofloxacin and chlorpyrifos, and their combination on vitamin A and E concentrations in the liver of rats. Results of this study indicated a reduction in the contents of vitamins A and E in the liver, which persisted for the entire period of the experiment. Vitamins A and E concentrations were slightly decreased (2-7%) in enrofloxacin-treated rats. In the group of rats intoxicated with chlorpyrifos, a significant decrease in the level of vitamin A was observed up to the 24th hour, and for vitamin E up to the 3rd day from the discontinuation of intoxication with the compounds under study. In the enrofloxacin-chlorpyrifos co-exposure group reduced vitamins A and E level was also noted. The greatest fall in vitamin A level was observed after 3h, while the contents of vitamin E decreased progressively up to the 3rd day. Changes in this group were less pronounced in comparison to the animals intoxicated with chlorpyrifos only. Copyright © 2015 Elsevier B.V. All rights reserved.

Determination of chlorpyrifos and its metabolites in cells and culture media by liquid chromatography-electrospray ionization tandem mass spectrometry.

PubMed

Yang, Xiangkun; Wu, Xian; Brown, Kyle A; Le, Thao; Stice, Steven L; Bartlett, Michael G

2017-09-15

A sensitive method to simultaneously quantitate chlorpyrifos, chlorpyrifos oxon and the detoxified product 3,5,6-trichloro-2-pyridinol (TCP) was developed using either liquid-liquid extraction for culture media samples, or protein precipitation for cell samples. Multiple reaction monitoring in positive ion mode was applied for the detection of chlorpyrifos and chlorpyrifos oxon, and selected ion recording in negative mode was applied to detect TCP. The method provided linear ranges from 5 to 500, 0.2-20 and 20-2000ng/mL for media samples and from 0.5-50, 0.02-2 and 2-200ng/million cells for CPF, CPO and TCP, respectively. The method was validated using selectivity, linearity, precision, accuracy, recovery, stability and dilution tests. All relative standard deviations (RSDs) and relative errors (REs) for QC samples were within 15% (except for LLOQ, within 20%). This method has been successfully applied to study the neurotoxicity and metabolism of chlorpyrifos in a human neuronal model. Copyright © 2017 Elsevier B.V. All rights reserved.

Measurements of Chlorpyrifos Levels in Forager Bees and Comparison with Levels that Disrupt Honey Bee Odor-Mediated Learning Under Laboratory Conditions.

PubMed

Urlacher, Elodie; Monchanin, Coline; Rivière, Coraline; Richard, Freddie-Jeanne; Lombardi, Christie; Michelsen-Heath, Sue; Hageman, Kimberly J; Mercer, Alison R

2016-02-01

Chlorpyrifos is an organophosphate pesticide used around the world to protect food crops against insects and mites. Despite guidelines for chlorpyrifos usage, including precautions to protect beneficial insects, such as honeybees from spray drift, this pesticide has been detected in bees in various countries, indicating that exposure still occurs. Here, we examined chlorpyrifos levels in bees collected from 17 locations in Otago, New Zealand, and compared doses of this pesticide that cause sub-lethal effects on learning performance under laboratory conditions with amounts of chlorpyrifos detected in the bees in the field. The pesticide was detected at 17 % of the sites sampled and in 12 % of the colonies examined. Amounts detected ranged from 35 to 286 pg.bee(-1), far below the LD50 of ~100 ng.bee(-1). We detected no adverse effect of chlorpyrifos on aversive learning, but the formation and retrieval of appetitive olfactory memories was severely affected. Chlorpyrifos fed to bees in amounts several orders of magnitude lower than the LD50, and also lower than levels detected in bees, was found to slow appetitive learning and reduce the specificity of memory recall. As learning and memory play a central role in the behavioral ecology and communication of foraging bees, chlorpyrifos, even in sublethal doses, may threaten the success and survival of this important insect pollinator.

Concentration-Dependent Interactions of the Organophosphates Chlorpyrifos Oxon and Methyl Paraoxon with Human Recombinant Acetylcholinesterase

PubMed Central

Kaushik, R.; Rosenfeld, Clint A.; Sultatos, L.G.

2007-01-01

For many decades it has been thought that oxygen analogs (oxons) of organophosphorus insecticides phosphylate the catalytic site of acetylcholinesterase by a mechanism that follows simple Michaelis-Menten kinetics. More recently, the interactions of at least some oxons have been shown to be far more complex, and likely involve binding of oxons to a second site on acetylcholinesterase that modulates the inhibitory capacity of other oxon molecules at the catalytic site. The current study has investigated the interactions of chlorpyrifos oxon and methyl paraoxon with human recombinant acetylcholinesterase. Both chlorpyrifos oxon and methyl paraoxon were found to have ki’s that change as a function of oxon concentration. Furthermore, 10 nM chlorpyrifos oxon resulted in a transient increase in acetylthiocholine hydrolysis, followed by inhibition. Moreover, in the presence of 100 nM chlorpyrifos oxon, acetylthiocholine was found to influence both the Kd (binding affinity) and k2 (phosphorylation constant) of this oxon. Collectively, these results demonstrate that the interactions of chlorpyrifos oxon and methyl paraoxon with acetylcholinesterase cannot be described by simple Michaelis-Menten kinetics, but instead support the hypothesis that these oxons bind to a secondary site on acetylcholinesterase, leading to activation/inhibition of the catalytic site, depending on the nature of the substrate and inhibitor. Additionally, these data raise questions regarding the adequacy of estimating risk of low levels of insecticide exposure from direct extrapolation of insecticide dose-response curves since the capacity of individual oxon molecules at low oxon levels could be greater than individual oxon molecules in vivo associated with the dose response curve. PMID:17467020

Prenatal Dexamethasone Augments the Neurobehavioral Teratology of Chlorpyrifos: Significance for Maternal Stress and Preterm Labor

PubMed Central

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

2014-01-01

Glucocorticoids are the consensus treatment given in preterm labor and are also elevated by maternal stress; organophosphate exposures are virtually ubiquitous, so human developmental coexposures to these two agents are common. This study explores how prenatal dexamethasone exposure modifies the neurobehavioral teratology of chlorpyrifos, one of the most widely used organophosphates. We administered dexamethasone to pregnant rats on gestational days 17-19 at a standard therapeutic dose (0.2 mg/kg); offspring were then given chlorpyrifos on postnatal days 1-4, at a dose (1 mg/kg) that produces barely-detectable (<10%) inhibition of brain cholinesterase activity. Dexamethasone did not alter brain chlorpyrifos concentrations, nor did either agent alone or in combination affect brain thyroxine levels. Assessments were carried out from adolescence through adulthood encompassing T-maze alternation, Figure-8 maze (locomotor activity, habituation), novelty-suppressed feeding and novel object recognition tests. For behaviors where chlorpyrifos or dexamethasone individually had small effects, the dual exposure produced larger, significant effects that reflected additivity (locomotor activity, novelty-suppressed feeding, novel object recognition). Where the individual effects were in opposite directions or were restricted to only one agent, we found enhancement of chlorpyrifos’ effects by prenatal dexamethasone (habituation). Finally, for behaviors where controls displayed a normal sex difference in performance, the combined treatment either eliminated or reversed the difference (locomotor activity, novel object recognition). Combined exposure to dexamethasone and chlorpyrifos results in a worsened neurobehavioral outcome, providing a proof-of-principle that prenatal glucocorticoids can create a subpopulation with enhanced vulnerability to environmental toxicants. PMID:24177596

REGRESSION MODELS OF RESIDENTIAL EXPOSURE TO CHLORPYRIFOS AND DIAZINON

EPA Science Inventory

This study examines the ability of regression models to predict residential exposures to chlorpyrifos and diazinon, based on the information from the NHEXAS-AZ database. The robust method was used to generate "fill-in" values for samples that are below the detection l...

Response of digestive enzymes and esterases of ecotoxicological concern in earthworms exposed to chlorpyrifos-treated soils.

PubMed

Sanchez-Hernandez, Juan C; Ríos, Juan Manuel; Attademo, Andrés M

2018-03-01

Assessment of organophosphorus (OP) pesticide exposure in non-target organisms rarely involves non-neural molecular targets. Here we performed a 30-d microcosm experiment with Lumbricus terrestris to determine whether the activity of digestive enzymes (phosphatase, β-glucosidase, carboxylesterase and lipase) was sensitive to chlorpyrifos (5 mg kg -1 wet soil). Likewise, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were measured in the wall muscle and gastrointestinal tissues as indicators of OP exposure. Chlorpyrifos inhibited the acid phosphatase (34% of controls), carboxylesterase (25.6%) and lipase activities (31%) in the gastrointestinal content. However, in the gastrointestinal tissue, only the carboxylesterase and lipase activities were significantly depressed (42-67% carboxylesterase inhibition in the foregut and crop/gizzard, and 15% lipase inhibition in the foregut). Chlorpyrifos inhibited the activity of both cholinesterases in the gastrointestinal tissues, whereas the AChE activity was affected in the wall muscle. These results suggested chlorpyrifos was widely distributed throughout the earthworm body after 30 d of incubation. Interestingly, we found muscle carboxylesterase activity strongly inhibited (92% of control) compared with that detected in the gastrointestinal tissues of the same OP-exposed individuals. This finding was explained by the occurrence of pesticide-resistant esterases in the gastrointestinal tissues, which were evidenced by zymography. Our results suggest that digestive processes of L. terrestris may be altered by chlorpyrifos, as a consequence of the inhibitory action of the insecticide on some digestive enzymes.

Toward Serotonin Fluorescent False Neurotransmitters: Development of Fluorescent Dual Serotonin and Vesicular Monoamine Transporter Substrates for Visualizing Serotonin Neurons.

PubMed

Henke, Adam; Kovalyova, Yekaterina; Dunn, Matthew; Dreier, Dominik; Gubernator, Niko G; Dincheva, Iva; Hwu, Christopher; Šebej, Peter; Ansorge, Mark S; Sulzer, David; Sames, Dalibor

2018-05-16

Ongoing efforts in our laboratories focus on design of optical reporters known as fluorescent false neurotransmitters (FFNs) that enable the visualization of uptake into, packaging within, and release from individual monoaminergic neurons and presynaptic sites in the brain. Here, we introduce the molecular probe FFN246 as an expansion of the FFN platform to the serotonergic system. Combining the acridone fluorophore with the ethylamine recognition element of serotonin, we identified FFN54 and FFN246 as substrates for both the serotonin transporter and the vesicular monoamine transporter 2 (VMAT2). A systematic structure-activity study revealed the basic structural chemotype of aminoalkyl acridones required for serotonin transporter (SERT) activity and enabled lowering the background labeling of these probes while maintaining SERT activity, which proved essential for obtaining sufficient signal in the brain tissue (FFN246). We demonstrate the utility of FFN246 for direct examination of SERT activity and SERT inhibitors in 96-well cell culture assays, as well as specific labeling of serotonergic neurons of the dorsal raphe nucleus in the living tissue of acute mouse brain slices. While we found only minor FFN246 accumulation in serotonergic axons in murine brain tissue, FFN246 effectively traces serotonin uptake and packaging in the soma of serotonergic neurons with improved photophysical properties and loading parameters compared to known serotonin-based fluorescent tracers.

The common insecticides cyfluthrin and chlorpyrifos alter the expression of a subset of genes with diverse functions in primary human astrocytes.

PubMed

Mense, Sarah M; Sengupta, Amitabha; Lan, Changgui; Zhou, Mei; Bentsman, Galina; Volsky, David J; Whyatt, Robin M; Perera, Frederica P; Zhang, Li

2006-09-01

Given the widespread use of insecticides in the environment, it is important to perform studies evaluating their potential effects on humans. Organophosphate insecticides, such as chlorpyrifos, are being phased out; however, the use of pyrethroids in household pest control is increasing. While chlorpyrifos is relatively well studied, much less is known about the potential neurotoxicity of cyfluthrin and other pyrethroids. To gain insights into the neurotoxicity of cyfluthrin, we compared and evaluated the toxicity profiles of chlorpyrifos and cyfluthrin in primary human fetal astrocytes. We found that at the same concentrations, cyfluthrin exerts as great as, or greater toxic effects on the growth, survival, and proper functioning of human astrocytes. By using microarray gene expression profiling, we systematically identified and compared the potential molecular targets of chlorpyrifos and cyfluthrin, at a genome-wide scale. We found that chlorpyrifos and cyfluthrin affect a similar number of transcripts. These targets include molecular chaperones, signal transducers, transcriptional regulators, transporters, and those involved in behavior and development. Further computational and biochemical analyses show that cyfluthrin and chlorpyrifos upregulate certain targets of the interferon-gamma and insulin-signaling pathways and that they increase the protein levels of activated extracellular signal-regulated kinase 1/2, a key component of insulin signaling; interleukin 6, a key inflammatory mediator; and glial fibrillary acidic protein, a marker of inflammatory astrocyte activation. These results suggest that inflammatory activation of astrocytes might be an important mechanism underlying neurotoxicity of both chlorpyrifos and cyfluthrin.

Artificial sweat enhances dermal transfer of chlorpyrifos from treated nylon carpet fibers.

PubMed

Williams, Ryan L; Reifenrath, William G; Krieger, Robert I

2005-01-01

The dermal transfer and absorption of 14C-ring-chlorpyrifos from nylon carpet fibers was measured in skin penetration-evaporation cells with excised pig skin. Prior to application, synthetic sweat was applied to skin in half of the cells. Radioactivity was measured in receptor fluid, dermis, epidermis, tape stripping samples, and vapor trap samples during a 24-h period. The sum of radiolabel recovered from the dermis and receptor fluid represented the absorbed dose. There was no significant difference (p > 0.05) in percutaneous absorption between cells that received the synthetic sweat application and "dry" cells (1.3 +/- 0.3% of applied dose). There was significantly more (p < 0.05) radiolabel recovered from tape stripping (5.4 +/- 2.1 vs. 2.8 +/- 0.6%) and in the epidermis (4.5 +/- 0.8 vs. 3.1 +/- 0.3%) from cells that received the synthetic sweat application, which indicated synthetic sweat facilitated transfer of chlorpyrifos from a treated substrate to the skin surface. The measured value for percutaneous absorption of chlorpyrifos agreed with the value predicted from an empirical model previously developed for nitro compound-containing soil.

Adaptation of the biobed composition for chlorpyrifos degradation to Southern Europe conditions.

PubMed

Coppola, Laura; Castillo, Maria d P; Monaci, Elga; Vischetti, Costantino

2007-01-24

Biobeds developed in Sweden bind and degrade pesticides from point sources. The objective of this work was to adapt the biobed to Italian operating conditions, for example, to identify organic materials as effective as those in the original Swedish composition. The capacity of urban and garden composts alone or mixed with citrus peel or straw to degrade chlorpyrifos and its metabolite TCP was compared to the typical Swedish biomix consisting of straw, peat, and soil. A tendency for higher 14C-chlorpyrifos mineralization and lower TCP levels was observed in the biomixes with garden compost alone or amended with straw. In a second trial, a high correlation of lower TCP with increasing levels of straw in typical Swedish biomixes was observed. Straw stimulates production of lignin-degrading enzymes such as manganese peroxidase (MnP), and further trials with pure MnP showed that this enzyme degrades TCP. Materials with an active lignin-degrading microflora are a prerequisite for effective dissipation of chlorpyrifos and non-accumulation of TCP. Thus, lignocellulosic materials as straw and garden composts should be present in biomixes to be used under Italian conditions.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaushik, R.; Rosenfeld, Clint A.; Sultatos, L.G.

2007-06-01

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

[Preliminary investigation of four anopheles larvae samples susceptibility to chlorpyrifos in Tunisia].

PubMed

Krida, G; Bouattour, A; Rhaim, A; el Kebir, A; Jlidi, R

1998-01-01

Larvae susceptibility to chlorpyrifos is studied on four Tunisian Anopheles larvas samples: Anopheles labranchiae from Rades (South of Tunis) and Menchar (region of Beja), in the North of Tunisia, A. sergentii from Meknassy and A. multicolor from Sidi Bouzid, both in the Centre of Tunisia. The test results of larvae susceplibility indicate that the LC50 and the LC95 values are less than 0.002 and 0.02 mg l-1 respectively and their 95% confidence limits overlap. We also notice that the studied samples show the same susceptibility to chlorpyrifos. The results can be used as a base data further studies on the susceptibility of Anopheles to chemical insecticides.

Physicochemical Characteristics and Slow Release Performances of Chlorpyrifos Encapsulated by Poly(butyl acrylate-co-styrene) with the Cross-Linker Ethylene Glycol Dimethacrylate.

PubMed

Wang, Yu; Gao, Zideng; Shen, Feng; Li, Yang; Zhang, Sainan; Ren, Xueqin; Hu, Shuwen

2015-06-03

Chlorpyrifos' application and delivery to the target substrate needs to be controlled to improve its use. Herein, poly(butyl acrylate-co-styrene) (poly(BA/St)) and poly(BA/St/ethylene glycol dimethacrylate (EGDMA)) microcapsules loaded with chlorpyrifos as a slow release formulation were prepared by emulsion polymerization. The effects of structural characteristics on the chlorpyrifos microcapsule particle size, entrapment rate (ER), pesticide loading (PL), and release behaviors in ethyl alcohol were investigated. Fourier transform infrared and thermogravimetric analysis confirmed the successful entrapment of chlorpyrifos. The ER and PL varied with the BA/St monomer ratio, chlorpyrifos/monomer core-to-shell ratio, and EGDMA cross-linker content with consequence that suitable PL was estimated to be smaller than 3.09% and the highest ER was observed as 96.74%. The microcapsule particle size (88.36-101.8 nm) remained mostly constant. The extent of sustainable release decreased with increasing content of BA, St, or chlorpyrifos in the oil phase. Specifically, an adequate degree of cross-linking with EGMDA (0.5-2.5%) increased the extent of sustainable release considerably. However, higher levels of cross-linking with EGDMA (5-10%) reduced the extent of sustainable release. Chlorpyrifos release from specific microcapsules (monomer ratio 1:2 with 0.5% EGDMA or 5 g chlopyrifos) tended to be a diffusion-controlled process, while for others, the kinetics probably indicated the initial rupture release.

Serotonin Receptors in Hippocampus

PubMed Central

Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

2012-01-01

Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system. PMID:22629209

Effect of serotonin on the expression of antigens and DNA levels in Yersinia pestis cells with different plasmid content

NASA Astrophysics Data System (ADS)

Klueva, Svetlana N.; Korsukov, Vladimir N.; Schukovskaya, Tatyana N.; Kravtsov, Alexander L.

2004-08-01

Using flow cytometry (FCM) the influence of exogenous serotonin on culture growth, DNA content and fluorescence intensity of cells binding FITC-labelled plague polyclonal immunoglobulins was studied in Yersinia pestis EV (pFra+, pCad+, pPst+), Yersinia pestis KM218 (pFra-, pCad-, pPst-), Yersinia pestis KM 216 (pFra-, pCad-, pPst+). The results have been obtained by FCM showed serotonin accelerated Yersinia pestis EV (pFra+, pCad+, pPst+), Yersinia pestis KM218 (pFra-, pCad-, pPst-) culture growth during cultivation in Hottinger broth pH 7.2 at 28°C at concentration of 10-5 M. The presence of 10-5 M serotonin in nutrient broth could modulate DNA content in 37°C growing population of plague microbe independently of their plasmid content. Serotonin have been an impact on the distribution pattern of the cells according to their phenotypical characteristics, which was reflected in the levels of population heterogeneity in the intensity of specific immunofluorescence determined by FMC.

What Gene Mutations Affect Serotonin in Mice?

PubMed

Tenpenny, Richard C; Commons, Kathryn G

2017-05-17

Although serotonin neurotransmission has been implicated in several neurodevelopmental and psychological disorders, the factors that drive dysfunction of the serotonin system are poorly understood. Current research regarding the serotonin system revolves around its dysfunction in neuropsychiatric disorders, but there is no database collating genetic mutations that result in serotonin abnormalities. To bridge this gap, we developed a list of genes in mice that, when perturbed, result in altered levels of serotonin either in brain or blood. Due to the intrinsic limitations of search, the current list should be considered a preliminary subset of all relevant cases. Nevertheless, it offered an opportunity to gain insight into what types of genes have the potential to impact serotonin by using gene ontology (GO). This analysis found that genes associated with monoamine metabolism were more often associated with increases in brain serotonin than decreases. Speculatively, this could be because several pathways (and therefore many genes) are responsible for the clearance and metabolism of serotonin whereas only one pathway (and therefore fewer genes) is directly involved in the synthesis of serotonin. Another contributor could be cross talk between monoamine systems such as dopamine. In contrast, genes that were associated with decreases in brain serotonin were more likely linked to a developmental process. Sensitivity of serotonin neurons to developmental perturbations could be due to their complicated neuroanatomy or possibly they may be negatively regulated by dysfunction of their innervation targets. Thus, these observations suggest hypotheses regarding the mechanisms underlying the vulnerability of brain serotonin neurotransmission.

Regulation of Bone Metabolism by Serotonin.

PubMed

Lavoie, Brigitte; Lian, Jane B; Mawe, Gary M

2017-01-01

The processes of bone growth and turnover are tightly regulated by the actions of various signaling molecules, including hormones, growth factors, and cytokines. Imbalances in these processes can lead to skeletal disorders such as osteoporosis or high bone mass disease. It is becoming increasingly clear that serotonin can act through a number of mechanisms, and at different locations in the body, to influence the balance between bone formation and resorption. Its actions on bone metabolism can vary, based on its site of synthesis (central or peripheral) as well as the cells and subtypes of receptors that are activated. Within the central nervous system, serotonergic neurons act via the hypothalamus to suppress sympathetic input to the bone. Since sympathetic input inhibits bone formation, brain serotonin has a net positive effect on bone growth. Gut-derived serotonin is thought to inhibit bone growth by attenuating osteoblast proliferation via activation of receptors on pre-osteoblasts. There is also evidence that serotonin can be synthesized within the bone and act to modulate bone metabolism. Osteoblasts, osteoclasts, and osteocytes all have the machinery to synthesize serotonin, and they also express the serotonin-reuptake transporter (SERT). Understanding the roles of serotonin in the tightly balanced system of bone modeling and remodeling is a clinically relevant goal. This knowledge can clarify bone-related side effects of drugs that affect serotonin signaling, including serotonin-specific reuptake inhibitors (SSRIs) and receptor agonists and antagonists, and it can potentially lead to therapeutic approaches for alleviating bone pathologies.

Effects of chlorpyrifos and chlorantraniliprole on fermentation quality of alfalfa (Medicago sativa L.) silage inoculated with or without Lactobacillus plantarum LP.

PubMed

Zhang, Qing; Yu, Zhu; Wang, Xianguo; Na, Risu

2017-03-01

The effects of pesticides and Lactobacillus plantarum (LP) on fermentation quality of alfalfa (Medicago sativa L.) silage were investigated. Chlorpyrifos and chlorantraniliprole were sprayed on the surface of alfalfa plants at 658.6 and 45.0 g active ingredient/ha, respectively. Alfalfa plants were harvested on day 5 post-application and ensiled with or without LP. Chlorpyrifos and chlorantraniliprole decreased the yeast count of alfalfa material (P < 0.05). Both pesticides increased the butyric acid content of alfalfa silage (P < 0.001). Chlorpyrifos increased pH and decreased lactic acid, acetic acid and short-chain fatty acid contents (P < 0.05). LP decreased pH and butyric acid content, and increased lactic acid and short-chain fatty acid contents of alfalfa silage treated with pesticides (P < 0.05). LP increased the concentration of chlorpyrifos residue in alfalfa silage (P < 0.05). Chlorpyrifos and chlorantraniliprole affected the microbial communities of the material before ensiling, especially coliform bacteria and yeast; the two pesticide residues were reduced after the fermentation of alfalfa silage and affected the fermentation process, whereas LP improved the fermentation quality of pesticides-contaminated alfalfa silage and slowed down the dissipation of chlorpyrifos. © 2016 Japanese Society of Animal Science.

Phenotypic malignant changes and untargeted lipidomic analysis of long-term exposed prostate cancer cells to endocrine disruptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bedia, Carmen, E-mail: carmen.bedia@idaea.csic.es; Dalmau, Núria, E-mail: nuria.dalmau@idaea.csic.es; Jaumot, Joaquim, E-mail: joaquim.jaumot@idaea.csic.es

2015-07-15

Endocrine disruptors (EDs) are a class of environmental toxic molecules able to interfere with the normal hormone metabolism. Numerous studies involve EDs exposure to initiation and development of cancers, including prostate cancer. In this work, three different EDs (aldrin, aroclor 1254 and chlorpyrifos (CPF)) were investigated as potential inducers of a malignant phenotype in DU145 prostate cancer cells after a chronic exposure. Epithelial to mesenchymal transition (EMT) induction, proliferation, migration, colony formation and release of metalloproteinase 2 (MMP-2) were analyzed in 50-day exposed cells to the selected EDs. As a result, aldrin and CPF exposure led to an EMT inductionmore » (loss of 16% and 14% of E-cadherin levels, respectively, compared to the unexposed cells). Aroclor and CPF presented an increased migration (134% and 126%, respectively), colony formation (204% and 144%, respectively) and MMP-2 release (137% in both cases) compared to the unexposed cells. An untargeted lipidomic analysis was performed to decipher the lipids involved in the observed transformations. As general results, aldrin exposure showed a global decrease in phospholipids and sphingolipids, and aroclor and CPF showed an increase of certain phospholipids, glycosphingolipids as well as a remarkable increase of some cardiolipin species. Furthermore, the three exposures resulted in an increase of some triglyceride species. In conclusion, some significant changes in lipids were identified and thus we postulate that some lipid compounds and lipid metabolic pathways could be involved in the acquisition of the malignant phenotype in exposed prostate cancer cells to the selected EDs. - Highlights: • Aldrin, aroclor and chlorpyrifos induced an aggressive phenotype in DU145 cells. • An untargeted lipidomic analysis has been performed on chronic exposed cells. • Lipidomic results showed changes in specific lipid species under chronic exposure. • These lipids may have a role in

Chlorpyrifos Accumulation Patterns for Child-Accessible Surfaces and Objects and Urinary Metabolite Excretion by Children for 2 Weeks after Crack-and-Crevice Application

PubMed Central

Hore, Paromita; Robson, Mark; Freeman, Natalie; Zhang, Jim; Wartenberg, Daniel; Özkaynak, Halûk; Tulve, Nicolle; Sheldon, Linda; Needham, Larry; Barr, Dana; Lioy, Paul J.

2005-01-01

The Children’s Post-Pesticide Application Exposure Study (CPPAES) was conducted to look at the distribution of chlorpyrifos within a home environment for 2 weeks after a routine professional crack-and-crevice application and to determine the amount of the chlorpyrifos that is absorbed by a child living within the home. Ten residential homes with a 2- to 5-year-old child in each were selected for study, and the homes were treated with chlorpyrifos. Pesticide measurements were made from the indoor air, indoor surfaces, and plush toys. In addition, periodic morning urine samples were collected from each of the children throughout the 2-week period. We analyzed the urine samples for 3,5,6-trichloropyridinol, the primary urinary metabolite of chlorpyrifos, and used the results to estimate the children’s absorbed dose. Average chlorpyrifos levels in the indoor air and surfaces were 26 (pretreatment)/120 (posttreatment) ng/m3 and 0.48 (pretreatment)/2.8 (posttreatment) ng/cm2, respectively, reaching peak levels between days 0 and 2; subsequently, concentrations decreased throughout the 2-week period. Chlorpyrifos in/on the plush toys ranged from 7.3 to 1,949 ng/toy postapplication, with concentrations increasing throughout the 2-week period, demonstrating a cumulative adsorption/absorption process indoors. The daily amount of chlorpyrifos estimated to be absorbed by the CPPAES children postapplication ranged from 0.04 to 4.8 μg/kg/day. During the 2 weeks after the crack-and-crevice application, there was no significant increase in the amount of chlorpyrifos absorbed by the CPPAES children. PMID:15687060

Chlorpyrifos accumulation patterns for child-accessible surfaces and objects and urinary metabolite excretion by children for 2 weeks after crack-and-crevice application.

PubMed

Hore, Paromita; Robson, Mark; Freeman, Natalie; Zhang, Jim; Wartenberg, Daniel; Ozkaynak, Halûk; Tulve, Nicolle; Sheldon, Linda; Needham, Larry; Barr, Dana; Lioy, Paul J

2005-02-01

The Children's Post-Pesticide Application Exposure Study (CPPAES) was conducted to look at the distribution of chlorpyrifos within a home environment for 2 weeks after a routine professional crack-and-crevice application and to determine the amount of the chlorpyrifos that is absorbed by a child living within the home. Ten residential homes with a 2- to 5-year-old child in each were selected for study, and the homes were treated with chlorpyrifos. Pesticide measurements were made from the indoor air, indoor surfaces, and plush toys. In addition, periodic morning urine samples were collected from each of the children throughout the 2-week period. We analyzed the urine samples for 3,5,6-trichloropyridinol, the primary urinary metabolite of chlorpyrifos, and used the results to estimate the children's absorbed dose. Average chlorpyrifos levels in the indoor air and surfaces were 26 (pretreatment)/120 (posttreatment) ng/m3 and 0.48 (pretreatment)/2.8 (posttreatment) ng/cm2, respectively, reaching peak levels between days 0 and 2; subsequently, concentrations decreased throughout the 2-week period. Chlorpyrifos in/on the plush toys ranged from 7.3 to 1,949 ng/toy postapplication, with concentrations increasing throughout the 2-week period, demonstrating a cumulative adsorption/absorption process indoors. The daily amount of chlorpyrifos estimated to be absorbed by the CPPAES children postapplication ranged from 0.04 to 4.8 microg/kg/day. During the 2 weeks after the crack-and-crevice application, there was no significant increase in the amount of chlorpyrifos absorbed by the CPPAES children.

Application of a Mathematical Model to Describe the Effects of Chlorpyrifos on Caenorhabditis elegans Development

PubMed Central

Boyd, Windy A.; Smith, Marjolein V.; Kissling, Grace E.; Rice, Julie R.; Snyder, Daniel W.; Portier, Christopher J.; Freedman, Jonathan H.

2009-01-01

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

Histopathological effects, responses of oxidative stress, inflammation, apoptosis biomarkers and alteration of gene expressions related to apoptosis, oxidative stress, and reproductive system in chlorpyrifos-exposed common carp (Cyprinus carpio L.).

PubMed

Altun, Serdar; Özdemir, Selçuk; Arslan, Harun

2017-11-01

In this study, we aimed to identify the toxic effects of chlorpyrifos exposure on the tissues of common carp. For this purpose, we evaluated histopathological changes in the brain, gills, liver, kidney, testis, and ovaries after 21 days of chlorpyrifos exposure. Activation of 8-OHdG, cleaved caspase-3, and iNOS were assesed by immunofluorescence assay in chlorpyrifos-exposed brain and liver tissue. Additionally, we measured the expression levels of caspase-3, caspase-8, iNOS, MT1, CYP1A, and CYP3A genes in chlorpyrifos-exposed brain tissue, as well as the expression levels of FSH and LH genes in chlorpyrifos-exposed ovaries, using qRT-PCR. We observed severe histopathological lesions, including inflammation, degeneration, necrosis, and hemorrhage, in the evaluated tissues of common carp after both high and low levels of exposure to chlorpyrifos. We detected strong and diffuse signs of immunofluorescence reaction for 8-OHdG, iNOS, and cleaved caspase-3 in the chlorpyrifos-exposed brain and liver tissues. Furthermore, we found that chlorpyrifos exposure significantly upregulated the expressions of caspase-3, caspase-8, iNOS, and MT1, and also moderately upregulated CYP1A and CYP3A in the brain tissue of exposed carp. We also noted downregulation of FSH and LH gene expressions in chlorpyrifos-exposed ovary tissues. Based on our results, chlorpyrifos toxication caused crucial histopathological lesions in vital organs, induced oxidative stress, inflammation, and apoptosis in liver and brain tissues, and triggered reproductive sterility in common carp. Therefore, we can propose that chlorpyrifos toxication is highly dangerous to the health of common carp. Moreover, chlorpyrifos pollution in the water could threaten the common carp population. Use of chlorpyrifos should be restricted, and aquatic systems should be monitored for chlorpyrifos pollution. Copyright © 2017 Elsevier Ltd. All rights reserved.

Is domestication driven by reduced fear of humans? Boldness, metabolism and serotonin levels in divergently selected red junglefowl (Gallus gallus).

PubMed

Agnvall, Beatrix; Katajamaa, Rebecca; Altimiras, Jordi; Jensen, Per

2015-09-01

Domesticated animals tend to develop a coherent set of phenotypic traits. Tameness could be a central underlying factor driving this, and we therefore selected red junglefowl, ancestors of all domestic chickens, for high or low fear of humans during six generations. We measured basal metabolic rate (BMR), feed efficiency, boldness in a novel object (NO) test, corticosterone reactivity and basal serotonin levels (related to fearfulness) in birds from the fifth and sixth generation of the high- and low-fear lines, respectively (44-48 individuals). Corticosterone response to physical restraint did not differ between selection lines. However, BMR was higher in low-fear birds, as was feed efficiency. Low-fear males had higher plasma levels of serotonin and both low-fear males and females were bolder in an NO test. The results show that many aspects of the domesticated phenotype may have developed as correlated responses to reduced fear of humans, an essential trait for successful domestication. © 2015 The Author(s).

Brain serotonin content regulates the manifestation of tramadol-induced seizures in rats: disparity between tramadol-induced seizure and serotonin syndrome.

PubMed

Fujimoto, Yohei; Funao, Tomoharu; Suehiro, Koichi; Takahashi, Ryota; Mori, Takashi; Nishikawa, Kiyonobu

2015-01-01

Tramadol-induced seizures might be pathologically associated with serotonin syndrome. Here, the authors investigated the relationship between serotonin and the seizure-inducing potential of tramadol. Two groups of rats received pretreatment to modulate brain levels of serotonin and one group was treated as a sham control (n = 6 per group). Serotonin modulation groups received either para-chlorophenylalanine or benserazide + 5-hydroxytryptophan. Serotonin, dopamine, and histamine levels in the posterior hypothalamus were then measured by microdialysis, while simultaneously infusing tramadol until seizure onset. In another experiment, seizure threshold with tramadol was investigated in rats intracerebroventricularly administered with either a serotonin receptor antagonist (methysergide) or saline (n = 6). Pretreatment significantly affected seizure threshold and serotonin fluctuations. The threshold was lowered in para-chlorophenylalanine group and raised in benserazide + 5-hydroxytryptophan group (The mean ± SEM amount of tramadol needed to induce seizures; sham: 43.1 ± 4.2 mg/kg, para-chlorophenylalanine: 23.2 ± 2.8 mg/kg, benserazide + 5-hydroxytryptophan: 59.4 ± 16.5 mg/kg). Levels of serotonin at baseline, and their augmentation with tramadol infusion, were less in the para-chlorophenylalanine group and greater in the benserazide + 5-hydroxytryptophan group. Furthermore, seizure thresholds were negatively correlated with serotonin levels (correlation coefficient; 0.71, P < 0.01), while intracerebroventricular methysergide lowered the seizure threshold (P < 0.05 vs. saline). The authors determined that serotonin-reduced rats were predisposed to tramadol-induced seizures, and that serotonin concentrations were negatively associated with seizure thresholds. Moreover, serotonin receptor antagonism precipitated seizure manifestation, indicating that tramadol-induced seizures are distinct from serotonin syndrome.

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

USGS Publications Warehouse

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

2002-01-01

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

Altered serotonin physiology in human breast cancers favors paradoxical growth and cell survival

PubMed Central

2009-01-01

Introduction The breast microenvironment can either retard or accelerate the events associated with progression of latent cancers. However, the actions of local physiological mediators in the context of breast cancers are poorly understood. Serotonin (5-HT) is a critical local regulator of epithelial homeostasis in the breast and other organs. Herein, we report complex alterations in the intrinsic mammary gland serotonin system of human breast cancers. Methods Serotonin biosynthetic capacity was analyzed in human breast tumor tissue microarrays using immunohistochemistry for tryptophan hydroxylase 1 (TPH1). Serotonin receptors (5-HT1-7) were analyzed in human breast tumors using the Oncomine database. Serotonin receptor expression, signal transduction, and 5-HT effects on breast cancer cell phenotype were compared in non-transformed and transformed human breast cells. Results In the context of the normal mammary gland, 5-HT acts as a physiological regulator of lactation and involution, in part by favoring growth arrest and cell death. This tightly regulated 5-HT system is subverted in multiple ways in human breast cancers. Specifically, TPH1 expression undergoes a non-linear change during progression, with increased expression during malignant progression. Correspondingly, the tightly regulated pattern of 5-HT receptors becomes dysregulated in human breast cancer cells, resulting in both ectopic expression of some isoforms and suppression of others. The receptor expression change is accompanied by altered downstream signaling of 5-HT receptors in human breast cancer cells, resulting in resistance to 5-HT-induced apoptosis, and stimulated proliferation. Conclusions Our data constitutes the first report of direct involvement of 5-HT in human breast cancer. Increased 5-HT biosynthetic capacity accompanied by multiple changes in 5-HT receptor expression and signaling favor malignant progression of human breast cancer cells (for example, stimulated proliferation

Altered serotonin physiology in human breast cancers favors paradoxical growth and cell survival.

PubMed

Pai, Vaibhav P; Marshall, Aaron M; Hernandez, Laura L; Buckley, Arthur R; Horseman, Nelson D

2009-01-01

The breast microenvironment can either retard or accelerate the events associated with progression of latent cancers. However, the actions of local physiological mediators in the context of breast cancers are poorly understood. Serotonin (5-HT) is a critical local regulator of epithelial homeostasis in the breast and other organs. Herein, we report complex alterations in the intrinsic mammary gland serotonin system of human breast cancers. Serotonin biosynthetic capacity was analyzed in human breast tumor tissue microarrays using immunohistochemistry for tryptophan hydroxylase 1 (TPH1). Serotonin receptors (5-HT1-7) were analyzed in human breast tumors using the Oncomine database. Serotonin receptor expression, signal transduction, and 5-HT effects on breast cancer cell phenotype were compared in non-transformed and transformed human breast cells. In the context of the normal mammary gland, 5-HT acts as a physiological regulator of lactation and involution, in part by favoring growth arrest and cell death. This tightly regulated 5-HT system is subverted in multiple ways in human breast cancers. Specifically, TPH1 expression undergoes a non-linear change during progression, with increased expression during malignant progression. Correspondingly, the tightly regulated pattern of 5-HT receptors becomes dysregulated in human breast cancer cells, resulting in both ectopic expression of some isoforms and suppression of others. The receptor expression change is accompanied by altered downstream signaling of 5-HT receptors in human breast cancer cells, resulting in resistance to 5-HT-induced apoptosis, and stimulated proliferation. Our data constitutes the first report of direct involvement of 5-HT in human breast cancer. Increased 5-HT biosynthetic capacity accompanied by multiple changes in 5-HT receptor expression and signaling favor malignant progression of human breast cancer cells (for example, stimulated proliferation, inappropriate cell survival). This occurs

Serotonin syndrome: a complex but easily avoidable condition.

PubMed

Dvir, Yael; Smallwood, Patrick

2008-01-01

Serotonin syndrome is a potentially life-threatening adverse drug reaction caused by excessive serotonergic agonism in central and peripheral nervous system serotonergic receptors (Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352:1112-1120). Symptoms are characterized by a triad of neuron-excitatory features, which include (a) neuromuscular hyperactivity -- tremor, clonus, myoclonus, hyperreflexia and, in advanced stages, pyramidal rigidity; (b) autonomic hyperactivity -- diaphoresis, fever, tachycardia and tachypnea; (c) altered mental status -- agitation, excitement and, in advanced stages, confusion (Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. Br J Anaesth 2005;95:434-441). It arises when pharmacological agents increase serotonin neurotransmission at postsynaptic 5-hydroxytryptamine 1A and 5-hydroxytryptamine 2A receptors through increased serotonin synthesis, decreased serotonin metabolism, increased serotonin release, inhibition of serotonin reuptake or direct agonism of the serotonin receptors (Houlihan D. Serotonin syndrome resulting from coadministration of tramodol, venlafaxine, and mirtazapine. Ann Pharmacother 2004;38:411-413). The etiology is often the result of therapeutic drug use, intentional overdosing of serotonergic agents or complex interactions between drugs that directly or indirectly modulate the serotonin system (Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352:1112-1120). Due to the increasing availability of agents with serotonergic activity, physicians need to more aware of serotonin syndrome. The following case highlights the complex nature in which serotonin syndrome can arise, as well as the proper recognition and treatment of a potentially life-threatening yet easily avoidable condition.

Reference values for acetyl and butyrylcholinesterases in cattle under actual management conditions, hepatic and renal function by application of chlorpyrifos.

PubMed

Ferré, Daniela M; Lentini, Valeria R; Romano, R Raquel; Ludueña, Hector R; Jotallán, Paola J; Gorla, Nora B M

2018-03-04

Chlorpyrifos is an anticholinesterase organophosphate insecticide widely used in Argentina in the production of food derived from animal, fruit and horticultural origin and is reported as a residue within these products. Local reference values for acetyl and butyrylcholinesterase were determined in Aberdeen Angus bovine and cross bred cattle (n = 25), a requirement to be able to evaluate toxicity of commercial organophosphate and carbamate formulations. The activity of cholinesterase enzymes presented an overall mean of 2,183.00 ± 485.6 IU L -1 for erythrocyte acetylcholinesterase and 203.1 ± 42.06 IU L -1 for plasma butyrylcholinesterase, which are used as reference values for meat steers within a system of intensive production in a semi-arid region. The toxic potential of chlorpyrifos in steers of the same breeds (n = 12) was assessed applying chlorpyrifos 15.00% Tipertox® in a single therapeutic dose of 7.50 mg kg -1 by topical route. Prior to application and then on day 1 and day 21 post-application, both blood cholinesterases, serum chlorpyrifos concentration by ultra-high resolution liquid chromatography with mass detector, analysis of blood counts, total proteins, liver enzymes, urea and creatinine were evaluated. The mean plasma concentration of chlorpyrifos was 27.90 ug L -1 at 24 h. The findings indicate that the therapeutic treatment of castrated male bovines treated with chlorpyrifos, applied by pour-on according to the manufacturer's instructions, does not cause changes in the variables evaluated.

