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[PMID]:28409689
[Au] Autor:Ozden-Akkaya O; Altunbas K; Yagci A
[Ad] Endereço:a Department of Histology and Embryology, Faculty of Veterinary Medicine , Afyon Kocatepe University , Afyonkarahisar , Turkey.
[Ti] Título:Effects of methoxychlor on IGF-I signaling pathway in rat ovary.
[So] Source:Biotech Histochem;92(3):230-242, 2017.
[Is] ISSN:1473-7760
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Follicular development and other ovarian functions are regulated by growth factors that can be affected by exogenous agents. Methoxychlor (MXC) is an organochloride pesticide that causes female infertility. We investigated how MXC affects the distribution of developing ovarian follicles in adult rats after treatment between embryonic day (E) 18 and postnatal day (PND) 7. We also measured insulin-like growth factor-I (IGF-I) and its receptor, IGF-IR, expressions in ovarian follicles and investigated whether MXC changed the levels of IGF-I and IGF-IR in the ovary. Using immunohistochemical (IHC) staining, we detected IGF-I expression in oocytes and granulosa cells of the follicles, luteal cells, interstitial cells, theca externa and theca interna, and the smooth muscle of ovarian vessels. IGF-IR was co-localized with IGF-I in the ovary except for the theca externa. IGF-I expression was decreased in granulosa cells of preantral and antral follicles after treatment with MXC compared to granulosa cells of preantral and antral follicles of the control group. We also observed that oocytes of secondary follicles and granulosa cells of secondary and preantral follicles of the MXC treated groups showed increased IGF-IR expression compared to oocytes of secondary follicles and granulosa cells of secondary and preantral follicles of the control group. We also detected more secondary and preantral follicles, and fewer primordial and antral follicles after MXC administration compared to controls. Therefore, the IGF signaling pathway may participate in MXC induced ovary dysfunction and female infertility.
[Mh] Termos MeSH primário: Fator de Crescimento Insulin-Like I/metabolismo
Metoxicloro/toxicidade
Ovário/efeitos dos fármacos
Transdução de Sinais/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Western Blotting
Poluentes Ambientais/toxicidade
Feminino
Imuno-Histoquímica
Ratos
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Environmental Pollutants); 67763-96-6 (Insulin-Like Growth Factor I); RIA79UD69L (Methoxychlor)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170515
[Lr] Data última revisão:
170515
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170415
[St] Status:MEDLINE
[do] DOI:10.1080/10520295.2017.1303193


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[PMID]:26635070
[Au] Autor:Bhardwaj JK; Saraf P
[Ad] Endereço:Reproductive Physiology Laboratory, Department of Zoology, Kurukshetra University, Kurukshetra, Haryana, 136119, India.
[Ti] Título:N-acetyl cysteine-mediated effective attenuation of methoxychlor-induced granulosa cell apoptosis by counteracting reactive oxygen species generation in caprine ovary.
[So] Source:Environ Toxicol;32(1):156-166, 2017 Jan.
[Is] ISSN:1522-7278
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Methoxychlor (MXC), an organochloride insecticide, is a potent toxicant-targeting female reproductive system and known to cause follicular atresia by inducing apoptosis within granulosa cells. Oxidative stress plays a pivotal role in apoptosis; thus, this study focuses on the ameliorative action of N-acetyl cysteine (NAC) on MXC-induced oxidative stress and apoptosis within granulosa cell of caprine ovary. Classic histology, fluorescence assay, and biochemical parameters were employed to evaluate the effect of varied concentration of NAC (1, 5, and 10 mM) on granulosa cell apoptosis after 24, 48, and 72 h exposure duration. Histomorphological studies revealed that NAC diminished the incidence of apoptotic attributes like condensed or marginated chromatin, pyknosis, crescent-shaped nucleus, empty cell spaces, and degenerated cellular structure along with the presence of cytoplasmic processes within granulosa cells in dose- and time-dependent manner. NAC significantly downregulated the percentage of MXC-induced granulosa cell apoptosis within healthy ovarian follicle with its increasing dose, maximum at 10 mM concentration. It also significantly (p < 0.05) upregulated the activity of antioxidant enzymes, namely catalase, superoxide dismutase, and glutathione-s-transferase, along with ferric reducing antioxidant power further declining lipid peroxidation in the MXC-treated caprine ovary. The results revealed a negative correlation between apoptosis frequency and antioxidant enzymes' activity (r = -0.67, r = -0.56, r = -0.31; p < 0.05) while a positive correlation was observed with lipid peroxidation (r = 0.63; p < 0.05) after NAC supplementation. Thus, NAC supplementation reduces the MXC-generated oxidative stress that perhaps declines the ROS generating signal transduction pathway of apoptosis, thereby preventing MXC-induced granulosa cell apoptosis and follicular atresia. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 156-166, 2017.
