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COMBINED EXPOSURE TO PYRIDOSTIGMINE BROMIDE (PB), DEET, AND PERMETHRIN WITH STRESS INCREASE BLOOD-BRAIN BARRIER (BBB) PERMEABILITY AND INHIBITS BRAIN ACETYLCHOLINESTERASE IN RATS.
Citation:
AbouDonia, M., W. Khan, H. Suliman, A AbdelRahman, AND K Jensen. COMBINED EXPOSURE TO PYRIDOSTIGMINE BROMIDE (PB), DEET, AND PERMETHRIN WITH STRESS INCREASE BLOOD-BRAIN BARRIER (BBB) PERMEABILITY AND INHIBITS BRAIN ACETYLCHOLINESTERASE IN RATS. Presented at Society of Toxicology, San Francisco, CA, 3/24-29/2001.
Description:
Two groups of 15 male Sprague-Dawley rats weighing 225-250 g, were administered PB (1.3mg/kg/d, oral), DEET (40mg/kg/d, dermal), and permethrin (0.13mg/kg/d, dermal) for 28 days. Animals in one group were stressed by placing them in a Plexiglas restraint tube for 5 mins. each day for the duration of the experiment. A third group of 15 animals were treated with similar treatment with stress and vehicle but no chemical and fourth group of 15 animals received only saline and ethanol and served as controls. Three sets of five animals from each group were processed for: 1) BBB permeability studies by injecting [3H]hexamethonium iodide; 2) i.v. injection of 2mg 10% type IV horseradish peroxidase (HRP) in saline; 3) biochemical assay for acetylcholinesterase (AChE) and m2 muscarinic receptor. Both stress and chemical treatment alone caused an increase in BBB permeability; however the chemical and stress combination caused even greater increase in BBB permeability. AChE activity was inhibited by a combination of chemical and stress treatment. M2 muscarinic receptor ligand binding density was decreased by treatment with chemical and stress in midbrain and cerebellum. HRP
staining revealed focal perivascular accumulation of the stain in cerebral cortex, white matter, deep gray matter and brainstem in the animals treated with chemical and stress. These results indicate that combined exposure of chemicals and stress produced changes in the BBB permeability that may cause neurologic deficits. Supported, in part by the U.S. Army Medical research and Materiel Command under contract # DAMD 17-99-1-9020. The views, opinion and/or findings contained in this report are those of the authors and should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.