Chlorpyrifos- and chlorpyrifos oxon-induced neurite retraction in pre-differentiated N2a cells is associated with transient hyperphosphorylation of neurofilament heavy chain and ERK 1/2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sindi, Ramya A., E-mail: ramya.sindi2010@my.ntu.ac

Chlorpyrifos (CPF) and CPF-oxon (CPO) are known to inhibit neurite outgrowth but little is known about their ability to induce neurite retraction in differentiating neuronal cells. The aims of this study were to determine the ability of these compounds to destabilize neurites and to identify the key molecular events involved. N2a cells were induced to differentiate for 20 h before exposure to CPF or CPO for 2–8 h. Fixed cell monolayers labeled with carboxyfluorescein succinimidyl ester or immunofluorescently stained with antibodies to tubulin (B512) or phosphorylated neurofilament heavy chain (Ta51) showed time- and concentration-dependent reductions in numbers and length ofmore » axon-like processes compared to the control, respectively, retraction of neurites being observed within 2 h of exposure by live cell imaging. Neurofilament disruption was also observed in treated cells stained by indirect immunofluorescence with anti-phosphorylated neurofilament heavy chain (NFH) monoclonal antibody SMI34, while the microtubule network was unaffected. Western blotting analysis revealed transiently increased levels of reactivity of Ta51 after 2 h exposure and reduced levels of reactivity of the same antibody following 8 h treatment with both compounds, whereas reactivity with antibodies to anti-total NFH or anti-tubulin was not affected. The alteration in NFH phosphorylation at 2 h exposure was associated with increased activation of extracellular signal-regulated protein kinase ERK 1/2. However, increased levels of phosphatase activity were observed following 8 h exposure. These findings suggest for the first time that organophosphorothionate pesticide-induced neurite retraction in N2a cells is associated with transient increases in NFH phosphorylation and ERK1/2 activation. - Highlights: • Chlorpyrifos and chlorpyrifos oxon induced rapid neurite retraction in N2a cells. • This occurred following transient hyperphosphorylation of ERK 1/2. • It was concomitant

Individual and combined effect of chlorpyrifos and cypermethrin on reproductive system of adult male albino rats.

PubMed

Alaa-Eldin, Eman Ahmad; El-Shafei, Dalia Abdallah; Abouhashem, Nehal S

2017-01-01

Commercial mixtures of chlorpyrifos and cypermethrin pesticides are widely used to enhance the toxic effects of cypermethrin on target insects. So, the purpose of the current study was to evaluate the individual and combined toxic effects of chlorpyrifos (CPF) and cypermethrin (CYP) on reproductive system of adult male albino rats. Forty adult male albino rats were randomized into main four groups: group I (control group) included 16 rats, subdivided into negative and positive control; group II (eight rats) received chlorpyrifos 6.75 mg/kg b.w./orally∕daily); group III (eight rats) (received cypermethrin 12.5 mg/kg b.w./orally∕daily); and group IV (eight rats) (received chlorpyrifos and cypermethrin at the same previously mentioned doses). All treatments were given by oral gavage for 12 weeks. We found that single CPF and CYP exposures significantly have adverse effects on reproductive function of adult male albino rats manifested by reduced testicular weight, decreased sperm count, motility and viability, significantly increased percent of morphologically abnormal spermatozoa, and significant increments in sperm DNA fragmentation index (DFI) with respect to control group. Furthermore, serum follicle stimulating hormone, luteinizing hormone, and testosterone levels were decreased significantly compared to control group. This was accompanied with histopathological changes in the testis of rats such as necrosis, degeneration, decreasing number of spermatogenic cells in some seminiferous tubules, edema, congested blood vessels, and exudate in interstitial tissue of the testis. Notably, all these changes were exaggerated in rats treated concomitantly with chlorpyrifos and cypermethrin rendering the mixture more toxic than the additive effects of each compound and causing greater damage on the reproductive system of male albino rats than the individual pesticides.

Serotonin-Labeled CdSe Nanocrystals: Applications for Neuroscience

NASA Astrophysics Data System (ADS)

Kippeny, Tadd; Adkins, Erika; Adams, Scott; Thomlinson, Ian; Schroeter, Sally; Defelice, Louis; Blakely, Randy; Rosenthal, Sandra

2000-03-01

Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter which has been linked to the regulation of critical behaviors including sleep, appetite, and mood. The serotonin transporter (SERT) is a 12-transmembrane domain protein responsible for clearance of serotonin from extracellular spaces following release. In order to assess the potential for use of ligand-conjugated nanocrystals to target cell surface receptors, ion channels, and transporters we have measured the ability of serotonin-labeled CdSe nanocrystals (SNACs) to block the uptake of tritiated serotonin by the human and Drosophila serotonin transporters (hSERT and dSERT). Estimated Ki values, the SNAC concentration at which half of the serotonin transport activity is blocked, were determined by nonlinear regression to be Ki (hSERT ) = 74uM and Ki (dSERT ) = 29uM. These values and our inability to detect free serotonin indicate that SNACs selectively interact with the serotonin recognition site of the transporter. We have also exposed the SNACs to cells containing ionotropic serotonin receptors and have measured the electrical response of the cell using a two microelectrode voltage clamp. We find that serotonin receptors do respond to the SNACs and we measure currents similar to the free serotonin response. These results indicate that ligand-conjugated nanocrystals can be used to label both receptor and transporter proteins. Initial fluorescence labeling experiments will be discussed.

Determination of selected pesticides in water samples adjacent to agricultural fields and removal of organophosphorus insecticide chlorpyrifos using soil bacterial isolates

NASA Astrophysics Data System (ADS)

Hossain, M. S.; Chowdhury, M. Alamgir Zaman; Pramanik, Md. Kamruzzaman; Rahman, M. A.; Fakhruddin, A. N. M.; Alam, M. Khorshed

2015-06-01

The use of pesticide for crops leads to serious environmental pollution, therefore, it is essential to monitor and develop approaches to remove pesticide from contaminated environment. In this study, water samples were collected to monitor pesticide residues, and degradation of chlorpyrifos was also performed using soil bacteria. Identification of pesticide residues and determination of their levels were performed by high-performance liquid chromatography with photodiode array detector. Among 12 samples, 10 samples were found contaminated with pesticides. Chlorpyrifos was detected in four tested samples and concentrations ranged from 3.27 to 9.31 μg/l whereas fenitrothion ranging from (Below Detection Limit, <0.1 μg/l) to 33.41 μg/l in the tested samples. Parathion was found in two tested samples at the concentration of 0.73 and 6.23 μg/l. None of the tested samples was found contaminated with Methoxychlor, DDT and Ethion. Three soil bacterial isolates, Pseudomonas peli BG1, Burkholderia caryophylli BG4 and Brevundimonas diminuta PD6 degraded chlorpyrifos completely in 8, 10 and 10 days, respectively, when 20 mg/l chlorpyrifos was supplied as sole source of carbon. Whereas, BG1, BG4 and PD6 took 14, 16 and 16 days, respectively, for complete removal of 50 mg/l chlorpyrifos. Chlorpyrifos degradation rates were found maximum by all three isolates at 2nd day of incubation for both tested concentrations. The results of the present study suggest the need for regular monitoring of pesticide residues in water, to protect the aquatic environment. Chlorpyrifos degrading bacterial isolates can be used to clean up environmental samples contaminated with the organophosphate pesticides.

Electrochemistry coupled online to liquid chromatography-mass spectrometry for fast simulation of biotransformation reactions of the insecticide chlorpyrifos.

PubMed

Mekonnen, Tessema F; Panne, Ulrich; Koch, Matthias

2017-05-01

An automated method is presented for fast simulation of (bio)transformation products (TPs) of the organophosphate insecticide chlorpyrifos (CPF) based on electrochemistry coupled online to liquid chromatography-mass spectrometry (EC-LC-MS). Oxidative TPs were produced by a boron doped diamond (BDD) electrode, separated by reversed phase HPLC and online detected by electrospray ionization-mass spectrometry (ESI-MS). Furthermore, EC oxidative TPs were investigated by HPLC-tandem mass spectrometry (LC-MS/MS) and FT-ICR high resolution mass spectrometry (HRMS) and compared to in vitro assay metabolites (rat and human liver microsomes). Main phase I metabolites of CPF: chlorpyrifos oxon (CPF oxon), trichloropyridinol (TCP), diethylthiophosphate (DETP), diethylphosphate (DEP), desethyl chlorpyrifos (De-CPF), and desethyl chlorpyrifos oxon (De-CPF oxon), were successfully identified by the developed EC-LC-MS method. The EC-LC-MS method showed similar metabolites compared to the in vitro assay with possibilities of determining reactive species. Our results reveal that online EC-(LC)-MS brings an advantage on time of analysis by eliminating sample preparation steps and matrix complexity compared to conventional in vivo or in vitro methods.

Residues of Lindane and Chlorpyrifos in firewood and woodsmoke

Treesearch

P.B. Bush; J.W. Taylor; Charles K. McMahon; D.G. Neary

1987-01-01

Abstract.Pine bark beetle insecticide treatment plots were established on the Ocala National Forest, in central Florida. Each plot consisted of five sand pine, pinus clausa (Chapm. Ex. Engelm) Vassey ex. Sarg., trees treated with either 0.5% lindane (benzene hexachloride) or 2% chlorpyrifos (O,O-diethyl O-(3,5,6-trichloro-2-pgridyl) phosphorothioate...

The roles of sex and serotonin transporter levels in age- and stress-related emotionality in mice.

PubMed

Joeyen-Waldorf, Jennifer; Edgar, Nicole; Sibille, Etienne

2009-08-25

Mood disorders are influenced by genetic make-up and differentially affect men and women. The s/l promoter polymorphism in the serotonin transporter (SERT) gene moderates both trait emotion and the vulnerability to develop depressive states in humans. Similarly, male mice lacking SERT (Knockout/KO) display an elevated emotionality phenotype. We now report that the SERT-KO phenotype is maintained throughout late-adulthood, and that female KO mice develop a larger emotionality phenotype with increasing age. Thus, to test the hypothesis that these findings reflected a putative sexual dimorphism in SERT-mediated modulation of emotionality, we submitted adult male and female wild-type, heterozygous (HZ) and KO mice to unpredictable chronic mild stress (UCMS) and assessed behavioral changes. In males, the elevated SERT-KO emotion-related behavior converged with other groups after UCMS. Conversely, female SERT-KO displayed a normal non-stressed baseline, but highest UCMS-induced emotionality. SERT-HZ displayed variable and intermediate phenotypes in both experiments. Thus, consistent results across different biological modalities (age, stress) revealed a high contribution of SERT genotype for baseline "trait" emotionality in males, and low contribution for females. In contrast, age-correlated and stress-induced behavioral changes resulted in a high SERT genotype-mediated behavioral variance in females, but low in males. This suggests that high emotionality states associated with low SERT were differentially achieved in males (high baseline/trait) compared to females (increased vulnerability to develop high emotionality). This sex-by-SERT double dissociation provides a framework to investigate molecular substrates of emotionality regulation in concert with serotonin function and may contribute to the sexually dimorphic features of mood disorders.

Effects of insecticides chlorpyrifos, emamectin benzoate and fipronil on Spodoptera litura might be mediated by OBPs and CSPs.

PubMed

Lin, X; Jiang, Y; Zhang, L; Cai, Y

2017-12-04

Spodoptera litura is a widespread polyphagous insect pest that can develop resistance and cross-resistance to insecticides, making it difficult to control. Insecticide exposure has previously been linked with induction of specific olfactory-related proteins, including some chemosensory proteins (CSPs) and odorant-binding proteins (OPBs), which may disrupt detection of environmental factors and reduce fitness. However, functional evidence supporting insecticide and OBPs/CSPs mediation remains unknown. Here we fed male S. litura moths with sucrose water containing one of three insecticides, chlorpyrifos, emamectin benzoate or fipronil, and used real-time quantitative polymerase chain reaction and RNAi to investigate OBPs and CSPs expression and their correlations with survival. Chlorpyrifos and emamectin benzoate increased expression of 78% of OBPs, plus 63 and 56% of CSP genes, respectively, indicating a major impact on these gene families. RNAi knockdown of SlituCSP18, followed by feeding with chlorpyrifos or fipronil, decreased survival rates of male moths significantly compared with controls. Survival rate also decreased significantly with the downregulation of SlituOBP9 followed by feeding with chlorpyrifos. Thus, although these three insecticides had different effects on OBP and CSP gene expression, we hypothesize that SlituOBPs and SlituCSPs might mediate their effects by increasing their expression levels to improve survival. Moreover, the differential response of S. litura male moths to the three insecticides indicated the potential specificity of chlorpyrifos affect SlituCSP18 and SlituOBP9 expression.

Toxicity of Chlorpyrifos and Dimethoate to the Ciliate Urostyla grandis, with Notes on Their Effects on Cell Ultrastructure

NASA Astrophysics Data System (ADS)

Mu, Weijie; Warren, Alan; Pan, Xuming; Ying, Chen

2018-06-01

Chlorpyrifos and dimethoate are overused agricultural pesticides that can trigger trophic cascades, resulting in toxicity to both terrestrial and aquatic organisms as well as altered ecosystems. In previous studies, substantial attention has been given to the effects of pesticides on vertebrate species and, to a lesser extent, species of zooplankton. The present study was designed to show that the fission time effective concentration in ciliates is a potential aquatic detection index for environmental monitoring. The ciliate Urostyla grandis was treated with doses of chlorpyrifos and dimethoate. After exposed to the pesticides, the LC 50 ( i.e., concentration that killed 50% of the ciliate cells within 24 h) values were 0.029 mg L-1 for chlorpyrifos and 0.0685 mg L-1 for dimethoate. The fission time effective concentrations after 168 h of exposure were 0.0075-0.0093 mg L-1 for chlorpyrifos and 0.2640-0.2750 mg L-1 for dimethoate. These results show that the fission time effective concentration is lower than the LC 50 value in ciliates, indicating that fission time effective concentration is more suitable than the LC 50 value for environmental monitoring using ciliates. The effects of chlorpyrifos and dimethoate on ciliate cell ultrastructures included agglutination of chromatin in the macronucleus, protruded and discontinuous macronuclear and micronuclear membranes, loss of integrity of mitochondrial membranes and contents, and abscission and deformation of the adoral zone of membranelles.

Cytochrome P450 genes from the aquatic midge Chironomus tentans: Atrazine-induced up-regulation of CtCYP6EX3 enhanced the toxicity of chlorpyrifos.

PubMed

Tang, Guanghui; Yao, Jianxiu; Li, Daqi; He, Yanping; Zhu, Yu-Cheng; Zhang, Xin; Zhu, Kun Yan

2017-11-01

The open reading frames of 19 cytochrome P450 monooxygenase (CYP) genes were sequenced from Chironomus tentans, a commonly used freshwater invertebrate model. Phylogenetic analysis of the 19 CYPs along with a previously reported CYP (CtCYP4G33) revealed that they belong to three different clans, including 3 in CYP4, 15 in CYP3, and 2 in mitochondria clan. When third-instar larvae were exposed to atrazine at 5000 μg/L, the transcription of CtCYP6EX3, CtCYP6EV3, CtCYP9AT1 and CtCYPEX1 was significantly up-regulated. To examine whether CtCYP6EX3 played a role in oxidative activation of chlorpyrifos to chlorpyrifos-oxon, we evaluated larval susceptibility to chlorpyrifos after CtCYP6EX3 transcript was suppressed by RNAi. The larvae fed chitosan/dsCtCYP6EX3 nanoparticles showed a significantly decreased CtCYP6EX3 transcript (53.1%) as compared with the control larvae fed chitosan/dsGFP nanoparticles. When the CtCYP6EX3-silenced larvae were exposed to chlorpyrifos at 6 μg/L or its binary mixture with atrazine (chlorpyrifos at 3 μg/L and atrazine at 1000 μg/L), the larvae became less susceptible to the pesticides as their mortalities decreased by 24.1% and 20.5%, respectively. These results along with our previous findings suggested that the increased toxicity of chlorpyrifos was likely due to an enhanced oxidative process from chlorpyrifos to chlorpyrifos-oxon by CtCYP6EX3 as RNAi of CtCYP6EX3 led to decreased susceptibility of C. tentans larvae to chlorpyrifos alone and the binary mixture of atrazine and chlorpyrifos. However, further study would be necessary to validate our results by functional assays using heterologously expressed CtCYP6EX3 enzyme. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

van Wijngaarden, René P A; Brock, Theo C M; Douglas, Mark T

2005-10-01

Three experiments were conducted to determine the impact of the insecticide chlorpyrifos (single applications of 0.01 to 10 microg AI litre(-1)) in plankton-dominated nutrient-rich microcosms. The microcosms (water volume approximately 14 litres) were established in the laboratory under temperature, light regimes and nutrient levels that simulated cool 'temperate' and warm 'Mediterranean' environmental conditions. The fate of chlorpyrifos in the water column was monitored and the effects on zooplankton, phytoplankton and community metabolism were followed for 4 or 5 weeks. The mean half-life (t1/2) of chlorpyrifos in the water of the test systems was 45 h under 'temperate' conditions and about 30 h under 'Mediterranean' environmental conditions. Microcrustaceans (cladocerans and copepod nauplii) were amongst the most sensitive organisms. All three experiments yielded community NOEC (no observed effect concentrations) of 0.1 microg AI litre(-1), similar to those derived from more complex outdoor studies. Above this threshold level, responses and effect chains, and time spans for recovery, differed between the experiments. For example, algal blooms as an indirect effect from the impact of exposure on grazing organisms were only observed under the 'Mediterranean' experimental conditions. The relatively simple indoor test system seems to be sufficient to provide estimates of safe threshold levels for the acute insecticidal effects of low-persistence compounds such as chlorpyrifos. The robustness of the community NOEC indicates that this threshold level is likely to be representative for many freshwater systems. Copyright (c) 2005 Society of Chemical Industry.

Purification of eutrophic water containing chlorpyrifos by aquatic plants and its effects on planktonic bacteria.

PubMed

Xu, Xing-Jian; Lai, Guo-Li; Chi, Chang-Qiao; Zhao, Jie-Yu; Yan, Ying-Chun; Nie, Yong; Wu, Xiao-Lei

2018-02-01

In this study, the removal of nutrients and chlorpyrifos as well as shifts of planktonic bacterial communities in constructed microcosms were investigated to evaluate the influence of Phragmites australis, Nymphaea alba, and Myriophyllum verticillatum, and their combination, on the restoration of eutrophic water containing chlorpyrifos. Plant-treated groups showed a higher pollutant removal rate than did no-remediation controls, indicating that treatment with plants is effective at remediation of eutrophic water containing chlorpyrifos. Different plants showed different performance on the remediation of eutrophic water, e.g., P. australis manifested stronger capacity for removal of sediment chlorpyrifos. This finding indicated that an appropriate plant combination is needed to deal with complex wastewater. During the treatments, the planktonic bacterial communities were influenced by the concentrations of nutrients and pollutants. The changes of composition of bacterial communities indicated a strong correlation between the bacterial communities and the concentrations of pollutants. The plants also influenced the planktonic bacterial communities, especially at the early phase of treatments. For example, P. australis increased the abundance of Limnohabitans and Nevskia significantly and decreased the abundance of Devosia, Luteolibacter, Methylibium, and Caulobacter significantly. The abundance of Hydrocarboniphaga significantly increased in N. alba-treated microcosms, whereas in M. verticillatum-treated microcosms, the abundance of Limnohabitans and Bdellovibrio significantly increased. Our results suggest that the planktonic bacterial communities may be altered during phytoremediation, and the functions of the affected bacteria should be concerned. Copyright © 2017 Elsevier Ltd. All rights reserved.

Serotonin research: contributions to understanding psychoses.

PubMed

Geyer, Mark A; Vollenweider, Franz X

2008-09-01

The history of serotonin research is closely related to the study of hallucinogenic drugs that function as agonists at serotonin-2A receptors. The fundamental idea that psychotic states seen in psychiatric disorders such as schizophrenia might be attributable, in part, to abnormalities in serotonergic systems began with the almost simultaneous discovery of lysergic acid diethylamide (LSD), psilocybin and serotonin. Sixty years of study have confirmed early speculations regarding the important relationship between serotonin and both drug-induced and disorder-based psychotic states. Now, modern biochemical, pharmacological, behavioral, neuroimaging, genetic and molecular biological sciences are converging to understand how serotonergic systems interact with other monoaminergic and glutamatergic systems to modulate states of consciousness and contribute to psychotic disorders such as the group of schizophrenias. This review summarizes experimental assessments of the serotonergic hallucinogen model psychosis in relation to the serotonin hypothesis of schizophrenia.

A novel role for antizyme inhibitor 2 as a regulator of serotonin and histamine biosynthesis and content in mouse mast cells.

PubMed

Acosta-Andrade, Carlos; Lambertos, Ana; Urdiales, José L; Sánchez-Jiménez, Francisca; Peñafiel, Rafael; Fajardo, Ignacio

2016-10-01

Antizymes and antizyme inhibitors are key regulatory proteins of polyamine levels by affecting ornithine decarboxylase and polyamine uptake. Our previous studies indicated a metabolic interplay among polyamines, histamine and serotonin in mast cells, and demonstrated that polyamines are present in mast cell secretory granules, being important for histamine storage and serotonin levels. Recently, the novel antizyme inhibitor-2 (AZIN2) was proposed as a local regulator of polyamine biosynthesis in association with mast cell serotonin-containing granules. To gain insight into the role of AZIN2 in the biosynthesis and storage of serotonin and histamine, we have generated bone marrow derived mast cells (BMMCs) from both wild-type and transgenic Azin2 hypomorphic mice, and have analyzed polyamines, serotonin and histamine contents, and some elements of their metabolisms. Azin2 hypomorphic BMMCs did not show major mast cell phenotypic alterations as judged by morphology and specific mast cell proteases. However, compared to wild-type controls, these cells showed reduced spermidine and spermine levels, and diminished growth rate. Serotonin levels were also reduced, whereas histamine levels tended to increase. Accordingly, tryptophan hydroxylase-1 (TPH1; the key enzyme for serotonin biosynthesis) mRNA expression and protein levels were reduced, whereas histidine decarboxylase (the enzyme responsible for histamine biosynthesis) enzymatic activity was increased. Furthermore, microphtalmia-associated transcription factor, an element involved in the regulation of Tph1 expression, was reduced. Taken together, our results show, for the first time, an element of polyamine metabolism -AZIN2-, so far described as exclusively devoted to the control of polyamine concentrations, involved in regulating the biosynthesis and content of other amines like serotonin and histamine.

Selective Serotonin Reuptake Inhibitors (SSRIs)

MedlinePlus

... dangerous reactions when combined with certain medications or herbal supplements. Serotonin syndrome. Rarely, an antidepressant can cause high ... antidepressants, certain pain or headache medications, and the herbal supplement St. John's wort. Signs and symptoms of serotonin ...

Effect of diet on carboxylesterase activity of tadpoles (Rhinella arenarum) exposed to chlorpyrifos.

PubMed

Attademo, A M; Sanchez-Hernandez, J C; Lajmanovich, R C; Peltzer, P M; Junges, C

2017-01-01

An outdoor microcosm was performed with tadpoles (Rhinella arenarum) exposed to 125μgL -1 chlorpyrifos and fed two types of food, i.e., lettuce (Lactuca sativa) and a formulated commercial pellet. Acetylcholinesterase (AChE) and carboxylesterase (CbE) activities were measured in liver and intestine after 10 days of pesticide exposure. Non-exposed tadpoles fed lettuce had an intestinal AChE activity almost two-fold higher than that of pellet-fed tadpoles. No significant differences were observed, however, in liver AChE activity between diets. Likewise, intestinal CbE activity - measured using two substrates, i.e. 1-naphthyl acetate (1-NA) and 4-nitrophenyl valerate (4-NPV) - was higher in tadpoles fed lettuce than in those fed pellets. However, the diet-dependent response of liver CbE activity was opposite to that in the intestine. Chlorpyrifos caused a significant inhibition of both esterase activities, which was tissue- and diet-specific. The highest inhibition degree was found in the intestinal AChE and CbE activities of lettuce-fed tadpoles (42-78% of controls) compared with pellet-fed tadpoles (<60%). Although chlorpyrifos significantly inhibited liver CbE activity of the group fed lettuce, this effect was not observed in the group fed pellets. In general, intestinal CbE activity was more sensitive to chlorpyrifos inhibition than AChE activity. This finding, together with the high levels of basal CbE activity found in the intestine, may be understood as a detoxification system able to reduce intestinal OP uptake. Moreover, the results of this study suggest that diet is a determinant factor in toxicity testing with tadpoles to assess OP toxicity, because it modulates levels of this potential detoxifying enzyme activity. Copyright © 2016 Elsevier Inc. All rights reserved.

Chronic toxicity of clothianidin, imidacloprid, chlorpyrifos, and dimethoate to Apis mellifera L. larvae reared in vitro.

PubMed

Dai, Pingli; Jack, Cameron J; Mortensen, Ashley N; Bustamante, Tomas A; Bloomquist, Jeffrey R; Ellis, James D

2018-06-21

The effects of chronic exposure to two neonicotinoids (clothianidin and imidacloprid) and two organophosphates (chlorpyrifos and dimethoate) on survival, developmental rate and larval weight of honey bee larvae reared in vitro were determined. Diets containing chemicals were fed to larvae with the range of concentrations for each compound based on published acute toxicity experiments and residues found in pollen and nectar, both components of the larval diet. Four concentrations of each compound and controls were tested: chlorpyrifos: 0.5, 0.8, 1.2, 8 mg/L; clothianidin: 0.1, 0.4, 2, 10 mg/L; dimethoate: 0.02, 1, 6, 45 mg/L; imidacloprid: 0.4, 2, 4, 10 mg/L; positive control: dimethoate (45 mg/L); solvent control: acetone or methanol; and negative control. A significant decrease in survival, relative to the solvent control, occurred in the 0.8, 1.2 and 8 mg/L chlorpyrifos, 0.4, 2 and 10 mg/L clothianidin, and 45 mg/L dimethoate diets, but not the imidacloprid diets. The treatment of larval diets with clothianidin, dimethoate and imidacloprid did not affect survival, developmental rate, or weight of immature honey bees; however, treatment with chlorpyrifos did. Overall, our results are valuable for evaluating the chronic toxicity of these pesticides to developing honey bees. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Fructose as a novel photosensitizer: Characterization of reactive oxygen species and an application in degradation of diuron and chlorpyrifos.

PubMed

Nayak, Shaila; Muniz, Juan; Sales, Christopher M; Tikekar, Rohan V

2016-02-01

The objective of this study was to identify reactive oxygen species (ROS) generated from the exposure of fructose solution to the 254 nm ultraviolet (UV) light and evaluate whether fructose can be used as a photosensitizer for accelerated photo-degradation of diuron and chlorpyrifos. We demonstrated that hydrogen peroxide, singlet oxygen ((1)O2) and acidic photolysis products were generated upon UV exposure of fructose. Consistent with these findings, UV induced degradation of chlorpyrifos and diuron was accelerated by the presence of 500 mM fructose. The average first order photo-degradation rate constants in the absence and presence of 500 mM fructose were 0.92 and 2.07 min(-1) respectively for diuron and 0.04 and 0.07 min(-1) for chlorpyrifos. The quantum yields (ɸ) for direct photo-degradation of diuron and chlorpyrifos were 0.003 and 0.001 respectively. In the presence of 500 mM fructose, these values increased to 0.006 and 0.002 respectively. Thus, fructose may be an effective photosensitizer. Copyright © 2015 Elsevier Ltd. All rights reserved.

CHLORPYRIFOS AND 3,5,6 TRICHLORO-2-PYRIDINOL DISTRIBUTION IN RAT BLOOD AND BRAIN DURING CHRONIC DIETARY AND REPEATED HIGH LEVEL ACUTE EXPOSURE TO CHLORPYRIFOS.

EPA Science Inventory

The aim of this study was to determine the concentrations of an organophosphorus pesticide, chlorpyrifos (CPF), and the metabolite 3,5,6 trichloro-2-pyridinol (TCP) in tissues from rats exposed to long-term, low-dose CPF. Adult, Long-Evans male rats received CPF for one year at ...

Proteomic Analysis Reveals Resistance Mechanism Against Chlorpyrifos in Frankliniella occidentalis (Thysanoptera: Thripidae).

PubMed

Yan, Dan-Kan; Hu, Min; Tang, Yun-Xia; Fan, Jia-Qin

2015-08-01

The western flower thrips is an economically important worldwide pest of many crops, and chlorpyrifos has been used to control western flower thrips for many years. To develop a better resistance-management strategy, a chlorpyrifos-resistant strain of western flower thrips (WFT-chl) was selected in the laboratory. More than 39-fold resistance was achieved after selected by chlorpyrifos for 19 generations in comparison with the susceptible strain (WFT-S). Proteome of western flower thrips (WFT-S and WFT-chl) was investigated using a quantitative proteomics approach with isobaric tag for relative and absolute quantification technique and liquid chromatography-tandem mass spectrometry technologies. According to the functional analysis, 773 proteins identified were grouped into 10 categories of molecular functions and 706 proteins were presented in 213 kinds of pathways. Comparing the proteome of WFT-chl with that of WFT-S, a total of eight proteins were found up-regulated and three down-regulated. The results from functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses indicated that the differentially expressed protein functions in binding, catalyzing, transporting, and enzyme regulation were most important in resistance development. A list of proteins functioning in biological processes of metabolism, biological regulation, and response to stimulus was found in WFT-chl, suggesting that they are possibly the major components of the resistance mechanism to chlorpyrifos in western flower thrips. Notably, several novel potential resistance-related proteins were identified such as ribosomal protein, Vg (vitellogenin), and MACT (muscle actin), which can be used to improve our understanding of the resistance mechanisms in western flower thrips. This study provided the first comprehensive view of the complicated resistance mechanism employed by WFT-S and WFT-chl through the isobaric tag for relative and absolute quantification coupled

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

PubMed Central

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

2013-01-01

Glucocorticoids are routinely given in preterm labor and are also elevated by maternal stress; organophosphate exposures are virtually ubiquitous, so coexposures to these two agents are pervasive. We administered dexamethasone to pregnant rats on gestational days 17–19 at a standard therapeutic dose (0.2 mg/kg); offspring were then given chlorpyrifos on postnatal days 1–4, at a dose (1 mg/kg) that produces barely-detectable (<10%) inhibition of brain cholinesterase activity. We evaluated indices for acetylcholine (ACh) synaptic function throughout adolescence, young adulthood and later adulthood, in brain regions possessing the majority of ACh projections and cell bodies; we measured nicotinic ACh receptor binding, hemicholinium-3 binding to the presynaptic choline transporter and choline acetyltransferase activity, all known targets for the adverse developmental effects of dexamethasone and chlorpyrifos given individually. Dexamethasone did not enhance the systemic toxicity of chlorpyrifos, as evidenced by weight gain and measurements of cholinesterase inhibition during chlorpyrifos treatment. Nevertheless, it enhanced the loss of presynaptic ACh function selectively in females, who ordinarily show sparing of organophosphate developmental neurotoxicity relative to males. Females receiving the combined treatment showed decrements in choline transporter binding and choline acetyltransferase activity that were unique (not found with either treatment alone), as well as additive decrements in nicotinic receptor binding. On the other hand, males given dexamethasone showed no augmentation of the effects of chlorpyrifos. Our findings indicate that prior dexamethasone exposure could create a subpopulation that is especially vulnerable to the adverse effects of organophosphates or other developmental neurotoxicants. PMID:23416428

Increased brain serotonin turnover in panic disorder patients in the absence of a panic attack: reduction by a selective serotonin reuptake inhibitor.

PubMed

Esler, Murray; Lambert, Elisabeth; Alvarenga, Marlies; Socratous, Florentia; Richards, Jeff; Barton, David; Pier, Ciaran; Brenchley, Celia; Dawood, Tye; Hastings, Jacqueline; Guo, Ling; Haikerwal, Deepak; Kaye, David; Jennings, Garry; Kalff, Victor; Kelly, Michael; Wiesner, Glen; Lambert, Gavin

2007-08-01

Since the brain neurotransmitter changes characterising panic disorder remain uncertain, we quantified brain noradrenaline and serotonin turnover in patients with panic disorder, in the absence of a panic attack. Thirty-four untreated patients with panic disorder and 24 matched healthy volunteers were studied. A novel method utilising internal jugular venous sampling, with thermodilution measurement of jugular blood flow, was used to directly quantify brain monoamine turnover, by measuring the overflow of noradrenaline and serotonin metabolites from the brain. Radiographic depiction of brain venous sinuses allowed differential venous sampling from cortical and subcortical regions. The relation of brain serotonin turnover to serotonin transporter genotype and panic disorder severity were evaluated, and the influence of an SSRI drug, citalopram, on serotonin turnover investigated. Brain noradrenaline turnover in panic disorder patients was similar to that in healthy subjects. In contrast, brain serotonin turnover, estimated from jugular venous overflow of the metabolite, 5-hydroxyindole acetic acid, was increased approximately 4-fold in subcortical brain regions and in the cerebral cortex (P < 0.01). Serotonin turnover was highest in patients with the most severe disease, was unrelated to serotonin transporter genotype, and was reduced by citalopram (P < 0.01). Normal brain noradrenaline turnover in panic disorder patients argues against primary importance of the locus coeruleus in this condition. The marked increase in serotonin turnover, in the absence of a panic attack, possibly represents an important underlying neurotransmitter substrate for the disorder, although this point remains uncertain. Support for this interpretation comes from the direct relationship which existed between serotonin turnover and illness severity, and the finding that SSRI administration reduced serotonin turnover. Serotonin transporter genotyping suggested that increased whole brain

Rotavirus and Serotonin Cross-Talk in Diarrhoea

PubMed Central

Nordgren, Johan; Karlsson, Thommie; Sharma, Sumit; Magnusson, Karl-Eric; Svensson, Lennart

2016-01-01

Rotavirus (RV) has been shown to infect and stimulate secretion of serotonin from human enterochromaffin (EC) cells and to infect EC cells in the small intestine of mice. It remains to identify which intracellularly expressed viral protein(s) is responsible for this novel property and to further establish the clinical role of serotonin in RV infection. First, we found that siRNA specifically silencing NSP4 (siRNANSP4) significantly attenuated secretion of serotonin from Rhesus rotavirus (RRV) infected EC tumor cells compared to siRNAVP4, siRNAVP6 and siRNAVP7. Second, intracellular calcium mobilization and diarrhoeal capacity from virulent and avirulent porcine viruses correlated with the capacity to release serotonin from EC tumor cells. Third, following administration of serotonin, all (10/10) infants, but no (0/8) adult mice, responded with diarrhoea. Finally, blocking of serotonin receptors using Ondansetron significantly attenuated murine RV (strain EDIM) diarrhoea in infant mice (2.9 vs 4.5 days). Ondansetron-treated mice (n = 11) had significantly (p < 0.05) less diarrhoea, lower diarrhoea severity score and lower total diarrhoea output as compared to mock-treated mice (n = 9). Similarly, Ondansetron-treated mice had better weight gain than mock-treated animals (p < 0.05). A most surprising finding was that the serotonin receptor antagonist significantly (p < 0.05) also attenuated total viral shedding. In summary, we show that intracellularly expressed NSP4 stimulates release of serotonin from human EC tumor cells and that serotonin participates in RV diarrhoea, which can be attenuated by Ondansetron. PMID:27459372

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

Short-term effects of chlorpyrifos and other pesticides on earthworm numbers

USDA-ARS?s Scientific Manuscript database

Chlorpyrifos is generally used on grasses grown for seed to control billbugs (Sphenophorus venatus confluens) and cutworms (various species), and on other crops for crane fly larvae (Tipula sp.), garden symphyllans (Scutigerella immaculate), and wireworms (Agriotes sp.). The indirect impact of cont...

Temporal changes in surface-water insecticide concentrations after the phaseout of diazinon and chlorpyrifos

USGS Publications Warehouse

Phillips, P.J.; Ator, S.W.; Nystrom, E.A.

2007-01-01

The recent (late 2001) federally mandated phaseout of diazinon and chlorpyrifos insecticide use in outdoor urban settings has resulted in a rapid decline in concentrations of these insecticides in urban streams and rivers in the northeastern and midwestern United States. Assessment of temporal insecticide trends at 20 sites showed that significant step decreases in diazinon concentrations occurred at 90% of the sites after the phaseout, with concentrations generally decreasing by over 50% in summer samples. Chlorpyrifos concentrations showed significant step decreases in at least 1 season at 3 of the 4 sites with sufficient data for analysis. The decrease in diazinon concentrations in response to the phaseout resulted in a decline in the frequency of concentrations exceeding the acute invertebrate water-quality benchmark of 0.1 ??g/L from 10% of pre-phaseout summer samples to fewer than 1% of post-phaseout summer samples. Although some studies have indicated an increase in concentrations of carbaryl in response to the organophosphorous phaseout, carbaryl concentrations only increased at 1 site after the phaseout. A full assessment of the effect of the phaseout of diazinon and chlorpyrifos on surface water will require data on other insecticides used to replace these compounds.

Effects of chlorpyrifos on in vitro sex steroid production and thyroid follicular development in adult and larval Lake Sturgeon, Acipenser fulvescens.

PubMed

Brandt, Catherine; Burnett, Duncan C; Arcinas, Liane; Palace, Vince; Gary Anderson, W

2015-08-01

Chlorpyrifos is a widely used organophosphate pesticide that has previously been shown to enter waterways in biologically relevant concentrations and has the potential to disrupt both thyroid hormone and sex steroid biosynthesis in vertebrates. Because gonadal maturation and larval development in Lake Sturgeon, Acipenser fulvescens, potentially coincide with the application of chlorpyrifos we examined the effects of chlorpyrifos on both thyroid follicular development in larval Lake Sturgeon, and sex hormone synthesis in adult Lake Sturgeon. For the first time, the present study reports steroidogenesis from testicular and ovarian tissue in Lake Sturgeon using an established in vitro bioassay. Furthermore, incubating gonad tissue with 5, 500 or 2000ngmL(-1) chlorpyrifos revealed an inhibitory effect on testosterone synthesis in both testicular (control, 40.29pgmg(-1) tissue wet weight(-1)h(-1) compared to experimental, 21.84pgmg(-1) tissue wet weight(-1)h(-1)) and ovarian (control, 33.83pgmg(-1) tissue wet weight(-1)h(-1) compared to experimental, 15.19pgmg(-1) tissue wet weight(-1)h(-1)) tissue. In a second series of experiments, larval Lake Sturgeon were exposed to equivalent concentrations of chlorpyrifos as above for 10days (d) between hatch and the onset of exogenous feeding. Larvae from each treatment group were raised until 67days post hatch (dph) and growth rates were compared alongside key indicators of thyroid follicle growth. Chlorpyrifos treatment had no effect on the measured indicators of thyroid follicular development. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ti/IrO2/SnO2 anode for electrochemical degradation of chlorpyrifos in water: optimization and degradation performances

NASA Astrophysics Data System (ADS)

Pathiraja, G. C.; Wijesingha, M. S.; Nanayakkara, N.

2017-05-01

Chlorpyrifos, a widely used organophosphate pesticide which can be found in surface water bodies, is harmful for human body. Thus, treating water contaminated with chlorpyrifos is important. In our previous studies, novel Ti/IrO2-SnO2 anode was successfully developed for electrochemical degradation of chlorpyrifos in chloride free water. In this study, optimization of previously developed Ti/IrO2-SnO2 anode for mineralization of chlorpyrifos was successfully performed through response surface methodology. During the optimization study, two-level factorial design was used to determine the optimal coating solutions concentration for developing the Ti/IrO2-SnO2 anode. Cyclic voltammetry and open circuit potential were performed to investigate the electrochemically active surface area and stability of these anodes. The response surface and contour plots show that 0.3 M of [Ir] and 7.5 mM of [Sn] coated electrode has both highest anodic charge and stability. Scanning Electron Microscopic (SEM) images show the evidence of having both compact and porous regions in the surface of the thin film, resulting larger surface area. Within 6 h, the best result for mineralization (55.56%) of chlorpyrifos was obtained with 0.3 M of [Ir] and 7.5 mM of [Sn] coated anode using Total organic Carbon (TOC) analyzer. Therefore, the optimum coating concentration was found as 0.3 M of [Ir] and 7.5 mM of [Sn]. It would require an energy consumption of 6 kWhm-3.

Evaluation of chlorpyrifos effects, alone and combined with lipopolysaccharide stress, on DNA integrity and immune responses of the three-spined stickleback, Gasterosteus aculeatus.

PubMed

Marchand, Adrien; Porcher, Jean-Marc; Turies, Cyril; Chadili, Edith; Palluel, Olivier; Baudoin, Patrick; Betoulle, Stéphane; Bado-Nilles, Anne

2017-11-01

Organism immune defences might be weakened by pollutants, largely detected in aquatic ecosystems, leading to the facilitation for opportunistic pathogens to infect organisms. In this context, destabilization of fish non-specific immune parameters and erythrocyte DNA integrity was tested, on a model fish species, the three-spined stickleback (Gasterosteus aculeatus), after exposure to chlorpyrifos (CPF). Alone, pesticide exposure induced a genotoxic potential (chlorpyrifos at 1.75 and 0.88µg/L) in addition to a decrease in phagocytosis capacity and a stimulation of respiratory burst. Then, to mimic pathogenic infection, fish exposure to chlorpyrifos was combined with lipopolysaccharides (LPS) stress. In this second experiment, an increase of DNA damage was observed in fish exposed to a lower concentration of chlorpyrifos and LPS. Moreover, at the higher concentration of chlorpyrifos, an early destabilization of innate immunity was observed as suggested by the absence of an increase of lysosomal presence in fish injected with LPS. This study highlighted the usefulness of stress on stress responses to better understand the impact of contaminants on the organism's health. Copyright © 2017 Elsevier Inc. All rights reserved.