[Mh] Termos MeSH primário: Acetilcisteína/farmacologia
Antioxidantes/farmacologia
Apoptose/efeitos dos fármacos
Cabras
Células da Granulosa/efeitos dos fármacos
Inseticidas/toxicidade
Metoxicloro/antagonistas & inibidores
Metoxicloro/toxicidade
Ovário/efeitos dos fármacos
Espécies Reativas de Oxigênio/metabolismo
[Mh] Termos MeSH secundário: Animais
Antioxidantes/metabolismo
Relação Dose-Resposta a Droga
Feminino
Células da Granulosa/patologia
Peroxidação de Lipídeos/efeitos dos fármacos
Ovário/patologia
Estresse Oxidativo/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Insecticides); 0 (Reactive Oxygen Species); RIA79UD69L (Methoxychlor); WYQ7N0BPYC (Acetylcysteine)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151205
[St] Status:MEDLINE
[do] DOI:10.1002/tox.22221


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[PMID]:27800487
[Au] Autor:Genuis SJ; Lane K; Birkholz D
[Ad] Endereço:University of Alberta, Edmonton, AB, Canada T6G 2R7; University of Calgary, Calgary, AB, Canada T2N 4N1.
[Ti] Título:Human Elimination of Organochlorine Pesticides: Blood, Urine, and Sweat Study.
[So] Source:Biomed Res Int;2016:1624643, 2016.
[Is] ISSN:2314-6141
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:. Many individuals have been exposed to organochlorinated pesticides (OCPs) through food, water, air, dermal exposure, and/or vertical transmission. Due to enterohepatic reabsorption and affinity to adipose tissue, OCPs are not efficiently eliminated from the human body and may accrue in tissues. Many epidemiological studies demonstrate significant exposure-disease relationships suggesting OCPs can alter metabolic function and potentially lead to illness. There is limited study of interventions to facilitate OCP elimination from the human body. This study explored the efficacy of induced perspiration as a means to eliminate OCPs. . Blood, urine, and sweat (BUS) were collected from 20 individuals. Analysis of 23 OCPs was performed using dual-column gas chromatography with electron-capture detectors. . Various OCPs and metabolites, including DDT, DDE, methoxychlor, endrin, and endosulfan sulfate, were excreted into perspiration. Generally, sweat samples showed more frequent OCP detection than serum or urine analysis. Many OCPs were not readily detected in blood testing while still being excreted and identified in sweat. No direct correlation was found among OCP concentrations in the blood, urine, or sweat compartments. . Sweat analysis may be useful in detecting some accrued OCPs not found in regular serum testing. Induced perspiration may be a viable clinical tool for eliminating some OCPs.
[Mh] Termos MeSH primário: Hidrocarbonetos Clorados/farmacocinética
Praguicidas/farmacocinética
Suor/química
[Mh] Termos MeSH secundário: Adulto
Idoso
Cromatografia Gasosa
DDT/farmacocinética
Diclorodifenil Dicloroetileno/farmacocinética
Endossulfano/análogos & derivados
Endossulfano/farmacocinética
Endrin/farmacocinética
Poluentes Ambientais/farmacocinética
Feminino
Seres Humanos
Masculino
Metoxicloro/farmacocinética
Meia-Idade
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Environmental Pollutants); 0 (Hydrocarbons, Chlorinated); 0 (Pesticides); 4M7FS82U08 (Dichlorodiphenyl Dichloroethylene); 8QTV9M19B2 (endosulfan sulfate); CIW5S16655 (DDT); OB9NVE7YCL (Endrin); OKA6A6ZD4K (Endosulfan); RIA79UD69L (Methoxychlor)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161102
[St] Status:MEDLINE


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[PMID]:27663972
[Au] Autor:Liu S; Li C; Wang Y; Hong T; Song T; Li L; Ye L; Lian Q; Ge RS
[Ad] Endereço:Department of Anesthesiology, The 2nd Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
[Ti] Título:In utero methoxychlor exposure increases rat fetal Leydig cell number but inhibits its function.
