title: Pyrethroid insecticide lambda-cyhalothrin and its metabolites induce liver injury through the activation of oxidative stress and proinflammatory gene expression in rats following acute and subchronic exposure.
abstract: Lambda-cyhalothrin (LTC) [α-cyano-3-phenoxybenzyl-3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethylcyclo-propanecarboxylate] is a synthetic type II pyrethroid insecticide commonly used in residential and agricultural areas. The potential hepatotoxicity of pyrethroids remains unclear and could easily be assessed by measuring common clinical indicators of liver disease. To understand more about the potential risks for humans associated with LTC exposure, male adult rats were orally exposed to 6.2 and 31.1 mg/kg bw of LTC for 7, 30, 45, and 60 days. Histopathological changes and alterations of main parameters related to oxidative stress and inflammatory responses in the liver were evaluated. Further, lambda-cyhalothrin metabolites [3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethyl-cyclopropane carboxylic acid (CFMP), 4-hydroxyphenoxybenzoic acid (4-OH-3-PBA), and 3-phenoxybenzoic acid (3-PBA)] in the liver tissues were identified and quantified by ultra-high-performance liquid chromatography coupled to quadripole time-of-flight mass spectrometry (UHPLC-MS-Q-ToF). Results revealed that LTC exposure significantly increased markers of hepatic oxidative stress in a time-dependent and dose-dependent manner, and this was associated with an accumulation of CFMP and 3-PBA in the liver tissues. In addition, the levels of tumor necrosis factor-α (TNF-α) and interleukin (IL-6 and IL-1β) gene expressions were significantly increased in the liver of exposed rats compared to controls. Correlation analyses revealed that CFMP and 3-PBA metabolite levels in the liver tissues were significantly correlated with the indexes of oxidative stress, redox status, and inflammatory markers in rats exposed to lambda-cyhalothin. Overall, this study provided novel evidence that hepatic damage is likely due to increased oxidative stress and inflammation under the condition of acute and subchronic exposure to lambda-cyhalothrin and that LTC metabolites (CFMP and 3-PBA) could be used as potential biomarker in human biomonitoring studies.
authors.affiliation: Laboratory of Toxicology and Environmental Health, UR11ES70, Sciences Faculty of Sfax, University of Sfax, BP 1171, 3000, Sfax, Tunisia.
authors.forename: Bakhta
authors.initials: B
authors.lastname: Aouey
authors.affiliation: Laboratory of Toxicology and Environmental Health, UR11ES70, Sciences Faculty of Sfax, University of Sfax, BP 1171, 3000, Sfax, Tunisia.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Derbali
authors.affiliation: Laboratory of Toxicology and Environmental Health, UR11ES70, Sciences Faculty of Sfax, University of Sfax, BP 1171, 3000, Sfax, Tunisia.
authors.forename: Yassine
authors.initials: Y
authors.lastname: Chtourou
authors.affiliation: Department of Environmental and Occupational Health, Chair in Toxicological Risk Assessment and Management and Research Institute of Public Health of the University of Montreal (IRSPUM), University of Montreal, Montreal, QC, Canada.
authors.forename: Michèle
authors.initials: M
authors.lastname: Bouchard
authors.affiliation: Laboratory of Histopathology, Habib Bourguiba Hospital, 4010, Medenine, Tunisia.
authors.forename: Abdelmajid
authors.initials: A
authors.lastname: Khabir
authors.affiliation: Laboratory of Toxicology and Environmental Health, UR11ES70, Sciences Faculty of Sfax, University of Sfax, BP 1171, 3000, Sfax, Tunisia. fetoui_hamadi@yahoo.fr.
authors.forename: Hamadi
authors.initials: H
authors.lastname: Fetoui
mesh_terms: D000818:Animals; D001565:Benzoates; D056486:Chemical and Drug Induced Liver Injury; D004784:Environmental Monitoring; D015870:Gene Expression; D007306:Insecticides / Q000633:toxicity*; D008107:Liver Diseases; D008297:Male; D009570:Nitriles / Q000633:toxicity*; D018384:Oxidative Stress; D011722:Pyrethrins / Q000633:toxicity*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha
chemical_list: D001565:Benzoates; D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; D014409:Tumor Necrosis Factor-alpha; C017618:3-phenoxybenzoic acid; C037304:cyhalothrin
keywords: Gene expression; Hepatic injury; Inflammation; Lambda-cyhalothrin; Oxidative stress