Serotonin shapes risky decision making in monkeys.

PubMed

Long, Arwen B; Kuhn, Cynthia M; Platt, Michael L

2009-12-01

Some people love taking risks, while others avoid gambles at all costs. The neural mechanisms underlying individual variation in preference for risky or certain outcomes, however, remain poorly understood. Although behavioral pathologies associated with compulsive gambling, addiction and other psychiatric disorders implicate deficient serotonin signaling in pathological decision making, there is little experimental evidence demonstrating a link between serotonin and risky decision making, in part due to the lack of a good animal model. We used dietary rapid tryptophan depletion (RTD) to acutely lower brain serotonin in three macaques performing a simple gambling task for fluid rewards. To confirm the efficacy of RTD experiments, we measured total plasma tryptophan using high-performance liquid chromatography (HPLC) with electrochemical detection. Reducing brain serotonin synthesis decreased preference for the safe option in a gambling task. Moreover, lowering brain serotonin function significantly decreased the premium required for monkeys to switch their preference to the risky option, suggesting that diminished serotonin signaling enhances the relative subjective value of the risky option. These results implicate serotonin in risk-sensitive decision making and, further, suggest pharmacological therapies for treating pathological risk preferences in disorders such as problem gambling and addiction.

High serum serotonin in sudden infant death syndrome.

PubMed

Haynes, Robin L; Frelinger, Andrew L; Giles, Emma K; Goldstein, Richard D; Tran, Hoa; Kozakewich, Harry P; Haas, Elisabeth A; Gerrits, Anja J; Mena, Othon J; Trachtenberg, Felicia L; Paterson, David S; Berry, Gerard T; Adeli, Khosrow; Kinney, Hannah C; Michelson, Alan D

2017-07-18

Sudden infant death syndrome (SIDS), the leading cause of postneonatal infant mortality, likely comprises heterogeneous disorders with the common phenotype of sudden death without explanation upon postmortem investigation. Previously, we reported that ∼40% of SIDS deaths are associated with abnormalities in serotonin (5-hydroxytryptamine, 5-HT) in regions of the brainstem critical in homeostatic regulation. Here we tested the hypothesis that SIDS is associated with an alteration in serum 5-HT levels. Serum 5-HT, adjusted for postconceptional age, was significantly elevated (95%) in SIDS infants ( n = 61) compared with autopsied controls ( n = 15) [SIDS, 177.2 ± 15.1 (mean ± SE) ng/mL versus controls, 91.1 ± 30.6 ng/mL] ( P = 0.014), as determined by ELISA. This increase was validated using high-performance liquid chromatography. Thirty-one percent (19/61) of SIDS cases had 5-HT levels greater than 2 SDs above the mean of the controls, thus defining a subset of SIDS cases with elevated 5-HT. There was no association between genotypes of the serotonin transporter promoter region polymorphism and serum 5-HT level. This study demonstrates that SIDS is associated with peripheral abnormalities in the 5-HT pathway. High serum 5-HT may serve as a potential forensic biomarker in autopsied infants with SIDS with serotonergic defects.

Dermal exposure of applicators to chlorpyrifos on rice farms in Ghana.

PubMed

Atabila, Albert; Phung, Dung Tri; Hogarh, Jonathan N; Osei-Fosu, Paul; Sadler, Ross; Connell, Des; Chu, Cordia

2017-07-01

Studies evaluating dermal exposure to pesticides among applicators in tropical countries have largely been conducted using the patch dosimetry and hand wiping/washing techniques. This study used the more accurate whole-body dosimetry technique to evaluate dermal exposure to chlorpyrifos among applicators on rice farms in Ghana. The exposure levels were plotted as Cumulative Probability Distribution (CPD). Total Dermal Exposure (TDE) of chlorpyrifos among the median exposed and the 5% highly exposed groups during a spray event were 24 mg and 48 mg, respectively. When these were converted as a percentage of the quantity of active ingredient applied (Unit Exposure, UE), UE values of 0.03% and 0.06% were found among the median exposed and the 5% highly exposed groups, respectively. Overall, the hands were the most contaminated anatomical regions of the applicators, both in terms of proportion of TDE (39%) and skin loading (13 μg/cm 2 ). Also, the lower anatomical region was more contaminated (82% of TDE) compared to the upper anatomical region (18% of TDE). The levels of chlorpyrifos TDE among the applicators were found to be influenced by the quantity of insecticide applied and the height of the crops sprayed (p < 0.05). The pesticide UE data of the present study can be used to estimate the levels of dermal exposure under similar pesticide use scenarios among applicators. The findings of the present study suggest that protecting the hands and the lower anatomical regions with appropriate PPE may significantly reduce exposure among applicators. Copyright © 2017 Elsevier Ltd. All rights reserved.

Delayed Hippocampal Effects From a Single Exposure of Prepubertal Guinea Pigs to sub-lethal dose of Chlorpyrifos: A Magnetic Resonance Imaging and Spectroscopy Study

PubMed Central

Mullins, Roger J.; Xu, Su; Pereira, Edna F.R.; Mamczarz, Jacek; Albuquerque, Edson X.; Gullapalli, Rao P.

2013-01-01

This study was designed to test the hypothesis that in vivo Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) can detect in adulthood the neurotoxic effects of a single exposure of prepubertal guinea pigs to the organophosphorus pesticide chlorpyrifos. Twelve female guinea pigs were given either a single dose of chlorpyrifos (0.6xLD50 or 300 mg/kg, sc) or peanut oil (vehicle; 0.5 ml/kg, sc) at 35–40 days of age. One year after the exposure, the animals were tested in the Morris water maze. Three days after the end of the behavioral testing, the metabolic and structural integrity of the brain of the animals was examined by means of MRI/MRS. In the Morris water maze, the chlorpyrifos-exposed guinea pigs showed significant memory deficit. Although no significant anatomical differences were found between the chlorpyrifos-exposed guinea pigs and the control animals by in vivo MRI, the chlorpyrifos-exposed animals showed significant decreases in hippocampal myo-inositol concentration using MRS. The present results indicate that a single sub-lethal exposure of prepubertal guinea pigs to the organophosphorus pesticide chlorpyrifos can lead to long-term memory deficits that are accompanied by significant reductions in the levels of hippocampal myo-inositol. PMID:23411083

A Dualistic Conformational Response to Substrate Binding in the Human Serotonin Transporter Reveals a High Affinity State for Serotonin*

PubMed Central

Bjerregaard, Henriette; Severinsen, Kasper; Said, Saida; Wiborg, Ove; Sinning, Steffen

2015-01-01

Serotonergic neurotransmission is modulated by the membrane-embedded serotonin transporter (SERT). SERT mediates the reuptake of serotonin into the presynaptic neurons. Conformational changes in SERT occur upon binding of ions and substrate and are crucial for translocation of serotonin across the membrane. Our understanding of these conformational changes is mainly based on crystal structures of a bacterial homolog in various conformations, derived homology models of eukaryotic neurotransmitter transporters, and substituted cysteine accessibility method of SERT. However, the dynamic changes that occur in the human SERT upon binding of ions, the translocation of substrate, and the role of cholesterol in this interplay are not fully elucidated. Here we show that serotonin induces a dualistic conformational response in SERT. We exploited the substituted cysteine scanning method under conditions that were sensitized to detect a more outward-facing conformation of SERT. We found a novel high affinity outward-facing conformational state of the human SERT induced by serotonin. The ionic requirements for this new conformational response to serotonin mirror the ionic requirements for translocation. Furthermore, we found that membrane cholesterol plays a role in the dualistic conformational response in SERT induced by serotonin. Our results indicate the existence of a subpopulation of SERT responding differently to serotonin binding than hitherto believed and that membrane cholesterol plays a role in this subpopulation of SERT. PMID:25614630

Plasma and serum serotonin concentrations and surface-bound platelet serotonin expression in Cavalier King Charles Spaniels with myxomatous mitral valve disease.

PubMed

Cremer, Signe E; Kristensen, Annemarie T; Reimann, Maria J; Eriksen, Nynne B; Petersen, Stine F; Marschner, Clara B; Tarnow, Inge; Oyama, Mark A; Olsen, Lisbeth H

2015-06-01

To investigate serum and plasma serotonin concentrations, percentage of serotonin-positive platelets, level of surface-bound platelet serotonin expression (mean fluorescence intensity [MFI]), and platelet activation (CD62 expression) in platelet-rich plasma from Cavalier King Charles Spaniels with myxomatous mitral valve disease (MMVD). Healthy dogs (n = 15) and dogs with mild MMVD (18), moderate-severe MMVD (19), or severe MMVD with congestive heart failure (CHF; 10). Blood samples were collected from each dog. Serum and plasma serotonin concentrations were measured with an ELISA, and surface-bound platelet serotonin expression and platelet activation were determined by flow cytometry. Dogs with mild MMVD had higher median serum (746 ng/mL) and plasma (33.3 ng/mL) serotonin concentrations, compared with MMVD-affected dogs with CHF (388 ng/mL and 9.9 ng/mL, respectively), but no other group differences were found. Among disease groups, no differences in surface-bound serotonin expression or platelet activation were found. Thrombocytopenic dogs had lower serum serotonin concentration (482 ng/mL) than nonthrombocytopenic dogs (731 ng/mL). In 26 dogs, a flow cytometry scatterplot subpopulation (FSSP) of platelets was identified; dogs with an FSSP had a higher percentage of serotonin-positive platelets (11.0%), higher level of surface-bound serotonin expression (MFI, 32,068), and higher platelet activation (MFI, 2,363) than did dogs without an FSSP (5.7%, 1,230, and 1,165, respectively). An FSSP was present in 93.8% of thrombocytopenic dogs and in 29.5% of nonthrombocytopenic dogs. A substantive influence of circulating serotonin on MMVD stages prior to CHF development in Cavalier King Charles Spaniels was not supported by the study findings. An FSSP of highly activated platelets with pronounced serotonin binding was strongly associated with thrombocytopenia but not MMVD.

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

EPA Science Inventory

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

MODELING OF CHLORPYRIFOS EXPOSURE, DOSE, AND BIOMARKER USING NHEXAS MINNESOTA CHILDREN'S DATA

EPA Science Inventory

Data from the National Human Exposure Assessment Survey (NHEXAS) are now becoming available. For the organophosphorus insecticide chlorpyrifos, available data for NHEXAS Minnesota children include concentrations in air, food, beverages, water, house dust (transferable surf...

Dissipation and leaching of acephate, chlorpyrifos, and their main metabolites in field soils of Malaysia.

PubMed

Chai, L K; Mohd-Tahir, N; Hansen, S; Hansen, H C B

2009-01-01

Preventive treatment with insecticides at high dosing rates before planting of a new crop- soil drenching- is a common practice in some tropical intensive cropping systems, which may increase the risk of leaching, soil functioning, and pesticide uptake in the next crop. The degradation rates and migration of acephate and chlorpyrifos and their primary metabolites, methamidophos and 3,5,6-trichloropyridinol (TCP), have been studied in clayey red yellow podzolic (Typic Paleudults), alluvial (Typic Udorthents), and red yellow podzolic soils (Typic Kandiudults) of Malaysia under field conditions. The initial concentrations of acephate and chlorpyrifos in topsoils were found to strongly depend on solar radiation. Both pesticides and their metabolites were detected in subsoils at the deepest sampling depth monitored (50 cm) and with maximum concentrations up to 2.3 mg kg(-1) at soil depths of 10 to 20 cm. Extraordinary high dissipation rates for weakly sorbed acephate was in part attributed to preferential flow which was activated due to the high moisture content of the soils, high precipitation and the presence of conducting macropores running from below the A horizons to at least 1 m, as seen from a dye tracer experiment. Transport of chlorpyrifos and TCP which both sorb strongly to soil organic matter was attributed to macropore transport with soil particles. The half-lives for acephate in topsoils were 0.4 to 2.6 d while substantially longer half-lives of between 12.6 and 19.8 d were observed for chlorpyrifos. The transport through preferential flow of strongly sorbed pesticides is of concern in the tropics.

Implications of genetic research on the role of the serotonin in depression: emphasis on the serotonin type 1A receptor and the serotonin transporter.

PubMed

Neumeister, Alexander; Young, Theresa; Stastny, Juergen

2004-08-01

Serotonin systems appear to play a key role in the pathophysiology of major depressive disorder. Consequently, ongoing research determines whether serotonin related genes account for the very robust differential behavioral and neural mechanisms that discriminate patients with depression from healthy controls. Serotonin type 1(A) receptors and the serotonin transporters are reduced in depression, and recent genetic research in animals and humans has implicated both in depression. Preclinical studies have utilized a variety of animal models that have been used to explain pathophysiological mechanisms in humans, although it is not clear at all whether these models constitute relevant models for depression in humans. However, data from preclinical studies can generate hypotheses that are tested in humans by combining genetic data with behavioral and physiological challenge paradigms and neuroimaging. These studies will enhance our understanding about combined influences from multiple interacting genes, as well as from environmental factors on brain circuits and their function, and about how these mechanisms may contribute to the pathophysiology of neuropsychiatric disorders.

Hepatotoxicity of Chlorpyrifos in Zebrafish Liver Cells by NMR-based Metabolomics

EPA Science Inventory

For decades chlorpyrifos (CPS) has been one of the most widely used organophosphate insecticides for a variety of agricultural and public health applications. The extensive use of CPS inevitably results in exposure to a small number of the human population. It is believed that ...

DOES THE DEVELOPMENTAL NEUROTOXICITY OF CHLORPYRIFOS INVOLVE GLIAL TARGETS? (U915722)

EPA Science Inventory

The widespread use of chlorpyrifos (CPF) has raised major concerns about its potential to cause fetal or neonatal neurobehavioral damage, even at doses that do not evoke acute toxicity. CPF has been shown to inhibit replication of brain cells, to elicit alterations in neurotro...

Ecstasy use and serotonin syndrome: a neglected danger to adolescents and young adults prescribed selective serotonin reuptake inhibitors.

PubMed

Dobry, Yuriy; Rice, Timothy; Sher, Leo

2013-01-01

At present, there are scarce clinical and basic lab data concerning the risk of acute serotonin toxicity from selective serotonin reuptake inhibitors (SSRIs) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) co-administration. The health care community can strongly benefit from efforts to address the high risks associated with serotonin syndrome from this specific drug combination. The aim of this work is to review the risk of serotonin syndrome in adolescents and young adults prescribed with SSRIs and are concurrently using ecstasy. An electronic search of the major behavioral science bibliographic databases (Pubmed, PsycINFO, Medline) was conducted to retrieve peer-reviewed articles, which detail the clinical characteristics, biological mechanisms and social implications of SSRIs, MDMA, and their potential synergism in causing serotonin syndrome in the pediatric and young adult population. Search terms included "serotonin syndrome", "ecstasy", "MDMA", "pediatric", and "SSRI". Additional references were incorporated from the bibliographies of these retrieved articles. MDMA, in combination with the widely-prescribed SSRI antidepressant class, can lead to rapid, synergistic rise of serotonin (5-HT) concentration in the central nervous system, leading to the acute medical emergency known as serotonin syndrome. This review addresses such complication through an exploration of the theoretical mechanisms and clinical manifestations of this life-threatening pharmacological interaction. The increasing incidences of recreational ecstasy use and SSRI pharmacotherapy among multiple psychiatric disorders in the adolescent population have made this an overlooked yet increasingly relevant danger, which poses a threat to public health. This can be curbed through further research, as well as greater health care provision and attention from a regulatory body owing.

Biotransformation of chlorpyrifos and endosulfan by bacteria and fungi.

PubMed

Supreeth, M; Raju, N S

2017-08-01

Large quantities of pesticides are applied on crops to protect them from pests in modern agricultural practices around the globe. The two insecticides, chlorpyrifos, belonging to the organophosphorous group and endosulfan, belonging to the organochlorine group, are vastly used insecticides on agricultural crops in the last three decades. Hence, both these insecticides are ubiquitous in the environment. Once applied, these two insecticides undergo transformation in the environment either biologically or non-biologically. Microbial degradation has been considered a safe and cost-effective method for removing contaminants from the environment. Both the insecticides have been subjected to biodegradation studies using various bacteria and fungi by the researchers. Here, in this review, we report on biotransformed products formed during the course of biodegradation of these two insecticides and also discuss about the aftereffects of their transformed metabolites. This is important, because the primary biotransformed metabolites 3,5,6, trichloro-2-pyridinol of chlorpyrifos and endosulfan sulfate of endosulfan are toxic as their parent compounds and are noxious to variety of organisms. In conclusion, it is recommended to obtain microbial cultures capable of mineralizing pesticides completely without formation of any such toxic by-product before adopting bioremediation or bioaugmentation technology.

Serotonin neurotransmission in anorexia nervosa.

PubMed

Haleem, Darakhshan Jabeen

2012-09-01

Patients with anorexia nervosa (AN) show extreme dieting weight loss, hyperactivity, depression/anxiety, self-control, and behavioral impulsivity. 5-Hydroxytryptamine (5-HT; serotonin) is involved in almost all the behavioral changes observed in AN patients. Both genetic and environmental factors contribute toward the pathogenesis of AN. It is a frequent disorder among adolescent girls and young women and starts as an attempt to lose weight to look beautiful and attractive. Failure to see the turning point when fasting becomes unreasonable leads to malnutrition and AN. Tryptophan, the precursor of serotonin and an essential amino acid, is only available in the diet. It is therefore likely that excessive diet restriction and malnutrition decrease brain serotonin stores because the precursor is less available to the rate-limiting enzyme of 5-HT biosynthesis, which normally exists unsaturated with its substrate. Evidence shows that diet restriction-induced exaggerated feedback control over 5-HT synthesis and the smaller availability of tryptophan decreases serotonin neurotransmission at postsynaptic sites, leading to hyperactivity, depression, and behavioral impulsivity. A compensatory upregulation of postsynaptic 5-HT-1A receptors and hypophagic serotonin receptors may be involved in anxiety and suppression of appetite. It is suggested that tryptophan supplementation may improve pharmacotherapy in AN.

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

USGS Publications Warehouse

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

1999-01-01

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

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

PubMed Central

Boatti, Lara; Robotti, Elisa; Marengo, Emilio; Viarengo, Aldo; Marsano, Francesco

2012-01-01

Mixtures of chemicals can have additive, synergistic or antagonistic interactions. We investigated the effects of the exposure to nickel, the organophosphate insecticide chlorpyrifos at effect concentrations (EC) of 25% and 50% and their binary mixture (Ec25 + EC25) on Dictyostelium discoideum amoebae based on lysosomal membrane stability (LMS). We treated D. discoideum with these compounds under controlled laboratory conditions and evaluated the changes in protein levels using a two-dimensional gel electrophoresis (2DE) proteomic approach. Nickel treatment at EC25 induced changes in 14 protein spots, 12 of which were down-regulated. Treatment with nickel at EC50 resulted in changes in 15 spots, 10 of which were down-regulated. Treatment with chlorpyrifos at EC25 induced changes in six spots, all of which were down-regulated; treatment with chlorpyrifos at EC50 induced changes in 13 spots, five of which were down-regulated. The mixture corresponding to EC25 of each compound induced changes in 19 spots, 13 of which were down-regulated. The data together reveal that a different protein expression signature exists for each treatment, and that only a few proteins are modulated in multiple different treatments. For a simple binary mixture, the proteomic response does not allow for the identification of each toxicant. The protein spots that showed significant differences were identified by mass spectrometry, which revealed modulations of proteins involved in metal detoxification, stress adaptation, the oxidative stress response and other cellular processes. PMID:23443088

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

EPA Science Inventory

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

Modulation of defensive reflex conditioning in snails by serotonin

PubMed Central

Andrianov, Vyatcheslav V.; Bogodvid, Tatiana K.; Deryabina, Irina B.; Golovchenko, Aleksandra N.; Muranova, Lyudmila N.; Tagirova, Roza R.; Vinarskaya, Aliya K.; Gainutdinov, Khalil L.

2015-01-01

Highlights Daily injection of serotonin before a training session accelerated defensive reflex conditioning in snails.Daily injection of 5-hydroxytryptophan before a training session in snails with a deficiency of serotonin induced by the “neurotoxic” analog of serotonin 5,7-dihydroxytryptamine, restored the ability of snails to learn.After injection of the “neurotoxic” analogs of serotonin 5,6- and 5,7-dihydroxytryptamine as well as serotonin, depolarization of the membrane and decrease of the threshold potential of premotor interneurons was observed. We studied the role of serotonin in the mechanisms of learning in terrestrial snails. To produce a serotonin deficit, the “neurotoxic” analogs of serotonin, 5,6- or 5,7-dihydroxytryptamine (5,6/5,7-DHT) were used. Injection of 5,6/5,7-DHT was found to disrupt defensive reflex conditioning. Within 2 weeks of neurotoxin application, the ability to learn had recovered. Daily injection of serotonin before a training session accelerated defensive reflex conditioning and daily injections of 5-HTP in snails with a deficiency of serotonin induced by 5,7-DHT restored the snail's ability to learn. We discovered that injections of the neurotoxins 5,6/5,7-DHT as well as serotonin, caused a decrease in the resting and threshold potentials of the premotor interneurons LPa3 and RPa3. PMID:26557063

Aqueous-phase disappearance of atrazine, metolachlor, and chlorpyrifos in laboratory aquaria and outdoor macrocosms

USGS Publications Warehouse

Mazanti, L.; Rice, C.; Bialek, K.; Sparling, D.; Stevenson, C.; Johnson, W.E.; Kangas, P.; Rheinstein, J.

2003-01-01

Dissipation processes are described for a combination of commonly used pesticides--atrazine (6-chloro-4--ethylamino-6-isopropylamino-s-triazine), metolachlor (2-chloro-N-[2-ethyl-6-methyl-phenyl]-N-[2-methoxy-l-methylethyl] acetamide), and chlorpyrifos (O-O diethyl O-[3,5,6-trichloro-2-pyridinyl] phosphorothioate)--in a laboratory and outdoor pond systems. Dosing rates and timing were designed to duplicate those common in the mid-Atlantic Coastal Plain, USA. Treatment ranged from 2 and 2.5 mg/L to 0.2 and 0.25 mg/L respectively for atrazine and metolachlor, and chlorpyrifos was added at 1.0 and 0.1 mg/L in the aquaria and at 0.1 mg/L in the outdoor macrocosms. Chlorpyrifos disappearance was rapid in all of the systems and followed a two-phase sequence. Initial half-lives varied from 0.16 da), to 0.38 day and showed similar rates in the aquaria and the outdoor systems. The second phase of the chlorpyrifos loss pattern was slower (18-20 days) in all the treatments except for the low herbicide treatment in the outdoor test, where it was 3.4 days. Compared to the outdoor system, herbicide losses were much slower in the aquaria, e.g., 150 days for atrazine and 55 days for metolachlor, and no appreciable loss of herbicide was apparent in the high-treated aquaria. In the outdoor systems, the half-lives for the low herbicide treatment were 27 days and 12 days, respectively, for atrazine and metolachlor, and 48 and 20 days, respectively for the high herbicide-treated pond. Very low levels of CIAT (6-amino-2-chloro-4-iso-propylamino-s-triazine) and CEAT (2-chloro-4-ethylamino-6-ethylamino-s-triazine), degradation products of atrazine, were observed in the outdoor studies.

Tissue-specific bioconcentration and biotransformation of cypermethrin and chlorpyrifos in a native fish (Jenynsia multidentata) exposed to these insecticides singly and in mixtures.

PubMed

Bonansea, Rocío Inés; Marino, Damián J G; Bertrand, Lidwina; Wunderlin, Daniel A; Amé, María Valeria

2017-07-01

The aim of the present study was to evaluate the accumulation of cypermethrin and chlorpyrifos when the fish Jenynsia multidentata was exposed to these pesticides singly and in technical and commercial mixtures. Adult female fish were exposed over 96 h to 0.04 μg/L of cypermethrin; 0.4 μg/L of chlorpyrifos; 0.04 μg/L of cypermethrin + 0.4 μg/L of chlorpyrifos in a technical mixture; and 0.04 μg/L of cypermethrin + 0.4 μg/L of chlorpyrifos in a mixture of commercial products. Fish exposed to cypermethrin accumulated this compound only in muscle, probably because of the low biotransformation capacity of this organ and the induction of cytochrome P4501A1 (CYP1A1) expression in the liver. The accumulation of chlorpyrifos occurred in fish exposed to the insecticide (intestine > liver > gills) even when these fish had higher gluthatione-S-transferase (GST) activity in gills and P-glycoprotein (P-gp) expression in the liver, compared with the control. Fish exposed to the technical mixture showed cypermethrin accumulation (liver > intestine > gills) with higher levels than those measured in fish after only cypermethrin exposure. Higher expression levels of CYP1A1 in the liver were also observed compared with the Control. Fish exposed to the commercial mixture accumulated both insecticides (cypermethrin: intestine > gills and chlorpyrifos: liver > intestine > gills > muscle). In the organs where accumulation occurred, biotransformation enzymes were inhibited. Consequently, the commercial formulation exposure provoked the highest accumulation of cypermethrin and chlorpyrifos in J. multidentata, possibly associated with the biotransformation system inhibition. Environ Toxicol Chem 2017;36:1764-1774. © 2016 SETAC. © 2016 SETAC.

Serotonin-Sensitive Adenylate Cyclase in Neural Tissue and Its Similarity to the Serotonin Receptor: A Possible Site of Action of Lysergic Acid Diethylamide

PubMed Central

Nathanson, James A.; Greengard, Paul

1974-01-01

An adenylate cyclase (EC 4.6.1.1) that is activated specifically by low concentrations of serotonin has been identified in homogenates of the thoracic ganglia of an insect nervous system. The activation of this enzyme by serotonin was selectively inhibited by extremely low concentrations of D-lysergic acid diethylamide (LSD), 2-bromo-LSD, and cyproheptadine, agents which are known to block certain serotonin receptors in vivo. The inhibition was competitive with respect to serotonin, and the calculated inhibitory constant of LSD for this serotonin-sensitive adenylate cyclase was 5 nM. The data are consistent with a model in which the serotonin receptor of neural tissue is intimately associated with a serotonin-sensitive adenylate cyclase which mediates serotonergic neurotransmission. The results are also compatible with the possibility that some of the physiological effects of LSD may be mediated through interaction with serotonin-sensitive adenylate cyclase. PMID:4595572

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

PubMed Central

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

2001-01-01

We studied chlorpyrifos, an insecticide present in a commercial dip for treating ectoparasites in dogs, to estimate the amount of transferable residues that children could obtain from their treated pets. Although the chlorpyrifos dip is no longer supported by the manufacturer, the methodology described herein can help determine transferable residues from other flea control insecticide formulations. Twelve dogs of different breeds and weights were dipped using the recommended guidelines with a commercial, nonprescription chlorpyrifos flea dip for 4 consecutive treatments at 3-week intervals (nonshampoo protocol) and another 12 dogs were dipped with shampooing between dips (shampoo protocol). The samples collected at 4 hr and 7, 14, and 21 days after treatment in the nonshampoo protocol averaged 971, 157, 70, and 26 microg chlorpyrifos, respectively; in the shampoo protocol the samples averaged 459, 49, 15, and 10 microg, respectively. The highest single sample was about 7,000 microg collected at 4 hr. The pretreatment specific activities in the plasma of the dogs were about 75 nmol/min/mg protein for butyrylcholinesterase (BChE), and 9 nmol/min/mg protein for acetylcholinesterase (AChE). BChE was inhibited 50-75% throughout the study, and AChE was inhibited 11-18% in the nonshampoo protocol; inhibition was not as great in the shampoo protocol. There was no correlation (pchlorpyrifos to chlorpyrifos-oxon. Plasma cholinesterase activity did not return to control levels during the 3-week period. The differences between the shampoo and nonshampoo protocols were explained by differences in the techniques of the dip

Genes affecting sensitivity to serotonin in Caenorhabditis elegans.

PubMed

Schafer, W R; Sanchez, B M; Kenyon, C J

1996-07-01

Regulating the response of a postsynaptic cell to neurotransmitter is an important mechanism for controlling synaptic strength, a process critical to learning. We have begun to define and characterize genes that may control sensitivity to the neurotransmitter serotonin in the nematode Caenorhabditis elegans by identifying serotonin-hypersensitive mutants. We reported previously that mutations in the gene unc-2, which encodes a putative calcium channel subunit, result in hypersensitivity to serotonin. Here we report that mutants defective in the unc-36 gene, which encodes a homologue of a calcium channel auxiliary subunit, are also serotonin-hypersensitive. Moreover, the unc-36 gene appears to be required in the same cells as unc-2 for control of the same behaviors. Mutations in several other genes, including unc-8, unc-10, unc-20, unc-35, unc-75, unc-77, and snt-1 also result in hypersensitivity to serotonin. Several of these mutations have previously been shown to confer resistance to acetylcholinesterase inhibitors, suggesting that they may affect acetylcholine release. Moreover, we found that mutations that decrease acetylcholine synthesis cause defective egg-laying and serotonin hypersensitivity. Thus, acetylcholine appears to negatively regulate the response to serotonin and may participate in the process of serotonin desensitization.

Genes Affecting Sensitivity to Serotonin in Caenorhabditis Elegans

PubMed Central

Schafer, W. R.; Sanchez, B. M.; Kenyon, C. J.

1996-01-01

Regulating the response of a postsynaptic cell to neurotransmitter is an important mechanism for controlling synaptic strength, a process critical to learning. We have begun to define and characterize genes that may control sensitivity to the neurotransmitter serotonin in the nematode Caenorhabditis elegans by identifying serotonin-hypersensitive mutants. We reported previously that mutations in the gene unc-2, which encodes a putative calcium channel subunit, result in hypersensitivity to serotonin. Here we report that mutants defective in the unc-36 gene, which encodes a homologue of a calcium channel auxiliary subunit, are also serotonin-hypersensitive. Moreover, the unc-36 gene appears to be required in the same cells as unc-2 for control of the same behaviors. Mutations in several other genes, including unc-8, unc-10, unc-20, unc-35, unc-75, unc-77, and snt-1 also result in hypersensitivity to serotonin. Several of these mutations have previously been shown to confer resistance to acetylcholinesterase inhibitors, suggesting that they may affect acetylcholine release. Moreover, we found that mutations that decrease acetylcholine synthesis cause defective egg-laying and serotonin hypersensitivity. Thus, acetylcholine appears to negatively regulate the response to serotonin and may participate in the process of serotonin desensitization. PMID:8807295

Chlorpyrifos induces oxidative stress in oligodendrocyte progenitor cells.

PubMed

Saulsbury, Marilyn D; Heyliger, Simone O; Wang, Kaiyu; Johnson, Deadre J

2009-05-02

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

Serotonin and Social Norms

PubMed Central

Bilderbeck, Amy C.; Brown, Gordon D. A.; Read, Judi; Woolrich, Mark; Cowen, Phillip J.; Behrens, Tim E. J.

2014-01-01

How do people sustain resources for the benefit of individuals and communities and avoid the tragedy of the commons, in which shared resources become exhausted? In the present study, we examined the role of serotonin activity and social norms in the management of depletable resources. Healthy adults, alongside social partners, completed a multiplayer resource-dilemma game in which they repeatedly harvested from a partially replenishable monetary resource. Dietary tryptophan depletion, leading to reduced serotonin activity, was associated with aggressive harvesting strategies and disrupted use of the social norms given by distributions of other players’ harvests. Tryptophan-depleted participants more frequently exhausted the resource completely and also accumulated fewer rewards than participants who were not tryptophan depleted. Our findings show that rank-based social comparisons are crucial to the management of depletable resources, and that serotonin mediates responses to social norms. PMID:24815611

Avoidance behaviour response and esterase inhibition in the earthworm, Lumbricus terrestris, after exposure to chlorpyrifos.

PubMed

Martínez Morcillo, S; Yela, J L; Capowiez, Y; Mazzia, C; Rault, M; Sanchez-Hernandez, Juan C

2013-05-01

The avoidance response of earthworms to polluted soils has been standardised using a simple and low-cost test, which facilitates soil toxicity screening. In this study, the avoidance response of Lumbricus terrestris was quantified in chlorpyrifos-spiked soils, depending on the pesticide concentration and exposure duration. The inhibition of acetylcholinesterase (AChE) and carboxylesterase (CbE) activities was also determined as indirect measures of pesticide bioavailability. The effects of different chlorpyrifos concentrations were examined in a standardised test (two-chamber system) with 0.6, 3 and 15 mg/kg chlorpyrifos. A modification of the test involved a pre-exposure step (24, 48 or 72 h) in soils spiked with 15 mg/kg. In both protocols, earthworms were unable to avoid the contaminated soils. However, the esterase activities showed that all earthworms were exposed to chlorpyrifos. Acetylcholinesterase activity did not change in earthworms in the standardised behavioural test (0.58 ± 0.20 U/mg protein, mean ± SD; n = 72), whereas the CbE activity was significantly inhibited (62-87 % inhibition) in earthworms exposed to 3 and 15 mg/kg. In the modified test, earthworms had greatly inhibited AChE activity (0.088 ± 0.034 U/mg protein, n = 72), which was supported by reactivation of the inhibited enzyme activity in the presence of pralidoxime (2-PAM). Similarly, the CbE activity was significantly inhibited in earthworms with all treatments. This study suggests that the avoidance behaviour test for organophosphorus-contaminated soils could be supported by specific biomarkers to facilitate a better understanding of pesticide exposure and toxicity during this test.

PRENATAL EXPOSURE TO CHLORPYRIFOS ALTERS NEUROTROPHIN IMMUNOREACTIVITY AND APOPTOSIS IN RAT BRAIN.

EPA Science Inventory

In the present study, the effects of the organophosphate pesticide chlorpyrifos [CPF; O,O'diethyl O-3,5,6-trichloro-2-pyridyl) phosphorothionate] on the regional distribution of three neurotrophic factors and on levels of apoptosis in gestational rat brain were characterized. P...

Serotonin Neuron Abnormalities in the BTBR Mouse Model of Autism

PubMed Central

Guo, Yue-Ping; Commons, Kathryn G.

2017-01-01

The inbred mouse strain BTBR T+ Itpr3tf/J (BTBR) i studied as a model of idiopathic autism because they are less social and more resistant to change than other strains. Forebrain serotonin receptors and the response to serotonin drugs are altered in BTBR mice, yet it remains unknown if serotonin neurons themselves are abnormal. In this study, we found that serotonin tissue content and the density of serotonin axons is reduced in the hippocampus of BTBR mice in comparison to C57BL/6J (C57) mice. This was accompanied by possible compensatory changes in serotonin neurons that were most pronounced in regions known to provide innervation to the hippocampus: the caudal dorsal raphe (B6) and the median raphe. These changes included increased numbers of serotonin neurons and hyperactivation of Fos expression. Metrics of serotonin neurons in the rostral 2/3 of the dorsal raphe and serotonin content of the prefrontal cortex were less impacted. Thus, serotonin neurons exhibit region-dependent abnormalities in the BTBR mouse that may contribute to their altered behavioral profile. PMID:27478061

Serotonin uptake inhibitors: uses in clinical therapy and in laboratory research.

PubMed

Fuller, R W

1995-01-01

Fluoxetine, zimelidine, sertraline, paroxetine, fluvoxamine, indalpine and citalopram are the selective inhibitors of serotonin uptake that have been most widely studied. Some of these compounds are or have been used clinically in the treatment of mental depression, obsessive-compulsive disorder and bulimia, and therapeutic benefit has been claimed in additional diseases as well. By blocking the membrane uptake carrier which transports serotonin from the extracellular space to inside the serotonin nerve terminals, these compounds increase extracellular concentrations of serotonin and amplify signals sent by serotonin neurons. Because serotonin neurons are widespread in the central nervous system, the functional consequences of blocking serotonin uptake are diverse, but are generally subtle. Animals treated with serotonin uptake inhibitors look normal in gross appearance, but effects such as reduced aggressive behavior, decreased food intake and altered food selection, analgesia, anticonvulsant activity, endocrine changes and neurochemical changes have been demonstrated and characterized. Serotonin uptake inhibitors have helped in revealing some dynamics of serotonin neurons; for example, when uptake is inhibited and extracellular serotonin concentration increases, presynaptic as well as postsynaptic receptors for serotonin are activated to a greater degree. A consequence of increased activation of autoreceptors on serotonin cell bodies and nerve terminals is a reduction in firing of serotonin neurons and a decrease in serotonin synthesis and release. The result is a limit on the degree to which extracellular serotonin and serotonergic neurotransmission are increased.(ABSTRACT TRUNCATED AT 250 WORDS)

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

EPA Science Inventory

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

Multiple mechanisms of serotonin 5-HT2 receptor desensitization.

PubMed

Rahman, S; Neuman, R S

1993-07-20

Desensitization of serotonin 5-HT2 receptor-mediated enhancement of the N-methyl-D-aspartate (NMDA) depolarization was studied in rat cortical neurons. Serotonin and (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) induced long term desensitization. Staurosporine, a nonspecific protein kinase C inhibitor, potentiated the serotonin and DOI facilitation, suggesting acute desensitization was operative. In the case of DOI, long term desensitization was prevented by staurosporine. Activators of protein kinase C abolished the serotonin facilitation, an action prevented by staurosporine. Concanavalin A potentiated the facilitation at 100 microM, but not 30 microM serotonin, suggesting these receptors undergo dose dependent internalization. Calmodulin antagonists prevent long term desensitization induced by serotonin. The depolarization induced by NMDA alone was not altered by staurosporine, protein kinase C activators, concanavalin A or calmodulin antagonists. Serotonin at 100 microM, but not 30 microM, induced heterologous desensitization of phenylephrine and carbachol induced facilitation of the NMDA depolarization. We conclude that serotonin 5-HT2 receptors both induce and undergo several forms of desensitization.

Stimulation of aortic smooth muscle cell mitogenesis by serotonin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nemecek, G.M.; Coughlin, S.R.; Handley, D.A.

1986-02-01

Bovine aortic smooth muscle cells in vitro responded to 1 nM to 10 ..mu..M serotonin with increased incorporation of (/sup 3/H)thymidine into DNA. The mitogenic effect of serotonin was half-maximal at 80 nM and maximal above 1 ..mu..M. At a concentration of 1 ..mu..M, serotonin stimulated smooth muscle cell mitogenesis to the same extent as human platelet-derived growth factor (PDGF) at 12 ng/ml. Tryptamine was approx. = 1/10th as potent as serotonin as a mitogen for smooth muscle cells. Other indoles that are structurally related to serotonin (D- and L-tryptophan, 5-hydroxy-L-tryptophan, N-acetyl-5-hydroxytryptamine, melatonin, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophol) and quipazine weremore » inactive. The stimulatory effect of serotonin on smooth muscle cell DNA synthesis required prolonged (20-24 hr) exposure to the agonist and was attenuated in the presence of serotonin D receptor antagonists. When smooth muscle cells were incubated with submaximal concentrations of serotonin and PDGF, synergistic rather than additive mitogenic responses were observed. These data indicate that serotonin has a significant mitogenic effect on smooth muscle cells in vitro, which appears to be mediated by specific plasma membrane receptors.« less

Human and soil exposure during mechanical chlorpyrifos, myclobutanil and copper oxychloride application in a peach orchard in Argentina.

PubMed

Berenstein, Giselle; Nasello, Soledad; Beiguel, Érica; Flores, Pedro; Di Schiena, Johanna; Basack, Silvana; Hughes, Enrique A; Zalts, Anita; Montserrat, Javier M

2017-05-15

The objective of this study was to measure the impact of the mechanized chlorpyrifos, copper oxychloride and myclobutanil application in a small peach orchard, on humans (operators, bystanders and residents) and on the productive soil. The mean Potential Dermal Exposure (PDE) of the workers (tractor drivers) was 30.8mL·h -1 ±16.4mL·h -1 , with no specific pesticide distribution on the laborers body. Although the Margin of Safety (MOS) factor for the application stage were above 1 (safe condition) for myclobutanil and cooper oxycloride it was below 1 for chlorpyrifos. The mix and load stage remained as the riskier operation. Pesticide found on the orchard soil ranged from 5.5% to 14.8% of the total chlorpyrifos, copper oxychloride and myclobutanil applied. Pesticide drift was experimentally measured, finding values in the range of 2.4% to 11.2% of the total pesticide applied. Using experimental drift values, bystander (for one application), resident (for 20 applications) and earthworm (for one application) risk indicators (RIs) were calculated for the chlorpyrifos plus copper oxychloride and for myclobutanil treatments for different distances to the orchard border. Earthworm RI was correlated with experimental Eisenia andrei ecotoxicological assays (enzymatic activities: cholinesterases, carboxylesterases and glutathione S-transferases; behavioral: avoidance and bait-lamina tests) with good correlation. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis and Characterization of Chlorpyrifos/Copper(II) Schiff Base Mesoporous Silica with pH Sensitivity for Pesticide Sustained Release.

PubMed

Chen, Huayao; Lin, Yueshun; Zhou, Hongjun; Zhou, Xinhua; Gong, Sheng; Xu, Hua

2016-11-02

The salicylaldehyde-modified mesoporous silica (SA-MCM-41) was prepared through a co-condensation method. Through the bridge effect from the copper ion, which also acts as the nutrition of the plant, the model drug chlorpyrifos (CH) was supported on the copper(II) Schiff base mesoporous silica (Cu-MCM-41) to form a highly efficient sustained-release system (CH-Cu-MCM-41) for pesticide delivery. The experimental results showed that the larger the concentration of the copper ion, the more adsorption capacity (AC) of Cu-MCM-41 for chlorpyrifos and the smaller its release rate. The results confirmed the existence of a coordination bond between SA-MCM-41 and copper ions as well as a coordination bond between Cu-MCM-41 and chlorpyrifos. The AC of SA-MCM-41 is 106 mg/g, while that of Cu-MCM-41 is 295 mg/g. The as-synthesized system showed significant pH sensitivity. Under the condition of pH ≤ 7, the release rate of chlorpyrifos decreased with increasing pH, whereas its release rate in weak base conditions was slightly larger than that in weak acid conditions. Meanwhile, the drug release rate of the as-synthesized system was also affected by the temperature. Their sustained-release curves can be described by the Korsmeyer-Peppas equation.