[So] Source:Toxicology;370:31-40, 2016 Aug 31.
[Is] ISSN:1879-3185
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:The objective of the present study is to determine whether in utero exposure to methoxychlor (MXC) affects rat fetal Leydig cell number, cell size, or functions. Pregnant Sprague Dawley dams were gavaged with corn oil (control, 0mg/kg/day MXC) or MXC at doses of 10, 50, or 100mg/kg/day from gestational day (GD) 12 to 21. The results show that MXC increased fetal Leydig cell numbers dose-dependently from 95±8×10 cells/testis (control, mean±SEM) to 101±6, 148±22, and 168±21×10 cells/testis, at the doses of 10, 50, and 100mg/kg, respectively. The increase of Leydig cell number by MXC was contributed by the increase of single cell population of Leydig cells, which increased from 21±2% of the control to 31±4%, 39±3%, or 40±4% at the doses of 10, 50 or 100mg/kg, respectively. Quantitative PCR results show that MXC increased Lhcgr expression at dose of 10mg/kg and Scarb1 and Cyp11a1 mRNA levels at doses of 50 and 100mg/kg. Immunohistochemical staining demonstrated the increase of CYP11A1 protein level from the dose of 10mg/kg. However, at the highest dose (100mg/kg) MXC reduced the testicular testosterone level and MXC (1µM) in vitro treatment also inhibited androgen production from isolated fetal Leydig cells. In conclusion, our findings indicate that at low dose MXC may increase fetal Leydig cell numbers and the expressions of some steroidogenic enzymes, but at high dose it reduces the testicular testosterone level leading to reproductive tract malformations in the male offspring.
[Mh] Termos MeSH primário: Células Intersticiais do Testículo/efeitos dos fármacos
Exposição Materna/efeitos adversos
Metoxicloro/toxicidade
[Mh] Termos MeSH secundário: Androgênios/metabolismo
Animais
Contagem de Células
Enzima de Clivagem da Cadeia Lateral do Colesterol/genética
Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo
Relação Dose-Resposta a Droga
Feminino
Feto/efeitos dos fármacos
Feto/metabolismo
Processamento de Imagem Assistida por Computador
Células Intersticiais do Testículo/metabolismo
Masculino
Gravidez
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Ratos
Ratos Sprague-Dawley
Reprodução/efeitos dos fármacos
Testículo/efeitos dos fármacos
Testículo/metabolismo
Testosterona/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androgens); 0 (RNA, Messenger); 3XMK78S47O (Testosterone); EC 1.14.15.6 (Cholesterol Side-Chain Cleavage Enzyme); RIA79UD69L (Methoxychlor)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170510
[Lr] Data última revisão:
170510
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160925
[St] Status:MEDLINE


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[PMID]:27391359
[Au] Autor:Martyniuk CJ; Doperalski NJ; Feswick A; Prucha MS; Kroll KJ; Barber DS; Denslow ND
[Ad] Endereço:Department of Physiological Sciences and Center for Environmental and Human Toxicology and Genetics Institute, University of Florida, Gainesville, FL 32611 USA. Electronic address: cmartyn@ufl.edu.
[Ti] Título:Transcriptional networks associated with the immune system are disrupted by organochlorine pesticides in largemouth bass (Micropterus salmoides) ovary.
[So] Source:Aquat Toxicol;177:405-16, 2016 Aug.
