Inflammatory and oxidative mechanisms potentiate bifenthrin-induced neurological alterations and anxiety-like behavior in adult rats

Autor: Bernd L. Fiebich, Hamadi Fetoui, Harsharan S. Bhatia, Michèle Bouchard, Brahim Gargouri
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
Insecticides
Nerve Tissue Proteins
Striatum
Anxiety
Toxicology
medicine.disease_cause
Superoxide dismutase
Lipid peroxidation
03 medical and health sciences
chemistry.chemical_compound
Random Allocation
0302 clinical medicine
Neuritis
Internal medicine
Pyrethrins
Tremor
medicine
Animals
Rats
Wistar
Maze Learning
chemistry.chemical_classification
Reactive oxygen species
biology
Behavior
Animal
Dose-Response Relationship
Drug
Chemistry
Glutathione peroxidase
General Medicine
Glutathione
Choline acetyltransferase
Cholinergic Neurons
Corpus Striatum
Frontal Lobe
Oxidative Stress
030104 developmental biology
Endocrinology
Gene Expression Regulation
biology.protein
Exploratory Behavior
Neurotoxicity Syndromes
Lipid Peroxidation
030217 neurology & neurosurgery
Oxidative stress
Biomarkers
Zdroj: Toxicology letters. 294
ISSN: 1879-3169
Popis: Bifenthrin (BF) is a synthetic pyrethroid pesticide widely used in several countries to manage insect pests on diverse agricultural crops. Growing evidence indicates that BF exposure is associated with an increased risk of developing neurodegenerative disorders. However, the mechanisms by which BF induces neurological and anxiety alterations in the frontal cortex and striatum are not well known. The present in vivo study was carried out to determine whether reactive oxygen species (ROS)-mediated oxidative stress (OS) and neuroinflammation are involved in such alterations. Thirty-six Wistar rats were thus randomly divided into three groups and were orally administered with BF (0.6 and 2.1 mg/kg body weight, respectively) or the vehicle (corn oil), on a daily basis for 60 days. Results revealed that BF exposure in rats enhanced anxiety-like behavior after 60 days of treatment, as assessed with the elevated plus-maze test by decreases in the percentage of time spent in open arms and frequency of entries into these arms. BF-treated rats also exhibited increased oxidation of lipids and carbonylated proteins in the frontal cortex and striatum, and decreased glutathione levels and antioxidant enzyme activities including superoxide dismutase, catalase and glutathione peroxidase. Treatment with BF also increased protein synthesis and mRNA expression of the inflammatory mediators cyclooxygenase-2 (COX-2), microsomal prostaglandin synthase-1 (mPGES-1) and nuclear factor-kappaBp65 (NF-kBp65), as well as the production of tumor necrosis factor-α (TNF-α) and ROS. Moreover, BF exposure significantly decreased protein synthesis and mRNA expression of nuclear factor erythroid-2 (Nrf2) and acetylcholinesterase (AChE), as well as gene expression of muscarinic-cholinergic receptors (mAchR) and choline acetyltransferase (ChAT) in the frontal cortex and striatum. These data suggest that BF induced neurological alterations in the frontal cortex and striatum of rats, and that this may be associated with neuroinflammation and oxidative stress via the activation of Nrf2/NF-kBp65 pathways, which might promote anxiety-like behavior.
Databáze: OpenAIRE
Externí odkaz: