Pyrethroid insecticide lambda-cyhalothrin induces hepatic cytochrome P450 enzymes, oxidative stress and apoptosis in rats

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dc.contributor.authorMartínez Caballero, María Aranzazu
dc.contributor.authorAres Lombán, Irma
dc.contributor.authorRodríguez, Jose Luis
dc.contributor.authorMartínez Caballero, Marta
dc.contributor.authorRoura-Martínez, David
dc.contributor.authorCastellano Santos, Víctor Jesús
dc.contributor.authorLópez Torres, Bernardo
dc.contributor.authorMartínez Larrañaga, María Rosa
dc.contributor.authorAnadón Navarro, Arturo Ramón
dc.date.accessioned2024-02-01T11:52:16Z
dc.date.available2024-02-01T11:52:16Z
dc.date.issued2018-08-01
dc.description.abstractThis study aimed to examine in rats the effects of the Type II pyrethroid lambda-cyhalothrin on hepatic microsomal cytochrome P450 (CYP) isoform activities, oxidative stress markers, gene expression of proinflammatory, oxidative stress and apoptosis mediators, and CYP isoform gene expression and metabolism phase I enzyme PCR array analysis. Lambda-cyhalothrin, at oral doses of 1, 2, 4 and 8 mg/kg bw for 6 days, increased, in a dose-dependent manner, hepatic activities of ethoxyresorufin O-deethylase (CYP1A1), methoxyresorufin O-demethylase (CYP1A2), pentoxyresorufin O-depentylase (CYP2B1/2), testosterone 7α- (CYP2A1), 16β-(CYP2B1), and 6β-hydroxylase (CYP3A1/2), and lauric acid 11- and 12-hydroxylase (CYP4A1/2). Similarly, lambda-cyhalothrin (4 and 8 mg/kg bw, for 6 days), in a dose-dependent manner, increased significantly hepatic CYP1A1, 1A2, 2A1, 2B1, 2B2, 2E1, 3A1, 3A2 and 4A1 mRNA levels and IL-1β, NFκB, Nrf2, p53, caspase-3 and Bax gene expressions. PCR array analysis showed from 84 genes examined (P b 0.05; fold change N 1.5), changes in mRNA levels in 18 genes: 13 up-regulated and 5 down-regulated. A greater fold change reversion than 3-fold was observed on the up-regulated ALDH1A1, CYP2B2, CYP2C80 and CYP2D4 genes. Ingenuity Pathway Analysis (IPA) groups the expressed genes into biological mechanisms that aremainly related to drug metabolism. In the top canonical pathways, Oxidative ethanol degradation III together with Fatty Acid α-oxidation may be significant pathways for lambda-cyhalothrin. Our results may provide further understanding of molecular aspects involved in lambda-cyhalothrin-induced liver injury.
dc.description.departmentDepto. de Farmacología y Toxicología
dc.description.facultyFac. de Veterinaria
dc.description.refereedTRUE
dc.description.sponsorshipComunidad de Madrid (S2013/ABI-2728)
dc.description.sponsorshipMinisterio de Economía, Industria y Competitividad (RTA2015-00010-C03-03)
dc.description.statuspub
dc.identifier.citationMartínez MA, Ares I, Rodríguez JL, Martínez M, Roura-Martínez D, Castellano V, Lopez-Torres B, Martínez-Larrañaga MR, Anadón A. Pyrethroid insecticide lambda-cyhalothrin induces hepatic cytochrome P450 enzymes, oxidative stress and apoptosis in rats. Sci Total Environ. 2018 Aug 1;631-632:1371-1382. doi: 10.1016/j.scitotenv.2018.03.030. Epub 2018 Mar 28. PMID: 29727961.
dc.identifier.doi10.1016/j.scitotenv.2018.03.030
dc.identifier.essn1879-1026
dc.identifier.issn0048-9697
dc.identifier.officialurlhttps://www.sciencedirect.com/science/article/pii/S004896971830785X
dc.identifier.urihttps://hdl.handle.net/20.500.14352/97624
dc.journal.titleScience of the Total Environment
dc.language.isoeng
dc.page.final1382
dc.page.initial1371
dc.publisherElsevier
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.cdu613.2.099
dc.subject.cdu636.09
dc.subject.keywordLambda-cyhalothrin
dc.subject.keywordOral exposure
dc.subject.keywordCytochrome P450 enzymes
dc.subject.keywordGene expression
dc.subject.keywordPathways
dc.subject.ucmVeterinaria
dc.subject.unesco3214 Toxicología
dc.titlePyrethroid insecticide lambda-cyhalothrin induces hepatic cytochrome P450 enzymes, oxidative stress and apoptosis in rats
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number631-632
dspace.entity.typePublication
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