[Is] ISSN:1879-1514
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Largemouth bass (Micropterus salmoides) inhabiting Lake Apopka, Florida are exposed to high levels of persistent organochlorine pesticides (OCPs) and dietary uptake is a significant route of exposure for these apex predators. The objectives of this study were to determine the dietary effects of two organochlorine pesticides (p, p'-dichlorodiphenyldichloroethylene; p, p' DDE and methoxychlor; MXC) on the reproductive axis of largemouth bass. Reproductive bass (late vitellogenesis) were fed one of the following diets: control pellets, 125ppm p, p'-DDE, or 10ppm MXC (mg/kg) for 84days. Due to the fact that both p,p' DDE and MXC have anti-androgenic properties, the anti-androgenic pharmaceutical flutamide was fed to a fourth group of largemouth bass (750ppm). Following a 3 month exposure, fish incorporated p,p' DDE and MXC into both muscle and ovary tissue, with the ovary incorporating 3 times more organochlorine pesticides compared to muscle. Endpoints assessed were those related to reproduction due to previous studies demonstrating that these pesticides impact the reproductive axis and we hypothesized that a dietary exposure would result in impaired reproduction. However, oocyte distribution, gonadosomatic index, plasma vitellogenin, and plasma sex steroids (17ß-estradiol, E2 and testosterone, T) were not different between control animals and contaminant-fed largemouth bass. Moreover, neither p, p' DDE nor MXC affected E2 or T production in ex vivo oocyte cultures from chemical-fed largemouth bass. However, both pesticides did interfere with the normal upregulation of androgen receptor that is observed in response to human chorionic gonadotropin in ex vivo cultures, an observation that may be related to their anti-androgenic properties. Transcriptomics profiling in the ovary revealed that gene networks related to cell processes such as leukocyte cell adhesion, ossification, platelet function and inhibition, xenobiotic metabolism, fibrinolysis, and thermoregulation were altered by p, p' DDE, MXC, and flutamide. Interestingly, immune-related gene networks were suppressed by all three chemicals. The data suggest that p, p' DDE and flutamide affected more genes in common with each other than either chemical with MXC, consistent with studies suggesting that p, p' DDE is a more potent anti-androgen than MXC. These data demonstrate that reproductive health was not affected by these specific dietary treatments, but rather the immune system, which may be a significant target of organochlorine pesticides. The interaction between the reproductive and immune systems should be considered in future studies on these legacy and persistent pesticides.
[Mh] Termos MeSH primário: Bass/imunologia
Diclorodifenil Dicloroetileno/toxicidade
Redes Reguladoras de Genes/efeitos dos fármacos
Metoxicloro/toxicidade
Ovário/efeitos dos fármacos
Praguicidas/toxicidade
Poluentes Químicos da Água/toxicidade
[Mh] Termos MeSH secundário: Animais
Bass/genética
Carga Corporal (Radioterapia)
Diclorodifenil Dicloroetileno/metabolismo
Dieta
Feminino
Sistema Imunitário/efeitos dos fármacos
Metoxicloro/metabolismo
Ovário/imunologia
Praguicidas/metabolismo
Reprodução/efeitos dos fármacos
Transcriptoma/efeitos dos fármacos
Transcriptoma/imunologia
Poluentes Químicos da Água/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Pesticides); 0 (Water Pollutants, Chemical); 4M7FS82U08 (Dichlorodiphenyl Dichloroethylene); RIA79UD69L (Methoxychlor)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170118
[Lr] Data última revisão:
170118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160709
[St] Status:MEDLINE


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[PMID]:27185525
[Au] Autor:Bischof I; Köster J; Segner H; Schlechtriem C
[Ad] Endereço:Fraunhofer Institute for Molecular Biology and Applied Ecology, Auf dem Aberg 1, 57392 Schmallenberg, Germany; Centre for Fish and Wildlife Health, University of Bern, Switzerland. Electronic address: ina.bischof@ime.fraunhofer.de.
[Ti] Título:Hepatocytes as in vitro test system to investigate metabolite patterns of pesticides in farmed rainbow trout and common carp: Comparison between in vivo and in vitro and across species.
[So] Source:Comp Biochem Physiol C Toxicol Pharmacol;187:62-73, 2016 Sep.
[Is] ISSN:1532-0456
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In vitro tools using isolated primary fish hepatocytes have been proposed as a useful model to study the hepatic metabolism of xenobiotics in fish. In order to evaluate the potential of in vitro fish hepatocyte assays to provide information on in vivo metabolite patterns of pesticides in farmed fish, the present study addressed the following questions: Are in vitro and in vivo metabolite patterns comparable? Are species specific differences of metabolite patterns in vivo reflected in vitro? Are metabolite patterns obtained from cryopreserved hepatocytes comparable to those from freshly isolated cells? Rainbow trout and common carp were dosed orally with feed containing the pesticide methoxychlor (MXC) for 14days. In parallel, in vitro incubations using suspensions of freshly isolated or cryopreserved primary hepatocytes obtained from both species were performed. In vivo and in vitro samples were analyzed by thin-layer chromatography with authentic standards supported by HPLC-MS. Comparable metabolite patterns from a qualitative perspective were observed in liver in vivo and in hepatocyte suspensions in vitro. Species specific differences of MXC metabolite patterns observed between rainbow trout and common carp in vivo were well reflected by experiments with hepatocytes in vitro. Finally, cryopreserved hepatocytes produced comparable metabolite patterns to freshly isolated cells. The results of this study indicate that the in vitro hepatocyte assay could be used to identify metabolite patterns of pesticides in farmed fish and could thus serve as a valuable tool to support in vivo studies as required for pesticides approval according to the EU regulation 1107.
