bifenthrin and Tremor

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.

Topics: Animals; Anxiety; Behavior, Animal; Biomarkers; Cholinergic Neurons; Corpus Striatum; Dose-Response Relationship, Drug; Exploratory Behavior; Frontal Lobe; Gene Expression Regulation; Insecticides; Lipid Peroxidation; Male; Maze Learning; Nerve Tissue Proteins; Neuritis; Neurotoxicity Syndromes; Oxidative Stress; Pyrethrins; Random Allocation; Rats, Wistar; Tremor

To test the hypothesis that altered neuronal activity may influence the extent and severity of the glio-vascular lesions produced by 1,3-dinitrobenzene (DNB), rats were either given the tremorgenic pyrethroid, Bifenthrin, or anaesthetised during various dosing schedules of DNB. When compared with controls dosed only with DNB, Bifenthrin tremor made both the ataxia and other functional effects caused by DNB more pronounced. Lesions in the brain stem were made significantly more severe and widespread across three dose levels of DNB. Centres such as facial nuclei, motor nuclei of fifth nerve, subthalamic nuclei and mamillary bodies, not damaged by DNB alone, were also affected in some animals. In contrast, general anaesthesia by either isoflurane ur urethane decreased the severity of the lesions, this being more pronounced with urethane. The character of the tissue changes, however, was not altered by these additional procedures. These findings support the suggestion that neuronal activity is one important determinant of the selective vulnerability of sensitive brain stem nuclei to glio-vascular damage from DNB intoxication.

Topics: Anesthetics; Animals; Brain; Cerebrovascular Circulation; Dinitrobenzenes; Isoflurane; Male; Neuroglia; Pyrethrins; Rats; Rats, Inbred F344; Tremor; Urethane

Topics: 6-Aminonicotinamide; Analysis of Variance; Anesthesia; Animals; Auditory Cortex; Auditory Threshold; Brain; Dinitrobenzenes; Inferior Colliculi; Injections, Intraperitoneal; Male; Metronidazole; Motor Activity; Neuroglia; Neurons; Pyrethrins; Radiation-Sensitizing Agents; Rats; Rats, Inbred F344; Regional Blood Flow; Tremor