Molecular imaging of serotonin degeneration in mild cognitive impairment.

PubMed

Smith, Gwenn S; Barrett, Frederick S; Joo, Jin Hui; Nassery, Najlla; Savonenko, Alena; Sodums, Devin J; Marano, Christopher M; Munro, Cynthia A; Brandt, Jason; Kraut, Michael A; Zhou, Yun; Wong, Dean F; Workman, Clifford I

2017-09-01

Neuropathological and neuroimaging studies have consistently demonstrated degeneration of monoamine systems, especially the serotonin system, in normal aging and Alzheimer's disease. The evidence for degeneration of the serotonin system in mild cognitive impairment is limited. Thus, the goal of the present study was to measure the serotonin transporter in vivo in mild cognitive impairment and healthy controls. The serotonin transporter is a selective marker of serotonin terminals and of the integrity of serotonin projections to cortical, subcortical and limbic regions and is found in high concentrations in the serotonergic cell bodies of origin of these projections (raphe nuclei). Twenty-eight participants with mild cognitive impairment (age 66.6±6.9, 16 males) and 28 healthy, cognitively normal, demographically matched controls (age 66.2±7.1, 15 males) underwent magnetic resonance imaging for measurement of grey matter volumes and high-resolution positron emission tomography with well-established radiotracers for the serotonin transporter and regional cerebral blood flow. Beta-amyloid imaging was performed to evaluate, in combination with the neuropsychological testing, the likelihood of subsequent cognitive decline in the participants with mild cognitive impairment. The following hypotheses were tested: 1) the serotonin transporter would be lower in mild cognitive impairment compared to controls in cortical and limbic regions, 2) in mild cognitive impairment relative to controls, the serotonin transporter would be lower to a greater extent and observed in a more widespread pattern than lower grey matter volumes or lower regional cerebral blood flow and 3) lower cortical and limbic serotonin transporters would be correlated with greater deficits in auditory-verbal and visual-spatial memory in mild cognitive impairment, not in controls. Reduced serotonin transporter availability was observed in mild cognitive impairment compared to controls in cortical and limbic

Effects of chlorpyrifos and trichloropyridinol on HEK 293 human embryonic kidney cells

EPA Science Inventory

Chlorpyrifos (CPF) [O, O-diethyl -O-3, 5, 6-trichloro-2-pyridyl phosphorothioate] is an organophosphate insecticide widely used for agricultural and urban pest control. Trichloropyridinol (TCP; 3,5,6-trichloro-2-pyridinol), the primary metabolite of CPF, is often used as a generi...

Atmospheric deposition flux estimates for chlorpyrifos and trifluralin in the chukchi sea

USDA-ARS?s Scientific Manuscript database

During the 1993 U.S.-Russian BERPAC expedition, residues of agricultural pesticides were detected in seawater, ice, surface microlayer, fog, and air of the Bering and Chukchi Seas. Gas exchange, wet deposition, and dry particle deposition fluxes of trifluralin and chlorpyrifos were estimated using m...

Activity patterns of serotonin neurons underlying cognitive flexibility

PubMed Central

Matias, Sara; Lottem, Eran; Dugué, Guillaume P; Mainen, Zachary F

2017-01-01

Serotonin is implicated in mood and affective disorders. However, growing evidence suggests that a core endogenous role is to promote flexible adaptation to changes in the causal structure of the environment, through behavioral inhibition and enhanced plasticity. We used long-term photometric recordings in mice to study a population of dorsal raphe serotonin neurons, whose activity we could link to normal reversal learning using pharmacogenetics. We found that these neurons are activated by both positive and negative prediction errors, and thus report signals similar to those proposed to promote learning in conditions of uncertainty. Furthermore, by comparing the cue responses of serotonin and dopamine neurons, we found differences in learning rates that could explain the importance of serotonin in inhibiting perseverative responding. Our findings show how the activity patterns of serotonin neurons support a role in cognitive flexibility, and suggest a revised model of dopamine–serotonin opponency with potential clinical implications. DOI: http://dx.doi.org/10.7554/eLife.20552.001 PMID:28322190

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

PubMed

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

2016-02-01

Helicoverpa armigera is a key pest in many vital crops, which is mainly controlled by chemical strategies. To manage this pest is becoming challenging due to its ability and evolution of resistance against insecticides. Further, its subsequent spread on nonhost plant is remarkable in recent times. Hence, decoding resistance mechanism against phytochemicals and synthetic insecticides is a major challenge. The present work describes that the digestion, defense and immunity related enzymes are associated with chlorpyrifos resistance in H. armigera. Proteomic analysis of H. armigera gut tissue upon feeding on chlorpyrifos containing diet (CH) and artificial diet (AD) using nano-liquid chromatography-mass spectrometry identified upregulated 23-proteins in CH fed larvae. Database searches combined with gene ontology analysis revealed that the identified gut proteins engrossed in digestion, proteins crucial for immunity, adaptive responses to stress, and detoxification. Biochemical and quantitative real-time polymerase chain reaction analysis of candidate proteins indicated that insects were struggling to get nutrients and energy in presence of CH, while at the same time endeavoring to metabolize chlorpyrifos. Moreover, we proposed a potential processing pathway of chlorpyrifos in H. armigera gut by examining the metabolites using gas chromatography-mass spectrometry. H. armigera exhibit a range of intriguing behavioral, morphological adaptations and resistance to insecticides by regulating expression of proteins involved in digestion and detoxification mechanisms to cope up with chlorpyrifos. In these contexts, as gut is a rich repository of biological information; profound analysis of gut tissues can give clues of detoxification and resistance mechanism in insects. © 2014 Institute of Zoology, Chinese Academy of Sciences.

Use of organic amendments as a bioremediation strategy to reduce the bioavailability of chlorpyrifos insecticide in soils. Effects on soil biology.

PubMed

Tejada, Manuel; Gómez, Isidoro; Del Toro, Marina

2011-10-01

The sorption capacity of both an organic municipal solid waste by-product (MSW) and a cow manure (CM) in a soil polluted with chlorpyrifos, as well as its effect on soil microbial activity, and weight, reproductive parameters and glutathione-S-transferase activity of two earthworm species (Eisenia fetida and Lumbricus terrestris) were studied. Chlorpyrifos was added at the recommended application rate (5 L ha(-1); 768 mg chlorpyrifos kg(-1)) and treated with MSW at a rate of 10% and CM at a rate of 5.8% in order to apply the same amount of organic matter to the soil. An unamended polluted soil was used as control. Earthworm cocoon number, average weight of cocoon, and number of juveniles per cocoon were measured after 30 days of incubation, whereas soil enzymatic activities, earthworm weight, and glutathione-S-transferase activity of earthworms were measured after 3, 45 and 90 days. Soil enzymatic activities, reproductive and glutathione-S-transferase activity in both worms decreased in polluted soil. The inhibition percentage of soil enzymatic activities, reproductive and glutathione-S-transferase activity in both worms was lower in MSW-amended soil than for CM-amended soil. The toxic effect of chlorpyrifos on E. fetida was lowest compared to L. terrestris. This suggested that the addition of organic wastes with higher humic than fulvic acid concentration is more beneficial for remediation of soils polluted with chlorpyrifos. Copyright © 2011 Elsevier Inc. All rights reserved.

Antidepressants differentially affect striatal amphetamine-stimulated dopamine and serotonin release in rats with high and low novelty-oriented behaviour.

PubMed

O'Leary, Aet; Kõiv, Kadri; Raudkivi, Karita; Harro, Jaanus

2016-11-01

In the studies of depression pathogenesis and antidepressant action, the monoaminergic hypothesis of depression has mainly focused on the serotonergic and noradrenergic mechanisms. However, dopaminergic neurotransmission is also linked to both depressive symptomatology as well as antidepressant effects. We have previously shown that persistent inter-individual differences in the rat behavioural activity in novel environments is associated with differences in the striatal extracellular levels of dopamine and serotonin, depressive-like behaviour and the expression of several depression-related genes. The aim of the current study was to investigate the relative potency of the tricyclic antidepressant imipramine, the selective serotonin re-uptake inhibitor fluoxetine, and the selective noradrenaline re-uptake inhibitor reboxetine (all drugs administered in the dose of 10mg/kg, i.p.) to enhance amphetamine-stimulated dopamine and serotonin release in the striatum using in vivo microdialysis in awake, freely-moving rats, categorized into high explorers (HE) and low explorers (LE) based on their spontaneous novelty-oriented behaviour. The basal extracellular dopamine and serotonin concentration in the striatum did not differ between the LE- and HE-rats. None of the antidepressants alone were able to modify baseline striatal dopamine levels, but the amphetamine-stimulated dopamine release was significantly higher in the HE-rats after acute and chronic imipramine (but not fluoxetine or reboxetine). Acute imipramine and fluoxetine, but not reboxetine, increased both the basal and amphetamine-stimulated levels of serotonin in the striatum. Again, the HE-rats had higher amphetamine-stimulated serotonin release after fluoxetine administration. These findings suggest that rats with depressive-like phenotype are less sensitive to the neurochemical effects of antidepressants in the striatum. These results may have relevance in understanding the neurobiological bases for inter

Tramadol and another atypical opioid meperidine have exaggerated serotonin syndrome behavioral effects, but decreased analgesic effects, in genetically-deficient serotonin transporter (SERT) mice

PubMed Central

Fox, Meredith A.; Jensen, Catherine L.; Murphy, Dennis L.

2009-01-01

The serotonin syndrome is a potential side effect of serotonin-enhancing drugs, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs). We recently reported a genetic mouse model for the serotonin syndrome, as serotonin transporter (SERT)-deficient mice have exaggerated serotonin syndrome behavioral responses to the MAOI tranylcypromine and the serotonin precursor 5-hydroxy-L-tryptophan (5-HTP). As numerous case reports implicate the atypical opioids tramadol and meperidine in the development of the human serotonin syndrome, we examined tramadol and meperidine as possible causative drugs in the rodent model of the serotonin syndrome in SERT wildtype (+/+), heterozygous (+/−) and knockout (−/−) mice. Comparisons were made to SERT mice treated with either vehicle or morphine, an opioid not implicated in the serotonin syndrome in humans. Here we show that tramadol and meperidine, but not morphine, induce serotonin syndrome-like behaviors in mice, and we show that this response is exaggerated in mice lacking one or two copies of SERT. The exaggerated response to tramadol in SERT −/− mice was blocked by pretreatment with the 5-HT1A antagonist WAY 100635. Further, we show that morphine-, meperidine- and tramadol-induced analgesia is markedly decreased in SERT −/− mice. These studies suggest that caution seems warranted in prescribing or not warning patients receiving SSRIs or MAOIs, that dangerous side effects may occur during concurrent use of tramadol and similar agents. These findings suggest that it is conceivable that there might be increased vulnerability in individuals with SERT polymorphisms that may reduce SERT by more than 50%, the level in SERT +/− mice. PMID:19275775

Characterization of soil organic matter by FT-IR spectroscopy and its relationship with chlorpyrifos sorption.

PubMed

Parolo, María Eugenia; Savini, Mónica Claudia; Loewy, Ruth Miriam

2017-07-01

Sorption of non-ionic organic compounds to soil is usually expressed as the carbon-normalized partition coefficient (K OC ) assuming that the main factor that influences the amount sorbed is the organic carbon content (OC) of the soil. However, K OC can vary across a range of soils. The influence of certain soil characteristics on the chlorpyrifos K OC values variation for 12 representative soils of the Northpatagonian Argentinian region with different physicochemical properties was investigated for this study. The chlorpyrifos sorption coefficients normalized by the OC content were experimentally obtained using the batch equilibrium method; the K OC values ranged between 9000-20,000 L kg -1 . The soil characteristics assessed were pH, clay content and spectral data indicative of soil organic matter (SOM) quality measured by FT-IR on the whole soil. The bands considered in the spectroscopic analyses were those corresponding to the aliphatic components, 2947-2858 cm -1 (band A) and the hydrophilic components, 1647-1633 cm -1 (band B). A significant relationship was found (R 2  = 0.66) between chlorpyrifos sorption (K OC ) and the variables pH and A/B height band ratio. The correlation between the values predicted by the derived model and the experimental data was significant (r = 0.89 p < 0.05). Thus, this methodology could be used to estimate chlorpyrifos sorption coefficient through the use of a simple, rapid, and environmentally-friendly measurement. K OC analysis in relation to soil properties represents a valuable contribution to the understanding of the attenuation phenomena of the organic contaminants off-site migration in the environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shenouda, Josephine; Green, Paula; Sultatos, Lester, E-mail: sultatle@umdnj.ed

2009-12-01

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

GESTATIONAL EXPOSURE TO CHLORPYRIFOS: QUALITATIVE AND QUANTITATIVE NEUROPATHOLOGICAL CHANGES IN THE FETAL NEOCORTEX.

EPA Science Inventory

This study investigated the qualitative and quantitative neuropathological changes that occur in the fetal brain following gestational exposure to chlorpyrifos [(O,O'diethyl O-3,5,6-trichloro-2-pyridyl) phosphorothionate], a commonly used organophosphorus insecticide. Two cohort...

Serotonin Test

MedlinePlus

... Cancer Therapy Glucose Tests Gonorrhea Testing Gram Stain Growth Hormone Haptoglobin hCG Pregnancy hCG Tumor Marker HDL Cholesterol ... Semen Analysis Serotonin Serum Free Light Chains Sex Hormone Binding Globulin ... Transferrin Receptor Stool Culture Stool Elastase Strep ...

Action potential-independent and pharmacologically unique vesicular serotonin release from dendrites

PubMed Central

Colgan, Lesley A.; Cavolo, Samantha L.; Commons, Kathryn G.; Levitan, Edwin S.

2012-01-01

Serotonin released within the dorsal raphe nucleus (DR) induces feedback inhibition of serotonin neuron activity and consequently regulates mood-controlling serotonin release throughout the forebrain. Serotonin packaged in vesicles is released in response to action potentials by the serotonin neuron soma and terminals, but the potential for release by dendrites is unknown. Here three-photon (3P) microscopy imaging of endogenous serotonin in living rat brain slice, immunofluorescence and immuno-gold electron microscopy detection of VMAT2 (vesicular monoamine transporter 2) establish the presence of vesicular serotonin within DR dendrites. Furthermore, activation of glutamate receptors is shown to induce vesicular serotonin release from dendrites. However, unlike release from the soma and terminals, dendritic serotonin release is independent of action potentials, relies on L-type Ca2+ channels, is induced preferentially by NMDA, and displays distinct sensitivity to the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine. The unique control of dendritic serotonin release has important implications for DR physiology and the antidepressant action of SSRIs, dihydropyridines and NMDA receptor antagonists. PMID:23136413

Serotonin at the Nexus of Impulsivity and Cue Reactivity in Cocaine Addiction

PubMed Central

Cunningham, Kathryn A.; Anastasio, Noelle C.

2014-01-01

Cocaine abuse and addiction remain great challenges on the public health agendas in the U.S. and the world. Increasingly sophisticated perspectives on addiction to cocaine and other drugs of abuse have evolved with concerted research efforts over the last 30 years. Relapse remains a particularly powerful clinical problem as, even upon termination of drug use and initiation of abstinence, the recidivism rates can be very high. The cycling course of cocaine intake, abstinence and relapse is tied to a multitude of behavioral and cognitive processes including impulsivity (a predisposition toward rapid unplanned reactions to stimuli without regard to the negative consequences), and cocaine cue reactivity (responsivity to cocaine-associated stimuli) cited as two key phenotypes that contribute to relapse vulnerability even years into recovery. Preclinical studies suggest that serotonin (5-hydroxytryptamine; 5-HT) neurotransmission in key neural circuits may contribute to these interlocked phenotypes well as the altered neurobiological states evoked by cocaine that precipitate relapse events. As such, 5-HT is an important target in the quest to to understand the neurobiology of relapse-predictive phenotypes, to successfully treat this complex disorder and improve diagnostic and prognostic capabilities. This review emphasizes the role of 5-HT and its receptor proteins in key addiction phenotypes and the implications of current findings to the future of therapeutics in addiction. PMID:23850573

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

EPA Science Inventory

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

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

PubMed

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

2009-11-01

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

Serotonin neuron abnormalities in the BTBR mouse model of autism.

PubMed

Guo, Yue-Ping; Commons, Kathryn G

2017-01-01

The inbred mouse strain BTBR T + Itpr3 tf /J (BTBR) is studied as a model of idiopathic autism because they are less social and more resistant to change than other strains. Forebrain serotonin receptors and the response to serotonin drugs are altered in BTBR mice, yet it remains unknown if serotonin neurons themselves are abnormal. In this study, we found that serotonin tissue content and the density of serotonin axons is reduced in the hippocampus of BTBR mice in comparison to C57BL/6J (C57) mice. This was accompanied by possible compensatory changes in serotonin neurons that were most pronounced in regions known to provide innervation to the hippocampus: the caudal dorsal raphe (B6) and the median raphe. These changes included increased numbers of serotonin neurons and hyperactivation of Fos expression. Metrics of serotonin neurons in the rostral 2/3 of the dorsal raphe and serotonin content of the prefrontal cortex were less impacted. Thus, serotonin neurons exhibit region-dependent abnormalities in the BTBR mouse that may contribute to their altered behavioral profile. Autism Res 2017, 10: 66-77. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Comparison of serum serotonin and serum 5-HIAA LC-MS/MS assays in the diagnosis of serotonin producing neuroendocrine neoplasms: A pilot study.

PubMed

Lindström, Mikael; Tohmola, Niina; Renkonen, Risto; Hämäläinen, Esa; Schalin-Jäntti, Camilla; Itkonen, Outi

2018-07-01

Serotonin (5-hydroxytyramine) is a mediator of gastrointestinal smooth muscle contraction, and is secreted by neuroendocrine neoplasms (NENs). We developed a liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for serum serotonin to be used in NEN diagnostics and follow-up. We used serum samples from healthy volunteers (n = 31) and patients suspected or monitored for NEN (n = 98). Serotonin-D 4 internal standard was added to samples before solid phase extraction (SPE) and quantification by LC-MS/MS. The effects of sample handling and preparation on serotonin stability were studied. Finally, we established a provisional reference range for serum serotonin and compared our assay with serum 5-hydroxyindoleacetic acid (5-HIAA) for detection of NENs. Our assay is sensitive and has a wide linear range (10-10,000 nmol/l). Serum serotonin is stable for 7 days at room temperature and for 3 months at -20 °C. Sampling temperature is not critical. Normal range for serum serotonin was 270-1490 nmol/l. We found that serum serotonin and 5-HIAA performed equally well as diagnostic tests for NENs. Our LC-MS/MS assay for serum serotonin is well suited for clinical research and patient diagnostics. Our results confirm that it can complement 5-HIAA in diagnosis of NENs. Copyright © 2018 Elsevier B.V. All rights reserved.

Transformation of chlorpyrifos in integrated recirculating constructed wetlands (IRCWs) as revealed by compound-specific stable isotope (CSIA) and microbial community structure analysis.

PubMed

Tang, Xiaoyan; Yang, Yang; Huang, Wenda; McBride, Murray B; Guo, Jingjing; Tao, Ran; Dai, Yunv

2017-06-01

Carbon isotope analysis and 454 pyrosequencing methods were used to investigate in situ biodegradation of chlorpyrifos during its transport through three model integrated recirculating constructed wetlands (IRCWs). Results show that plant and Fe-impregnated biochar promoted degradation of chlorpyrifos and its metabolite 3,5,6-trichloro-2-pyridinol (TCP). Carbon isotope ratios in the IRCWs shifted to -31.24±0.58‰ (IRCW1, plant free), -26.82±0.60‰ (IRCW2, with plant) and -24.76±0.94‰ (IRCW3, with plant and Fe-biochar). The enrichment factors (Ɛ bulk,c ) were determined as -0.69±0.06‰ (IRCW1), -0.91±0.07‰ (IRCW2) and -1.03±0.09‰ (IRCW3). Microbial community analysis showed that IRCW3 was dominated by members of Bacillus, which can utilize and degrade chlorpyrifos. These results reveal that plant and Fe-biochar can induce carbon isotope fractionation and have a positive impact on the chlorpyrifos degradation efficiency by influencing the development of beneficial microbial communities. Copyright © 2017. Published by Elsevier Ltd.

Regulation of serotonin release from enterochromaffin cells of rat cecum mucosa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simon, C.; Ternaux, J.P.

1990-05-01

The release of endogenous serotonin or previously taken up tritiated serotonin from isolated strips of rat cecum mucosa containing enterochromaffin cells was studied in vitro. Release of tritiated serotonin was increased by potassium depolarization and was decreased by tetrodotoxin, veratridine and the absence of calcium. Endogenous serotonin was released at a lower rate than tritiated serotonin; endogenous serotonin release was stimulated by potassium depolarization but was unaffected by tetrodotoxin, veratridine or the absence of calcium. Carbachol, norepinephrine, clonidine and isoproterenol decreased release of tritiated serotonin but had less or reverse effect on release of endogenous serotonin. The results suggest twomore » different serotoninergic pools within the enterochromaffin cell population.« less

Impact of Maternal Serotonin Transporter Genotype on Placental Serotonin, Fetal Forebrain Serotonin, and Neurodevelopment

PubMed Central

Muller, Christopher L; Anacker, Allison MJ; Rogers, Tiffany D; Goeden, Nick; Keller, Elizabeth H; Forsberg, C Gunnar; Kerr, Travis M; Wender, Carly LA; Anderson, George M; Stanwood, Gregg D; Blakely, Randy D; Bonnin, Alexandre; Veenstra-VanderWeele, Jeremy

2017-01-01

Biomarker, neuroimaging, and genetic findings implicate the serotonin transporter (SERT) in autism spectrum disorder (ASD). Previously, we found that adult male mice expressing the autism-associated SERT Ala56 variant have altered central serotonin (5-HT) system function, as well as elevated peripheral blood 5-HT levels. Early in gestation, before midbrain 5-HT projections have reached the cortex, peripheral sources supply 5-HT to the forebrain, suggesting that altered maternal or placenta 5-HT system function could impact the developing embryo. We therefore used different combinations of maternal and embryo SERT Ala56 genotypes to examine effects on blood, placenta and embryo serotonin levels and neurodevelopment at embryonic day E14.5, when peripheral sources of 5-HT predominate, and E18.5, when midbrain 5-HT projections have reached the forebrain. Maternal SERT Ala56 genotype was associated with decreased placenta and embryonic forebrain 5-HT levels at E14.5. Low 5-HT in the placenta persisted, but forebrain levels normalized by E18.5. Maternal SERT Ala56 genotype effects on forebrain 5-HT levels were accompanied by a broadening of 5-HT-sensitive thalamocortical axon projections. In contrast, no effect of embryo genotype was seen in concepti from heterozygous dams. Blood 5-HT levels were dynamic across pregnancy and were increased in SERT Ala56 dams at E14.5. Placenta RNA sequencing data at E14.5 indicated substantial impact of maternal SERT Ala56 genotype, with alterations in immune and metabolic-related pathways. Collectively, these findings indicate that maternal SERT function impacts offspring placental 5-HT levels, forebrain 5-HT levels, and neurodevelopment. PMID:27550733

Toxicokinetics and toxicodynamics of chlorpyrifos is altered in embryos of Japanese medaka exposed to oil sands process-affected water: evidence for inhibition of P-glycoprotein.

PubMed

Alharbi, Hattan A; Alcorn, Jane; Al-Mousa, Ahmed; Giesy, John P; Wiseman, Steve B

2017-05-01

Oil sands process-affected water (OSPW) is generated during extraction of bitumen in the surface mining oil sands industry in Alberta, Canada. Studies were performed in vitro by use of Caco-2 cells, and in vivo with larvae of Japanese medaka (Oryzias latipes) to determine if organic compounds from the aqueous phase of OSPW inhibit ATP binding cassette protein ABCB1 (permeability-glycoprotein, P-gp). Neutral and basic fractions of OSPW inhibited activity of P-gp in Caco-2 cells by 1.9- and 2.0-fold, respectively, while the acidic fraction had the least effect. The organophosphate pesticides chlorpyrifos (a substrate of P-gp) and malathion (not a substrate of P-gp), were used as model chemicals to investigate inhibition of P-gp in larvae. Co-exposure to chlorpyrifos and an extract of OSPW containing basic and neutral compounds reduced survival of larvae to 26.5% compared to survival of larvae exposed only to chlorpyrifos, which was 93.7%. However, co-exposure to malathion and the extract of OSPW did not cause acute lethality compared to exposure only to malathion. Accumulation and bioconcentration of chlorpyrifos, but not malathion, was greater in larvae co-exposed with the extract of OSPW. The terminal elimination half-life of chlorpyrifos in larvae exposed to chlorpyrifos in freshwater was 5 days compared with 11.3 days in larvae exposed to chlorpyrifos in OSPW. Results suggest that in non-acute exposures, basic and neutral organic compounds in the water-soluble fraction of OSPW inhibit activity of P-gp, which suggests that OSPW has the potential to cause adverse effects by chemosensitization. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Serotonin delays habituation of leech swim response to touch.

PubMed

Alkatout, Bilal A; Marvin, Nicole M; Crisp, Kevin M

2007-08-22

Serotonin, acting through a cAMP-signaling pathway, delayed habituation to criterion of the leech's swim response to touch. This delay was reversed by crushing the connective between serotonin-exposed and serotonin-naive ganglia, and correlated with an increase in spontaneous impulse activity in this connective. We suggest that increased activity in intersegmental interneurons may play a role in maintaining swim responsiveness when concentrations of serotonin are elevated.

[Metabolism of serotonin in autism in children].

PubMed

Bursztejn, C; Ferrari, P; Dreux, C; Braconnier, A; Lancrenon, S

1988-01-01

In this controlled study of 22 autistic children and 22 normal controls matched for age and sex, the frequency of hyperserotonemia in infantile autism was confirmed. Platelet serotonin was elevated in patients. Comparative to controls, serotonin was also high in urine of autistic patients, while, on the contrary there was no difference for the urinary excretion of 5-HIAA. No difference was observed either for serotonin uptake and efflux or for MAO activity, in isolated platelets. The elevation of plasma free tryptophan - significant only with the Kolmogorov Smirnov test - suggests that 5-HT biosynthesis might be enhanced. In the group of patient reported in this study, disorders of serotonin metabolism are associated with disturbances of platelet catecholamines, and also with elevated immunoglobulins and enhanced cellular immunity reactions.

A study of blood serotonin and serotonin transporter promoter variant (5-HTTLPR) polymorphism in Egyptian autistic children.

PubMed

Meguid, Nagwa A; Gebril, Ola H; Khalil, Rehab O

2015-01-01

Autism spectrum disorder (ASD) is a complex, heterogeneous neurodevelopmental disorder with onset during early childhood. Most studies have reported an elevation in platelet serotonin in persons with autism. The serotonin (5-hydroxytryptamine; 5-HT) transporter in the brain uptakes 5-HT from extracellular spaces. It is also present in platelets, where it takes up 5-HT from plasma. Polymorphisms in serotonin transporter gene (SLC6A4) were frequently studied in many neuropsychiatric disorders. We have measured the plasma 5-HT levels in 20 autistic male children and 20 control male children by the enzyme-linked immunosorbent assay (ELISA) method. In addition, the SLC6A4 promoter region (5-HTTLPR) insertion/deletion (I/D) polymorphism was studied, using whole genomic DNA. Plasma serotonin was significantly low in autistic children compared to control (P = 0.001), although correlation to severity of autism was not significant. The frequency of short (S) allele in autism cases was 10% and in the control group it was absent. Our study demonstrated an increased prevalence of 5-HTTLPR S allele in autism subjects. Significantly decreased plasma serotonin was detected in autism subjects, with no significant relationship between 5-HTTLPR genotype and plasma 5-HT being evident.

A study of blood serotonin and serotonin transporter promoter variant (5-HTTLPR) polymorphism in Egyptian autistic children

PubMed Central

Meguid, Nagwa A.; Gebril, Ola H.; Khalil, Rehab O.

2015-01-01

Background: Autism spectrum disorder (ASD) is a complex, heterogeneous neurodevelopmental disorder with onset during early childhood. Most studies have reported an elevation in platelet serotonin in persons with autism. The serotonin (5-hydroxytryptamine; 5-HT) transporter in the brain uptakes 5-HT from extracellular spaces. It is also present in platelets, where it takes up 5-HT from plasma. Polymorphisms in serotonin transporter gene (SLC6A4) were frequently studied in many neuropsychiatric disorders. Materials and Methods: We have measured the plasma 5-HT levels in 20 autistic male children and 20 control male children by the enzyme-linked immunosorbent assay (ELISA) method. In addition, the SLC6A4 promoter region (5-HTTLPR) insertion/deletion (I/D) polymorphism was studied, using whole genomic DNA. Results: Plasma serotonin was significantly low in autistic children compared to control (P = 0.001), although correlation to severity of autism was not significant. The frequency of short (S) allele in autism cases was 10% and in the control group it was absent. Conclusion: Our study demonstrated an increased prevalence of 5-HTTLPR S allele in autism subjects. Significantly decreased plasma serotonin was detected in autism subjects, with no significant relationship between 5-HTTLPR genotype and plasma 5-HT being evident. PMID:26015920

Serotonin and conditioning: focus on Pavlovian psychostimulant drug conditioning.

PubMed

Carey, Robert J; Damianopoulos, Ernest N

2015-04-01

Serotonin containing neurons are located in nuclei deep in the brainstem and send axons throughout the central nervous system from the spinal cord to the cerebral cortex. The vast scope of these connections and interactions enable serotonin and serotonin analogs to have profound effects upon sensory/motor processes. In that conditioning represents a neuroplastic process that leads to new sensory/motor connections, it is apparent that the serotonin system has the potential for a critical role in conditioning. In this article we review the basics of conditioning as well as the serotonergic system and point up the number of non-associative ways in which manipulations of serotonin neurotransmission have an impact upon conditioning. We focus upon psychostimulant drug conditioning and review the contribution of drug stimuli in the use of serotonin drugs to investigate drug conditioning and the important impact drug stimuli can have on conditioning by introducing new sensory stimuli that can create or mask a CS. We also review the ways in which experimental manipulations of serotonin can disrupt conditioned behavioral effects but not the associative processes in conditioning. In addition, we propose the use of the recently developed memory re-consolidation model of conditioning as an approach to assess the possible role of serotonin in associative processes without the complexities of performance effects related to serotonin treatment induced alterations in sensory/motor systems. Copyright © 2014 Elsevier B.V. All rights reserved.

Pharmacokinetics and effects on serum cholinesterase activities of organophosphorus pesticides acephate and chlorpyrifos in chimeric mice transplanted with human hepatocytes.

PubMed

Suemizu, Hiroshi; Sota, Shigeto; Kuronuma, Miyuki; Shimizu, Makiko; Yamazaki, Hiroshi

2014-11-01

Organophosphorus pesticides acephate and chlorpyrifos in foods have potential to impact human health. The aim of the current study was to investigate the pharmacokinetics of acephate and chlorpyrifos orally administered at lowest-observed-adverse-effect-level doses in chimeric mice transplanted with human hepatocytes. Absorbed acephate and its metabolite methamidophos were detected in serum from wild type mice and chimeric mice orally administered 150mg/kg. Approximately 70% inhibition of cholinesterase was evident in plasma of chimeric mice with humanized liver (which have higher serum cholinesterase activities than wild type mice) 1day after oral administrations of acephate. Adjusted animal biomonitoring equivalents from chimeric mice studies were scaled to human biomonitoring equivalents using known species allometric scaling factors and in vitro metabolic clearance data with a simple physiologically based pharmacokinetic (PBPK) model. Estimated plasma concentrations of acephate and chlorpyrifos in humans were consistent with reported concentrations. Acephate cleared similarly in humans and chimeric mice but accidental/incidental overdose levels of chlorpyrifos cleared (dependent on liver metabolism) more slowly from plasma in humans than it did in mice. The data presented here illustrate how chimeric mice transplanted with human hepatocytes in combination with a simple PBPK model can assist evaluations of toxicological potential of organophosphorus pesticides. Copyright © 2014 Elsevier Inc. All rights reserved.

Measuring the serotonin uptake site using (/sup 3/H)paroxetine--a new serotonin uptake inhibitor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gleiter, C.H.; Nutt, D.J.

1988-01-01

Serotonin is an important neurotransmitter that may be involved in ethanol preference and dependence. It is possible to label the serotonin uptake site in brain using the tricyclic antidepressant imipramine, but this also binds to other sites. We have used the new high-affinity uptake blocker paroxetine to define binding to this site and report it to have advantages over imipramine as a ligand.

Effect of chlorpyrifos on the inhibition of the enzyme acetylcholinesterase by cross-linking in water-supply samples and milk from dairy cattle.

PubMed

Catalina Rodríguez, Diana; Carvajal, Stephanie; Peñuela, Gustavo

2013-07-15

A methodology for the determination of chlorpyrifos in water-supply samples and in milk from dairy cattle was developed. An amperometric biosensor was used to inhibit the enzyme acetylcholinesterase (AChE), which was immobilized by the cross-linking method (crosslinks between the enzyme and the sensor). The potential applied, the amount of enzyme to be immobilized and the acetylthiocholine (ACTh) concentration were optimized before calibration and analysis of the samples was performed. The concentration of chlorpyrifos was determined in the range of 1.0×10(-6) M to 5.0×10(-2) M with a detection limit of 5.0×10(-6) M. Spiked water samples showed high recoveries (91.32% and 93.98% for low and high chlorpyrifos levels, respectively), while milk samples exhibited a matrix effect with recoveries of 82.81% and 79.77% for high and low chlorpyrifos levels, respectively. The average concentration of chlorpyrifos in the water supply samples (5.11×10(-6) M), determined using the biosensor, was compared using gas chromatography and gave an average value of 3.04×10(-6) M. The results allow it to be concluded that although chromatographic methods are still more exact, biosensors are promising tools for the determination of analytes in the field, as they have a low cost, a reduced analysis time and good reproducibility in the data. Copyright © 2013 Elsevier B.V. All rights reserved.

Reduced sympathetic innervation after alteration of target cell neurotransmitter phenotype in transgenic mice.

PubMed Central

Cho, S; Son, J H; Park, D H; Aoki, C; Song, X; Smith, G P; Joh, T H

1996-01-01

Neurotransmitters play a variety of important roles during nervous system development. In the present study, we hypothesized that neurotransmitter phenotype of both projecting and target cells is an important factor for the final synaptic linkage and its specificity. To test this hypothesis, we used transgenic techniques to convert serotonin/melatonin-producing cells of the pineal gland into cells that also produce dopamine and investigated the innervation of the phenotypically altered target cells. This phenotypic alteration markedly reduced the noradrenergic innervation originating from the superior cervical ganglia. Although the mechanism by which the reduction occurs is presently unknown, quantitative enzyme-linked immunoassay showed the presence of the equivalent amounts of nerve growth factor (NGF) in the control and transgenic pineal glands, suggesting that it occurred in a NGF-independent manner. The results suggest that target neurotransmitter phenotype influences the formation of afferent connections during development. Images Fig. 3 Fig. 4 PMID:8610132

Non-conventional features of peripheral serotonin signalling - the gut and beyond.

PubMed

Spohn, Stephanie N; Mawe, Gary M

2017-07-01

Serotonin was first discovered in the gut, and its conventional actions as an intercellular signalling molecule in the intrinsic and extrinsic enteric reflexes are well recognized, as are a number of serotonin signalling pharmacotherapeutic targets for treatment of nausea, diarrhoea or constipation. The latest discoveries have greatly broadened our understanding of non-conventional actions of peripheral serotonin within the gastrointestinal tract and in a number of other tissues. For example, it is now clear that bacteria within the lumen of the bowel influence serotonin synthesis and release by enterochromaffin cells. Also, serotonin can act both as a pro-inflammatory and anti-inflammatory signalling molecule in the intestinal mucosa via activation of serotonin receptors (5-HT 7 or 5-HT 4 receptors, respectively). For decades, serotonin receptors have been known to exist in a variety of tissues other than the gut, but studies have now provided strong evidence for physiological roles of serotonin in several important processes, including haematopoiesis, metabolic homeostasis and bone metabolism. Furthermore, evidence for serotonin synthesis in peripheral tissues outside of the gut is emerging. In this Review, we expand the discussion beyond gastrointestinal functions to highlight the roles of peripheral serotonin in colitis, haematopoiesis, energy and bone metabolism, and how serotonin is influenced by the gut microbiota.

Identification of multi-insecticide residues using GC-NPD and the degradation kinetics of chlorpyrifos in sweet corn and soils.

PubMed

Wang, Peidan; Rashid, Muhammad; Liu, Jie; Hu, Meiying; Zhong, Guohua

2016-12-01

Because more than one insecticide is applied to crops to protect plants from pests, an analytical multi-residue determination method was developed using gas chromatography with a nitrogen phosphorus detector (GC-NPD). The retention time for 12 insecticides was 3.7-27.7min. Under the selected conditions, the limits of detection (LOD) and quantification (LOQ) were below the maximum residue limits (MRLs) and in the range of 0.00315-0.05μgmL(-1) and 0.01-0.165μgmL(-1), respectively. Using GC-NPD, we investigated the dissipation dynamics and final residual levels of chlorpyrifos in sweet corn and soil and determined that the half-lives was 4-7days, that is, that chlorpyrifos is safe to use on sweet corn with a pre-harvest interval of 16-22days before harvest. These results provide new insights into chlorpyrifos degradation in plants and its environmental behavior. Copyright © 2016. Published by Elsevier Ltd.

Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency.

PubMed

Weng, Rui; Shen, Sensen; Tian, Yonglu; Burton, Casey; Xu, Xinyuan; Liu, Yi; Chang, Cuilan; Bai, Yu; Liu, Huwei

2015-07-08

Serotonin is an important neurotransmitter that broadly participates in various biological processes. While serotonin deficiency has been associated with multiple pathological conditions such as depression, schizophrenia, Alzheimer's disease and Parkinson's disease, the serotonin-dependent mechanisms remain poorly understood. This study therefore aimed to identify novel biomarkers and metabolic pathways perturbed by serotonin deficiency using metabolomics approach in order to gain new metabolic insights into the serotonin deficiency-related molecular mechanisms. Serotonin deficiency was achieved through pharmacological inhibition of tryptophan hydroxylase (Tph) using p-chlorophenylalanine (pCPA) or genetic knockout of the neuronal specific Tph2 isoform. This dual approach improved specificity for the serotonin deficiency-associated biomarkers while minimizing nonspecific effects of pCPA treatment or Tph2 knockout (Tph2-/-). Non-targeted metabolic profiling and a targeted pCPA dose-response study identified 21 biomarkers in the pCPA-treated mice while 17 metabolites in the Tph2-/- mice were found to be significantly altered compared with the control mice. These newly identified biomarkers were associated with amino acid, energy, purine, lipid and gut microflora metabolisms. Oxidative stress was also found to be significantly increased in the serotonin deficient mice. These new biomarkers and the overall metabolic pathways may provide new understanding for the serotonin deficiency-associated mechanisms under multiple pathological states.

Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency

NASA Astrophysics Data System (ADS)

Weng, Rui; Shen, Sensen; Tian, Yonglu; Burton, Casey; Xu, Xinyuan; Liu, Yi; Chang, Cuilan; Bai, Yu; Liu, Huwei

2015-07-01

Serotonin is an important neurotransmitter that broadly participates in various biological processes. While serotonin deficiency has been associated with multiple pathological conditions such as depression, schizophrenia, Alzheimer’s disease and Parkinson’s disease, the serotonin-dependent mechanisms remain poorly understood. This study therefore aimed to identify novel biomarkers and metabolic pathways perturbed by serotonin deficiency using metabolomics approach in order to gain new metabolic insights into the serotonin deficiency-related molecular mechanisms. Serotonin deficiency was achieved through pharmacological inhibition of tryptophan hydroxylase (Tph) using p-chlorophenylalanine (pCPA) or genetic knockout of the neuronal specific Tph2 isoform. This dual approach improved specificity for the serotonin deficiency-associated biomarkers while minimizing nonspecific effects of pCPA treatment or Tph2 knockout (Tph2-/-). Non-targeted metabolic profiling and a targeted pCPA dose-response study identified 21 biomarkers in the pCPA-treated mice while 17 metabolites in the Tph2-/- mice were found to be significantly altered compared with the control mice. These newly identified biomarkers were associated with amino acid, energy, purine, lipid and gut microflora metabolisms. Oxidative stress was also found to be significantly increased in the serotonin deficient mice. These new biomarkers and the overall metabolic pathways may provide new understanding for the serotonin deficiency-associated mechanisms under multiple pathological states.

Serotonin, carbohydrates, and atypical depression.

PubMed

Møller, S E

1992-01-01

At least three categories of atypical depression have been described. The hysteroid dysphoria is characterized by repeated episodes of depressed mood in response to feeling rejected, and a craving for sweets and chocolate. Two other issues are characterized by a cyclical occurrence of changes of mood and appetite, i.e., the late luteal phase dysphoric disorder (DSM-III-R, appendix), or "the premenstrual syndrome" (PMS), and the major depression with seasonal pattern (DSM-III-R), or seasonal affective disorder (SAD). The reactive mood changes are frequently accompanied by features as hypersomnia, lethargy and increased appetite, particularly with a preference for carbohydrates. Central serotonin pathways participate in the regulation of mood and behavioural impulsivity, and modulate eating patterns qualitatively and quantitatively. Depressives with PMS og SAD benefit, in general, from treatments with serotonin potentiating drugs, suggesting that brain serotonin plays a role in the pathophysiology. Ingestion of carbohydrates increases the plasma ratio of tryptophan to other large neutral amino acids in man and animal, and the serotonin synthesis in the rat brain. Based on these findings it has been suggested that the excessive carbohydrate intake by patients with PMS and SAD reflects a self-medication that temporarily relieves the vegetative symptoms via an increased central serotonergic activity.