[Mh] Termos MeSH primário: Carpas/metabolismo
Pesqueiros
Hepatócitos/efeitos dos fármacos
Fígado/efeitos dos fármacos
Metabolômica
Metoxicloro/metabolismo
Oncorhynchus mykiss/metabolismo
Praguicidas/metabolismo
Poluentes Químicos da Água/metabolismo
[Mh] Termos MeSH secundário: Animais
Biotransformação
Cromatografia Líquida de Alta Pressão
Cromatografia em Camada Delgada
Criopreservação
Hepatócitos/metabolismo
Fígado/metabolismo
Espectrometria de Massas
Metabolômica/métodos
Metoxicloro/toxicidade
Praguicidas/toxicidade
Especificidade da Espécie
Fatores de Tempo
Poluentes Químicos da Água/toxicidade
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Pesticides); 0 (Water Pollutants, Chemical); RIA79UD69L (Methoxychlor)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170213
[Lr] Data última revisão:
170213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160518
[St] Status:MEDLINE


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[PMID]:27023821
[Au] Autor:Yang YX; Pi N; Zhang JB; Huang Y; Yao PP; Xi YJ; Yuan HM
[Ad] Endereço:School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai, 200237, China. yxyang@ecust.edu.cn.
[Ti] Título:USPIO assisting degradation of MXC by host/guest-type immobilized laccase in AOT reverse micelle system.
[So] Source:Environ Sci Pollut Res Int;23(13):13342-54, 2016 Jul.
[Is] ISSN:1614-7499
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The laccase and ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) have been assembled inside the tubular mesoporous silica via co-adsorption technology to prepare host/guest-type immobilized laccase, which is applied to degrade methoxychlor (MXC) in aqueous and reverse micelle environments. The effects of various parameters on degradation of MXC were studied. Under the optimum conditions, the degradation rate could reach maximum value of 45.6 % and remain at 20.8 % after seven cycles. Moreover, the addition of small molecular compound 2, 2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) to the system could greatly improve the degradation efficiency. The MXC degradation process is a first-order reaction, and the activation energy of MXC degradation catalyzed by immobilized laccase (41.46 kJ mol(-1)) is relatively lower than that catalyzed by free laccase (44.91 kJ mol(-1)). Based on the degradation products measured by gas chromatograph-mass spectrometer (GC-MS) and nuclear magnetic resonance (NMR), the degradation mechanism of MXC has also been proposed.
[Mh] Termos MeSH primário: Dextranos/química
Enzimas Imobilizadas/química
Inseticidas/química
Lacase/química
Nanopartículas de Magnetita/química
Metoxicloro/química
[Mh] Termos MeSH secundário: Adsorção
Benzotiazóis/química
Catálise
Micelas
Dióxido de Silício/química
Ácidos Sulfônicos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzothiazoles); 0 (Dextrans); 0 (Enzymes, Immobilized); 0 (Insecticides); 0 (Magnetite Nanoparticles); 0 (Micelles); 0 (Sulfonic Acids); 0 (ferumoxtran-10); 28752-68-3 (2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid); 7631-86-9 (Silicon Dioxide); EC 1.10.3.2 (Laccase); RIA79UD69L (Methoxychlor)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:171103
[Lr] Data última revisão:
171103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160330
[St] Status:MEDLINE
[do] DOI:10.1007/s11356-016-6502-y


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[PMID]:26961610
[Au] Autor:Umeda K; Kotake Y; Miyara M; Ishida K; Sanoh S; Ohta S
[Ad] Endereço:Graduate School of Biomedical and Health Sciences, Hiroshima University.
[Ti] Título:Methoxychlor and fenvalerate induce neuronal death by reducing GluR2 expression.
[So] Source:J Toxicol Sci;41(2):255-64, 2016 Apr.
