RT Journal Article
T1 Pyrethroid insecticide lambda-cyhalothrin induces hepatic cytochrome P450 enzymes, oxidative stress and apoptosis in rats
A1 Martínez Caballero, María Aranzazu
A1 Ares Lombán, Irma
A1 Rodríguez, Jose Luis
A1 Martínez Caballero, Marta
A1 Roura-Martínez, David
A1 Castellano Santos, Víctor Jesús
A1 López Torres, Bernardo
A1 Martínez Larrañaga, María Rosa
A1 Anadón Navarro, Arturo Ramón
AB This 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.
PB Elsevier
SN 0048-9697
YR 2018
FD 2018-08-01
LK https://hdl.handle.net/20.500.14352/97624
UL https://hdl.handle.net/20.500.14352/97624
LA eng
NO Martínez 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.
NO Comunidad de Madrid (S2013/ABI-2728)
NO Ministerio de Economía, Industria y Competitividad (RTA2015-00010-C03-03)
DS Docta Complutense
RD 6 oct 2024