Serotonin induces peripheral antinociception via the opioidergic system.

PubMed

Diniz, Danielle Aguiar; Petrocchi, Júlia Alvarenga; Navarro, Larissa Caldeira; Souza, Tâmara Cristina; Castor, Marina Gomes Miranda E; Duarte, Igor Dimitri Gama; Romero, Thiago Roberto Lima

2018-01-01

Studies conducted since 1969 have shown that the release of serotonin (5-HT) in the dorsal horn of the spinal cord contributes to opioid analgesia. In the present study, the participation of the opioidergic system in antinociceptive effect serotonin at the peripheral level was examined. The paw pressure test was used with mice (Swiss, males from 35 g) which had increased pain sensitivity by intraplantar injection of PGE 2 (2 μg). Serotonin (250 ng), administered locally to the right paw of animals, produces antinociception in this model. The selective antagonists for mu, delta and kappa opioid receptors, clocinnamox clocinnamox (40 μg), naltrindole (60 μg) and nor-binaltorfimina (200 μg), respectively, inhibited the antinociceptive effect induced by serotonin. Additionally, bestatin (400 μg), an inhibitor of enkephalinases that degrade peptides opioids, enhanced the antinociceptive effect induced by serotonin (low dose of 62.5 ng). These results suggest that serotonin possibly induce peripheral antinociception through the release of endogenous opioid peptides, possible from immune cells or keratinocytes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Increased hypothalamic serotonin turnover in inflammation-induced anorexia.

PubMed

Dwarkasing, J T; Witkamp, R F; Boekschoten, M V; Ter Laak, M C; Heins, M S; van Norren, K

2016-05-20

Anorexia can occur as a serious complication of disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections between peripheral inflammation, anorexia and hypothalamic serotonin metabolism and signaling pathways. First, we investigated the response of two hypothalamic neuronal cell lines to TNFα, IL-6 and LPS. Next, we studied transcriptomic changes and serotonergic activity in the hypothalamus of mice after intraperitoneal injection with TNFα, IL-6 or a combination of TNFα and IL-6. In vitro, we showed that hypothalamic neurons responded to inflammatory mediators by releasing cytokines. This inflammatory response was associated with an increased serotonin release. Mice injected with TNFα and IL-6 showed decreased food intake, associated with altered expression of inflammation-related genes in the hypothalamus. In addition, hypothalamic serotonin turnover showed to be elevated in treated mice. Overall, our results underline that peripheral inflammation reaches the hypothalamus where it affects hypothalamic serotoninergic metabolism. These hypothalamic changes in serotonin pathways are associated with decreased food intake, providing evidence for a role of serotonin in inflammation-induced anorexia.

Maternal 25-hydroxyvitamin D is inversely correlated with foetal serotonin.

PubMed

Murthi, Padma; Davies-Tuck, Miranda; Lappas, Martha; Singh, Harmeet; Mockler, Joanne; Rahman, Rahana; Lim, Rebecca; Leaw, Bryan; Doery, James; Wallace, Euan M; Ebeling, Peter R

2017-03-01

Maternal vitamin D deficiency during pregnancy has been linked to impaired neurocognitive development in childhood. The mechanism by which vitamin D affects childhood neurocognition is unclear but may be via interactions with serotonin, a neurotransmitter involved in foetal brain development. In this study, we aimed to explore associations between maternal and foetal vitamin D concentrations, and foetal serotonin concentrations at term. Serum 25-hydroxyvitamin D (25(OH)D, nmol/l) and serotonin (5-HT, nmol/l) concentrations were measured in maternal and umbilical cord blood from mother-infant pairs (n = 64). Association between maternal 25(OH)D, cord 25(OH)D and cord serotonin was explored using linear regression, before and after adjusting for maternal serotonin levels. We also assessed the effects of siRNA knockdown of the vitamin D receptor (VDR) and administration of 10 nm 1,25-dihydroxyvitamin D 3 on serotonin secretion in human umbilical vein endothelial cells (HUVECs) in vitro. We observed an inverse relationship between both maternal and cord 25(OH)D concentrations with cord serotonin concentrations. The treatment of HUVECs with 1,25-dihydroxyvitamin D 3 in vitro decreased the release of serotonin (193·9 ±14·8 nmol/l vs 458·9 ± 317·5 nmol/l, control, P < 0·05). Conversely, inactivation of VDR increased serotonin release in cultured HUVECs. These observations provide the first evidence of an inverse relationship between maternal 25(OH)D and foetal serotonin concentrations. We propose that maternal vitamin D deficiency increases foetal serotonin concentrations and thereby contributes to longer-term neurocognitive impairment in infants and children. © 2016 John Wiley & Sons Ltd.

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

PubMed Central

Wheelock, Craig E.; Eder, Kai J.; Werner, Inge; Huang, Huazhang; Jones, Paul D.; Brammell, Benjamin F.; Elskus, Adria A.; Hammock, Bruce D.

2006-01-01

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

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

USGS Publications Warehouse

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

2005-01-01

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

Developmental and polyamine metabolism alterations in Rhinella arenarum embryos exposed to the organophosphate chlorpyrifos.

PubMed

Sotomayor, Verónica; Lascano, Cecilia; de D'Angelo, Ana María Pechen; Venturino, Andrés

2012-09-01

Organophosphorus pesticides (OPs) are widely applied in the Alto Valle of Río Negro and Neuquén, Argentina, due to intensive fruit growing. Amphibians are particularly sensitive to environmental pollution, and OPs may transiently accumulate in ponds and channels of the region during their reproductive season. Organophosphorus pesticide exposure may alter amphibian embryonic development and the reproductive success of autochthonous species. In the present study, embryos of the common toad Rhinella arenarum were employed to assess developmental alterations and to study polyamine metabolism, which is essential to normal growth, as a possible target underlying the effects of the OP chlorpyrifos. As the duration of chlorpyrifos exposure increased and embryonic development progressed, the median lethal concentration (LC50) values decreased, and the percentage of malformed embryos increased. Developmental arrest was also observed and several morphological alterations were recorded, such as incomplete and abnormal closure of the neural tube, dorsal curvature of the caudal fin, reduction of body size and caudal fin length, atrophy, and edema. An early decrease in ornithine decarboxylase (ODC) activity and polyamine levels was also observed in embryos exposed to chlorpyrifos. The decrease in polyamine contents in tail bud embryos might be a consequence of the reduction in ODC activity. The alteration of polyamine metabolism occurred before embryonic growth was interrupted and embryonic malformations were observed and may be useful as a biomarker in environmental studies. Copyright © 2012 SETAC.

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

NASA Astrophysics Data System (ADS)

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

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

Peripheral Serotonin: a New Player in Systemic Energy Homeostasis

PubMed Central

Namkung, Jun; Kim, Hail; Park, Sangkyu

2015-01-01

Whole body energy balance is achieved through the coordinated regulation of energy intake and energy expenditure in various tissues including liver, muscle and adipose tissues. A positive energy imbalance by excessive energy intake or insufficient energy expenditure results in obesity and related metabolic diseases. Although there have been many obesity treatment trials aimed at the reduction of energy intake, these strategies have achieved only limited success because of their associated adverse effects. An ancient neurotransmitter, serotonin is among those traditional pharmacological targets for anti-obesity treatment because it exhibits strong anorectic effect in the brain. However, recent studies suggest the new functions of peripheral serotonin in energy homeostasis ranging from the endocrine regulation by gut-derived serotonin to the autocrine/paracrine regulation by adipocyte-derived serotonin. Here, we discuss the role of serotonin in the regulation of energy homeostasis and introduce peripheral serotonin as a possible target for anti-obesity treatment. PMID:26628041

MODELED ESTIMATES OF CHLORPYRIFOS EXPOSURE AND DOSE FOR THE MINNESOTA AND ARIZONA NHEXAS POPULATIONS

EPA Science Inventory

This paper presents a probabilistic, multimedia, multipathway exposure model and assessment for chlorpyrifos developed as part of the National Human Exposure Assessment Survey (NHEXAS). The model was constructed using available information prior to completion of the NHEXAS stu...

Time-resolved fluorescence sensing of pesticides chlorpyrifos, crotoxyphos and endosulfan by the luminescent Eu(III)-8-allyl-3-carboxycoumarin probe

NASA Astrophysics Data System (ADS)

Azab, Hassan A.; Khairy, Gasser M.; Kamel, Rasha M.

2015-09-01

This work describes the application of time resolved fluorescence in microtiter plates for investigating the interactions of europium-allyl-3-carboxycoumarin with pesticides chlorpyrifos, endosulfan and crotoxyphos. Stern-Volmer studies at different temperatures for chlorpyrifos and crotoxyphos shows dynamic and static quenching mechanisms respectively. Direct methods for the determination of the pesticides under investigation have been developed using the luminescence variations of the probe in solution. The detection limits are 6.53, 0.004, 3.72 μmol/L for chlorpyrifos, endosulfan, and crotoxyphos, respectively. The binding constants and thermodynamic parameters of the pesticides with probe were evaluated. A thermodynamic analysis showed that the reaction is spontaneous with negative ΔG. Effect of some relevant interferents on the detection of pesticides has been investigated. The new method was applied to the determination of the pesticides in different types of water samples (tap, mineral, and waste water).

4-haloethenylphenyl tropane:serotonin transporter imaging agents

DOEpatents

Goodman, Mark M.; Martarello, Laurent

2005-01-18

A series of compounds in the 4-fluoroalkyl-3-halophenyl nortropanes and 4-haloethenylphenyl tropane families are described as diagnostic and therapeutic agents for diseases associated with serotonin transporter dysfunction. These compounds bind to serotonin transporter protein with high affinity and selectivity. The invention provides methods of synthesis which incorporate radioisotopic halogens at a last step which permit high radiochemical yield and maximum usable product life. The radiolabeled compounds of the invention are useful as imaging agents for visualizing the location and density of serotonin transporter by PET and SPECT imaging.

Perturbation of Serotonin Homeostasis during Adulthood Affects Serotonergic Neuronal Circuitry.

PubMed

Pratelli, Marta; Migliarini, Sara; Pelosi, Barbara; Napolitano, Francesco; Usiello, Alessandro; Pasqualetti, Massimo

2017-01-01

Growing evidence shows that the neurotransmitter serotonin (5-HT) modulates the fine-tuning of neuron development and the establishment of wiring patterns in the brain. However, whether serotonin is involved in the maintenance of neuronal circuitry in the adult brain remains elusive. Here, we use a Tph2 fl ° x conditional knockout (cKO) mouse line to assess the impact of serotonin depletion during adulthood on serotonergic system organization. Data show that the density of serotonergic fibers is increased in the hippocampus and decreased in the thalamic paraventricular nucleus (PVN) as a consequence of brain serotonin depletion. Strikingly, these defects are rescued following reestablishment of brain 5-HT signaling via administration of the serotonin precursor 5-hydroxytryptophan (5-HTP). Finally, 3D reconstruction of serotonergic fibers reveals that changes in serotonin homeostasis affect axonal branching complexity. These data demonstrate that maintaining proper serotonin homeostasis in the adult brain is crucial to preserve the correct serotonergic axonal wiring.

The effect of chlorpyrifos upon ATPase activity of sarcoplasmic reticulum and biomechanics of skeleta l muscle contraction.

PubMed

Nozdrenko, D M; Miroshnychenko, M S; Soroca, V M; Korchins ka, L V; Zavodovskiy, D O

2016-01-01

We investigated the effect of chlorpyrifos, an organophosphate insecticide, on Ca2+,Mg2+-ATPase activity of sarcoplasmic reticulum and on contraction dynamics (force and length changes) of Rana temporaria m. tibialis anterior muscle fiber bundles. All of the used concentrations of chlorpyrifos (10-6 to 10-5 M) caused decrease of Ca2+,Mg2+-ATPase activity. The inhibition of Ca2+,Mg2+-ATPase activity by chlorpyriphos in concentrations of 10-6 M to 7.5·10-6 M is due to permeation of sarcoplasmic reticulum rather than due to direct enzyme inhibition by organophosphate insecticides. The inhibitory properties of the compound were higher at increased concentration and exposure timeframes. Chlorpyrifos in concentration range of 10-6 to 7.5·10-6 M causes changes in muscle fiber response force that were more pronounced than changes in contractile length. We demonstrated inhibition of Ca2+,Mg2+-ATPase activity caused by noncholinergic effects of chlorpyriphos. It is possible to conclude that influence of organophosphate insecticides happens not only in the neuromuscular transmission but also on the level of subcellular structures.

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

EPA Science Inventory

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

76 FR 52945 - Chlorpyrifos Registration Review; Preliminary Human Health Risk Assessment; Extension of Comment...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-24

... Review; Preliminary Human Health Risk Assessment; Extension of Comment Period AGENCY: Environmental... chlorpyrifos registration review; preliminary human health risk assessment. This document extends the comment... review, preliminary human health risk assessment, established in the Federal Register of Wednesday, July...

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

USGS Publications Warehouse

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

1986-01-01

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

Effects of mipafox, paraoxon, chlorpyrifos and its metabolite chlorpyrifos-oxon on the expression of biomarker genes of differentiation in D3 mouse embryonic stem cells.

PubMed

Sogorb, Miguel A; Fuster, Encarnación; Del Río, Eva; Estévez, Jorge; Vilanova, Eugenio

2016-11-25

Chlorpyrifos (CPS) is an organophosphorus compound (OP) capable of causing well-known cholinergic and delayed syndromes through the inhibition of acetylcholinesterase and Neuropathy Target Esterase (NTE), respectively. CPS is also able to induce neurodevelopmental toxicity in animals. NTE is codified by the Pnpla6 gene and plays a central role in differentiation and neurodifferentiation. We tested, in D3 mouse embryonic stem cells under differentiation, the effects of the NTE inhibition by the OPs mipafox, CPS and its main active metabolite chlorpyrifos-oxon (CPO) on the expression of genes Vegfa, Bcl2, Amot, Nes and Jun, previously reported to be under- or overexpressed after Pnpla6 silencing in this same cellular model. Mipafox did not significantly alter the expression of such genes at concentrations that significantly inhibited NTE. However, CPS and CPO at concentrations that caused NTE inhibition at similar levels to mipafox statistically and significantly altered the expression of most of these genes. Paraoxon (another OP with capability to inhibit esterases but not NTE) caused similar effects to CPS and CPO. These findings suggest that the molecular mechanism for the neurodevelopmental toxicity induced by CPS is not based on NTE inhibition, and that other unknown esterases might be potential targets of neurodevelopmental toxicity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency

PubMed Central

Weng, Rui; Shen, Sensen; Tian, Yonglu; Burton, Casey; Xu, Xinyuan; Liu, Yi; Chang, Cuilan; Bai, Yu; Liu, Huwei

2015-01-01

Serotonin is an important neurotransmitter that broadly participates in various biological processes. While serotonin deficiency has been associated with multiple pathological conditions such as depression, schizophrenia, Alzheimer’s disease and Parkinson’s disease, the serotonin-dependent mechanisms remain poorly understood. This study therefore aimed to identify novel biomarkers and metabolic pathways perturbed by serotonin deficiency using metabolomics approach in order to gain new metabolic insights into the serotonin deficiency-related molecular mechanisms. Serotonin deficiency was achieved through pharmacological inhibition of tryptophan hydroxylase (Tph) using p-chlorophenylalanine (pCPA) or genetic knockout of the neuronal specific Tph2 isoform. This dual approach improved specificity for the serotonin deficiency-associated biomarkers while minimizing nonspecific effects of pCPA treatment or Tph2 knockout (Tph2-/-). Non-targeted metabolic profiling and a targeted pCPA dose-response study identified 21 biomarkers in the pCPA-treated mice while 17 metabolites in the Tph2-/- mice were found to be significantly altered compared with the control mice. These newly identified biomarkers were associated with amino acid, energy, purine, lipid and gut microflora metabolisms. Oxidative stress was also found to be significantly increased in the serotonin deficient mice. These new biomarkers and the overall metabolic pathways may provide new understanding for the serotonin deficiency-associated mechanisms under multiple pathological states. PMID:26154191

The involvement of serotonin polymorphisms in autistic spectrum symptomatology.

PubMed

Hervás, Amaia; Toma, Claudio; Romarís, Patricia; Ribasés, Marta; Salgado, Marta; Bayes, Mònica; Balmaña, Noemí; Cormand, Bru; Maristany, Marta; Guijarro, Silvina; Arranz, María J

2014-08-01

Autism spectrum disorders (ASD) are highly inherited developmental syndromes, resulting from a complex interaction between environmental and genetic factors. To date, only a limited number of genetic variants have been discovered with respect to autism, and their contribution to the development of the disorder has not been clearly determined. Investigation of specific autistic symptomatology may improve the chances of identifying related genes and may help to better understand these disorders. We investigated the contribution of 80 genetic variants in 15 serotonin genes to ASD phenotypes [intelligence quotation (IQ), intellectual disability (ID) and language onset delay (LD)] in a cohort of 141 children and young adults (121 male patients and 20 female patients, average age 14.5±5.1 years). Two polymorphisms in the HTR2B gene, rs10194776 and rs16827801, were associated with IQ (P=0.0004 and 0.003, respectively), ID (P=0.02 and 0.03) and LD (P=0.04 and 0.004). Nominal associations were also detected between the ASD phenotypes investigated and 5-HT2A, 5-HT4 and 5-HT6 genetic variants. Our study provides evidence of the contribution of serotonergic variants to IQ, ID and LD in ASD patients.

Serum serotonin concentration associated with bone mineral density in Chinese postmenopausal women.

PubMed

Wei, Qiu-Shi; Chen, Zhen-Qiu; Tan, Xin; Kang, Lu-Chen; Jiang, Xiao-Bing; Liang, Jiang; He, Wei; Deng, Wei-Min

2017-02-01

Recent studies have shown that circulating serotonin plays a potential role in bone metabolism. However, conflicting results have been reported for the relationship between serum serotonin concentrations and bone mineral density (BMD). We investigated whether the serum serotonin concentrations related to BMD in Chinese postmenopausal women. Serum serotonin and bone turnover concentrations of 117 premenopausal women and 262 asymptomatic postmenopausal women were analyzed by enzyme-linked immunosorbent assay. BMD at the lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry. The relationship between serotonin and BMD was investigated. The postmenopausal women had lower mean serum serotonin concentrations compared to the premenopausal women. Serotonin concentrations were negatively associated with age, weight, BMI, fat mass, and β-CTX concentrations in postmenopausal women. No significant correlations were found between serotonin and these parameters in premenopausal women. In postmenopausal women, age- and BMI-adjusted serotonin concentrations were positively correlated with BMD of the lumbar spine and femoral neck. Multiple regression analyses showed serum serotonin and β-CTX were the predictors for lumbar spine BMD. Only serum serotonin was the determinant for femoral neck BMD. In conclusion, lower serum serotonin concentrations are linked to low lumbar spine and femoral neck BMD in postmenopausal women.

Resistance Mechanisms to Chlorpyrifos and F392W Mutation Frequencies in the Acetylcholine Esterase Ace1 Allele of Field Populations of the Tobacco Whitefly, Bemisia tabaci in China

PubMed Central

Zhang, Ning-ning; Liu, Cai-feng; Yang, Fang; Dong, Shuang-lin; Han, Zhao-jun

2012-01-01

The tobacco whitefly B-biotype Bemisia tabaci Gennadius (Hemiptera: Aleyrodidae) is a worldwide pest of many crops. In China, chlorpyrifos has been used to control this insect for many years and is still being used despite the fact that some resistance has been reported. To combat resistance and maintain good control efficiency of chlorpyrifos, it is essential to understand resistance mechanisms. A chlorpyrifos resistant tobacco whitefly strain (NJ-R) and a susceptible strain (NJ-S) were derived from a field-collected population in Nanjing, China, and the resistance mechanisms were investigated. More than 30-fold resistance was achieved after selected by chlorpyrifos for 13 generations in the laboratory. However, the resistance dropped significantly to about 18-fold in only 4 generations without selection pressure. Biochemical assays indicated that increased esterase activity was responsible for this resistance, while acetylcholine esterase, glutathione S-transferase, and microsomal-O-demethylase played little or no role. F392W mutations in acel were prevalent in NJ-S and NJ-R strains and 6 field-collected populations of both B and Q-biotype from locations that cover a wide geographical area of China. These findings provide important information about tobacco whitefly chlorpyrifos resistance mechanisms and guidance to combat resistance and optimize use patterns of chlorpyrifos and other organophosphate and carbamate insecticides. PMID:22954331

Serotonin syndrome following methylene blue administration during cardiothoracic surgery.

PubMed

Smith, Christina J; Wang, Dorothy; Sgambelluri, Anna; Kramer, Robert S; Gagnon, David J

2015-04-01

Despite its favorable safety profile, there have been reports of methylene blue-induced encephalopathy and serotonin syndrome in patients undergoing parathyroidectomy. We report a case of serotonin syndrome following methylene blue administration in a cardiothoracic surgery patient. A 59-year-old woman taking preoperative venlafaxine and trazodone was given a single dose of 2 mg/kg methylene blue (167 mg) during a planned coronary artery bypass and mitral valve repair. Postoperatively, she was febrile to 38.7°C and developed full-body tremors, rhythmic twitching of the perioral muscles, slow conjugate roving eye movements, and spontaneous movements of the upper extremities. Electroencephalography revealed generalized diffuse slowing consistent with toxic encephalopathy, and a computed tomography scan showed no acute process. The patient's symptoms were most consistent with a methylene blue-induced serotonin syndrome. Her motor symptoms resolved within 48 hours and she was eventually discharged home. Only 2 cases of methylene blue-induced serotonin syndrome during cardiothoracic surgery have been described in the literature, with this report representing the third case. Methylene blue and its metabolite, azure B, are potent, reversible inhibitors of monoamine oxidase A which is responsible for serotonin metabolism. Concomitant administration of methylene blue with serotonin-modulating agents may precipitate serotonin syndrome. © The Author(s) 2015.

Serotonin and Blood Pressure Regulation

PubMed Central

Morrison, Shaun F.; Davis, Robert Patrick; Barman, Susan M.

2012-01-01

5-Hydroxytryptamine (5-HT; serotonin) was discovered more than 60 years ago as a substance isolated from blood. The neural effects of 5-HT have been well investigated and understood, thanks in part to the pharmacological tools available to dissect the serotonergic system and the development of the frequently prescribed selective serotonin-reuptake inhibitors. By contrast, our understanding of the role of 5-HT in the control and modification of blood pressure pales in comparison. Here we focus on the role of 5-HT in systemic blood pressure control. This review provides an in-depth study of the function and pharmacology of 5-HT in those tissues that can modify blood pressure (blood, vasculature, heart, adrenal gland, kidney, brain), with a focus on the autonomic nervous system that includes mechanisms of action and pharmacology of 5-HT within each system. We compare the change in blood pressure produced in different species by short- and long-term administration of 5-HT or selective serotonin receptor agonists. To further our understanding of the mechanisms through which 5-HT modifies blood pressure, we also describe the blood pressure effects of commonly used drugs that modify the actions of 5-HT. The pharmacology and physiological actions of 5-HT in modifying blood pressure are important, given its involvement in circulatory shock, orthostatic hypotension, serotonin syndrome and hypertension. PMID:22407614

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

EPA Science Inventory

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

Severe Serotonin Depletion after Conditional Deletion of the Vesicular Monoamine Transporter 2 Gene in Serotonin Neurons: Neural and Behavioral Consequences

PubMed Central

Narboux-Nême, Nicolas; Sagné, Corinne; Doly, Stephane; Diaz, Silvina L; Martin, Cédric B P; Angenard, Gaelle; Martres, Marie-Pascale; Giros, Bruno; Hamon, Michel; Lanfumey, Laurence; Gaspar, Patricia; Mongeau, Raymond

2011-01-01

The vesicular monoamine transporter type 2 gene (VMAT2) has a crucial role in the storage and synaptic release of all monoamines, including serotonin (5-HT). To evaluate the specific role of VMAT2 in 5-HT neurons, we produced a conditional ablation of VMAT2 under control of the serotonin transporter (slc6a4) promoter. VMAT2sert−cre mice showed a major (−95%) depletion of 5-HT levels in the brain with no major alterations in other monoamines. Raphe neurons contained no 5-HT immunoreactivity in VMAT2sert−cre mice but developed normal innervations, as assessed by both tryptophan hydroxylase 2 and 5-HT transporter labeling. Increased 5-HT1A autoreceptor coupling to G protein, as assessed with agonist-stimulated [35S]GTP-γ-S binding, was observed in the raphe area, indicating an adaptive change to reduced 5-HT transmission. Behavioral evaluation in adult VMAT2sert−cre mice showed an increase in escape-like reactions in response to tail suspension and anxiolytic-like response in the novelty-suppressed feeding test. In an aversive ultrasound-induced defense paradigm, VMAT2sert−cre mice displayed a major increase in escape-like behaviors. Wild-type-like defense phenotype could be rescued by replenishing intracellular 5-HT stores with chronic pargyline (a monoamine oxidase inhibitor) treatment. Pargyline also allowed some form of 5-HT release, although in reduced amounts, in synaptosomes from VMAT2sert−cre mouse brain. These findings are coherent with the notion that 5-HT has an important role in anxiety, and provide new insights into the role of endogenous 5-HT in defense behaviors. PMID:21814181

[The serotonin syndrome. Fatal course of intoxication with citalopram and moclobemide].

PubMed

Cassens, S; Nickel, E A; Quintel, M; Neumann, P

2006-11-01

The serotonin syndrome is caused by a drug-induced increase of the intrasynaptic serotonin concentration. Milder forms of the syndrome may be difficult to diagnose because of the variability of symptoms. Severe forms often rapidly turn into a life-threatening situation, therefore the serotonin syndrome may be a challenge for physicians. We describe the pathophysiology and therapeutic options of the serotonin syndrome and report about a 42-year-old female patient who ingested large amounts of moclobemide, a monoamine oxidase inhibitor, and citalopram, a selective serotonin reuptake inhibitor, for attempted suicide. Within a few hours the patient developed a lethal serotonin syndrome although ICU therapy was initiated immediately.

The Role of Serotonin in Ventricular Repolarization in Pregnant Mice

PubMed Central

Park, Hyelim; Mun, Dasom; Lee, Seung-Hyun; Kim, Hyoeun; Yun, Nuri; Kim, Hail; Kim, Michael; Pak, Hui-Nam; Lee, Moon-Hyoung

2018-01-01

Purpose The mechanisms underlying repolarization abnormalities during pregnancy are not fully understood. Although maternal serotonin (5-hydroxytryptamine, 5-HT) production is an important determinant for normal fetal development in mice, its role in mothers remains unclear. We evaluated the role of serotonin in ventricular repolarization in mice hearts via 5Htr3 receptor (Htr3a) and investigated the mechanism of QT-prolongation during pregnancy. Materials and Methods We measured current amplitudes and the expression levels of voltage-gated K+ (Kv) channels in freshly-isolated left ventricular myocytes from wild-type non-pregnant (WT-NP), late-pregnant (WT-LP), and non-pregnant Htr3a homozygous knockout mice (Htr3a−/−-NP). Results During pregnancy, serotonin and tryptophan hydroxylase 1, a rate-limiting enzyme for the synthesis of serotonin, were markedly increased in hearts and serum. Serotonin increased Kv current densities concomitant with the shortening of the QT interval in WT-NP mice, but not in WT-LP and Htr3a−/−-NP mice. Ondansetron, an Htr3 antagonist, decreased Kv currents in WT-LP mice, but not in WT-NP mice. Kv4.3 directly interacted with Htr3a, and this binding was facilitated by serotonin. Serotonin increased the trafficking of Kv4.3 channels to the cellular membrane in WT-NP. Conclusion Serotonin increases repolarizing currents by augmenting Kv currents. Elevated serotonin levels during pregnancy counterbalance pregnancy-related QT prolongation by facilitating Htr3-mediated Kv currents. PMID:29436197

The Role of Serotonin in Ventricular Repolarization in Pregnant Mice.

PubMed

Cui, Shanyu; Park, Hyewon; Park, Hyelim; Mun, Dasom; Lee, Seung Hyun; Kim, Hyoeun; Yun, Nuri; Kim, Hail; Kim, Michael; Pak, Hui Nam; Lee, Moon Hyoung; Joung, Boyoung

2018-03-01

The mechanisms underlying repolarization abnormalities during pregnancy are not fully understood. Although maternal serotonin (5-hydroxytryptamine, 5-HT) production is an important determinant for normal fetal development in mice, its role in mothers remains unclear. We evaluated the role of serotonin in ventricular repolarization in mice hearts via 5Htr3 receptor (Htr3a) and investigated the mechanism of QT-prolongation during pregnancy. We measured current amplitudes and the expression levels of voltage-gated K⁺ (Kv) channels in freshly-isolated left ventricular myocytes from wild-type non-pregnant (WT-NP), late-pregnant (WT-LP), and non-pregnant Htr3a homozygous knockout mice (Htr3a(-/-)-NP). During pregnancy, serotonin and tryptophan hydroxylase 1, a rate-limiting enzyme for the synthesis of serotonin, were markedly increased in hearts and serum. Serotonin increased Kv current densities concomitant with the shortening of the QT interval in WT-NP mice, but not in WT-LP and Htr3a(-/-)-NP mice. Ondansetron, an Htr3 antagonist, decreased Kv currents in WT-LP mice, but not in WT-NP mice. Kv4.3 directly interacted with Htr3a, and this binding was facilitated by serotonin. Serotonin increased the trafficking of Kv4.3 channels to the cellular membrane in WT-NP. Serotonin increases repolarizing currents by augmenting Kv currents. Elevated serotonin levels during pregnancy counterbalance pregnancy-related QT prolongation by facilitating Htr3-mediated Kv currents. © Copyright: Yonsei University College of Medicine 2018

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baireddy, Praveena; Liu, Jing; Hinsdale, Myron

2011-11-15

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

Anorectic activities of serotonin uptake inhibitors: correlation with their potencies at inhibiting serotonin uptake in vivo and /sup 3/H-mazindol binding in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Angel, I.; Taranger, M.A.; Claustre, Y.

1988-01-01

The mechanism of anorectic action of several serotonin uptake inhibitors was investigated by comparing their anorectic potencies with several biochemical and pharmacological properties and in reference to the novel compound SL 81.0385. The anorectic effect of the potent serotonin uptake inhibitor SL 81.0385 was potentiated by pretreatment with 5-hydroxytryptophan and blocked by the serotonin receptor antagonist metergoline. A good correlation was obtained between the ED/sub 50/ values of anorectic action and the ED/sub 50/ values of serotonin uptake inhibition in vivo (but not in vitro) for several specific serotonin uptake inhibitors. Most of the drugs tested displaced (/sup 3/H)-mazindol frommore » its binding to the anorectic recognition site in the hypothalamus, except the pro-drug zimelidine which was inactive. Excluding zimelidine, a good correlation was obtained between the affinities of these drugs for (/sup 3/H)-mazindol binding and their anorectic action indicating that their anorectic activity may be associated with an effect mediated through this site. Taken together these results suggest that the anorectic action of serotonin uptake inhibitors is directly associated to their ability to inhibit serotonin uptake and thus increasing the synaptic levels of serotonin. The interactions of these drugs with the anorectic recognition site labelled with (/sup 3/H)-mazindol is discussed in connection with the serotonergic regulation of carbohydrate intake.« less

Organization of monosynaptic inputs to the serotonin and dopamine neuromodulatorysystems

PubMed Central

Ogawa, Sachie K.; Cohen, Jeremiah Y.; Hwang, Dabin; Uchida, Naoshige; Watabe-Uchida, Mitsuko

2014-01-01

SUMMARY Serotonin and dopamine are major neuromodulators. Here we used a modified rabies virus to identify monosynaptic inputs to serotonin neurons in the dorsal and median raphe (DR and MR). We found that inputs to DR and MR serotonin neurons are spatially shiftedin the forebrain, with MRserotonin neurons receiving inputs from more medial structures. We then compared these data with inputs to dopamine neurons in the ventral tegmental area (VTA) and substantianigra pars compacta (SNc). We found that DR serotonin neurons receive inputs from a remarkably similar set of areas as VTA dopamine neurons, apart from the striatum, which preferentially targets dopamine neurons. Ourresults suggest three majorinput streams: amedial stream regulates MR serotonin neurons, anintermediate stream regulatesDR serotonin and VTA dopamine neurons, and alateral stream regulatesSNc dopamine neurons. These results providefundamental organizational principlesofafferent control forserotonin and dopamine. PMID:25108805

The Reliability of Using Urinary Biomarkers to Estimate Human Exposures to Chlorpyrifos and Diazinon

EPA Science Inventory

A few studies have reported concurrent levels of chlorpyrifos (CPF) and diazinon (DZN) and their environmentally occurring metabolites, 3,5,6-trichloro-2-pyridinol (TCP) and 2-isopropyl-6-methyl-4-pyrimidinol (IMP), in food and in environmental media. This information raises ques...

Serotonin storage pools in basophil leukemia and mast cells: characterization of two types of serotonin binding protein and radioautographic analysis of the intracellular distribution of (/sup 3/H)serotonin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tamir, H.; Theoharides, T.C.; Gershon, M.D.

1982-06-01

The binding of serotonin to protein(s) derived from rat basophil leukemia (RBL) cells and mast cells was studied. Two types of serotonin binding protein in RBL cells was found. These proteins differed from one another in molecular weight and eluted in separate peaks from sephadex G-200 columns. Peak I protein (KD = 1.9 x 10/sup -6/ M) was a glycoprotein that bound to concanavalin A (Con A); Peak II protein (KD/sub 1/ = 4.5 x 10/sup -/8 M; KD/sub 2/ = 3.9 x 10/sup -6/ M) did not bind to Con A. Moreover, binding of (/sup 3/H)serotonin to protein ofmore » Peak I was sensitive to inhibition by reserpine, while binding of (/sup 3/H)serotonin to protein of Peak II resisted inhibition by that drug. Other differences between the two types of binding protein were found, the most significant of which was the far more vigorous conditions of homogenization required to extract Peak I than Peak II protein. Electron microscope radioautographic analysis of the intracellular distribution of (/sup 3/H) serotonin taken up in vitro by RBL cells or in vivo by murine mast cells indicated that essentially all of the labeled amine was located in cytoplasmic granules.No evidence for a pool in the cytosol was found and all granules were capable of becoming labeled. The presence of two types of intracellular serotonin binding proteins in these cells may indicate that there are two intracellular storage compartments for the amine. Both may be intragranular, but Peak I protein may be associated with the granular membrane while Peak II protein may be more free within the granular core. Different storage proteins may help to explain the differential release of amines from mast cell granules.« less

Nutrient-induced glucagon like peptide-1 release is modulated by serotonin.

PubMed

Ripken, Dina; van der Wielen, Nikkie; Wortelboer, Heleen M; Meijerink, Jocelijn; Witkamp, Renger F; Hendriks, Henk F J

2016-06-01

Glucagon like peptide-1 (GLP-1) and serotonin are both involved in food intake regulation. GLP-1 release is stimulated upon nutrient interaction with G-protein coupled receptors by enteroendocrine cells (EEC), whereas serotonin is released from enterochromaffin cells (ECC). The central hypothesis for the current study was that nutrient-induced GLP-1 release from EECs is modulated by serotonin through a process involving serotonin receptor interaction. This was studied by assessing the effects of serotonin reuptake inhibition by fluoxetine on nutrient-induced GLP-1, PYY and CCK release from isolated pig intestinal segments. Next, serotonin-induced GLP-1 release was studied in enteroendocrine STC-1 cells, where effects of serotonin receptor inhibition were studied using specific and non-specific antagonists. Casein (1% w/v), safflower oil (3.35% w/v), sucrose (50mM) and rebaudioside A (12.5mM) stimulated GLP-1 release from intestinal segments, whereas casein only stimulated PYY and CCK release. Combining nutrients with fluoxetine further increased nutrient-induced GLP-1, PYY and CCK release. Serotonin release from intestinal tissue segments was stimulated by casein and safflower oil while sucrose and rebaudioside A had no effect. The combination with fluoxetine (0.155μM) further enhanced casein and safflower oil induced-serotonin release. Exposure of ileal tissue segments to serotonin (30μM) stimulated GLP-1 release whereas it did not induce PYY and CCK release. Serotonin (30 and 100μM) also stimulated GLP-1 release from STC-1 cells, which was inhibited by the non-specific 5HT receptor antagonist asenapine (1 and 10μM). These data suggest that nutrient-induced GLP-1 release is modulated by serotonin through a receptor mediated process. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Conundrums in neurology: diagnosing serotonin syndrome - a meta-analysis of cases.

PubMed

Werneke, Ursula; Jamshidi, Fariba; Taylor, David M; Ott, Michael

2016-07-12

Serotonin syndrome is a toxic state, caused by serotonin (5HT) excess in the central nervous system. Serotonin syndrome's main feature is neuro-muscular hyperexcitability, which in many cases is mild but in some cases can become life-threatening. The diagnosis of serotonin syndrome remains challenging since it can only be made on clinical grounds. Three diagnostic criteria systems, Sternbach, Radomski and Hunter classifications, are available. Here we test the validity of four assumptions that have become widely accepted: (1) The Hunter classification performs clinically better than the Sternbach and Radomski criteria; (2) in contrast to neuroleptic malignant syndrome, the onset of serotonin syndrome is usually rapid; (3) hyperthermia is a hallmark of severe serotonin syndrome; and (4) serotonin syndrome can readily be distinguished from neuroleptic malignant syndrome on clinical grounds and on the basis of medication history. Systematic review and meta-analysis of all cases of serotonin syndrome and toxicity published between 2004 and 2014, using PubMed and Web of Science. Two of the four assumptions (1 and 2) are based on only one published study each and have not been independently validated. There is little agreement between current criteria systems for the diagnosis of serotonin syndrome. Although frequently thought to be the gold standard for the diagnosis of the serotonin syndrome, the Hunter criteria did not perform better than the Sternbach and Radomski criteria. Not all cases seem to be of rapid onset and only relatively few cases may present with hyperthermia. The 0 differential diagnosis between serotonin syndrome and neuroleptic malignant syndrome is not always clear-cut. Our findings challenge four commonly made assumptions about serotonin syndrome. We propose our meta-analysis of cases (MAC) method as a new way to systematically pool and interpret anecdotal but important clinical information concerning uncommon or emergent phenomena that cannot be

FOXO1 orchestrates the bone-suppressing function of gut-derived serotonin

PubMed Central

Kode, Aruna; Mosialou, Ioanna; Silva, Barbara C.; Rached, Marie-Therese; Zhou, Bin; Wang, Ji; Townes, Tim M.; Hen, Rene; DePinho, Ronald A.; Guo, X. Edward; Kousteni, Stavroula

2012-01-01

Serotonin is a critical regulator of bone mass, fulfilling different functions depending on its site of synthesis. Brain-derived serotonin promotes osteoblast proliferation, whereas duodenal-derived serotonin suppresses it. To understand the molecular mechanisms of duodenal-derived serotonin action on osteoblasts, we explored its transcriptional mediation in mice. We found that the transcription factor FOXO1 is a crucial determinant of the effects of duodenum-derived serotonin on bone formation We identified two key FOXO1 complexes in osteoblasts, one with the transcription factor cAMP-responsive element–binding protein 1 (CREB) and another with activating transcription factor 4 (ATF4). Under normal levels of circulating serotonin, the proliferative activity of FOXO1 was promoted by a balance between its interaction with CREB and ATF4. However, high circulating serotonin levels prevented the association of FOXO1 with CREB, resulting in suppressed osteoblast proliferation. These observations identify FOXO1 as the molecular node of an intricate transcriptional machinery that confers the signal of duodenal-derived serotonin to inhibit bone formation. PMID:22945629

Monitoring of selected pesticides residue levels in water samples of paddy fields and removal of cypermethrin and chlorpyrifos residues from water using rice bran.

PubMed

Bhattacharjee, Shubhra; Fakhruddin, A N M; Chowdhury, M A Z; Rahman, M A; Alam, M K

2012-08-01

Consumption of pesticides associated foods increased in recent decades in Bangladesh. Most of the pesticides come from paddy, as rice is the main food items here and about 70 % pesticides are used only on paddy fields. Water samples of paddy fields and Kaliganga River of Manikganj district were analyzed to provide base line data on cypermethrin, chlorpyrifos and diazinon residue by using high performance liquid chromatography. Levels of Cypermethrin, chlorpyrifos and diazinon detected in the paddy field water samples were (0.605 ± 0.011 μg/L), (0.06 ± 0.001 μg/L) and (0.039 ± 0.002 μg/L), respectively. 0.11 ± 0.003 μg/L of cypermethrin and 0.012 ± 0.0006 μg/L of chlorpyrifos were also identified in the water samples of Kaligonga River. Diazinon residue was not detected in the river water samples. The detected concentrations of pesticide residues in the river water were below the accepted maximum residue limit (MRL) value of drinking water (0.1 μg/l) adopted by the FAO/WHO Codex Alimentarius Commission. Cypermethrin and chlorpyrifos were chosen for decontamination through rice bran, as it was found in river water. Two gm rice bran could easily decontaminated 95.6 % and 96.4 % of cypermethrin and chlorpyrifos. The result of this study showed that pesticide residue was detected in water samples were below the MRLs value, which can easily be decontaminated through absorption of rice bran.

