Articles producció científica> Enginyeria Química

Chlorpyrifos, permethrin and cyfluthrin effect on cell survival, permeability, and tight junction in an in-vitro model of the human blood-brain barrier (BBB)

  • Identification data

    Identifier: imarina:9282889
    Authors:
    Deepika, DeepikaKumar, SauravBravo, NataliaEsplugas, RoserCapodiferro, MarcoSharma, Raju PrasadSchuhmacher, MartaGrimalt, Joan OBlanco, JordiKumar, Vikas
    Abstract:
    The blood-brain barrier (BBB) is a structural and functional interface between the plasma and the human brain. Predictive BBB in-vitro models like immortalized human capillary microvascular endothelial cells (HCMEC/D3) can be used to explore the BBB disruption potential of daily exposed chemicals. The present study was focused on investigating the human BBB permeation potential of one organophosphate pesticide, chlorpyrifos (CPF), and two pyrethroids, permethrin (PMT) and cyfluthrin (CFT). HCMEC/D3 cells were exposed to the chemical and the time-dependent pass across BBB along with permeation coefficient (Papp) was calculated. Transendothelial electrical resistance (TEER) was measured for the cells to check the monolayer formation and later to check the reduction in integrity after chemical exposure. Real time PCR was conducted to investigate the effect of chemicals on the expression BBB´s tight and adherens junction proteins. Calculated Papp value for three chemicals was in the following order: CPF>CFT>PMT, where CPF showed the highest permeation coefficient. TEER calculation showed that the integrity decreased after CPF exposure which was in concordance with Papp value whereas for other chemicals, no change in TEER after exposure was observed. In addition, the transwell study showed a higher efflux ratio (ER) (>2) of CFT indicating that CFT could be a substrate for active transport. For CPF and PMT, ER was less than 2, so no active transport seems to be involved. The evaluation of the mRNA expression analysis revealed a statistically significant decrease in Occludin (OCLN) gene expression for CPF, VE-Cadherin (CDH5) for PMT and Zonula Occludens (ZO1) expression for CFT. Our study showed that CPF has the highest potential for inducing cell death, higher permeation, and
  • Others:

