PMID- 29775722 OWN - NLM STAT- MEDLINE DCOM- 20180717 LR - 20180717 IS - 1879-3169 (Electronic) IS - 0378-4274 (Linking) VI - 294 DP - 2018 Sep 15 TI - Inflammatory and oxidative mechanisms potentiate bifenthrin-induced neurological alterations and anxiety-like behavior in adult rats. PG - 73-86 LID - S0378-4274(18)30201-7 [pii] LID - 10.1016/j.toxlet.2018.05.020 [doi] AB - 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-alpha (TNF-alpha) 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. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Gargouri, Brahim AU - Gargouri B AD - Neurochemistry and Neuroimmunology Research Group, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; Laboratory of Toxicology-Microbiology and Environmental Health, UR11ES70, Sciences Faculty of Sfax, University of Sfax, BP1171, 3000, Sfax, Tunisia. Electronic address: brahim.gargouri@uniklinik-freiburg.de. FAU - Bhatia, Harsharan S AU - Bhatia HS AD - Neurochemistry and Neuroimmunology Research Group, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universitat Munchen, Ludwig Maximilians University of Munich (LMU), Munich, Germany. Electronic address: harsharan.bhatia@med.uni-muenchen.de. FAU - Bouchard, Michele AU - Bouchard M AD - 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. FAU - Fiebich, Bernd L AU - Fiebich BL AD - Neurochemistry and Neuroimmunology Research Group, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany. Electronic address: bernd.fiebich@uniklinik-freiburg.de. FAU - Fetoui, Hamadi AU - Fetoui H AD - Laboratory of Toxicology-Microbiology and Environmental Health, UR11ES70, Sciences Faculty of Sfax, University of Sfax, BP1171, 3000, Sfax, Tunisia. Electronic address: hamadi.fetoui@fss.usf.tn. LA - eng PT - Journal Article DEP - 20180526 PL - Netherlands TA - Toxicol Lett JT - Toxicology letters JID - 7709027 RN - 0 (Biomarkers) RN - 0 (Insecticides) RN - 0 (Nerve Tissue Proteins) RN - 0 (Pyrethrins) RN - 6B66JED0KN (bifenthrin) SB - IM MH - Animals MH - Anxiety/*etiology MH - Behavior, Animal/drug effects MH - Biomarkers/metabolism MH - Cholinergic Neurons/drug effects/immunology/metabolism MH - Corpus Striatum/drug effects/immunology/metabolism MH - Dose-Response Relationship, Drug MH - Exploratory Behavior/drug effects MH - Frontal Lobe/drug effects/immunology/metabolism MH - Gene Expression Regulation/drug effects MH - Insecticides/administration & dosage/*toxicity MH - Lipid Peroxidation/drug effects MH - Male MH - Maze Learning/drug effects MH - Nerve Tissue Proteins/agonists/antagonists & inhibitors/genetics/metabolism MH - Neuritis/*chemically induced/immunology/metabolism/physiopathology MH - Neurotoxicity Syndromes/immunology/metabolism/*physiopathology MH - Oxidative Stress/*drug effects MH - Pyrethrins/administration & dosage/*toxicity MH - Random Allocation MH - Rats, Wistar MH - Tremor/*etiology OTO - NOTNLM OT - AChE OT - Anxiety OT - Bifenthrin OT - Inflammatory OT - Muscarinic cholinergic receptors OT - Nrf2 OT - ROS EDAT- 2018/05/19 06:00 MHDA- 2018/07/18 06:00 CRDT- 2018/05/19 06:00 PHST- 2018/03/30 00:00 [received] PHST- 2018/05/06 00:00 [revised] PHST- 2018/05/14 00:00 [accepted] PHST- 2018/05/19 06:00 [pubmed] PHST- 2018/07/18 06:00 [medline] PHST- 2018/05/19 06:00 [entrez] AID - S0378-4274(18)30201-7 [pii] AID - 10.1016/j.toxlet.2018.05.020 [doi] PST - ppublish SO - Toxicol Lett. 2018 Sep 15;294:73-86. doi: 10.1016/j.toxlet.2018.05.020. Epub 2018 May 26.