Serotonin Transporter Gene (SLC6A4) Polymorphism and Mucosal Serotonin Levels in Southeastern Iranian Patients with Irritable Bowel Syndrome

PubMed Central

Mohammadi, Mojgan; Tahmasebi Abdar, Hossein; Mollaei, Hamid Reza; Hajghani, Hossein; Baneshi, Mohammad Reza; Hayatbakhsh, Mohammad Mahdi

2017-01-01

BACKGROUND Irritable bowel syndrome (IBS) is a digestive system disorder with an unknown etiology. Serotonin has a key role in the secretion and motility of the intestine. Polymorphism in serotonin re-uptake transporter (SERT or SLC6A4) gene may have a functional role in the gut of patients with IBS. The aims of the present study were to investigate the association between SLC6A4 gene polymorphism and IBS and to detect the correlation between rectal serotonin levels and IBS sub-types. METHODS SLC6A4 gene polymorphism in 131 patients with IBS and 211 healthy controls were analysed using the quantitative polymerase chain reaction high-resolution melting (qPCR-HRM) curve technique. Serotonin was measured in rectal biopsies of patients with IBS using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS The patients were categorized into three groups: IBS with diarrhoea (IBS-D): 70 patients, IBS with constipation (IBS-C): 18 patients, and IBS with mixed symptoms (IBS-M): 43 patients. The frequency of SLC6A4 s/s and l/s genotypes was significantly higher in IBS-C than IBS-D, IBS-M, and controls (p=0.036). Serotonin levels were similar in IBS sub-types. CONCLUSION SLC6A4 polymorphism is a possible candidate gene associated with the pathogenesis of IBS-C. Although serotonin levels did not differ in rectal biopsies of IBS sub-types, further investigation is recommended. PMID:28316763

Voltammetric and Mathematical Evidence for Dual Transport Mediation of Serotonin Clearance In Vivo

PubMed Central

Wood, Kevin M.; Zeqja, Anisa; Nijhout, H. Frederik; Reed, Michael C.; Best, Janet; Hashemi, Parastoo

2014-01-01

The neurotransmitter serotonin underlies many of the brain’s functions. Understanding serotonin neurochemistry is important for improving treatments for neuropsychiatric disorders such as depression. Antidepressants commonly target serotonin clearance via serotonin transporters (SERTs) and have variable clinical effects. Adjunctive therapies, targeting other systems including serotonin autoreceptors, also vary clinically and carry adverse consequences. Fast scan cyclic voltammetry (FSCV) is particularly well suited for studying antidepressant effects on serotonin clearance and autoreceptors by providing real-time chemical information on serotonin kinetics in vivo. However, the complex nature of in vivo serotonin responses makes it difficult to interpret experimental data with established kinetic models. Here, we electrically stimulated the mouse medial forebrain bundle (MFB) to provoke and detect terminal serotonin in the substantia nigra reticulata (SNr). In response to MFB stimulation we found three dynamically distinct serotonin signals. To interpret these signals we developed a computational model that supports two independent serotonin reuptake mechanisms (high affinity, low efficiency reuptake mechanism and low affinity, high efficiency reuptake system) and bolsters an important inhibitory role for the serotonin autoreceptors. Our data and analysis, afforded by the powerful combination of voltammetric and theoretical methods, gives new understanding of the chemical heterogeneity of serotonin dynamics in the brain. This diverse serotonergic matrix likely contributes to clinical variability of antidepressants. PMID:24702305

Serotonin Control of Thermotaxis Memory Behavior in Nematode Caenorhabditis elegans

PubMed Central

Guo, Yuling; Wang, Daoyong; Li, Chaojun; Wang, Dayong

2013-01-01

Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory. In the present study, we employed C. elegans assay system of thermotaxis memory to investigate the possible role of serotonin neurotransmitter in memory control. Our data showed that both mutations of tph-1, bas-1, and cat-4 genes, required for serotonin synthesis, and mutations of mod-5 gene, encoding a serotonin reuptake transporter, resulted in deficits in thermotaxis memory behavior. Exogenous treatment with serotonin effectively recovered the deficits in thermotaxis memory of tph-1 and bas-1 mutants to the level of wild-type N2. Neuron-specific activity assay of TPH-1 suggests that serotonin might regulate the thermotaxis memory behavior by release from the ADF sensory neurons. Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf)) increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants. Moreover, serotonin released from the ADF sensory neurons might act through the G-protein-coupled serotonin receptors of SER-4 and SER-7 to regulate the thermotaxis memory behavior. Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior. Thus, our results suggest the possible crucial role of serotonin and ADF sensory neurons in thermotaxis memory control in C. elegans. PMID:24223727

Non-target effect of continuous application of chlorpyrifos on soil microbes, nematodes and its persistence under sub-humid tropical rice-rice cropping system.

PubMed

Kumar, Upendra; Berliner, J; Adak, Totan; Rath, Prakash C; Dey, Avro; Pokhare, Somnath S; Jambhulkar, Nitiprasad N; Panneerselvam, P; Kumar, Anjani; Mohapatra, Shyamranjan D

2017-01-01

Application of pesticide in agricultural fields is "unnecessary evil" for non-target microflora and fauna. Hence, to identify the safer pesticide molecules against non-target microbes, a long-term pesticide experiment was initiated at National Rice Research Institute, Cuttack, India. In the present study, the effect of continuous application of chlorpyrifos (0.5kgha -1 ) in rice fields on non-target groups of soil microbes and nematodes was studied for seven seasons (four wet and three dry seasons) during 2009-2013. Treatments were arranged in a randomized complete block design with four replications of chlorpyrifos-treated (0.5kg a.i. ha -1 ) (CT) and untreated control (UT) plots. During seven seasons of experimentation, regular application of chlorpyrifos had no significant effect on population of heterotrophic aerobic, anaerobic, oligotrophic and copiotrophic bacteria in CT compared to UT, whereas, population of asymbiotic aerobic nitrogen fixer, nitrifiers, denitrifiers, gram positive and spore-forming bacteria were significantly reduced by nearly 0.25-2 fold in CT than UT. However, comparatively less deviation in population of actinomycetes, fungi, phosphate solubilizing and sulfur oxidizing bacteria were observed in CT than UT. Significant interactions were found between effects of chlorpyrifos with time in population dynamics of microbes. In plant parasitic nematode species, Meloidogyne graminicola (RRKN) and Hirschmanniella spp. (RRN), were significantly lower (p<0.01) in CT compared to UT after first year onwards. The overall observation of five years data indicated that the RRKN population showed a decreasing trend (R 2 =0.644) whereas RRN showed increasing trend (R 2 =0.932) in CT. The drastic chlorpyrifos dissipation was noticed after 15 days of application from the initial residue of 0.25mgkg -1 soil, which indicated that chlorpyrifos residue in rice field soil was not persistent and its half-life was found to be 4.02 days. Overall, the present

Biodegradation of Chlorpyrifos, Malathion, and Dimethoate by Three Strains of Bacteria Isolated from Pesticide-Polluted Soils in Sudan.

PubMed

Ishag, Abd Elaziz S A; Abdelbagi, Azhari O; Hammad, Ahmed M A; Elsheikh, Elsiddig A E; Elsaid, Osama E; Hur, J-H; Laing, Mark D

2016-11-16

This study was done to identify pesticide-biodegrading microorganisms and to characterize degradation rates. Bacillus safensis strain FO-36b T , Bacillus subtilis subsp. inaquosorum strain KCTC13429 T , and Bacillus cereus strain ATCC14579 T were isolated from pesticide-polluted soil in Sudan, separately incubated with each pesticide with periodic samples drawn for GC and GC-MS. Pesticide biodegradation followed a biphasic model. α and β half-lives (days) of chlorpyrifos, malathion, and dimethoate in B. safensis culture were 2.13, 4.76; 2.59, 5.66; and 9.5, 11.0, respectively. Values in B. subtilis and B. cereus cultures were 4.09, 9.45 and 4.33, 9.99 for chlorpyrifos; 2.99, 5.36 and 2.43, 4.71 for malathion; and 9.53, 15.11 and 4.16, 9.27 for dimethoate. No metabolite was detected in B. subtilis cultures, whereas a few were detected from B. safensis and B. cereus cultures. Bacterial efficiency can be ordered as B. safensis > B. subtilis > B. cereus for chlorpyrifos and B. cereus > B. subtilis > B. safensis for malathion and dimethoate.

Association between salivary serotonin and the social sharing of happiness

PubMed Central

Ishii, Keiko; Ohtsubo, Yohsuke; Noguchi, Yasuki; Ochi, Misaki; Yamasue, Hidenori

2017-01-01

Although human saliva contains the monoamine serotonin, which plays a key role in the modulation of emotional states, the association between salivary serotonin and empathic ability remains unclear. In order to elucidate the associations between salivary serotonin levels, trait empathy, and the sharing effect of emotions (i.e., sharing emotional experiences with others), we performed a vignette-based study. Participants were asked to evaluate their happiness when they experience several hypothetical life events, whereby we manipulated the valence of the imagined event (positive, neutral, or negative), as well as the presence of a friend (absent, positive, or negative). Results indicated that the presence of a happy friend significantly enhanced participants’ happiness. Correlation analysis demonstrated that salivary serotonin levels were negatively correlated with happiness when both the self and friend conditions were positive. Correlation analysis also indicated a negative relationship between salivary serotonin levels and trait empathy (particularly in perspective taking), which was measured by the Interpersonal Reactivity Index. Furthermore, an exploratory multiple regression analysis suggested that mothers’ attention during childhood predicted salivary serotonin levels. Our findings indicate that empathic abilities and the social sharing of happiness decreases as a function of salivary serotonin levels. PMID:28683075

Association between salivary serotonin and the social sharing of happiness.

PubMed

Matsunaga, Masahiro; Ishii, Keiko; Ohtsubo, Yohsuke; Noguchi, Yasuki; Ochi, Misaki; Yamasue, Hidenori

2017-01-01

Although human saliva contains the monoamine serotonin, which plays a key role in the modulation of emotional states, the association between salivary serotonin and empathic ability remains unclear. In order to elucidate the associations between salivary serotonin levels, trait empathy, and the sharing effect of emotions (i.e., sharing emotional experiences with others), we performed a vignette-based study. Participants were asked to evaluate their happiness when they experience several hypothetical life events, whereby we manipulated the valence of the imagined event (positive, neutral, or negative), as well as the presence of a friend (absent, positive, or negative). Results indicated that the presence of a happy friend significantly enhanced participants' happiness. Correlation analysis demonstrated that salivary serotonin levels were negatively correlated with happiness when both the self and friend conditions were positive. Correlation analysis also indicated a negative relationship between salivary serotonin levels and trait empathy (particularly in perspective taking), which was measured by the Interpersonal Reactivity Index. Furthermore, an exploratory multiple regression analysis suggested that mothers' attention during childhood predicted salivary serotonin levels. Our findings indicate that empathic abilities and the social sharing of happiness decreases as a function of salivary serotonin levels.

Serotonin toxicity caused by moclobemide too soon after paroxetine-selegiline.

PubMed

Wu, Ming-Ling; Deng, Jou-Fang

2009-08-01

Serotonin toxicity is an iatrogenic complication of serotonergic drug therapy. It is due to an overstimulation of central and peripheral serotonin receptors that lead to neuromuscular, mental and autonomic changes. Moclobemide is a reversible inhibitor of monoamine oxidase (MAO)-A, selegiline is an irreversible selective inhibitor of MAO-B, and paroxetine is a selective serotonin reuptake inhibitor. Combined use of these agents is known to cause serotonin toxicity. A 53-year-old woman had been treated with paroxetine and selegiline. After moclobemide was prescribed in place of paroxetine without a washout period, she quickly developed confusion, agitation, ataxia, diaphoresis, tremor, mydriasis, ocular clonus, hyperreflexia, tachycardia, moderately elevated blood pressure and high fever, symptoms that were consistent with serotonin toxicity. Discontinuation of the drugs, hydration and supportive care were followed by remarkable improvement of baseline status within 3 days. This case demonstrates that serotonin toxicity may occur even with small doses of paroxetine, selegiline and moclobemide in combination. Physicians managing patients with depression must be aware of the potential for serotonin toxicity and should be able to recognize and treat or, ideally, anticipate and avoid this pharmacodynamically-mediated interaction that may occur between prescribed drugs.

A specific role for serotonin in overcoming effort cost.

PubMed

Meyniel, Florent; Goodwin, Guy M; Deakin, Jf William; Klinge, Corinna; MacFadyen, Christine; Milligan, Holly; Mullings, Emma; Pessiglione, Mathias; Gaillard, Raphaël

2016-11-08

Serotonin is implicated in many aspects of behavioral regulation. Theoretical attempts to unify the multiple roles assigned to serotonin proposed that it regulates the impact of costs, such as delay or punishment, on action selection. Here, we show that serotonin also regulates other types of action costs such as effort. We compared behavioral performance in 58 healthy humans treated during 8 weeks with either placebo or the selective serotonin reuptake inhibitor escitalopram. The task involved trading handgrip force production against monetary benefits. Participants in the escitalopram group produced more effort and thereby achieved a higher payoff. Crucially, our computational analysis showed that this effect was underpinned by a specific reduction of effort cost, and not by any change in the weight of monetary incentives. This specific computational effect sheds new light on the physiological role of serotonin in behavioral regulation and on the clinical effect of drugs for depression. ISRCTN75872983.

Serotonin: Modulator of a Drive to Withdraw

ERIC Educational Resources Information Center

Tops, Mattie; Russo, Sascha; Boksem, Maarten A. S.; Tucker, Don M.

2009-01-01

Serotonin is a fundamental neuromodulator in both vertebrate and invertebrate nervous systems, with a suspected role in many human mental disorders. Yet, because of the complexity of serotonergic function, researchers have been unable to agree on a general theory. One function suggested for serotonin systems is the avoidance of threat. We propose…

Biochemical effects of chlorpyrifos on two developmental stages of Xenopus laevis.

PubMed

Richards, Sean M; Kendall, Ron J

2002-09-01

Abstract-The effects of a 96-h static exposure to chlorpyrifos were examined in two developmental stages of larval Xenopus laevis (premetamorph and metamorph). Measures of effect included mortality, deformity, cholinesterase (ChE) activity, and DNA and protein concentration. All parameters indicated that metamorphs were more sensitive than were premetamorphs. For larvae exposed as premetamorphs, the median lethal concentration and median effective concentration were 14.6 mg/L and 1.71 mg/L; for those exposed as metamorphs, values were 0.56 mg/L and 0.24 mg/L, respectively. Cholinesterase activity was the most sensitive biochemical parameter. Exposure to chlorpyrifos at 0.01 mg/L caused significant decreases in the ChE activity of metamorphs; 0.1 mg/L significantly decreased premetamorph ChE activity. Metamorph DNA was significantly decreased at 0.1 mg/L; premetamorph DNA was not reduced until exposure to 1.0 mg/L. Whole-body protein was the least sensitive biochemical measure of effect. Premetamorphs did not experience a reduction in protein concentrations. Metamorph protein concentration was significantly decreased at 1.0 mg/L. Based on current surface water data, the most sensitive effect would not have a high probability (< or = 4.2%) of occurring in the environment.

Urinary Biomarker, Dermal, and Air Measurement Results for 2,4-D and Chlorpyrifos Farm Applicators in the Agricultural Health Study

PubMed Central

Thomas, Kent; Dosemeci, Mustafa; Hoppin, Jane A.; Sheldon, Linda; Croghan, Carry; Gordon, Sydney; Jones, Martin; Reynolds, Stephen; Raymer, James; Akland, Gerald; Lynch, Charles F.; Knott, Charles; Sandler, Dale P.; Blair, Aaron; Alavanja, Michael

2010-01-01

Epidemiologic studies increasingly rely on improved exposure assessments to characterize pesticide exposures in agricultural populations. A subset of private pesticide applicators in the AHS epidemiological cohort was monitored around the time of their agricultural use of 2,4-D and chlorpyrifos to assess exposure levels and potential exposure factors. Measurements included pre- and post-application urine samples, and patch, hand wipe, and personal air samples. Broadcast or hand spray application methods were used by applicators for 2,4-D products. Chlorpyrifos products were applied using spray applications and in-furrow application of granular products. Geometric mean (GM) values for 69 2,4-D applicators were 7.8 and 25 µg/L in pre- and post-application urine, respectively (p < 0.05 for difference); 0.39 mg for estimated hand loading; 2.9 mg for estimated body loading; and 0.37 µg/m3 for concentration in personal air. Significant correlations were found between all media for 2,4-D. GM values for 17 chlorpyrifos applicators were 11 µg/L in both pre- and post-application urine for the 3,5,6-trichloro-2-pyridinol metabolite, 0.28 mg for body loading, and 0.49 µg/m3 for air concentration. Only 53% of the chlorpyrifos applicators had measureable hand loading results; their median hand loading was 0.02 mg. Factors associated with differences in 2,4-D measurements included application method and glove use; and, for hand spray applicators, use of adjuvants, equipment repair, duration of use, and contact with treated vegetation. Spray applications of liquid chlorpyrifos products were associated with higher measurements than in-furrow granular product applications. This study provides information on exposures and possible exposure determinants for several application methods commonly used by farmers in the cohort and will provide information to assess and refine exposure classification in the Agricultural Health Study. Results may also be of use in pesticide safety

On the Mechanism of Serotonin-Induced Dipsogenesis in the Rat

NASA Technical Reports Server (NTRS)

Kikta, Dianne C.; Barney, Christopher C.; Threatte, Rose M.; Fregly, Melvin J.; Rowland, Neil E.; Greenleaf, John E.

1983-01-01

Subcutaneous administration of 1-5-hydroxytryptophan (5-HTP), the precursor of serotonin, to female rats induces copious drinking accompanied by activation of the renin-angiotensin system. Neither a reduction in blood pressure nor body temperature accompanied administration of 5-HTP. The objective of the present study was to determine whether serotonin-induced dipsogenesis, like that of 5-HTP, is mediated via the renin-angiotensin system. Serotonin (2 mg/kg, SC)-induced drinking was inhibited by the dopaminergic antagonist, haloperidol (150 /micro g/kg, IP), which also inhibits angiotensin II-induced drinking, Both captopril (35 mg/kg, IP), an angiotensin converting enzyme inhibitor, and propranolol (6 micro g/kg, IP), a beta-adrenergic antagonist, blocked serotonin-induced dipsogenesis. The alpha(sub a),-adrenergic agonist, clonidine (6.25 micro g/kg, SC), which suppresses renin release from the kidney, attenuated serotonin-induced water intake. The dipsogenic responses to submaximal concentrations of both serotonin (1 mg/kg, SC) and isoproterenol (8 micro g/kg, SC) were additive rather than interactive suggesting that similar pathways mediate both responses. The serotonergic receptor antagonist, methysergide (3 mg/kg, IP), inhibited serotonin-induced drinking but had no effect on isoproterenol (25micro g/kg, SC)-induced dipsogenesis. However, neither serotonin (2 mg/kg, SC) nor isoproterenol (25 micro g/kg, SC)-induced drinking was inhibited by cinansefin (25 micro g/kg, IP). These data indicate that serotonin induces drinking in rats via the renin-angiotensin system. However, the results of the studies using methysergide suggest that scrotonin appears to act at a point prior to activation of beta-adrenoceptors in the pathway leading to release of renin from the kidneys.

Dextromethorphan, chlorphenamine and serotonin toxicity: case report and systematic literature review

PubMed Central

Monte, Andrew A; Chuang, Ryan; Bodmer, Michael

2010-01-01

The aim of this review was to describe a patient with serotonin toxicity after an overdose of dextromethorphan and chlorphenamine and to perform a systematic literature review exploring whether dextromethorphan and chlorphenamine may be equally contributory in the development of serotonin toxicity in overdose. A Medline literature review was undertaken to identify cases of serotonin toxicity due to dextromethorphan and/or chlorphenamine. Case reports were included if they included information on the ingested dose or plasma concentrations of dextromethorphan and/or chlorphenamine, information about co-ingestions and detailed clinical information to evaluate for serotonin toxicity. Cases were reviewed by two toxicologists and serotonin toxicity, defined by the Hunter criteria, was diagnosed when appropriate. The literature was then reviewed to evaluate whether chlorphenamine may be a serotonergic agent. One hundred and fifty-five articles of dextromethorphan or chlorphenamine poisoning were identified. There were 23 case reports of dextromethorphan, of which 18 were excluded for lack of serotonin toxicity. No cases were identified in which serotonin toxicity could be solely attributed to chlorphenamine. This left six cases of dextrometorphane and/or chlorphenamine overdose, including our own, in which serotonin toxicity could be diagnosed based on the presented clinical information. In three of the six eligible cases dextromethorphan and chlorphenamine were the only overdosed drugs. There is substantial evidence from the literature that chlorphenamine is a similarly potent serotonin re-uptake inhibitor when compared with dextrometorphan. Chlorphenamine is a serotonergic medication and combinations of chlorphenamine and dextromethorphan may be dangerous in overdose due to an increased risk of serotonin toxicity. PMID:21175434

Leaching potential of chlorpyrifos in an Andisol and Entisol: adsorption-desorption and degradation studies

NASA Astrophysics Data System (ADS)

Mosquera-Vivas, Carmen; Walther Hansen, Eddy; Garcia-Santos, Glenda; Obregón-Neira, Nelson; Celis-Ossa, Raul Ernesto; González-Murillo, Carlos Alberto; Juraske, Ronnie; Hellweg, Stefanie; Guerrero-Dallos, Jairo Arturo

2017-04-01

Ecological status of tropical soils like high OC content and microbial activity plays a key role to reduce the leaching of insecticide chlorpyrifos through the soil profile and therefore into groundwater. We found that chlorpyrifos has "transitional" leaching potential (GUS values varied between 1.8 and 2.5) throughout the soil depth, which differs from the "nonleacher" classification for temperate soils as based on surface level t1/2 and Koc values from international databases. These findings provide strong evidence of the importance of estimating the transport parameters and insecticide concentrations in different soil layers, especially when the amount and type of OC content vary throughout the soil profile. We got to such conclusions after studying the soil profile structural composition of soil organic matter and the adsorption/desorption characteristics of the insecticide in two different soil profiles (Andisol and Entisol) under agriculture production using Fourier transform infrared spectroscopy, nuclear magnetic resonance, and batch analysis methods.

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

USGS Publications Warehouse

Sparling, D.W.; Fellers, G.

2007-01-01

Organophosphorus pesticides (OPs) are ubiquitous in the environment and are highly toxic to amphibians. They deactivate cholinesterase, resulting in neurological dysfunction. Most chemicals in this group require oxidative desulfuration to achieve their greatest cholinesterase-inhibiting potencies. Oxon derivatives are formed within liver cells but also by bacterial decay of parental pesticides. This study examines the toxicity of chlorpyrifos, malathion and diazinon and their oxons on the foothill yellow-legged frog (Rana boylii). R. boylii is exposed to agricultural pesticides in the California Central Valley. Median lethal concentrations of the parental forms during a 96 h exposure were 3.00 mg/L (24 h) for chlorpyrifos, 2.14 mg/L for malathion and 7.49 mg/L for diazinon. Corresponding oxons were 10 to 100 times more toxic than their parental forms. We conclude that environmental concentrations of these pesticides can be harmful to R. boylii populations. ?? 2006 Elsevier Ltd. All rights reserved.

Myocardial serotonin exchange: negligible uptake by capillary endothelium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moffett, T.C.; Chan, I.S.; Bassingthwaighte, J.B.

1988-03-01

The extraction of serotonin from the blood during transorgan passage through the heart was studied using Langendorff-perfused rabbit hearts. Outflow dilution curves of /sup 131/I- or /sup 125/I-labeled albumin, (/sup 14/C)sucrose, and (3H)serotonin injected simultaneously into the inflow were fitted with an axially distributed blood-tissue exchange model to examine the extraction process. The model fits of the albumin and sucrose outflow dilution curves were used to define flow heterogeneity, intravascular dispersion, capillary permeability, and the volume of the interstitial space, which reduced the degrees of freedom in fitting the model to the serotonin curves. Serotonin extractions, measured against albumin, duringmore » single transcapillary passage, ranged from 24 to 64%. The ratio of the capillary permeability-surface area products for serotonin and sucrose, based on the maximum instantaneous extraction, was 1.37 +/- 0.2 (n = 18), very close to the predicted value of 1.39, the ratio of free diffusion coefficients calculated from the molecular weights. This result shows that the observed uptake of serotonin can be accounted for solely on the basis of diffusion between endothelial cells into the interstitial space. Thus it appears that the permeability of the luminal surface of the endothelial cell is negligible in comparison to diffusion through the clefts between endothelial cells. In 18 sets of dilution curves, with and without receptor and transport blockers or competitors (ketanserin, desipramine, imipramine, serotonin), the extractions and estimates of the capillary permeability-surface area product were not reduced, nor were the volumes of distribution. The apparent absence of transporters and receptors in rabbit myocardial capillary endothelium contrasts with their known abundance in the pulmonary vasculature.« less

BEHAVIORAL AND NEUROCHEMICAL EFFECTS OF ACUTE CHLORPYRIFOS IN RATS: TOLERANCE TO PROLONGED INHIBITION OF CHOLINESTERASE

EPA Science Inventory

Chlorpyrifos (CPF), a commercially prevalent organophosphate (OP) pesticide, inhibits blood and brain cholinesterase for up to 10 weeks after acute s.c. injection in rats. his prolonged inhibition suggested that acute CPF may affect muscarinic receptors and behavior as does repea...

The serotonin system in autism spectrum disorder: from biomarker to animal models

PubMed Central

Muller, Christopher L.; Anacker, Allison M.J.; Veenstra-VanderWeele, Jeremy

2015-01-01

Elevated whole blood serotonin, or hyperserotonemia, was the first biomarker identified in autism spectrum disorder (ASD) and is present in more than 25% of affected children. The serotonin system is a logical candidate for involvement in ASD due to its pleiotropic role across multiple brain systems both dynamically and across development. Tantalizing clues connect this peripheral biomarker with changes in brain and behavior in ASD, but the contribution of the serotonin system to ASD pathophysiology remains incompletely understood. Studies of whole blood serotonin levels in ASD and in a large founder population indicate greater heritability than for the disorder itself and suggest an association with recurrence risk. Emerging data from both neuroimaging and postmortem samples also indicate changes in the brain serotonin system in ASD. Genetic linkage and association studies of both whole blood serotonin levels and of ASD risk point to the chromosomal region containing the serotonin transporter (SERT) gene in males but not in females. In ASD families with evidence of linkage to this region, multiple rare SERT amino acid variants lead to a convergent increase in serotonin uptake in cell models. A knock-in mouse model of one of these variants, SERT Gly56Ala, recapitulates the hyperserotonemia biomarker and shows increased brain serotonin clearance, increased serotonin receptor sensitivity, and altered social, communication, and repetitive behaviors. Data from other rodent models also suggest an important role for the serotonin system in social behavior, in cognitive flexibility, and in sensory development. Recent work indicates that reciprocal interactions between serotonin and other systems, such as oxytocin, may be particularly important for social behavior. Collectively, these data point to the serotonin system as a prime candidate for treatment development in a subgroup of children defined by a robust, heritable biomarker. PMID:26577932

Selective serotonin reuptake inhibitors and adverse pregnancy outcomes.

PubMed

Wen, Shi Wu; Yang, Qiuying; Garner, Peter; Fraser, William; Olatunbosun, Olufemi; Nimrod, Carl; Walker, Mark

2006-04-01

The purpose of this study was to assess the safety of the use of selective serotonin reuptake inhibitors in pregnancy. We carried out a retrospective cohort study of 972 pregnant women who had been given at least 1 selective serotonin reuptake inhibitor prescription in the year before delivery and 3878 pregnant women who did not receive selective serotonin reuptake inhibitors and who were matched by the year of the infant's birth, the type of institute at birth, and the mother's postal code from 1990 to 2000 in the Canadian province of Saskatchewan. The risks of low birth weight (adjusted odds ratio, 1.58; 95% CI, 1.19, 2.11), preterm birth (adjusted odds ratio, 1.57; 95% CI, 1.28, 1.92), fetal death (adjusted odds ratio, 2.23; 95% CI, 1.01, 4.93), and seizures (adjusted odds ratio, 3.87; 95% CI, 1.00, 14.99) were increased in infants who were born to mothers who had received selective serotonin reuptake inhibitor therapy. The use of selective serotonin reuptake inhibitors in pregnancy may increase the risks of low birth weight, preterm birth, fetal death, and seizures.

The effects of glycogen synthase kinase-3beta in serotonin neurons.

PubMed

Zhou, Wenjun; Chen, Ligong; Paul, Jodi; Yang, Sufen; Li, Fuzeng; Sampson, Karen; Woodgett, Jim R; Beaulieu, Jean Martin; Gamble, Karen L; Li, Xiaohua

2012-01-01

Glycogen synthase kinase-3 (GSK3) is a constitutively active protein kinase in brain. Increasing evidence has shown that GSK3 acts as a modulator in the serotonin neurotransmission system, including direct interaction with serotonin 1B (5-HT1B) receptors in a highly selective manner and prominent modulating effect on 5-HT1B receptor activity. In this study, we utilized the serotonin neuron-selective GSK3β knockout (snGSK3β-KO) mice to test if GSK3β in serotonin neurons selectively modulates 5-HT1B autoreceptor activity and function. The snGSK3β-KO mice were generated by crossbreeding GSK3β-floxed mice and ePet1-Cre mice. These mice had normal growth and physiological characteristics, similar numbers of tryptophan hydroxylase-2 (TpH2)-expressing serotonin neurons, and the same brain serotonin content as in littermate wild type mice. However, the expression of GSK3β in snGSK3β-KO mice was diminished in TpH2-expressing serotonin neurons. Compared to littermate wild type mice, snGSK3β-KO mice had a reduced response to the 5-HT1B receptor agonist anpirtoline in the regulation of serotonergic neuron firing, cAMP production, and serotonin release, whereas these animals displayed a normal response to the 5-HT1A receptor agonist 8-OH-DPAT. The effect of anpirtoline on the horizontal, center, and vertical activities in the open field test was differentially affected by GSK3β depletion in serotonin neurons, wherein vertical activity, but not horizontal activity, was significantly altered in snGSK3β-KO mice. In addition, there was an enhanced anti-immobility response to anpirtoline in the tail suspension test in snGSK3β-KO mice. Therefore, results of this study demonstrated a serotonin neuron-targeting function of GSK3β by regulating 5-HT1B autoreceptors, which impacts serotonergic neuron firing, serotonin release, and serotonin-regulated behaviors.

Structure and Function of Serotonin G protein Coupled Receptors

PubMed Central

McCorvy, John D.; Roth, Bryan L.

2015-01-01

Serotonin receptors are prevalent throughout the nervous system and the periphery, and remain one of the most lucrative and promising drug discovery targets for disorders ranging from migraine headaches to neuropsychiatric disorders such as schizophrenia and depression. There are 14 distinct serotonin receptors, of which 13 are G protein coupled receptors (GPCRs), which are targets for approximately 40% of the approved medicines. Recent crystallographic and biochemical evidence has provided a converging understanding of the basic structure and functional mechanics of GPCR activation. Currently, two GPCR crystal structures exist for the serotonin family, the 5-HT1B and 5-HT2B receptor, with the antimigraine and valvulopathic drug ergotamine bound. The first serotonin crystal structures not only provide the first evidence of serotonin receptor topography but also provide mechanistic explanations into functional selectivity or biased agonism. This review will detail the findings of these crystal structures from a molecular and mutagenesis perspective for driving rational drug design for novel therapeutics incorporating biased signaling. PMID:25601315

Gastric pentadecapeptide BPC 157 effective against serotonin syndrome in rats.

PubMed

Boban Blagaic, Alenka; Blagaic, Vladimir; Mirt, Mirela; Jelovac, Nikola; Dodig, Goran; Rucman, Rudolf; Petek, Marijan; Turkovic, Branko; Anic, Tomislav; Dubovecak, Miroslav; Staresinic, Mario; Seiwerth, Sven; Sikiric, Predrag

2005-04-11

Serotonin syndrome commonly follows irreversible monoamine oxidase (MAO)-inhibition and subsequent serotonin (5-HT) substrate (in rats with fore paw treading, hind limbs abduction, wet dog shake, hypothermia followed by hyperthermia). A stable gastric pentadecapeptide BPC 157 with very safe profile (inflammatory bowel disease clinical phase II, PL-10, PLD-116, PL-14736, Pliva) reduced the duration of immobility to a greater extent than imipramine, and, given peripherally, has region specific influence on brain 5-HT synthesis (alpha-[14C]methyl-L-tryptophan autoradiographic measurements) in rats, different from any other serotonergic drug. Thereby, we investigate this peptide (10 microg, 10 ng, 10 pg/kg i.p.) in (i) full serotonin syndrome in rat combining pargyline (irreversible MAO-inhibition; 75 mg/kg i.p.) and subsequent L-tryptophan (5-HT precursor; 100 mg/kg i.p.; BPC 157 as a co-treatment), or (ii, iii) using pargyline or L-tryptophan given separately, as a serotonin-substrate with (ii) pargyline (BPC 157 as a 15-min posttreatment) or as a potential serotonin syndrome inductor with (iii) L-tryptophan (BPC 157 as a 15 min-pretreatment). In all experiments, gastric pentadecapeptide BPC 157 contrasts with serotonin-syndrome either (i) presentation (i.e., particularly counteracted) or (ii) initiation (i.e., neither a serotonin substrate (counteraction of pargyline), nor an inductor for serotonin syndrome (no influence on L-tryptophan challenge)). Indicatively, severe serotonin syndrome in pargyline + L-tryptophan rats is considerably inhibited even by lower pentadecapeptide BPC 157 doses regimens (particularly disturbances such as hyperthermia and wet dog shake thought to be related to stimulation of 5-HT2A receptors), while the highest pentadecapeptide dose counteracts mild disturbances present in pargyline rats (mild hypothermia, feeble hind limbs abduction). Thereby, in severe serotonin syndrome, gastric pentadecapeptide BPC 157 (alone, no behavioral or

Serotonin produces monoamine oxidase-dependent oxidative stress in human heart valves.

PubMed

Peña-Silva, Ricardo A; Miller, Jordan D; Chu, Yi; Heistad, Donald D

2009-10-01

Heart valve disease and pulmonary hypertension, in patients with carcinoid tumors and people who used the fenfluramine-phentermine combination for weight control, have been associated with high levels of serotonin in blood. The mechanism by which serotonin induces valvular changes is not well understood. We recently reported that increased oxidative stress is associated with valvular changes in aortic valve stenosis in humans and mice. In this study, we tested the hypothesis that serotonin induces oxidative stress in human heart valves, and examined mechanisms by which serotonin may increase reactive oxygen species. Superoxide (O2*.-) was measured in heart valves from explanted human hearts that were not used for transplantation. (O2*.-) levels (lucigenin-enhanced chemoluminescence) were increased in homogenates of cardiac valves and blood vessels after incubation with serotonin. A nonspecific inhibitor of flavin-oxidases (diphenyliodonium), or inhibitors of monoamine oxidase [MAO (tranylcypromine and clorgyline)], prevented the serotonin-induced increase in (O2*.-). Dopamine, another MAO substrate that is increased in patients with carcinoid syndrome, also increased (O2*.-) levels in heart valves, and this effect was attenuated by clorgyline. Apocynin [an inhibitor of NAD(P)H oxidase] did not prevent increases in (O2*.-) during serotonin treatment. Addition of serotonin to recombinant human MAO-A generated (O2*.-), and this effect was prevented by an MAO inhibitor. In conclusion, we have identified a novel mechanism whereby MAO-A can contribute to increased oxidative stress in human heart valves and pulmonary artery exposed to serotonin and dopamine.

Plasma serotonin in patients with chronic tension headaches.

PubMed

Anthony, M; Lance, J W

1989-02-01

Previous reports have suggested that platelet level of serotonin in chronic tension headache (CTH) is lower than in normal control subjects, and that there is continuous activation of platelets both in migraine and in CTH. In this study we compared platelet serotonin concentration in 95 patients with CTH, 166 patients with migraine and 35 normal control subjects. Mean platelet serotonin (ng/10(9) platelets) was 310 for the CTH group, 384 during migraine headache, 474 for normal control subjects and 514 in headache-free migrainous patients. There was significant statistical difference of values between CTH patients and those of normal control subjects as well as headache-free migrainous patients, but not of those of migrainous patients during headache. It is suggested that CTH is a low serotonin syndrome, representing one end of the spectrum of idiopathic headache, the other end being represented by migraine.

Histopathological effects of chlorpyrifos on the gills, hepatopancreas and gonads of the freshwater crab Zilchiopsis collastinensis. Persistent effects after exposure.

PubMed

Negro, C L; Collins, P

2017-06-01

Sublethal effects of the pesticide chlorpyrifos were evaluated in the crab Zilchiopsis collastinensis (Decapoda, Trichodactylidae). Crabs were exposed to high concentrations of chlorpyrifos at the beginning of the experiment and controlled dilution, under natural light and temperature conditions. A control and three concentrations (22.4, 41.25 and 61.4µg chlorpyrifos L -1 ) were evaluated in triplicate. Nine crabs per concentration and day were used. The gills, hepatopancreas and ovaries were sampled before pesticide exposure (day 0) and 8, 15 and 22 days later, when concentrations were diluted and below the detection limits. The histopathological effects and their variations in time were observed and quantified. In gills, hyperplasias were observed in several cases, mainly in crabs exposed to chlorpyrifos. The number of collapsed lamellae and the number of affected lamellae quickly increased in exposed crabs, as effects were observed on day 8 and remained until day 22. In hepatopancreas there was an increase in the number of F and B -cells and affected tubules, especially after 22 days of exposure (p<0.05). In ovaries, there were no effects on gonadosomatic indexes or oocyte volume, but there was a significant increase in the atretic oocyte proportion related to pesticide exposure (p<0.05). The histopathological effects on the gills, hepatopancreas and ovaries were observed after exposure and persist even after dilution, and might be related to earlier exposures. Thus, these histopathological effects might be used as pesticide biomarkers even after the pesticide is not detected by chemical methods. Copyright © 2017 Elsevier Inc. All rights reserved.

Delayed effects of chlorpyrifos across metamorphosis on dispersal-related traits in a poleward moving damselfly.

PubMed

Dinh, Khuong Van; Janssens, Lizanne; Therry, Lieven; Bervoets, Lieven; Bonte, Dries; Stoks, Robby

2016-11-01

How exposure to contaminants may interfere with the widespread poleward range expansions under global warming is largely unknown. Pesticide exposure may negatively affect traits shaping the speed of range expansion, including traits related to population growth rate and dispersal-related traits. Moreover, rapid evolution of growth rates during poleward range expansions may come at a cost of a reduced investment in detoxification and repair thereby increasing the vulnerability to contaminants at expanding range fronts. We tested effects of a sublethal concentration of the widespread pesticide chlorpyrifos on traits related to range expansion in replicated edge and core populations of the poleward moving damselfly Coenagrion scitulum reared at low and high food levels in a common garden experiment. Food limitation in the larval stage had strong negative effects both in the larval stage and across metamorphosis in the adult stage. Exposure to chlorpyrifos during the larval stage did not affect larval traits but caused delayed effects across metamorphosis by increasing the incidence of wing malformations during metamorphosis and by reducing a key component of the adult immune response. There was some support for an evolutionary trade-off scenario as the faster growing edge larvae suffered a higher mortality during metamorphosis. Instead, there was no clear support for the faster growing edge larvae being more vulnerable to chlorpyrifos. Our data indicate that sublethal delayed effects of pesticide exposure, partly in association with the rapid evolution of faster growth rates, may slow down range expansions. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

USDA-ARS?s Scientific Manuscript database

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

Serotonin disrupts esophageal mucosal integrity: an investigation using a stratified squamous epithelial model.

PubMed

Wu, Liping; Oshima, Tadayuki; Tomita, Toshihiko; Ohda, Yoshio; Fukui, Hirokazu; Watari, Jiro; Miwa, Hiroto

2016-11-01

Serotonin regulates gastrointestinal function, and mast cells are a potential nonneuronal source of serotonin in the esophagus. Tight junction (TJ) proteins in the esophageal epithelium contribute to the barrier function, and the serotonin signaling pathway may contribute to epithelial leakage in gastroesophageal reflux disease. Therefore, the aim of this study was to investigate the role of serotonin on barrier function, TJ proteins, and related signaling pathways. Normal primary human esophageal epithelial cells were cultured with use of an air-liquid interface system. Serotonin was added to the basolateral compartment, and transepithelial electrical resistance (TEER) was measured. The expression of TJ proteins and serotonin receptor 7 (5-HT 7 ) was assessed by Western blotting. The involvement of 5-HT 7 was assessed with use of an antagonist and an agonist. The underlying cellular signaling pathways were examined with use of specific blockers. Serotonin decreased TEER and reduced the expression of TJ proteins ZO-1, occludin, and claudin 1, but not claudin 4. A 5-HT 7 antagonist blocked the serotonin-induced decrease in TEER, and a 5-HT 7 agonist decreased TEER. Inhibition of p38 mitogen-activated protein kinase (MAPK) reduced the serotonin-induced decrease in TEER. Inhibition of p38 MAPK blocked the decrease of ZO-1 levels, whereas extracellular-signal-regulated kinase (ERK) inhibition blocked the decrease in occludin levels. Cell signaling pathway inhibitors had no effect on serotonin-induced alterations in claudin 1 and claudin 4 levels. Serotonin induced phosphorylation of p38 MAPK and ERK, and a 5-HT 7 antagonist partially blocked serotonin-induced phosphorylation of p38 MAPK but not that of ERK. Serotonin disrupted esophageal squamous epithelial barrier function by modulating the levels of TJ proteins. Serotonin signaling pathways may mediate the pathogenesis of gastroesophageal reflux disease.

Natural enemies of Atta vollenweideri (Hymenoptera: Formicidae) leaf-cutter ants negatively affected by synthetic pesticides, chlorpyrifos and fipronil.