    Author, as appears in the article.: Deepika, Deepika; Kumar, Saurav; Bravo, Natalia; Esplugas, Roser; Capodiferro, Marco; Sharma, Raju Prasad; Schuhmacher, Marta; Grimalt, Joan O; Blanco, Jordi; Kumar, Vikas
    Department: Enginyeria Química Ciències Mèdiques Bàsiques
    URV's Author/s: , Deepika / Blanco Pérez, Jordi / Esplugas Borràs, Roser / Kumar, Vikas / Schuhmacher Ansuategui, Marta
    Keywords: Pyrethroids Permethrin Permeability P-glycoprotein Insecticides Hcmec/d3 Efflux ratio Cyfluthrin Chlorpyrifos Blood-brain-barrier Blood -brain -barrier rats pyrethroids pyrethroid insecticide protein pharmacokinetics permethrin permeability pbpk/pd model microsomes insecticides insecticide chlorpyrifos hcmec efflux ratio developmental neurotoxicity d3 cyfluthrin combined exposure chlorpyrifos
    Abstract: The blood-brain barrier (BBB) is a structural and functional interface between the plasma and the human brain. Predictive BBB in-vitro models like immortalized human capillary microvascular endothelial cells (HCMEC/D3) can be used to explore the BBB disruption potential of daily exposed chemicals. The present study was focused on investigating the human BBB permeation potential of one organophosphate pesticide, chlorpyrifos (CPF), and two pyrethroids, permethrin (PMT) and cyfluthrin (CFT). HCMEC/D3 cells were exposed to the chemical and the time-dependent pass across BBB along with permeation coefficient (Papp) was calculated. Transendothelial electrical resistance (TEER) was measured for the cells to check the monolayer formation and later to check the reduction in integrity after chemical exposure. Real time PCR was conducted to investigate the effect of chemicals on the expression BBB´s tight and adherens junction proteins. Calculated Papp value for three chemicals was in the following order: CPF>CFT>PMT, where CPF showed the highest permeation coefficient. TEER calculation showed that the integrity decreased after CPF exposure which was in concordance with Papp value whereas for other chemicals, no change in TEER after exposure was observed. In addition, the transwell study showed a higher efflux ratio (ER) (>2) of CFT indicating that CFT could be a substrate for active transport. For CPF and PMT, ER was less than 2, so no active transport seems to be involved. The evaluation of the mRNA expression analysis revealed a statistically significant decrease in Occludin (OCLN) gene expression for CPF, VE-Cadherin (CDH5) for PMT and Zonula Occludens (ZO1) expression for CFT. Our study showed that CPF has the highest potential for inducing cell death, higher permeation, and capability to induce BBB dysfunction than among the above-mentioned chemicals. Additionally, the results of the permeation study could be useful to build a human PBPK model using in vitro-to-in vivo extrapolation approach.
    Thematic Areas: Zootecnia / recursos pesqueiros Toxicology Saúde coletiva Química Psicología Pharmacology & pharmacy Odontología Neurosciences Neuroscience (miscellaneous) Neuroscience (all) Medicina veterinaria Medicina ii Medicina i Matemática / probabilidade e estatística Interdisciplinar General neuroscience General medicine Farmacia Enfermagem Educação física Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Ciência de alimentos Biotecnología Biodiversidade
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    Author's mail: vikas.kumar@urv.cat deepika@urv.cat deepika@urv.cat jordi.blanco@urv.cat marta.schuhmacher@urv.cat
    Author identifier: 0000-0002-9795-5967 0000-0001-8016-0984 0000-0003-4381-2490
    Record's date: 2024-10-12
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://www.sciencedirect.com/science/article/pii/S0161813X22001553?via%3Dihub
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Neurotoxicology. 93 152-162
    APA: Deepika, Deepika; Kumar, Saurav; Bravo, Natalia; Esplugas, Roser; Capodiferro, Marco; Sharma, Raju Prasad; Schuhmacher, Marta; Grimalt, Joan O; Blanco (2022). Chlorpyrifos, permethrin and cyfluthrin effect on cell survival, permeability, and tight junction in an in-vitro model of the human blood-brain barrier (BBB). Neurotoxicology, 93(), 152-162. DOI: 10.1016/j.neuro.2022.09.010
    Article's DOI: 10.1016/j.neuro.2022.09.010
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2022
    Publication Type: Journal Publications
  • Keywords:

    Neuroscience (Miscellaneous),Neurosciences,Pharmacology & Pharmacy,Toxicology
    Pyrethroids
    Permethrin
    Permeability
    P-glycoprotein
    Insecticides
    Hcmec/d3
    Efflux ratio
    Cyfluthrin
    Chlorpyrifos
    Blood-brain-barrier
    Blood -brain -barrier
    rats
    pyrethroids
    pyrethroid insecticide
    protein
    pharmacokinetics
    permethrin
    permeability
    pbpk/pd model
    microsomes
    insecticides
    insecticide chlorpyrifos
    hcmec
    efflux ratio
    developmental neurotoxicity
    d3
    cyfluthrin
    combined exposure
    chlorpyrifos
    Zootecnia / recursos pesqueiros
    Toxicology
    Saúde coletiva
    Química
    Psicología
    Pharmacology & pharmacy
    Odontología
    Neurosciences
    Neuroscience (miscellaneous)
    Neuroscience (all)
    Medicina veterinaria
    Medicina ii
    Medicina i
    Matemática / probabilidade e estatística
    Interdisciplinar
    General neuroscience
    General medicine
    Farmacia
    Enfermagem
    Educação física
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Ciências ambientais
    Ciências agrárias i
    Ciência de alimentos
    Biotecnología
    Biodiversidade
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