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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

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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.

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Abbreviations

ALAT:

Alanine aminotransferase

AOPP:

Advanced oxidation protein products

ASAT:

Aspartate aminotransferase

CAT:

Catalase

CFMP:

3-(2-Chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethyl-cyclopropane carboxylic acid

CYP450:

Cytochrome P450

CYP2E:

Cytochrome P450 2E1

CYP1A:

Cytochrome P450 1A

GSH:

Glutathione

GPx:

Glutathione peroxidase

IL-6:

Interleukin 6

IL-1β:

Interleukin 1β

IFN:

Interferon gamma-γ

iNOS:

Nitric oxide synthases

LTC:

Lambda-cyhalothrin

LPO:

Lipid peroxidation

MDA:

Malondialdehyde

NO:

Nitric oxide

NPSH:

Non-protein bound

4-OH-3-PBA:

4-Hydroxyphenoxybenzoic acid

3-PBA:

3-Phenoxybenzoic acid

PYRs:

Synthetic pyrethroids

PCO:

Protein carbonyl

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

RT-qPCR:

Real-time quantitative polymerase chain reaction

SOD:

Superoxide dismutase

TNF-α:

Tumor necrosis factor-α

t-SH:

Total sulfhydryl groups

UHPLC-MS-Q-ToF:

Ultra-high-performance liquid chromatography coupled to quadripole time-of-flight mass spectrometry

Vit C:

Acid ascorbic

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Aouey, B., Derbali, M., Chtourou, Y. et al. 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. Environ Sci Pollut Res 24, 5841–5856 (2017). https://doi.org/10.1007/s11356-016-8323-4

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