PubMed

Guillade, Andrea C; Folgarait, Patricia J

2014-02-01

In southern South America, Ada vollenweideri Forel (Hymenoptera: Formicidae) is a significant pest of several crops and forestry, also considered to reduce the carrying capacity of pastures. The most usual control method used in Latin America is the application of synthetic pesticides, mainly chlorpyrifos and fipronil. However, no studies have assessed the effects of these agrochemicals on natural enemies of ants. We aimed to evaluate the efficiency of these pesticides on leaf-cutter ants' control and to test their effect on phorid fly parasitoids. Chlorpyrifos failed to exert complete control over ant colonies in the field and was gravely detrimental to specific parasitoids, reducing their percentage of parasitism, pupal survivorship, and adult longevity. Fipronil, however, exerted complete control over the treated colonies. Laboratory tests using both pesticides, either on ants from foraging trails or on pupariae, showed that chlorpyrifos and fipronil decreased larval and pupal survivorship, as well as adult longevity of parasitoids, in comparison to controls. In conclusion, these pesticides will likely affect parasitoids with regard to their reproductive capacity, leading to the decreased levels of natural parasitism observed in the field after treatments. We discuss why neither pesticide should be taken into account for integrated pest management programs.

NEUROBEHAVIORAL EFFECTS OF CHRONIC DIETARY AND REPEATED HIGH-LEVEL SPIKE EXPOSURE TO CHLORPYRIFOS IN RATS.

EPA Science Inventory

This study aimed to model long-term subtoxic human exposure to an organophosphorus pesticide, chlorpyrifos, and to examine the influence of that exposure on the response to intermittent high-dose acute challenges. Adult Long-Evans male rats were maintained at 350g body weight by...

Optimization of the Use of His₆-OPH-Based Enzymatic Biocatalysts for the Destruction of Chlorpyrifos in Soil.

PubMed

Senko, Olga; Maslova, Olga; Efremenko, Elena

2017-11-23

Applying enzymatic biocatalysts based on hexahistidine-containing organophosphorus hydrolase (His₆-OPH) is suggested for the decomposition of chlorpyrifos, which is actively used in agriculture in many countries. The application conditions were optimized and the following techniques was suggested to ensure the highest efficiency of the enzyme: first, the soil is alkalinized with hydrated calcitic lime Ca(OH)₂, then the enzyme is introduced into the soil at a concentration of 1000 U/kg soil. Non-equilibrium low temperature plasma (NELTP)-modified zeolite is used for immobilization of the relatively inexpensive polyelectrolyte complexes containing the enzyme His₆-OPH and a polyanionic polymer: poly-l-glutamic acid (PLE 50 ) or poly-l-aspartic acid (PLD 50 ). The soil's humidity is then increased up to 60-80%, the top layer (10-30 cm) of soil is thoroughly stirred, and then exposed for 48-72 h. The suggested approach ensures 100% destruction of the pesticide within 72 h in soils containing as much as 100 mg/kg of chlorpyrifos. It was concluded that using this type of His₆-OPH-based enzyme chemical can be the best approach for soils with relatively low humus concentrations, such as sandy and loam-sandy chestnut soils, as well as types of soil with increased alkalinity (pH 8.0-8.4). Such soils are often encountered in desert, desert-steppe, foothills, and subtropical regions where chlorpyrifos is actively used.

Electrochemical quantification of serotonin in the live embryonic zebrafish intestine

PubMed Central

Njagi, John; Ball, Michael; Best, Marc; Wallace, Kenneth N.; Andreescu, Silvana

2010-01-01

We monitored real-time in vivo levels of serotonin release in the digestive system of intact zebrafish embryos during early development (5 dpf) using differential pulse voltammetry with implanted carbon fiber microelectrodes modified with carbon nanotubes dispersed in nafion. A detection limit of 1 nM, a linear range between 5 to 200 nM and a sensitivity of 83.65 nA·μM−1 were recorded. The microelectrodes were implanted at various locations in the intestine of zebrafish embryos. Serotonin levels of up to 29.9(±1.13) nM were measured in vivo in normal physiological conditions. Measurements were performed in intact live embryos without additional perturbation beyond electrode insertion. The sensor was able to quantify pharmacological alterations in serotonin release and provide the longitudinal distribution of this neurotransmitter along the intestine with high spatial resolution. In the presence of fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), concentrations of 54.1(±1.05) nM were recorded while in the presence of p-chloro-phenylalanine (PCPA), a tryptophan hydroxylase inhibitor, the serotonin levels decreased to 7.2(±0.45) nM. The variation of serotonin levels was correlated with immunohistochemical analysis. We have demonstrated the first use of electrochemical microsensors for in vivo monitoring of intestinal serotonin levels in intact zebrafish embryos. PMID:20148518

Serotonin is critical for rewarded olfactory short-term memory in Drosophila.

PubMed

Sitaraman, Divya; LaFerriere, Holly; Birman, Serge; Zars, Troy

2012-06-01

The biogenic amines dopamine, octopamine, and serotonin are critical in establishing normal memories. A common view for the amines in insect memory performance has emerged in which dopamine and octopamine are largely responsible for aversive and appetitive memories. Examination of the function of serotonin begins to challenge the notion of one amine type per memory because altering serotonin function also reduces aversive olfactory memory and place memory levels. Could the function of serotonin be restricted to the aversive domain, suggesting a more specific dopamine/serotonin system interaction? The function of the serotonergic system in appetitive olfactory memory was examined. By targeting the tetanus toxin light chain (TNT) and the human inwardly rectifying potassium channel (Kir2.1) to the serotonin neurons with two different GAL4 driver combinations, the serotonergic system was inhibited. Additional use of the GAL80(ts1) system to control expression of transgenes to the adult stage of the life cycle addressed a potential developmental role of serotonin in appetitive memory. Reduction in appetitive olfactory memory performance in flies with these transgenic manipulations, without altering control behaviors, showed that the serotonergic system is also required for normal appetitive memory. Thus, serotonin appears to have a more general role in Drosophila memory, and implies an interaction with both the dopaminergic and octopaminergic systems.

Multiple Cellular Responses to Serotonin Contribute to Epithelial Homeostasis

PubMed Central

Pai, Vaibhav P.; Horseman, Nelson D.

2011-01-01

Epithelial homeostasis incorporates the paradoxical concept of internal change (epithelial turnover) enabling the maintenance of anatomical status quo. Epithelial cell differentiation and cell loss (cell shedding and apoptosis) form important components of epithelial turnover. Although the mechanisms of cell loss are being uncovered the crucial triggers that modulate epithelial turnover through regulation of cell loss remain undetermined. Serotonin is emerging as a common autocrine-paracine regulator in epithelia of multiple organs, including the breast. Here we address whether serotonin affects epithelial turnover. Specifically, serotonin's roles in regulating cell shedding, apoptosis and barrier function of the epithelium. Using in vivo studies in mouse and a robust model of differentiated human mammary duct epithelium (MCF10A), we show that serotonin induces mammary epithelial cell shedding and disrupts tight junctions in a reversible manner. However, upon sustained exposure, serotonin induces apoptosis in the replenishing cell population, causing irreversible changes to the epithelial membrane. The staggered nature of these events induced by serotonin slowly shifts the balance in the epithelium from reversible to irreversible. These finding have very important implications towards our ability to control epithelial regeneration and thus address pathologies of aberrant epithelial turnover, which range from degenerative disorders (e.g.; pancreatitis and thyrioditis) to proliferative disorders (e.g.; mastitis, ductal ectasia, cholangiopathies and epithelial cancers). PMID:21390323

The serotonin transporter: Examination of the changes in transporter affinity induced by ligand binding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Humphreys, C.J.

1989-01-01

The plasmalemmal serotonin transporter uses transmembrane gradients of Na{sup +}, Cl{sup {minus}} and K{sup +} to accumulate serotonin within blood platelets. Transport is competitively inhibited by the antidepressant imipramine. Like serotonin transport, imipramine binding requires Na{sup +}. Unlike serotonin, however, imipramine does not appear to be transported. To gain insight into the mechanism of serotonin transport the author have analyzed the influences of Na{sup +} and Cl{sup {minus}}, the two ions cotransported with serotonin, on both serotonin transport and the interaction of imipramine and other antidepressant drugs with the plasmalemmal serotonin transporter of human platelets. Additionally, the author have synthesized,more » purified and characterized the binding of 2-iodoimipramine to the serotonin transporter. Finally, the author have conducted a preliminary study of the inhibition of serotonin transport and imipramine binding produced by dicyclohexylcarbodiimide. My results reveal many instances of positive heterotropic cooperativity in ligand binding to the serotonin transporter. Na{sup +} binding enhances the transporters affinity for imipramine and several other antidepressant drugs, and also increases the affinity for Cl{sup {minus}}. Cl{sup {minus}} enhances the transporters affinity for imipramine, as well as for Na{sup +}. At concentrations in the range of its K{sub M} for transport serotonin is a competitive inhibitor of imipramine binding. At much higher concentrations, however, serotonin also inhibits imipramines dissociation rate constant. This latter effect which is Na{sup +}-independent and species specific, is apparently produced by serotonin binding at a second, low affinity site on, or near, the transporter complex. Iodoimipramine competitively inhibit both ({sup 3}H)imipramine binding and ({sup 3}H)serotonin transport.« less

Intestinal crosstalk between microbiota and serotonin and its impact on gut motility.

PubMed

Ge, Xiaolong; Pan, Junhai; Liu, Yichang; Wang, Hongkan; Zhou, Wei; Wang, Xianfa

2018-05-27

The gastrointestinal tract harbours a diverse bacterial community that contributes to health and disease. A number of studies have demonstrated that the gut microbiota plays a critical role in the metabolism of serotonin. Microbial-derived metabolites, such as bile acids and short-chain fatty acids, are reported to affect the production of serotonin which, in turn, directly or indirectly regulates gut motility. Enterochromaffin cells are important specialized endocrine cells found in the intestine, which is the major location of serotonin biosynthesis. The relationship between microbiota and gut motility are studied depended on microbial-derived metabolites and serotonin. Both bile acids and short-chain fatty acids can modulate serotonin metabolism in hosts by affecting key intermediates of the serotonin pathway. Thus, gut motility may be regulated through microbial modifications of host serotonin biosynthesis, which continues to be evaluated as a target for functional gastrointestinal disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Lung damage and pulmonary uptake of serotonin in intact dogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dawson, C.A.; Christensen, C.W.; Rickaby, D.A.

1985-06-01

The authors examined the influence of glass bead embolization and oleic acid, dextran, and imipramine infusion on the pulmonary uptake of trace doses of (/sup 3/H)serotonin and the extravascular volume accessible to (/sup 14/C)antipyrine in anesthetized dogs. Embolization and imipramine decreased serotonin uptake by 53 and 61%, respectively, but no change was observed with oleic acid or dextran infusion. The extravascular volume accessible to the antipyrine was reduced by 77% after embolization and increased by 177 and approximately 44% after oleic acid and dextran infusion, respectively. The results suggest that when the perfused endothelial surface is sufficiently reduced, as withmore » embolization, the uptake of trace doses of serotonin will be depressed. In addition, decreases in serotonin uptake in response to imipramine in this study and in response to certain endothelial toxins in other studies suggest that serotonin uptake can reveal certain kinds of changes in endothelial function. However, the lack of a response to oleic acid-induced damage in the present study suggests that serotonin uptake is not sensitive to all forms of endothelial damage.« less

Serotonin, atherosclerosis, and collateral vessel spasm

NASA Technical Reports Server (NTRS)

Hollenberg, N.

1988-01-01

Studies on animal models demonstrate that platelet products contribute to vascular spasm in ischemic syndromes and that this is reversible with administration of ketanserin and thromboxane synthesis inhibitors. Laboratory animals (dogs, rabbits, and rats) that had femoral artery ligations exhibited supersensitivity to serotonin within days in their collateral blood vessels. This supersensitivity lasted at least 6 months. The response to serotonin was reversed by ketanserin, but not by 5HT-1 antagonists. Supersensitivity does not extend to norepinephrine, and alpha blockers do not influence the response to serotonin. It appears that platelet activation by endothelial injury contributes to ischemia through blood vessel occlusion and vascular spasm. When platelet activation occurs in vivo, blood vessel occlusion and vascular spasm are reversible in part by using ketanserin or agents that block thromboxane synthesis or its action. Combining both classes of agents reverses spasm completely. These findings support existing evidence that platelet products contribute to vascular disease, and provide an approach to improved management with currently available pharmacologic agents.

Dietary Precursors of Serotonin and Newborn State Behavior.

ERIC Educational Resources Information Center

Yogman, Michael W.; Zeisel, Steven

Although previous research with adult humans and nonhumans has suggested a relationship between sleep behavior and brain serotonin levels, no studies have been made of the relationship of normal children's or infants' sleep patterns to serotonin levels, tryptophan metabolism, or diet. This study investigates the relationship between dietary…

Diverse Neurotoxicants Target the Differentiation of Embryonic Neural Stem Cells into Neuronal and Glial Phenotypes

PubMed Central

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

2016-01-01

The large number of compounds that need to be tested for developmental neurotoxicity drives the need to establish in vitro models to evaluate specific neurotoxic endpoints. We used neural stem cells derived from rat neuroepithelium on embryonic day 14 to evaluate the impact of diverse toxicants on their ability to differentiate into glia and neurons: a glucocorticoid (dexamethasone), organophosphate insecticides (chlorpyrifos, diazinon, parathion), insecticides targeting the GABAA receptor (dieldrin, fipronil), heavy metals (Ni2+, Ag+), nicotine and tobacco smoke extract. We found three broad groupings of effects. One diverse set of compounds, dexamethasone, the organophosphate pesticides, Ni2+ and nicotine, suppressed expression of the glial phenotype while having little or no effect on the neuronal phenotype. The second pattern was restricted to the pesticides acting on GABAA receptors. These compounds promoted the glial phenotype and suppressed the neuronal phenotype. Notably, the actions of compounds eliciting either of these differentiation patterns were clearly unrelated to deficits in cell numbers: dexamethasone, dieldrin and fipronil all reduced cell numbers, whereas organophosphates and Ni2+ had no effect. The third pattern, shared by Ag+ and tobacco smoke extract, clearly delineated cytotoxicity, characterized major cell loss with suppression of differentiation into both glial and neuronal phenotypes; but here again, there was some selectivity in that glia were suppressed more than neurons. Our results, from this survey with diverse compounds, point to convergence of neurotoxicant effects on a specific “decision node” that controls the emergence of neurons and glia from neural stem cells. PMID:27816694

Serotonin 2c receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis

USDA-ARS?s Scientific Manuscript database

Energy and glucose homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor a...

Association of Serotonin Concentration to Behavior and IQ in Autistic Children.

ERIC Educational Resources Information Center

Kuperman, Samuel; And Others

1987-01-01

The IQ and behavior patterns on the Autism Behavior Checklist (ABC) of 25 boys were compared to blood concentrations of platelet rich plasma (PRP) serotonin. Although no correlations were found between serotonin levels and IQ or ABC scales, four individual ABC items did correlate with serotonin concentrations. (Author/DB)

Toxicity assessment of chlorpyrifos-degrading fungal bio-composites and their environmental risks.

PubMed

Liu, Jie; Zhang, Xiaoying; Yang, Mengran; Hu, Meiying; Zhong, Guohua

2018-02-01

Bioremediation techniques coupling with functional microorganisms have emerged as the most promising approaches for in-situ elimination of pesticide residue. However, the environmental safety of bio-products based on microorganisms or engineered enzymes was rarely known. Here, we described the toxicity assessment of two previously fabricated fungal bio-composites which were used for the biodegradation of chlorpyrifos, to clarify their potential risks on the environment and non-target organisms. Firstly, the acute and chronic toxicity of prepared bio-composites were evaluated using mice and rabbits, indicating neither acute nor chronic effect was induced via short-term or continuous exposure. Then, the acute mortality on zebrafish was investigated, which implied the application of fungal bio-composites had no lethal risk on aquatic organisms. Meanwhile, the assessment on soil organic matters suggested that no threat was posed to soil quality. Finally, by monitoring, the germination of cabbage was not affected by the exposure to two bio-products. Therefore, the application of fungal bio-composites for chlorpyrifos elimination cannot induce toxic risk to the environment and non-target organisms, which insured the safety of these engineered bio-products for realistic management of pesticide residue, and provided new insights for further development of bioremediation techniques based on functional microorganisms.

21 CFR 862.1390 - 5-Hydroxyindole acetic acid/serotonin test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false 5-Hydroxyindole acetic acid/serotonin test system... Test Systems § 862.1390 5-Hydroxyindole acetic acid/serotonin test system. (a) Identification. A 5-hydroxyindole acetic acid/serotonin test system is a device intended to measure 5-hydroxyindole acetic acid...

21 CFR 862.1390 - 5-Hydroxyindole acetic acid/serotonin test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false 5-Hydroxyindole acetic acid/serotonin test system... Test Systems § 862.1390 5-Hydroxyindole acetic acid/serotonin test system. (a) Identification. A 5-hydroxyindole acetic acid/serotonin test system is a device intended to measure 5-hydroxyindole acetic acid...

21 CFR 862.1390 - 5-Hydroxyindole acetic acid/serotonin test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false 5-Hydroxyindole acetic acid/serotonin test system... Test Systems § 862.1390 5-Hydroxyindole acetic acid/serotonin test system. (a) Identification. A 5-hydroxyindole acetic acid/serotonin test system is a device intended to measure 5-hydroxyindole acetic acid...

21 CFR 862.1390 - 5-Hydroxyindole acetic acid/serotonin test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false 5-Hydroxyindole acetic acid/serotonin test system... Test Systems § 862.1390 5-Hydroxyindole acetic acid/serotonin test system. (a) Identification. A 5-hydroxyindole acetic acid/serotonin test system is a device intended to measure 5-hydroxyindole acetic acid...

THE RELATIONSHIP BETWEEN WHOLE BLOOD SEROTONIN AND REPETITIVE BEHAVIORS IN AUTISM

PubMed Central

Kolevzon, Alexander; Newcorn, Jeffrey H.; Kryzak, Lauren; Chaplin, William; Watner, Dryden; Hollander, Eric; Smith, Christopher J.; Cook, Edwin H.; Silverman, Jeremy M.

2009-01-01

This study was conducted to examine the relationship between whole blood serotonin level and behavioral symptoms in 78 subjects with autism. No significant associations were found between serotonin level and the primary behavioral outcome measures. However, a significant inverse relationship between serotonin level and self-injury was demonstrated. PMID:20044143

Social regulation of serotonin in the auditory midbrain

PubMed Central

Hall, Ian C.; Sell, Gabrielle L.; Hurley, Laura M .

2011-01-01

The neuromodulator serotonin regulates auditory processing and can increase within minutes in response to stimuli like broadband noise as well as non-auditory stressors. Little is known about the serotonergic response in the auditory system to more natural stimuli such as social interactions, however. Using carbon-fiber voltammetry, we measured extracellular serotonin in the auditory midbrain of resident male mice during encounters with a male intruder. Serotonin increased in the inferior colliculus (IC) over the course of a 15 minute interaction, but not when mice were separated with a perforated barrier. Several behaviors, including the amount of immobility and anogenital investigation performed by the resident, were correlated with the serotonergic response. Multiple intrinsic factors associated with individual mice also correlated with the serotonergic response. One of these was age: older mice had smaller serotonergic responses to the social interaction. In a second interaction, individual identity predicted serotonergic responses that were highly consistent with those in the first interaction, even when mice were paired with different intruders. Serotonin was also significantly elevated in the second social interaction relative to the first, suggesting a role for social experience. These findings show that during social interaction, serotonin in the IC is influenced by extrinsic factors such as the directness of social interaction and intrinsic factors including age, individual identity, and experience. PMID:21787041

Effects of delayed laboratory processing on platelet serotonin levels.

PubMed

Sanner, Jennifer E; Frazier, Lorraine; Udtha, Malini

2013-01-01

Despite the availability of established guidelines for measuring platelet serotonin, these guidelines may be difficult to follow in a hospital setting where time to processing may vary from sample to sample. The purpose of this study was to evaluate the effect of the time to processing of human blood samples on the stability of the enzyme-linked immunosorbent assay (ELISA) for the determination of platelet serotonin levels in human plasma. Human blood samples collected from a convenience sample of eight healthy volunteers were analyzed to determine platelet serotonin levels from plasma collected in ethylene diamine tetra acetic acid (EDTA) tubes and stored at 4°C for 3 hr, 5 hr, 8 hr, and 12 hr. Refrigeration storage at 4°C for 3 hr, 5 hr, 8 hr, and 12 hr altered the platelet serotonin measurement when compared to immediate processing. The bias for the samples stored at 4°C for 3 hr was 102.3 (±217.39 ng/10(9) platelets), for 5 hr was 200.1 (±132.76 ng/10(9) platelets), for 8 hr was 146.9 (±221.41 ng/10(9) platelets), and for 12 hr was -67.6 (±349.60 ng/10(9) platelets). Results from this study show that accurate measurement of platelet serotonin levels is dependent on time to processing. Researchers should therefore follow a standardized laboratory guideline for obtaining immediate platelet serotonin levels after blood sample collection.

Brain serotonin transporter density and aggression in abstinent methamphetamine abusers.

PubMed

Sekine, Yoshimoto; Ouchi, Yasuomi; Takei, Nori; Yoshikawa, Etsuji; Nakamura, Kazuhiko; Futatsubashi, Masami; Okada, Hiroyuki; Minabe, Yoshio; Suzuki, Katsuaki; Iwata, Yasuhide; Tsuchiya, Kenji J; Tsukada, Hideo; Iyo, Masaomi; Mori, Norio

2006-01-01

In animals, methamphetamine is known to have a neurotoxic effect on serotonin neurons, which have been implicated in the regulation of mood, anxiety, and aggression. It remains unknown whether methamphetamine damages serotonin neurons in humans. To investigate the status of brain serotonin neurons and their possible relationship with clinical characteristics in currently abstinent methamphetamine abusers. Case-control analysis. A hospital research center. Twelve currently abstinent former methamphetamine abusers (5 women and 7 men) and 12 age-, sex-, and education-matched control subjects recruited from the community. The brain regional density of the serotonin transporter, a structural component of serotonin neurons, was estimated using positron emission tomography and trans-1,2,3,5,6,10-beta-hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]isoquinoline ([(11)C](+)McN-5652). Estimates were derived from region-of-interest and statistical parametric mapping methods, followed by within-case analysis using the measures of clinical variables. The duration of methamphetamine use, the magnitude of aggression and depressive symptoms, and changes in serotonin transporter density represented by the [(11)C](+)McN-5652 distribution volume. Methamphetamine abusers showed increased levels of aggression compared with controls. Region-of-interest and statistical parametric mapping analyses revealed that the serotonin transporter density in global brain regions (eg, the midbrain, thalamus, caudate, putamen, cerebral cortex, and cerebellum) was significantly lower in methamphetamine abusers than in control subjects, and this reduction was significantly inversely correlated with the duration of methamphetamine use. Furthermore, statistical parametric mapping analyses indicated that the density in the orbitofrontal, temporal, and anterior cingulate areas was closely associated with the magnitude of aggression in methamphetamine abusers. Protracted abuse of methamphetamine may reduce

Imaging Phenotypes of Major Depressive Disorder: Genetic Correlates

PubMed Central

Savitz, Jonathan B; Drevets, Wayne C

2009-01-01

Imaging techniques are a potentially powerful method of identifying phenotypes that are associated with, or are indicative of a vulnerability to developing major depressive disorder (MDD). Here we identify seven promising MDD-associated traits identified by magnetic resonance imaging (MRI) or positron emission tomography (PET). We evaluate whether these traits are state-independent, heritable endophenotypes, or state-dependent phenotypes that may be useful markers of treatment efficacy. In MDD, increased activity of the amygdala in response to negative stimuli appears to be a mood-congruent phenomenon, and is likely moderated by the serotonin transporter gene (SLC6A4) promoter polymorphism (5-HTTLPR). Hippocampal volume loss is characteristic of elderly or chronically-ill samples and may be impacted by the val66met brain-derived neurotrophic factor (BDNF) gene variant and the 5-HTTLPR SLC6A4 polymorphism. White matter pathology is salient in elderly MDD cohorts but is associated with cerebrovascular disease, and is unlikely to be a useful marker of a latent MDD diathesis. Increased blood flow or metabolism of the subgenual anterior cingulate cortex (sgACC), together with gray matter volume loss in this region, is a well-replicated finding in MDD. An attenuation of the usual pattern of fronto-limbic connectivity, particularly a decreased temporal correlation in amygdala-anterior cingulate cortex (ACC) activity, is another MDD-associated trait. Concerning neuroreceptor PET imaging, decreased 5-HT1A binding potential in the raphe, medial temporal lobe, and medial prefrontal cortex (mPFC) has been strongly associated with MDD, and may be impacted by a functional single nucleotide polymorphism in the promoter region of the 5-HT1A gene (HTR1A: –1019C/G; rs6295). Potentially indicative of inter-study variation in MDD etiology or mood state, both increased and decreased binding potential of the serotonin transporter has been reported. Challenges facing the field include

A novel 5HT3 antagonist 4i (N-(3-chloro-2-methylphenyl)quinoxalin-2-carboxamide) prevents diabetes-induced depressive phenotypes in mice: Modulation of serotonergic system.

PubMed

Gupta, Deepali; Thangaraj, Devadoss; Radhakrishnan, Mahesh

2016-01-15

Despite the presence of a multitudinous pharmacotherapy, diabetes-induced depressive disorder remains undertreated. Evidence suggests that brain serotonergic deficits are associated with depressive-like behavior in diabetes and that 5HT3 receptor (5HT3R) antagonists have serotonergic facilitatory effects. This study examined the effects of a novel 5HT3R antagonist, 4i (N-(3-chloro-2-methylphenyl)quinoxalin-2-carboxamide), in diabetes-induced depressive phenotypes. Experimentally, (1) to evaluate the effects of 4i, mice with 8-weeks of diabetes (induced by streptozotocin, 200mg/kg, i.p.) were treated with vehicle, 4i (0.5 and 1mg/kg/day, i.p.), fluoxetine (10mg/kg/day, i.p.) for 4-weeks and subjected to neurobehavioral assays, followed by biochemical estimation of serotonin levels in midbrain, prefrontal-cortex and cerebellum. (2) To evaluate the role of 5HT3R in the postulated effect of 4i, diabetic mice were given 4i (1mg/kg/day, i.p.) after 1h of 1-(m-chlorophenyl)-biguanide (mCPBG, a 5HT3R agonist, 10mg/kg/day, i.p.) treatment and subjected to the same protocol. The results showed that diabetic mice exhibited a significant behavioral deficit, including depression-like behavior in forced swim test, anxiety-like in open field test and sociability deficits in social interaction test, along with a significant decrease in serotonin level in these brain regions. 4i (1mg/kg), similar to fluoxetine, prevented these behavioral abnormalities and normalized brain serotonin levels. 4i (0.5mg/kg) ameliorated only diabetes-induced depressive-like behavior and serotonin deficits, but not anxiety-like effects. mCPBG blunted 4i-mediated behavioral response and increase in brain serotonin levels. Altogether, this study suggests that 4i prevents diabetes-induced depressive phenotypes in mice, which may involve antagonism of 5HT3Rs and increase in serotonin levels in discrete brain regions. Copyright © 2015 Elsevier B.V. All rights reserved.

Multiple receptor subtypes mediate the effects of serotonin on rat subfornical organ neurons

NASA Technical Reports Server (NTRS)

Scrogin, K. E.; Johnson, A. K.; Schmid, H. A.

1998-01-01

The subfornical organ (SFO) receives significant serotonergic innervation. However, few reports have examined the functional effects of serotonin on SFO neurons. This study characterized the effects of serotonin on spontaneously firing SFO neurons in the rat brain slice. Of 31 neurons tested, 80% responded to serotonin (1-100 microM) with either an increase (n = 15) or decrease (n = 10) in spontaneous activity. Responses to serotonin were dose dependent and persisted after synaptic blockade. Excitatory responses could also be mimicked by the 5-hydroxytryptamine (5-HT)2A/2C receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI; 1-10 microM) and could be blocked by the 5-HT2A/2C-receptor antagonist LY-53,857 (10 microM). LY-53,857 unmasked inhibitory responses to serotonin in 56% of serotonin-excited cells tested. Serotonin-inhibited cells were also inhibited by the 5-HT1A-receptor agonist 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT; 1-10 microM; n = 7). The data indicate that SFO neurons are responsive to serotonin via postsynaptic activation of multiple receptor subtypes. The results suggest that excitatory responses to serotonin are mediated by 5-HT2A or 5-HT2C receptors and that inhibitory responses may be mediated by 5-HT1A receptors. In addition, similar percentages of serotonin-excited and -inhibited cells were also sensitive to ANG II. As such the functional relationship between serotonin and ANG II in the SFO remains unclear.

Multiple receptor subtypes mediate the effects of serotonin on rat subfornical organ neurons.

PubMed

Scrogin, K E; Johnson, A K; Schmid, H A

1998-12-01

The subfornical organ (SFO) receives significant serotonergic innervation. However, few reports have examined the functional effects of serotonin on SFO neurons. This study characterized the effects of serotonin on spontaneously firing SFO neurons in the rat brain slice. Of 31 neurons tested, 80% responded to serotonin (1-100 microM) with either an increase (n = 15) or decrease (n = 10) in spontaneous activity. Responses to serotonin were dose dependent and persisted after synaptic blockade. Excitatory responses could also be mimicked by the 5-hydroxytryptamine (5-HT)2A/2C receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI; 1-10 microM) and could be blocked by the 5-HT2A/2C-receptor antagonist LY-53,857 (10 microM). LY-53,857 unmasked inhibitory responses to serotonin in 56% of serotonin-excited cells tested. Serotonin-inhibited cells were also inhibited by the 5-HT1A-receptor agonist 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT; 1-10 microM; n = 7). The data indicate that SFO neurons are responsive to serotonin via postsynaptic activation of multiple receptor subtypes. The results suggest that excitatory responses to serotonin are mediated by 5-HT2A or 5-HT2C receptors and that inhibitory responses may be mediated by 5-HT1A receptors. In addition, similar percentages of serotonin-excited and -inhibited cells were also sensitive to ANG II. As such the functional relationship between serotonin and ANG II in the SFO remains unclear.

Noninvasive measurement of lung carbon-11-serotonin extraction in man

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coates, G.; Firnau, G.; Meyer, G.J.

1991-04-01

The fraction of serotonin extracted on a single passage through the lungs is being used as an early indicator of lung endothelial damage but the existing techniques require multiple arterial blood samples. We have developed a noninvasive technique to measure lung serotonin uptake in man. We utilized the double indicator diffusion principle, a positron camera, {sup 11}C-serotonin as the substrate, and {sup 11}CO-erythrocytes as the vascular marker. From regions of interest around each lung, we recorded time-activity curves in 0.5-sec frames for 30 sec after a bolus injection of first the vascular marker {sup 11}CO-erythrocytes and 10 min later {supmore » 11}C-serotonin. A second uptake measurement was made after imipramine 25-35 mg was infused intravenously. In three normal volunteers, the single-pass uptake of {sup 11}C-serotonin was 63.9% +/- 3.6%. This decreased in all subjects to a mean of 53.6% +/- 1.4% after imipramine. The rate of lung washout of {sup 11}C was also significantly prolonged after imipramine. This noninvasive technique can be used to measure lung serotonin uptake to detect early changes in a variety of conditions that alter the integrity of the pulmonary endothelium.« less

Serotonin Regulates the Feeding and Reproductive Behaviors of Pratylenchus penetrans.

PubMed

Han, Ziduan; Boas, Stephanie; Schroeder, Nathan E

2017-07-01

The success of all plant-parasitic nematodes is dependent on the completion of several complex behaviors. The lesion nematode Pratylenchus penetrans is an economically important parasite of a diverse range of plant hosts. Unlike the cyst and root-knot nematodes, P. penetrans moves both within and outside of the host roots and can feed from both locations. Adult females of P. penetrans require insemination by actively moving males for reproduction and can lay eggs both within and outside of the host roots. We do not have a complete understanding of the molecular basis for these behaviors. One candidate modulator of these behaviors is the neurotransmitter serotonin. Previous research demonstrated an effect of exogenously applied serotonin on the feeding and male mating behaviors of cyst and root-knot nematodes. However, there are no data on the role of exogenous serotonin on lesion nematodes. Similarly, there are no data on the presence and function of endogenous serotonin in any plant-parasitic nematode. Here, we establish that exogenous serotonin applied to P. penetrans regulates both feeding and sex-specific behaviors. Furthermore, using immunohistochemistry and pharmacological assays, our data suggest that P. penetrans utilizes endogenous serotonin to regulate both feeding and sex-specific behaviors.

Incidence and prognostic value of serotonin secretion in pancreatic neuroendocrine tumours.

PubMed

Zandee, Wouter T; van Adrichem, Roxanne C; Kamp, Kimberly; Feelders, Richard A; van Velthuysen, Marie-Louise F; de Herder, Wouter W

2017-08-01

Serotonin secretion occurs in approximately 1%-4% of patients with a pancreatic neuroendocrine tumour (PNET), but the incidence is not well defined. The aim of this study was to determine the incidence of serotonin secretion with and without carcinoid syndrome and the prognostic value for overall survival (OS). Data were collected from 255 patients with a PNET if 24-hours urinary 5-hydroxyindoleacetic acid excretion (5-HIAA) was assessed. Patients were diagnosed with serotonin secretion if 24-hours urinary 5-HIAA excretion was more than 3× the upper limit of normal (ULN) of 50 μmol/24 hours during follow-up. The effect of serotonin secretion on OS was estimated with uni- and multivariate analyses using a Cox regression. Two (0.8%) patients were diagnosed with carcinoid syndrome, and another 20 (7.8%) had a serotonin-secreting PNET without symptoms. These patients mostly had ENETS stage IV disease with high chromogranin A (CgA). Serotonin secretion was a negative prognostic factor in univariate analysis (HR 2.2, 95% CI: 1.27-3.81), but in multivariate analysis, only CgA>10× ULN (HR: 1.81, 95% CI: 1.10-2.98) and neuron-specific enolase (NSE) >ULN (HR: 3.51, 95% CI: 2.26-5.46) were predictors for OS. Immunohistochemical staining for serotonin was positive in 28.6% of serotonin-secreting PNETs (one with carcinoid syndrome) and negative in all controls. Carcinoid syndrome is rare in patients with a PNET, but serotonin secretion occurs often. This is a negative prognostic factor for OS, but after correction for CgA and NSE, it is no longer a predictor and probably only a "not-so innocent bystander" in patients with high tumour burden. © 2017 John Wiley & Sons Ltd.

AGE-RELATED BRAIN CHOLINESTERASE INHIBITION KINETICS FOLLOWING IN VITRO INCUBATION WITH CHLORPYRIFOS-OXON AND DIAZINON-OXON

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

2007-01-01

Chlorpyrifos and diazinon are two commonly used organophosphorus (OP) insecticides, and their primary mechanism of action involves the inhibition of acetylcholinesterase (AChE) by their metabolites chlorpyrifos-oxon (CPO) and diazinon-oxon (DZO), respectively. The study objectives were to assess the in vitro age-related inhibition kinetics of neonatal rat brain cholinesterase (ChE) by estimating the bimolecular inhibitory rate constant (ki) values for CPO and DZO. Brain ChE inhibition and ki values following CPO and DZO incubation with neonatal Sprague-Dawley rats rat brain homogenates were determined at post natal day (PND) -5, -12 and -17 and compared with the corresponding inhibition and ki valuesmore » obtained in the adult rat. A modified Ellman method was utilized for measuring the ChE activity. Chlorpyrifos-oxon resulted in greater ChE inhibition than DZO consistent with the estimated ki values of both compounds. Neonatal brain ChE inhibition kinetics exhibited a marked age-related sensitivity to CPO, where the order of ChE inhibition was PND-5 > PND-7 > PND-17 with ki values of 0.95, 0.50 and 0.22 nM-1hr-1, respectively. In contrast, DZO did not exhibit an age-related inhibition of neonatal brain ChE, and the estimated ki value at all PND ages was 0.02 nM-1hr-1. These results demonstrated an age- and chemical-related OP-selective inhibition of rat brain ChE which may be critically important in understanding the potential sensitivity of juvenile humans to specific OP exposures.« less

Effect of plasma membrane fluidity on serotonin transport by endothelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Block, E.R.; Edwards, D.

1987-11-01

To evaluate the effect of plasma membrane fluidity of lung endothelial cells on serotonin transport, porcine pulmonary artery endothelial cells were incubated for 3 h with either 0.1 mM cholesterol hemisuccinate, 0.1 mM cis-vaccenic acid, or vehicle (control), after which plasma membrane fluidity and serotinin transport were measured. Fluorescence spectroscopy was used to measure fluidity in the plasma membrane. Serotonin uptake was calculated from the disappearance of ({sup 14}C)-serotonin from the culture medium. Cholesterol decreased fluidity in the subpolar head group and central and midacyl side-chain regions of the plasma membrane and decreased serotonin transport, whereas cis-vaccenic acid increased fluiditymore » in the central and midacyl side-chain regions of the plasma membrane and also increased serotonin transport. Cis-vaccenic acid had no effect of fluidity in the subpolar head group region of the plasma membrane. These results provide evidence that the physical state of the central and midacyl chains within the pulmonary artery endothelial cell plasma membrane lipid bilayer modulates transmembrane transport of serotonin by these cells.« less

Evaluation of temephos and chlorpyrifos-methyl against Culex pipiens (Diptera: Culicidae) larvae in septic tanks in Antalya, Turkey.

PubMed

Cetin, H; Yanikoglu, A; Kocak, O; Cilek, J E

2006-11-01

The larvicidal activity of chlorpyrifos-methyl and temephos was evaluated against Culex pipiens L. (Diptera: Culicidae) in septic tanks in Antalya, Turkey. Chlorpyrifos-methyl (Pyrifos MT 25 emulsifiable concentrate [EC] ) was evaluated at application rates of 0.04, 0.08, and 0.12 mg active ingredient (AI)/liter, and temephos (Temeguard 50 EC) was evaluated at 0.02, 0.04, and 0.06 mg (AI)/liter during a 21-d study. Generally, overall larval reduction in septic tanks from single- and multifamily dwellings treated with either larvicide was significantly greater than pretreatment levels and control tanks for the duration of the study. At 14 d posttreatment, duration of control was greatest in multifamily tanks treated with chlorpyrifos-methyl at the highest application rate with similar levels of control through 21 d for single-family dwellings (range 97-100%). Septic tanks from both types of family dwellings treated at the highest application rate of temephos resulted in >90% reduction through day 21 (range 91-100%). Laboratory bioassays of septic tank water treated at field application rates, without daily dilution, revealed that complete larval mortality was achieved for 21 d at each application rate and formulation. It is thought that daily addition of water and organic matter to the septic tanks in the single and multifamily dwellings influenced the duration of effectiveness of the larvicides.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Sookwang; Poet, Torka S.; Smith, Jordan N.

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

Screening for the Pesticides Atrazine, Chlorpyrifos, Diazinon, Metolachlor, and Simazine in Selected Michigan Streams, March-November 2005

USGS Publications Warehouse

Fogarty, Lisa R.; Duris, Joseph W.

2007-01-01

From March through November 2005, the U.S. Geological Survey, in cooperation with the Michigan Department of Environmental Quality (MDEQ), did a statewide screening to aid in understanding the occurrence and distribution of selected pesticides in Michigan streams. Stream-water samples were collected from 23 sites throughout Michigan. In all, 320 water samples were analyzed by use of rapid immunoassay methods for the herbicides atrazine, metolachlor, and simazine and the insecticides chlorpyrifos and diazinon. On one occasion (June, 2005), atrazine concentrations exceeded the Michigan water-quality value (7.3 micrograms per liter) at the Black River in St. Clair County. Neither chlorpyrifos nor diazinon was detected during April through September. MDEQ detected chlorpyrifos in streams throughout the state in November. Herbicide concentrations were highest in samples influenced by intensive agriculture; however, median herbicide concentrations were similar among agricultural and urban sites. Concentrations of herbicides were very low to undetected in undeveloped areas. Seasonal patterns were also evident during the sampling period. Increased concentrations generally occurred in late spring to early summer. At 11 sites, daily sampling was done every day for 5 days following a rainfall after herbicide application in the area. Substantial changes in concentrations of herbicides - greater than tenfold from the previous day - were observed during the daily sampling. No consistent relation was found between concentration and streamflow. Results of this study may be used to aid in the development of a more comprehensive pesticide monitoring study for the State of Michigan.

NEUROBEHAVIORAL EVALUATION OF RATS EXPOSED TO CHLORPYRIFOS VIA CHRONIC DIETARY AND REPEATED HIGH-LEVEL SPIKE EXPOSURE.

EPA Science Inventory

This study aimed to model long-term subtoxic human exposure to an organophosphorus pesticide, chlorpyrifos (CPF), and to examine the influence of that exposure on the response to intermittent high-dose acute challenges. Adult Long-Evans male rats were maintained at 350g body wei...

Serotonin and calcium homeostasis during the transition period.

PubMed

Weaver, S R; Laporta, J; Moore, S A E; Hernandez, L L

2016-07-01

The transition from pregnancy to lactation puts significant, sudden demands on maternal energy and calcium reserves. Although most mammals are able to effectively manage these metabolic adaptations, the lactating dairy cow is acutely susceptible to transition-related disorders because of the high amounts of milk being produced. Hypocalcemia is a common metabolic disorder that occurs at the onset of lactation. Hypocalcemia is also known to result in poor animal welfare conditions. In addition, cows that develop hypocalcemia are more susceptible to a host of other negative health outcomes. Different feeding tactics, including manipulating the dietary cation-anion difference and administering low-calcium diets, are commonly used preventative strategies. Despite these interventions, the incidence of hypocalcemia in the subclinical form is still as high as 25% to 30% in the United States dairy cow population, with a 5% to 10% incidence of clinical hypocalcemia. In addition, although there are various effective treatments in place, they are administered only after the cow has become noticeably ill, at which point there is already significant metabolic damage. This emphasizes the need for developing alternative prevention strategies, with the monoamine serotonin implicated as a potential therapeutic target. Our research in rodents has shown that serotonin is critical for the induction of mammary parathyroid hormone-related protein, which is necessary for the mobilization of bone tissue and subsequent restoration of maternal calcium stores during lactation. We have shown that circulating serotonin concentrations are positively correlated with serum total calcium on the first day of lactation in dairy cattle. Administration of serotonin's immediate precursor through feeding, injection, or infusion to various mammalian species has been shown to increase circulating serotonin concentrations, with positive effects on other components of maternal metabolism. Most recently

Receptors and Other Signaling Proteins Required for Serotonin Control of Locomotion in Caenorhabditis elegans

PubMed Central

Gürel, Güliz; Gustafson, Megan A.; Pepper, Judy S.; Horvitz, H. Robert; Koelle, Michael R.

