Pyrethroid bifenthrin induces oxidative stress, neuroinflammation, and neuronal damage, associated with cognitive and memory impairment in murine hippocampus
| Autor: | Nizar M. Yousif, Bernd L. Fiebich, Yassine Chtourou, Brahim Gargouri, Hamadi Fetoui, Abdelraheim Attaai, Michèle Bouchard |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Hippocampus medicine.disease_cause Superoxide dismutase 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound Cognition 0302 clinical medicine Internal medicine Pyrethrins medicine Animals Cognitive Dysfunction Rats Wistar Neuroinflammation Inflammation chemistry.chemical_classification Memory Disorders biology Glutathione peroxidase Interleukin Cell Biology Glutathione Malondialdehyde Oxidative Stress 030104 developmental biology Endocrinology chemistry biology.protein Biomarkers 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Neurochemistry International. 120:121-133 |
| ISSN: | 0197-0186 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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