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Neurochem Int. 2018 Nov;120:121-133. doi: 10.1016/j.neuint.2018.08.004. Epub 2018 Aug 10.

Pyrethroid bifenthrin induces oxidative stress, neuroinflammation, and neuronal damage, associated with cognitive and memory impairment in murine hippocampus.

Author information

1
Neurochemistry and Neuroimmunology Research Group, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hauptstrasse 5, 79104, Freiburg, Germany; Laboratory of Toxicology-Microbiology and Environmental Health (17ES06), Sciences Faculty of Sfax, University of Sfax, BP1171, 3000, Sfax, Tunisia. Electronic address: brahim.gargouri@uniklinik-freiburg.de.
2
Neurochemistry and Neuroimmunology Research Group, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hauptstrasse 5, 79104, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany. Electronic address: nizar.yousif@uniklinik-freiburg.de.
3
Institute for Anatomy and Cell Biology, Department of Molecular Embryology, Albert-Ludwigs-University Freiburg, Albertstraße 17, 79104, Freiburg Germany; Department of Anatomy and Histology, Faculty of Veterinary Medicine, Assiut University, Egypt. Electronic address: abdelraheim.attaai@vet.au.edu.eg.
4
Department of Environmental and Occupational Health, Chair in 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: michele.bouchard@umontreal.ca.
5
Laboratory of Toxicology-Microbiology and Environmental Health (17ES06), Sciences Faculty of Sfax, University of Sfax, BP1171, 3000, Sfax, Tunisia. Electronic address: yacine_chtourou@yahoo.fr.
6
Neurochemistry and Neuroimmunology Research Group, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hauptstrasse 5, 79104, Freiburg, Germany. Electronic address: bernd.fiebich@uniklinik-freiburg.de.
7
Laboratory of Toxicology-Microbiology and Environmental Health (17ES06), Sciences Faculty of Sfax, University of Sfax, BP1171, 3000, Sfax, Tunisia. Electronic address: fetoui_hamadi@yahoo.fr.

Abstract

Exposure to synthetic pyrethroid (SPs) pesticides such as bifenthrin (BF) has been associated with adverse neurodevelopmental outcomes and cognitive impairments, but the underlying neurobiological mechanism is poorly understood so far. The present study has been designed to evaluate changes in behavior and in biomarkers of oxidative stress and neuroinflammation in the hippocampus of rats subchronically treated with BF. Rats exposed daily to BF at doses of 0.6 and 2.1 mg/kg b. w. for 60 days exhibited spatial and cognitive impairments as well as memory dysfunction after 60 days. This repeated BF treatment also significantly increased mRNA expression of pro-inflammatory cytokines tumor necrosis factor (TNF-α), interleukin (IL-1β), (IL-6), nuclear factor erythroid-2 (Nrf2), cyclooxygenase-2 (COX-2), nuclear factor-kappaB pathway (NF-kappaB), and prostaglandin E2 (PGE2) in the hippocampus. It further resulted in a significant increase in protein levels of Nrf2, COX-2, microsomal prostaglandin synthase-1 (mPGES-1) and NF-kappaB. This was accompanied by oxidative/nitrosative stress in the hippocampus of treated rats, as shown by increased levels of malondialdehyde (MDA), protein carbonyls (PCO), and nitric oxide (NO), and reduced levels of enzymatic (catalase, superoxide dismutase, and glutathione peroxidase) and non-enzymatic (reduced glutathione) antioxidants. The data are in line with those obtained in organotypic hippocampal slice cultures (OHSCs) isolated from mouse brain and exposed to BF for 72 h, showing neuronal death only at the high dose of 20 μM when compared to controls. These findings suggest that exposure to BF induces neuronal damage, alters redox state, and causes neuroinflammation in the hippocampus, which might lead to cognitive and memory impairment.

KEYWORDS:

Bifenthrin; Cognitive impairment; Cytokines; Hippocampus; Nrf2; Oxidative stress

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