[Is] ISSN:1880-3989
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:GluR2, an α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunit, plays important roles in neuronal survival. We previously showed that exposure of cultured rat cortical neurons to several chemicals decreases GluR2 protein expression, leading to neuronal toxicity. Methoxychlor, the bis-p-methoxy derivative of dichlorodiphenyltrichloroethane, and fenvalerate, a synthetic pyrethroid chemical, have been used commercially as agricultural pesticides in several countries. In this study, we investigated the effects of long-term methoxychlor and fenvalerate exposure on neuronal glutamate receptors. Treatment of cultured rat cortical neurons with 1 or 10 µM methoxychlor and fenvalerate for 9 days selectively decreased GluR2 protein expression; the expression of other AMPA receptor subunits GluR1, GluR3, and GluR4 did not change under the same conditions. Importantly, the decreases in GluR2 protein expression were also observed on the cell surface membrane where AMPA receptors typically function. In addition, both chemicals decreased neuronal viability, which was blocked by pretreatment with 1-naphtylacetylspermine, an antagonist of GluR2-lacking AMPA receptors, and MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist. These results suggest that long-term exposure to methoxychlor and fenvalerate decreases GluR2 protein expression, leading to neuronal death via overactivation of GluR2-lacking AMPA and NMDA receptors.
[Mh] Termos MeSH primário: Expressão Gênica/efeitos dos fármacos
Metoxicloro/toxicidade
Neurônios/efeitos dos fármacos
Nitrilos/toxicidade
Praguicidas/toxicidade
Piretrinas/toxicidade
Receptores de AMPA/genética
Receptores de AMPA/metabolismo
[Mh] Termos MeSH secundário: Animais
Morte Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Sobrevivência Celular/genética
Células Cultivadas
Córtex Cerebral/citologia
Feminino
Expressão Gênica/genética
Gravidez
Ratos Wistar
Receptores de AMPA/fisiologia
Receptores de N-Metil-D-Aspartato/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Nitriles); 0 (Pesticides); 0 (Pyrethrins); 0 (Receptors, AMPA); 0 (Receptors, N-Methyl-D-Aspartate); 0 (glutamate receptor ionotropic, AMPA 2); RIA79UD69L (Methoxychlor); Z6MXZ39302 (fenvalerate)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160311
[St] Status:MEDLINE
[do] DOI:10.2131/jts.41.255


  9 / 481 MEDLINE  
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[PMID]:26735933
[Au] Autor:Liu S; Mao B; Bai Y; Liu J; Li H; Li X; Lian Q; Ge RS
[Ad] Endereço:Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang China.
[Ti] Título:Effects of Methoxychlor and Its Metabolite Hydroxychlor on Human Placental 3ß-Hydroxysteroid Dehydrogenase 1 and Aromatase in JEG-3 Cells.
[So] Source:Pharmacology;97(3-4):126-33, 2016.
[Is] ISSN:1423-0313
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Progesterone and estradiol produced by the human placenta are critical for maintenance of pregnancy and fetal development. In the human placenta, 3ß-hydroxysteroid dehydrogenase 1 (HSD3B1) is responsible for the formation of progesterone from pregnenolone and aromatase (CYP19A1) for the production of estradiol from androgen. Insecticide methoxychlor (MXC) and its metabolite hydroxychlor (HPTE) may disrupt the activities of these 2 enzymes. In this study, we investigated the effects of MXC and HPTE on steroid production in human placental JEG-3 cells and on HSD3B1 and CYP19A1 activities. MXC and HPTE inhibited progesterone and estradiol production in JEG-3 cells. MXC and HPTE were potent HSD3B1 inhibitors with the half maximal inhibitory concentration (IC50) values of 2.339 ± 0.096 and 1.918 ± 0.078 µmol/l, respectively. MXC had no inhibition on CYP19A1 at 100 µmol/l, while HPTE was a weak inhibitor with IC50 of 97.16 ± 0.10 µmol/l. When pregnenolone was used to determine the inhibitory mode, MXC and HPTE were found to be competitive inhibitors of HSD3B1. When cofactor NAD+ was used, MXC and HPTE were the noncompetitive inhibitors of HSD3B1. When testosterone was used, HPTE was a mixed inhibitor of CYP19A1. In conclusion, MXC and HPTE are potent inhibitors of human HSD3B1, and HPTE is a weak CYP19A1 inhibitor.
