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
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
Entity: Universitat Rovira i Virgili
Journal publication year: 2022
Publication Type: Journal Publications
Repositori URV