2012-01-01

A better understanding of the molecular mechanisms of signaling by the neurotransmitter serotonin is required to assess the hypothesis that defects in serotonin signaling underlie depression in humans. Caenorhabditis elegans uses serotonin as a neurotransmitter to regulate locomotion, providing a genetic system to analyze serotonin signaling. From large-scale genetic screens we identified 36 mutants of C. elegans in which serotonin fails to have its normal effect of slowing locomotion, and we molecularly identified eight genes affected by 19 of the mutations. Two of the genes encode the serotonin-gated ion channel MOD-1 and the G-protein-coupled serotonin receptor SER-4. mod-1 is expressed in the neurons and muscles that directly control locomotion, while ser-4 is expressed in an almost entirely non-overlapping set of sensory and interneurons. The cells expressing the two receptors are largely not direct postsynaptic targets of serotonergic neurons. We analyzed animals lacking or overexpressing the receptors in various combinations using several assays for serotonin response. We found that the two receptors act in parallel to affect locomotion. Our results show that serotonin functions as an extrasynaptic signal that independently activates multiple receptors at a distance from its release sites and identify at least six additional proteins that appear to act with serotonin receptors to mediate serotonin response. PMID:23023001

Glucocorticoids Inhibit Basal and Hormone-Induced Serotonin Synthesis in Pancreatic Beta Cells

PubMed Central

Hasni Ebou, Moina; Singh-Estivalet, Amrit; Launay, Jean-Marie; Callebert, Jacques; Tronche, François; Ferré, Pascal; Gautier, Jean-François; Guillemain, Ghislaine; Bréant, Bernadette

2016-01-01

Diabetes is a major complication of chronic Glucocorticoids (GCs) treatment. GCs induce insulin resistance and also inhibit insulin secretion from pancreatic beta cells. Yet, a full understanding of this negative regulation remains to be deciphered. In the present study, we investigated whether GCs could inhibit serotonin synthesis in beta cell since this neurotransmitter has been shown to be involved in the regulation of insulin secretion. To this aim, serotonin synthesis was evaluated in vitro after treatment with GCs of either islets from CD1 mice or MIN6 cells, a beta-cell line. We also explored the effect of GCs on the stimulation of serotonin synthesis by several hormones such as prolactin and GLP 1. We finally studied this regulation in islet in two in vivo models: mice treated with GCs and with liraglutide, a GLP1 analog, and mice deleted for the glucocorticoid receptor in the pancreas. We showed in isolated islets and MIN6 cells that GCs decreased expression and activity of the two key enzymes of serotonin synthesis, Tryptophan Hydroxylase 1 (Tph1) and 2 (Tph2), leading to reduced serotonin contents. GCs also blocked the induction of serotonin synthesis by prolactin or by a previously unknown serotonin activator, the GLP-1 analog exendin-4. In vivo, activation of the Glucagon-like-Peptide-1 receptor with liraglutide during 4 weeks increased islet serotonin contents and GCs treatment prevented this increase. Finally, islets from mice deleted for the GR in the pancreas displayed an increased expression of Tph1 and Tph2 and a strong increased serotonin content per islet. In conclusion, our results demonstrate an original inhibition of serotonin synthesis by GCs, both in basal condition and after stimulation by prolactin or activators of the GLP-1 receptor. This regulation may contribute to the deleterious effects of GCs on beta cells. PMID:26901633

Optogenetic activation of dorsal raphe serotonin neurons enhances patience for future rewards.

PubMed

Miyazaki, Kayoko W; Miyazaki, Katsuhiko; Tanaka, Kenji F; Yamanaka, Akihiro; Takahashi, Aki; Tabuchi, Sawako; Doya, Kenji

2014-09-08

Serotonin is a neuromodulator that is involved extensively in behavioral, affective, and cognitive functions in the brain. Previous recording studies of the midbrain dorsal raphe nucleus (DRN) revealed that the activation of putative serotonin neurons correlates with the levels of behavioral arousal [1], rhythmic motor outputs [2], salient sensory stimuli [3-6], reward, and conditioned cues [5-8]. The classic theory on serotonin states that it opposes dopamine and inhibits behaviors when aversive events are predicted [9-14]. However, the therapeutic effects of serotonin signal-enhancing medications have been difficult to reconcile with this theory [15, 16]. In contrast, a more recent theory states that serotonin facilitates long-term optimal behaviors and suppresses impulsive behaviors [17-21]. To test these theories, we developed optogenetic mice that selectively express channelrhodopsin in serotonin neurons and tested how the activation of serotonergic neurons in the DRN affects animal behavior during a delayed reward task. The activation of serotonin neurons reduced the premature cessation of waiting for conditioned cues and food rewards. In reward omission trials, serotonin neuron stimulation prolonged the time animals spent waiting. This effect was observed specifically when the animal was engaged in deciding whether to keep waiting and was not due to motor inhibition. Control experiments showed that the prolonged waiting times observed with optogenetic stimulation were not due to behavioral inhibition or the reinforcing effects of serotonergic activation. These results show, for the first time, that the timed activation of serotonin neurons during waiting promotes animals' patience to wait for a delayed reward. Copyright © 2014 Elsevier Ltd. All rights reserved.

Plasma Serotonin in Heart Failure: Possible Marker and Potential Treatment Target.

PubMed

Selim, Ahmed M; Sarswat, Nitasha; Kelesidis, Iosif; Iqbal, Muhammad; Chandra, Ramesh; Zolty, Ronald

2017-05-01

The relationship between heart failure (HF) and the serotonergic system has been established in animal studies. However, data on human plasma serotonin level in HF and its significance over the course of the disease is lacking. Serotonin levels were measured in 173 patients (108 males, 65 females), 116 were stable HF and 40 were acute decompensated HF patients. The normal control group included 17 healthy volunteers with no known medical or psychiatric conditions. Patients receiving medications affecting serotonin receptors and those with pulmonary hypertension were excluded. All patients, except for those in the decompensated group, were on stable doses of HF medications. Plasma serotonin levels were significantly elevated in decompensated HF patients compared with stable patients (P=0.002). Higher plasma serotonin levels were associated with worse HF symptoms (NYHA class) and the presence of systolic dysfunction, and was borderline associated with low peak oxygen consumption during cardiopulmonary exercise testing (P=0.055). These results were independent of age, gender, race, hypertension, diabetes, renal failure, weight, coronary artery disease (CAD), atrial fibrillation and medication use. Serotonin is a marker for decompensation in patients with chronic heart failure. Higher serotonin levels were associated with worse HF symptoms and systolic dysfunction. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Serotonin modulates insect hemocyte phagocytosis via two different serotonin receptors

PubMed Central

Qi, Yi-xiang; Huang, Jia; Li, Meng-qi; Wu, Ya-su; Xia, Ren-ying; Ye, Gong-yin

2016-01-01

Serotonin (5-HT) modulates both neural and immune responses in vertebrates, but its role in insect immunity remains uncertain. We report that hemocytes in the caterpillar, Pieris rapae are able to synthesize 5-HT following activation by lipopolysaccharide. The inhibition of a serotonin-generating enzyme with either pharmacological blockade or RNAi knock-down impaired hemocyte phagocytosis. Biochemical and functional experiments showed that naive hemocytes primarily express 5-HT1B and 5-HT2B receptors. The blockade of 5-HT1B significantly reduced phagocytic ability; however, the blockade of 5-HT2B increased hemocyte phagocytosis. The 5-HT1B-null Drosophila melanogaster mutants showed higher mortality than controls when infected with bacteria, due to their decreased phagocytotic ability. Flies expressing 5-HT1B or 5-HT2B RNAi in hemocytes also showed similar sensitivity to infection. Combined, these data demonstrate that 5-HT mediates hemocyte phagocytosis through 5-HT1B and 5-HT2B receptors and serotonergic signaling performs critical modulatory functions in immune systems of animals separated by 500 million years of evolution. DOI: http://dx.doi.org/10.7554/eLife.12241.001 PMID:26974346

Serotonin enhances the impact of health information on food choice.

PubMed

Vlaev, Ivo; Crockett, Molly J; Clark, Luke; Müller, Ulrich; Robbins, Trevor W

2017-06-01

Serotonin has been implicated in promoting self-control, regulation of hunger and physiological homeostasis, and regulation of caloric intake. However, it remains unclear whether the effects of serotonin on caloric intake reflect purely homeostatic mechanisms, or whether serotonin also modulates cognitive processes involved in dietary decision making. We investigated the effects of an acute dose of the serotonin reuptake inhibitor citalopram on choices between food items that differed along taste and health attributes, compared with placebo and the noradrenaline reuptake inhibitor atomoxetine. Twenty-seven participants attended three sessions and received single doses of atomoxetine, citalopram, and placebo in a double-blind randomised cross-over design. Relative to placebo, citalopram increased choices of more healthy foods over less healthy foods. Citalopram also increased the emphasis on health considerations in decisions. Atomoxetine did not affect decision making relative to placebo. The results support the hypothesis that serotonin may influence food choice by enhancing a focus on long-term goals. The findings are relevant for understanding decisions about food consumption and also for treating health conditions such as eating disorders and obesity.

Serotonin inhibits low-threshold spike interneurons in the striatum

PubMed Central

Cains, Sarah; Blomeley, Craig P; Bracci, Enrico

2012-01-01

Low-threshold spike interneurons (LTSIs) are important elements of the striatal architecture and the only known source of nitric oxide in this nucleus, but their rarity has so far prevented systematic studies. Here, we used transgenic mice in which green fluorescent protein is expressed under control of the neuropeptide Y (NPY) promoter and striatal NPY-expressing LTSIs can be easily identified, to investigate the effects of serotonin on these neurons. In sharp contrast with its excitatory action on other striatal interneurons, serotonin (30 μm) strongly inhibited LTSIs, reducing or abolishing their spontaneous firing activity and causing membrane hyperpolarisations. These hyperpolarisations persisted in the presence of tetrodotoxin, were mimicked by 5-HT2C receptor agonists and reversed by 5-HT2C antagonists. Voltage-clamp slow-ramp experiments showed that serotonin caused a strong increase in an outward current activated by depolarisations that was blocked by the specific M current blocker XE 991. In current-clamp experiments, XE 991 per se caused membrane depolarisations in LTSIs and subsequent application of serotonin (in the presence of XE 991) failed to affect these neurons. We concluded that serotonin strongly inhibits striatal LTSIs acting through postsynaptic 5-HT2C receptors and increasing an M type current. PMID:22495583

Engineering of Escherichia coli for the synthesis of N-hydroxycinnamoyl tryptamine and serotonin.

PubMed

Lee, Su Jin; Sim, Geun-Young; Lee, Youngshim; Kim, Bong-Gyu; Ahn, Joong-Hoon

2017-11-01

Plants synthesize various phenol amides. Among them, hydroxycinnamoyl (HC) tryptamines and serotonins exhibit antioxidant, anti-inflammatory, and anti-atherogenic activities. We synthesized HC-tryptamines and HC-serotonin from several HCs and either tryptamine or serotonin using Escherichia coli harboring the 4CL (4-coumaroyl CoA ligase) and CaHCTT [hydroxycinnamoyl-coenzyme A:serotonin N-(hydroxycinnamoyl)transferase] genes. E. coli was engineered to synthesize N-cinnamoyl tryptamine from glucose. TDC (tryptophan decarboxylase) and PAL (phenylalanine ammonia lyase) along with 4CL and CaHCTT were introduced into E. coli and the phenylalanine biosynthetic pathway of E. coli was engineered. Using this strategy, approximately 110.6 mg/L of N-cinnamoyl tryptamine was synthesized. By feeding 100 μM serotonin into the E. coli culture, which could induce the synthesis of cinnamic acid or p-coumaric acid, more than 99 μM of N-cinnamoyl serotonin and N-(p-coumaroyl) serotonin were synthesized.

MODELED RESIDENTIAL CHLORPYRIFOS EXPOSURE AND DOSE TO CHILDREN VIA DERMAL SURFACE RESIDUE CONTACT AND NON-DIETARY INGESTION

EPA Science Inventory

A physically-based stochastic model has been applied to estimate residential chlorpyrifos exposure and dace to children via the non-dietary ingestion and dermal residue contact pathways. Time-location-activity data for 2825 children were sampled from national surveys to generat...

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

EPA Science Inventory

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

Serotonin induces ecdysteroidogenesis and methyl farnesoate synthesis in the mud crab, Scylla serrata.

PubMed

Girish, B P; Swetha, C H; Reddy, P Sreenivasula

2017-09-02

In the current study, we have examined the role of serotonin in regulating the levels of methyl farnesoate and ecdysteroids in the giant mud crab Scylla serrata and validated that serotonin indeed is a reproductive hormone. Administration of serotonin elevated circulatory levels of methyl farnesoate and ecdysteroids in crabs. Since methyl farnesoate and ecdysteroid act through retinoid X receptor (RXR) and ecdysteroid receptor (EcR) respectively and these receptors are involved in the regulation of reproduction in crustaceans, we have determined the mRNA levels of RXR and EcR in hepatopancreas and ovary after serotonin administration. The expression levels of both RXR and EcR increased significantly in the hepatopancreas and ovary of serotonin injected crabs when compared to the controls. In vitro organ culture studies revealed that incubation of Y-orgas and mandibular organ explants in the presence of serotonin resulted in a significant increase in the secretion of ecdysteroids by Y-organs, but without alterations in MF synthesis in mandibular organs. From the above studies it is evident that serotonin stimulates Y organs resulting in increased ecdysteroidogenesis. Though the circulatory levels methyl farnesoate elevated after serotonin administration, organ culture studies revealed serotonin mediated methyl farnesaote synthesis is indirect probably by inhibiting release of mandibular organ inhibiting hormone from eyestalks. Copyright © 2017 Elsevier Inc. All rights reserved.

Kinetics of biotransformation of chlorpyrifos in aqueous and soil slurry environments.

PubMed

Tiwari, Manoj K; Guha, Saumyen

2014-03-15

The attenuation of chlorpyrifos (CPF) by the enriched indigenous soil microorganism was studied in 15 d aerobic and 60 d anaerobic batch experiments in aqueous and soil slurry (1:3 w/w) media. At the end of the batch experiments, 2.78 ± 0.11 μM of CPF was degraded by 82% in aerobic and 66% in anaerobic aqueous environments, while 12.4 ± 0.5 μM of CPF was degraded by 48% in aerobic and 31% in anaerobic soil slurries. The reduced degradation in the soil slurries was due to the significantly (2-10 times) slower rate of degradation of soil phase CPF compared with its degradation rate in water. The pathways of degradation of CPF were identified, including a partial anaerobic degradation pathway that is constructed for the first time. The simulation of the various conversions in the degradation pathways using first order kinetics was used to analyze relative persistence of metabolites. The common metabolite 3,5,6-trichloro-2-pyridinol (TCP) accumulated (increased monotonically during the period of experiments) in aerobic soil slurry and in anaerobic aqueous as well as soil slurry systems but did not accumulate in aerobic aqueous system. The most toxic compound in the pathway, chlorpyrifos oxon (CPFO) was not detected in anaerobic environment. In aerobic environment, CPFO was short lived in aqueous medium, but accumulated slowly in the soils. Copyright © 2013 Elsevier Ltd. All rights reserved.

The effect of early trauma exposure on serotonin type 1B receptor expression revealed by reduced selective radioligand binding.

PubMed

Murrough, James W; Czermak, Christoph; Henry, Shannan; Nabulsi, Nabeel; Gallezot, Jean-Dominique; Gueorguieva, Ralitza; Planeta-Wilson, Beata; Krystal, John H; Neumaier, John F; Huang, Yiyun; Ding, Yu-Shin; Carson, Richard E; Neumeister, Alexander

2011-09-01

Serotonergic dysfunction is implicated in the pathogenesis of posttraumatic stress disorder (PTSD), and recent animal models suggest that disturbances in serotonin type 1B receptor function, in particular, may contribute to chronic anxiety. However, the specific role of the serotonin type 1B receptor has not been studied in patients with PTSD. To investigate in vivo serotonin type 1B receptor expression in individuals with PTSD, trauma-exposed control participants without PTSD (TC), and healthy (non-trauma-exposed) control participants (HC) using positron emission tomography and the recently developed serotonin type 1B receptor selective radiotracer [(11)C]P943. Cross-sectional positron emission tomography study under resting conditions. Academic and Veterans Affairs medical centers. Ninety-six individuals in 3 study groups: PTSD (n = 49), TC (n = 20), and HC (n = 27). Main Outcome Measure  Regional [(11)C]P943 binding potential (BP(ND)) values in an a priori-defined limbic corticostriatal circuit investigated using multivariate analysis of variance and multiple regression analysis. A history of severe trauma exposure in the PTSD and TC groups was associated with marked reductions in [(11)C]P943 BP(ND) in the caudate, the amygdala, and the anterior cingulate cortex. Participant age at first trauma exposure was strongly associated with low [(11)C]P943 BP(ND). Developmentally earlier trauma exposure also was associated with greater PTSD symptom severity and major depression comorbidity. These data suggest an enduring effect of trauma history on brain function and the phenotype of PTSD. The association of early age at first trauma and more pronounced neurobiological and behavioral alterations in PTSD suggests a developmental component in the cause of PTSD.

Ethanol intake and sup 3 H-serotonin uptake I: A study in Fawn-Hooded rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Daoust, M.; Compagnon, P.; Legrand, E.

1991-01-01

Ethanol intake and synaptosomal {sup 3}H-serotonin uptake were studied in male Fawn-Hooded and Sprague-Dawley rats. Fawn-Hooded rats consumed more alcohol and more water than Sprague-Dawley rats. Plasma alcohol levels of Sprague-Dawley rats were not detectable but were about 5 mg/dl in Fawn-Hooded rats. Ethanol intake increased the Vmax of serotonin uptake in Fawn-Hooded rats in hippocampus and cortex, but not in thalamus. In Fawn-Hooded rats, serotonin uptake (Vmax) was higher than in Sprague-Dawley rats cortex. Ethanol intake reduced the Vmax of serotonin uptake in Fawn-Hooded rats in hippocampus and cortex. In cortex, the carrier affinity for serotonin was increased inmore » alcoholized Fawn-Hooded rats. These results indicate that synaptosomal {sup 3}H-serotonin uptake is affected by ethanol intake. In Fawn-Hooded rats, high ethanol consumption is associated with high serotonin uptake. In rats presenting high serotonin uptake, alcoholization reduces {sup 3}H-serotonin internalization in synaptosomes, indicating a specific sensitivity to alcohol intake of serotonin uptake system.« less

Revisiting the Serotonin-Aggression Relation in Humans: A Meta-analysis

PubMed Central

Duke, Aaron A.; Bègue, Laurent; Bell, Rob; Eisenlohr-Moul, Tory

2013-01-01

The inverse relation between serotonin and human aggression is often portrayed as “reliable,” “strong,” and “well-established” despite decades of conflicting reports and widely recognized methodological limitations. In this systematic review and meta-analysis we evaluate the evidence for and against the serotonin deficiency hypothesis of human aggression across four methods of assessing serotonin: (a) cerebrospinal fluid levels of 5-hydroxyindoleacetic acid (CSF 5-HIAA), (b) acute tryptophan depletion, (c) pharmacological challenge, and (d) endocrine challenge. Results across 175 independent samples and over 6,500 total participants were heterogeneous, but, in aggregate, revealed a small, inverse correlation between central serotonin functioning and aggression, anger, and hostility, r = −.12. Pharmacological challenge studies had the largest mean weighted effect size, r = −.21, and CSF 5-HIAA studies had the smallest, r = −.06, p = .21. Potential methodological and demographic moderators largely failed to account for variability in study outcomes. Notable exceptions included year of publication (effect sizes tended to diminish with time) and self-versus other-reported aggression (other-reported aggression was positively correlated to serotonin functioning). We discuss four possible explanations for the pattern of findings: unreliable measures, ambient correlational noise, an unidentified higher-order interaction, and a selective serotonergic effect. Finally, we provide four recommendations for bringing much needed clarity to this important area of research: acknowledge contradictory findings and avoid selective reporting practices; focus on improving the reliability and validity of serotonin and aggression measures; test for interactions involving personality and/or environmental moderators; and revise the serotonin deficiency hypothesis to account for serotonin’s functional complexity. PMID:23379963

Serotonin blockade delays learning performance in a cooperative fish.

PubMed

Soares, Marta C; Paula, José R; Bshary, Redouan

2016-09-01

Animals use learning and memorizing to gather information that will help them to make ecologically relevant decisions. Neuro-modulatory adjustments enable them to make associations between stimuli and appropriate behavior. A key candidate for the modulation of cooperative behavior is serotonin. Previous research has shown that modulation of the serotonergic system spontaneously affects the behavior of the cleaner wrasse Labroides dimidiatus during interactions with so-called 'client' reef fish. Here, we asked whether shifts in serotonin function affect the cleaners' associative learning abilities when faced with the task to distinguish two artificial clients that differ in their value as a food source. We found that the administration of serotonin 1A receptor antagonist significantly slowed learning speed in comparison with saline treated fish. As reduced serotonergic signaling typically enhances fear, we discuss the possibility that serotonin may affect how cleaners appraise, acquire information and respond to client-derived stimuli via manipulation of the perception of danger.

Serotonin Affects Movement Gain Control in the Spinal Cord

PubMed Central

Glaser, Joshua I.; Deng, Linna; Thompson, Christopher K.; Stevenson, Ian H.; Wang, Qining; Hornby, Thomas George; Heckman, Charles J.; Kording, Konrad P.

2014-01-01

A fundamental challenge for the nervous system is to encode signals spanning many orders of magnitude with neurons of limited bandwidth. To meet this challenge, perceptual systems use gain control. However, whether the motor system uses an analogous mechanism is essentially unknown. Neuromodulators, such as serotonin, are prime candidates for gain control signals during force production. Serotonergic neurons project diffusely to motor pools, and, therefore, force production by one muscle should change the gain of others. Here we present behavioral and pharmaceutical evidence that serotonin modulates the input–output gain of motoneurons in humans. By selectively changing the efficacy of serotonin with drugs, we systematically modulated the amplitude of spinal reflexes. More importantly, force production in different limbs interacts systematically, as predicted by a spinal gain control mechanism. Psychophysics and pharmacology suggest that the motor system adopts gain control mechanisms, and serotonin is a primary driver for their implementation in force production. PMID:25232107

Elevated brain serotonin turnover in patients with depression: effect of genotype and therapy.

PubMed

Barton, David A; Esler, Murray D; Dawood, Tye; Lambert, Elisabeth A; Haikerwal, Deepak; Brenchley, Celia; Socratous, Florentia; Hastings, Jacqueline; Guo, Ling; Wiesner, Glen; Kaye, David M; Bayles, Richard; Schlaich, Markus P; Lambert, Gavin W

2008-01-01

The biological basis for the development of major depressive disorder (MDD) remains incompletely understood. To quantify brain serotonin (5-hydroxytryptamine [5-HT]) turnover in patients with MDD. Patients with depression were studied both untreated and during administration of a selective serotonin reuptake inhibitor (SSRI) in an unblinded study of sequential design. Healthy volunteers were examined on only 1 occasion. Direct internal jugular venous blood sampling was used to directly quantify brain serotonin turnover. The effect of serotonin transporter (5-HTT) genotype on brain serotonin turnover was evaluated and the influence of SSRI therapy on serotonin turnover was investigated. Participants were recruited from the general community following media advertisement. Experimental procedures were performed in the research catheterization laboratory of a major training hospital and medical research institute. Studies were performed in 21 patients fulfilling the DSM-IV and International Statistical Classification of Diseases, 10th Revision diagnostic criteria for MDD and in 40 healthy volunteers. Treatment for patients consisted of SSRI administration for approximately 12 weeks. Brain serotonin turnover before and after SSRI therapy. Brain serotonin turnover was significantly elevated in unmedicated patients with MDD compared with healthy subjects (mean [SD] internal jugular venoarterial 5-hydroxyindoleacetic acid plasma concentration difference, 4.4 [4.3] vs 1.6 [2.4] nmol/L, respectively; P = .003). Analysis of the influence of the 5-HTT genotype in MDD indicated that carriage of the s allele compared with the l allele was associated with greater than a 2-fold increase in brain serotonin turnover (mean [SD] internal jugular venoarterial 5-hydroxyindoleacetic acid plasma concentration difference, 6.5 [4.7] vs 2.7 [2.9] nmol/L, respectively; P = .04). Following SSRI therapy, brain serotonin turnover was substantially reduced (mean [SD] internal jugular venoarterial

Characterization and regulation of (/sup 3/H)-serotonin uptake and release in rodent spinal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stauderman, K.A.

1986-01-01

The uptake and release of (/sup 3/H)-serotonin were investigated in rat spinal cord synaptosomes. In the uptake experiments, sodium-dependent and sodium-independent (/sup 3/H)-serotonin accumulation processes were found. Sodium-dependent (/sup 3/H)-serotonin accumulation was: linear with sodium concentrations up to 180 mM; decreased by disruption of membrane integrity or ionic gradients; associated with purified synaptosomal fractions; and reduced after description of descending serotonergic neurons in the spinal cord. Of the uptake inhibitors tested, the most potent was fluoxetine (IC/sub 50/ 75 nM), followed by desipramine (IC/sub 50/ 430 nM) and nomifensine (IC/sub 50/ 950 nM). The sodium-independent (/sup 3/H)-serotonin accumulation process wasmore » insensitive to most treatments and probably represents nonspecific membrane binding. Thus, only sodium-dependent (/sup 3/H)-serotonin uptake represents the uptake process of serotonergic nerve terminals in rat spinal cord homogenates. In the release experiments, K/sup +/-induced release of previously accumulated (/sup 3/H)-serotonin was Ca/sup 2 +/-dependent, and originated from serotonergic synaptosomes. Exogenous serotonin and 5-methyoxy-N,N-dimethyltryptamine inhibited (/sup 3/H)-serotonin release in a concentration-dependent way. Of the antagonists tested, only methiothepin effectively blocked the effect of serotonin. These data support the existence of presynaptic serotonin autoreceptors on serotonergic nerve terminals in the rat spinal cord that act to inhibit a voltage and Ca/sup 2 +/-sensitive process linked to serotonin release. Alteration of spinai cord serotonergic function may therefore be possible by drugs acting on presynaptic serotonin autoreceptors in the spinal cord.« less

Plasma serotonin in horses undergoing surgery for small intestinal colic

PubMed Central

Torfs, Sara C.; Maes, An A.; Delesalle, Catherine J.; Pardon, Bart; Croubels, Siska M.; Deprez, Piet

2015-01-01

This study compared serotonin concentrations in platelet poor plasma (PPP) from healthy horses and horses with surgical small intestinal (SI) colic, and evaluated their association with postoperative ileus, strangulation and non-survival. Plasma samples (with EDTA) from 33 horses with surgical SI colic were collected at several pre- and post-operative time points. Serotonin concentrations were determined using liquid-chromatography tandem mass spectrometry. Results were compared with those for 24 healthy control animals. The serotonin concentrations in PPP were significantly lower (P < 0.01) in pre- and post-operative samples from surgical SI colic horses compared to controls. However, no association with postoperative ileus or non-survival could be demonstrated at any time point. In this clinical study, plasma serotonin was not a suitable prognostic factor in horses with SI surgical colic. PMID:25694668

Bioinformatic analyses to select phenotype affecting polymorphisms in HTR2C gene.

PubMed

Piva, Francesco; Giulietti, Matteo; Baldelli, Luisa; Nardi, Bernardo; Bellantuono, Cesario; Armeni, Tatiana; Saccucci, Franca; Principato, Giovanni

2011-08-01

Single nucleotide polymorphisms (SNPs) in serotonin related genes influence mental disorders, responses to pharmacological and psychotherapeutic treatments. In planning association studies, researchers that want to investigate new SNPs have to select some among a large number of candidates. Our aim is to guide researchers in the selection of the most likely phenotype affecting polymorphisms. Here, we studied serotonin receptor 2C (HTR2C) SNPs because, till now, only relatively few of about 2000 are investigated. We used the most updated and assessed bioinformatic tools to predict which variations can give rise to biological effects among 2450 HTR2C SNPs. We suggest 48 SNPs that are worth considering in future association studies in the field of psychiatry, psychology and pharmacogenomics. Moreover, our analyses point out the biological level probably affected, such as transcription, splicing, miRNA regulation and protein structure, thus allowing to suggest future molecular investigations. Although few association studies are available in literature, their results are in agreement with our predictions, showing that our selection methods can help to guide future association studies. Copyright © 2011 John Wiley & Sons, Ltd.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Jing; Parsons, Loren; Pope, Carey, E-mail: carey.pope@okstate.edu

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 extracellularmore » 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

Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice

PubMed Central

Suidan, Georgette L.; Demers, Melanie; Herr, Nadine; Carbo, Carla; Brill, Alexander; Cifuni, Stephen M.; Mauler, Maximilian; Cicko, Sanja; Bader, Michael; Idzko, Marco; Bode, Christoph

2013-01-01

The majority of peripheral serotonin is stored in platelets, which secrete it on activation. Serotonin releases Weibel-Palade bodies (WPBs) and we asked whether absence of platelet serotonin affects neutrophil recruitment in inflammatory responses. Tryptophan hydroxylase (Tph)1–deficient mice, lacking non-neuronal serotonin, showed mild leukocytosis compared with wild-type (WT), primarily driven by an elevated neutrophil count. Despite this, 50% fewer leukocytes rolled on unstimulated mesenteric venous endothelium of Tph1−/− mice. The velocity of rolling leukocytes was higher in Tph1−/− mice, indicating fewer selectin-mediated interactions with endothelium. Stimulation of endothelium with histamine, a secretagogue of WPBs, or injection of serotonin normalized the rolling in Tph1−/− mice. Diminished rolling in Tph1−/− mice resulted in reduced firm adhesion of leukocytes after lipopolysaccharide treatment. Blocking platelet serotonin uptake with fluoxetine in WT mice reduced serum serotonin by > 80% and similarly reduced leukocyte rolling and adhesion. Four hours after inflammatory stimulation, neutrophil extravasation into lung, peritoneum, and skin wounds was reduced in Tph1−/− mice, whereas in vitro neutrophil chemotaxis was independent of serotonin. Survival of lipopolysaccharide-induced endotoxic shock was improved in Tph1−/− mice. In conclusion, platelet serotonin promotes the recruitment of neutrophils in acute inflammation, supporting an important role for platelet serotonin in innate immunity. PMID:23243271

Resistance of rice to insect pests mediated by suppression of serotonin biosynthesis.

PubMed

Lu, Hai-Ping; Luo, Ting; Fu, Hao-Wei; Wang, Long; Tan, Yuan-Yuan; Huang, Jian-Zhong; Wang, Qing; Ye, Gong-Yin; Gatehouse, Angharad M R; Lou, Yong-Gen; Shu, Qing-Yao

2018-05-07

Rice is one of the world's most important foods, but its production suffers from insect pests, causing losses of billions of dollars, and extensive use of environmentally damaging pesticides for their control 1,2 . However, the molecular mechanisms of insect resistance remain elusive. Although a few resistance genes for planthopper have been cloned, no rice germplasm is resistant to stem borers. Here, we report that biosynthesis of serotonin, a neurotransmitter in mammals 3 , is induced by insect infestation in rice, and its suppression confers resistance to planthoppers and stem borers, the two most destructive pests of rice 2 . Serotonin and salicylic acid derive from chorismate 4 . In rice, the cytochrome P450 gene CYP71A1 encodes tryptamine 5-hydroxylase, which catalyses conversion of tryptamine to serotonin 5 . In susceptible wild-type rice, planthopper feeding induces biosynthesis of serotonin and salicylic acid, whereas in mutants with an inactivated CYP71A1 gene, no serotonin is produced, salicylic acid levels are higher and plants are more insect resistant. The addition of serotonin to the resistant rice mutant and other brown planthopper-resistant genotypes results in a loss of insect resistance. Similarly, serotonin supplementation in artificial diet enhances the performance of both insects. These insights demonstrate that regulation of serotonin biosynthesis plays an important role in defence, and may prove valuable for breeding insect-resistant cultivars of rice and other cereal crops.

Exploration of the chlorpyrifos escape pathway from acylpeptide hydrolases using steered molecular dynamics simulations.

PubMed

Wang, Dongmei; Jin, Hanyong; Wang, Junling; Guan, Shanshan; Zhang, Zuoming; Han, Weiwei

2016-01-01

Acylpeptide hydrolases (APH) catalyze the removal of an N-acylated amino acid from blocked peptides. APH is significantly more sensitive than acetylcholinesterase, a target of Alzheimer's disease, to inhibition by organophosphorus (OP) compounds. Thus, OP compounds can be used as a tool to probe the physiological functions of APH. Here, we report the results of a computational study of molecular dynamics simulations of APH bound to the OP compounds and an exploration of the chlorpyrifos escape pathway using steered molecular dynamics (SMD) simulations. In addition, we apply SMD simulations to identify potential escape routes of chlorpyrifos from hydrolase hydrophobic cavities in the APH-inhibitor complex. Two previously proposed APH pathways were reliably identified by CAVER 3.0, with the estimated relative importance of P1 > P2 for its size. We identify the major pathway, P2, using SMD simulations, and Arg526, Glu88, Gly86, and Asn65 are identified as important residues for the ligand leaving via P2. These results may help in the design of APH-targeting drugs with improved efficacy, as well as in understanding APH selectivity of the inhibitor binding in the prolyl oligopeptidase family.

Development of resistance to serotonin-induced itch in bile duct ligated mice.

PubMed

Ostadhadi, Sattar; Haddadi, Nazgol-Sadat; Foroutan, Arash; Azimi, Ehsan; Elmariah, Sarina; Dehpour, Ahmad-Reza

2017-06-01

Cholestatic itch can be severe and significantly impair the quality of life of patients. The serotonin system is implicated in cholestatic itch; however, the pruritogenic properties of serotonin have not been evaluated in cholestatic mice. Here, we investigated the serotonin-induced itch in cholestatic mice which was induced by bile duct ligation (BDL). Serotonin, sertraline or saline were administered intradermally to the rostral back area in BDL and sham operated (SHAM) mice, and the scratching behaviour was videotaped for 1 hour. Bile duct ligated mice had significantly increased scratching responses to saline injection on the seventh day after surgery. Additionally, serotonin or sertraline significantly induced scratching behaviour in BDL mice compared to saline at day 7 after surgery, while it did not induce itch at day 5. The scratching behaviour induced by serotonin or sertraline was significantly less in BDL mice compared to SHAM mice. Likewise, the locomotor activity of BDL or SHAM mice was not significantly different from unoperated (UNOP) mice on the fifth and seventh day, suggesting that the scratching behaviour was not affected by motor dysfunctions. Our data suggest that despite the potentiation of evoked itch, a resistance to serotonin-induced itch is developed in cholestatic mice. © 2017 John Wiley & Sons Australia, Ltd.

Serotonin 2C receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis.

PubMed

Berglund, Eric D; Liu, Chen; Sohn, Jong-Woo; Liu, Tiemin; Kim, Mi Hwa; Lee, Charlotte E; Vianna, Claudia R; Williams, Kevin W; Xu, Yong; Elmquist, Joel K

2013-12-01

Energy and glucose homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor agonists on energy and glucose homeostasis are unknown. Here, we show that mice lacking serotonin 2C receptors (Htr2c) specifically in pro-opiomelanocortin (POMC) neurons had normal body weight but developed glucoregulatory defects including hyperinsulinemia, hyperglucagonemia, hyperglycemia, and insulin resistance. Moreover, these mice did not show anorectic responses to serotonergic agents that suppress appetite and developed hyperphagia and obesity when they were fed a high-fat/high-sugar diet. A requirement of serotonin 2C receptors in POMC neurons for the maintenance of normal energy and glucose homeostasis was further demonstrated when Htr2c loss was induced in POMC neurons in adult mice using a tamoxifen-inducible POMC-cre system. These data demonstrate that serotonin 2C receptor-expressing POMC neurons are required to control energy and glucose homeostasis and implicate POMC neurons as the target for the effect of serotonin 2C receptor agonists on weight-loss induction and improved glycemic control.

Optimization of the Use of His6-OPH-Based Enzymatic Biocatalysts for the Destruction of Chlorpyrifos in Soil

PubMed Central

Senko, Olga; Efremenko, Elena

2017-01-01

Applying enzymatic biocatalysts based on hexahistidine-containing organophosphorus hydrolase (His6-OPH) is suggested for the decomposition of chlorpyrifos, which is actively used in agriculture in many countries. The application conditions were optimized and the following techniques was suggested to ensure the highest efficiency of the enzyme: first, the soil is alkalinized with hydrated calcitic lime Ca(OH)2, then the enzyme is introduced into the soil at a concentration of 1000 U/kg soil. Non-equilibrium low temperature plasma (NELTP)-modified zeolite is used for immobilization of the relatively inexpensive polyelectrolyte complexes containing the enzyme His6-OPH and a polyanionic polymer: poly-l-glutamic acid (PLE50) or poly-l-aspartic acid (PLD50). The soil’s humidity is then increased up to 60–80%, the top layer (10–30 cm) of soil is thoroughly stirred, and then exposed for 48–72 h. The suggested approach ensures 100% destruction of the pesticide within 72 h in soils containing as much as 100 mg/kg of chlorpyrifos. It was concluded that using this type of His6-OPH-based enzyme chemical can be the best approach for soils with relatively low humus concentrations, such as sandy and loam-sandy chestnut soils, as well as types of soil with increased alkalinity (pH 8.0–8.4). Such soils are often encountered in desert, desert-steppe, foothills, and subtropical regions where chlorpyrifos is actively used. PMID:29168784

Effect of chronic D-fenfluramine administration on rat hypothalamic serotonin levels and release

NASA Technical Reports Server (NTRS)

Schaechter, Judith D.; Wurtman, Richard J.

1989-01-01

The effect of administering to rats (in doses of 1.25, 2.5, 5, or 10 mg/kg/day for 10 days) of an anorectic agent, D-fenfluramine, on the serotonin levels in hypothalamic tissue and on the in vitro release of serotonin by hypothalamic slices was investigated in rats which were sacrificed six days after the end of treatment. It was found that D-fenfuramine had no effect on tissue serotonin in doses from 1.25 to 5 mg/kg. However, given at 10 mg/kg level, serotonin led to a 22 percent decrease. The release of serotonin was found to be not affected by D-fenfluramine.

A case of serotonin syndrome associated with methadone overdose.

PubMed

Martinez, Terry T; Martinez, Daniel N

2008-01-01

A chronic pain patient prescribed 20 mg of methadone per day was seen at the Emergency Department within one hour following a witnessed intentional 200 mg ingestion. In addition, he was taking the serotonin re-uptake inhibitor antidepressant drugs, sertraline and venlafaxine as prescribed. Methadone is also a serotonin re-uptake inhibitor which has been involved in serotonin toxicity reactions. Initially, no symptoms of narcotic overdose (depressed central nervous system, respiration, or blood pressure) could be distinguished, and the standard narcotic urine screen was negative. No decontamination or antagonist therapy was given, and the patient was discharged to a psychiatric unit for observation. At 5 hours post-ingestion he presented in a panic with hallucinations and elevated blood pressure, pulse, and respiration. These symptoms are characteristic of serotonin syndrome which is often described as mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. At 10 hours post-ingestion the patient was found unconscious. He had aspirated stomach contents into his lungs. His respiration, blood pressure, and pulse were all severely depressed. He never regained conciousness, and he died 5 days later. The medical examiner's finding was probable acute methadone intoxication. In this case serotonin syndrome appears to have opposed and delayed typical narcotic symptoms. Methadone has additional pharmacologic and toxicologic properties which may complicate the assessment and treatment in overdose situations.

Associations between serotonin-related gene polymorphisms and panic disorder.

PubMed

Maron, Eduard; Lang, Aavo; Tasa, Gunnar; Liivlaid, Liivi; Tõru, Innar; Must, Anne; Vasar, Veiko; Shlik, Jakov

2005-06-01

Studies suggest that vulnerability to panic attacks and panic disorder (PD) may be related to a deficient serotonin (5-HT) neurotransmission. In the present case-control study we investigated possible associations between PD phenotype and five candidate polymorphisms including 5-HT transporter (5-HTTLPR and VNTR), monoamine oxidase A (MAOA promoter region), tryptophan hydroxylase 1 (TPH1 218A/C) and 5-HT1B receptor (5-HT1BR 861G/C) genes. The study sample consisted of 158 patients with PD and 215 healthy control subjects. The analysis showed higher frequencies of LL genotype (p = 0.016) and L allele variant (p = 0.007) of 5-HTTLPR in the patients. No significant associations were observed between PD and other candidate gene polymorphisms. However, a higher frequency of longer allele genotypes of the MAOA promoter region was observed in female PD patients with agoraphobia than in female controls (p = 0.016). These findings indicate that genetic variants conceivably related to lower 5-HT neurotransmission may be involved in the development of PD.

Serotonin and aggressive motivation in crustaceans: altering the decision to retreat.

PubMed

Huber, R; Smith, K; Delago, A; Isaksson, K; Kravitz, E A

1997-05-27

In crustaceans, as in most animal species, the amine serotonin has been suggested to serve important roles in aggression. Here we show that injection of serotonin into the hemolymph of subordinate, freely moving animals results in a renewed willingness of these animals to engage the dominants in further agonistic encounters. By multivariate statistical analysis, we demonstrate that this reversal results principally from a reduction in the likelihood of retreat and an increase in the duration of fighting. Serotonin infusion does not alter other aspects of fighting behavior, including which animal initiates an encounter, how quickly fighting escalates, or which animal eventually retreats. Preliminary studies suggest that serotonin uptake plays an important role in this behavioral reversal.