[Mh] Termos MeSH primário: Inibidores da Aromatase/farmacologia
Inseticidas/farmacologia
Metoxicloro/farmacologia
Complexos Multienzimáticos/antagonistas & inibidores
Fenóis/farmacologia
Progesterona Redutase/antagonistas & inibidores
Esteroide Isomerases/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Aromatase/metabolismo
Células COS
Linhagem Celular Tumoral
Cercopithecus aethiops
Desidroepiandrosterona/farmacologia
Estradiol/metabolismo
Feminino
Seres Humanos
Complexos Multienzimáticos/genética
Complexos Multienzimáticos/metabolismo
Placenta/citologia
Placenta/enzimologia
Gravidez
Progesterona/metabolismo
Progesterona Redutase/genética
Progesterona Redutase/metabolismo
Esteroide Isomerases/genética
Esteroide Isomerases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase); 0 (Aromatase Inhibitors); 0 (Insecticides); 0 (Multienzyme Complexes); 0 (Phenols); 459AG36T1B (Dehydroepiandrosterone); 4G7DS2Q64Y (Progesterone); 4TI98Z838E (Estradiol); EC 1.1.1.145 (Progesterone Reductase); EC 1.14.14.1 (Aromatase); EC 1.14.14.1 (CYP19A1 protein, human); EC 5.3.3.- (Steroid Isomerases); H58165YO91 (2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane); RIA79UD69L (Methoxychlor)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160107
[St] Status:MEDLINE
[do] DOI:10.1159/000442711


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[PMID]:26571271
[Au] Autor:Haque MM; Holder LB; Skinner MK
[Ad] Endereço:Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, Washington, 99164-4236, United States of America.
[Ti] Título:Genome-Wide Locations of Potential Epimutations Associated with Environmentally Induced Epigenetic Transgenerational Inheritance of Disease Using a Sequential Machine Learning Prediction Approach.
[So] Source:PLoS One;10(11):e0142274, 2015.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Environmentally induced epigenetic transgenerational inheritance of disease and phenotypic variation involves germline transmitted epimutations. The primary epimutations identified involve altered differential DNA methylation regions (DMRs). Different environmental toxicants have been shown to promote exposure (i.e., toxicant) specific signatures of germline epimutations. Analysis of genomic features associated with these epimutations identified low-density CpG regions (<3 CpG / 100bp) termed CpG deserts and a number of unique DNA sequence motifs. The rat genome was annotated for these and additional relevant features. The objective of the current study was to use a machine learning computational approach to predict all potential epimutations in the genome. A number of previously identified sperm epimutations were used as training sets. A novel machine learning approach using a sequential combination of Active Learning and Imbalance Class Learner analysis was developed. The transgenerational sperm epimutation analysis identified approximately 50K individual sites with a 1 kb mean size and 3,233 regions that had a minimum of three adjacent sites with a mean size of 3.5 kb. A select number of the most relevant genomic features were identified with the low density CpG deserts being a critical genomic feature of the features selected. A similar independent analysis with transgenerational somatic cell epimutation training sets identified a smaller number of 1,503 regions of genome-wide predicted sites and differences in genomic feature contributions. The predicted genome-wide germline (sperm) epimutations were found to be distinct from the predicted somatic cell epimutations. Validation of the genome-wide germline predicted sites used two recently identified transgenerational sperm epimutation signature sets from the pesticides dichlorodiphenyltrichloroethane (DDT) and methoxychlor (MXC) exposure lineage F3 generation. Analysis of this positive validation data set showed a 100% prediction accuracy for all the DDT-MXC sperm epimutations. Observations further elucidate the genomic features associated with transgenerational germline epimutations and identify a genome-wide set of potential epimutations that can be used to facilitate identification of epigenetic diagnostics for ancestral environmental exposures and disease susceptibility.
[Mh] Termos MeSH primário: DDT/toxicidade
Epigênese Genética
Estudo de Associação Genômica Ampla
Aprendizado de Máquina
Metoxicloro/toxicidade
Mutação
[Mh] Termos MeSH secundário: Teorema de Bayes
Cromossomos/ultraestrutura
Análise por Conglomerados
Biologia Computacional/métodos
Ilhas de CpG
Metilação de DNA
Bases de Dados Genéticas
Exposição Ambiental
Feminino
Predisposição Genética para Doença
Células da Granulosa/efeitos dos fármacos
Células da Granulosa/metabolismo
Seres Humanos
Masculino
Fenótipo
Reprodutibilidade dos Testes
Análise de Sequência de DNA
Células de Sertoli/efeitos dos fármacos
Células de Sertoli/metabolismo
Espermatozoides/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
CIW5S16655 (DDT); RIA79UD69L (Methoxychlor)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151117
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0142274



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