Bifenthrin insecticide promotes oxidative stress and increases inflammatory mediators in human neuroblastoma cells through NF-kappaB pathway

Brahim Gargouri, Khadija Boukholda, Asit Kumar, Abdelhamid Benazzouz, Hamadi Fetoui, Bernd L. Fiebich, Michèle Bouchard
Toxicology in Vitro. 2020-06-01; 65: 104792
DOI: 10.1016/j.tiv.2020.104792

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Gargouri B(1), Boukholda K(2), Kumar A(3), Benazzouz A(4), Fetoui H(2), Fiebich BL(5), Bouchard M(6).

Author information:
(1)Neurochemistry and Neuroimmunology Research Group, Department of Psychiatry
and Psychotherapy, Medical Center – University of Freiburg, Faculty of Medicine,
University of Freiburg, Haupt strasse 5, 79104 Freiburg, Germany; Laboratory of
Toxicology-Microbiology and Environmental Health (17ES06), Faculty of Sciences
of Sfax, University of Sfax, BP1171, 3000 Sfax, Tunisia.
(2)Laboratory of Toxicology-Microbiology and Environmental Health (17ES06),
Faculty of Sciences of Sfax, University of Sfax, BP1171, 3000 Sfax, Tunisia.
(3)Department of Neurology, Richard T Johnson Division of Neuroimmunology and
Neurological Infections, Johns Hopkins University School of Medicine, Baltimore,
MD, USA.
(4)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR
5293, F-33000 Bordeaux, France.
(5)Neurochemistry and Neuroimmunology Research Group, Department of Psychiatry
and Psychotherapy, Medical Center – University of Freiburg, Faculty of Medicine,
University of Freiburg, Haupt strasse 5, 79104 Freiburg, Germany. Electronic
address: .
(6)Department of Environmental and Occupational Health, Toxicological Risk
Assessment and Management, University of Montreal, Roger-Gaudry Building, U424,
P.O. Box 6128, Main Station, Montreal, Quebec H3C 3J7, Canada. Electronic
address: .

The extensive application of bifenthrin (BF) insecticide in agriculture has
raised serious concerns with regard to increased risks of developing
neurodegenerative diseases. Recently, our group showed that BF exposure in
rodent models induced oxidative stress and inflammation markers in various
regions of the brain (frontal cortex, striatum and hippocampus) and this was
associated with behavioral changes. This study aimed to confirm such
inflammatory and oxidative stress in an in vitro cell culture model of SK-N-SH
human neuroblastoma cells. Markers of oxidative stress (ROS, NO, MDA, H2O2),
antioxidant enzyme activities (CAT, GPx, SOD) and inflammatory response (TNF-α,
IL-6, PGE2) were analyzed in SK-N-SH cells after 24 h of exposure to different
concentrations of BF (1-20 μM). Protein synthesis and mRNA expression of the
enzymes implicated in the synthesis of PGE2 were also measured (COX-2, mPGES-1)
as well as nuclear factor κappaB (NF-κBp65) and antioxidant nuclear erythroid-2
like factor-2 (Nrf-2). Cell viability was analyzed by MTT-tetrazolio (MTT) and
lactate dehydrogenase (LDH) assays. Exposure of SK-N-SH cells to BF resulted in
a concentration-dependent reduction in the number of viable cells (reduction of
MTT and increase in LDH activity). There was also a BF concentration-dependent
increase in oxidative stress markers (ROS release, NO, MDA and H2O2) and
decrease in the activity of antioxidant enzymes (CAT and GPx activities). There
was further a concentration-dependent increase in pro-inflammatory cytokines
(TNF-α and IL-6) and inflammatory mediator PGE2, increase in protein synthesis
and mRNA expression of inflammatory markers (COX-2, mPGES-1 and NF-κBp65) and
decrease in protein synthesis and mRNA expression of antioxidant Nrf-2. Our data
shows that BF induces various oxidative stress and inflammatory markers in
SK-N-SH human neuroblastoma cells as well as the activation of NF-κBp65
signaling pathway. This is in line with prior results in brain regions of
rodents exposed in vivo to BF showing increased oxidative stress in response to
BF exposure, occurring in pro-inflammatory conditions and likely activating
programmed cell death.

Copyright © 2020. Published by Elsevier Ltd.

 

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