Abou-Donia Mohamed B, Dechkovskaia Anjelika M, Goldstein Larry B, Abdel-Rahman Ali, Bullman Sarah L, Khan Wasiuddin A
Department of Pharmacology and Cancer Biology, Duke University Medical Center, P.O. Box 3813, Durham, NC 27710, USA.
Pharmacol Biochem Behav. 2004 Feb;77(2):253-62. doi: 10.1016/j.pbb.2003.10.018.
Military personnel deployed in the Persian Gulf War (PGW) were exposed to a combination of chemicals, including pyridostigmine bromide (PB), DEET, and permethrin. We investigated the dose-response effects of these chemicals, alone or in combination, on the sensorimotor performance and cholinergic system of male Sprague-Dawley rats. Animals were treated with a daily dermal dose of DEET and/or permethrin for 60 days and/or PB (gavage) during the last 15 days. Neurobehavioral performance was assessed on day 60 following the beginning of the treatment with DEET and permethrin. The rats were sacrificed 24 h after the last treatment for biochemical evaluations. PB alone, or in combination with DEET, or DEET and permethrin resulted in deficits in beam-walk score and longer beam-walk times compared to controls. PB alone, or in combination with DEET, permethrin, or DEET and permethrin caused impairment in incline plane performance and forepaw grip strength. PB alone at all doses slightly inhibited plasma butyrylcholinesterase activity, whereas combination of PB with DEET or permethrin increased its activity. Brainstem acetylcholinesterase (AChE) activity significantly increased following treatment with combinations of either DEET or permethrin at all doses, whereas the cerebellum showed a significant increase in AChE activity following treatment with a combination of PB/DEET/permethrin. Co-exposure to PB, DEET, and permethrin resulted in significant inhibition in AChE in midbrain. PB alone or in combination with DEET and permethrin at all doses increased ligand binding for m2 muscarinic acetylcholine receptor in the cortex. In addition, PB and DEET together or a combination of PB, DEET, and permethrin significantly increased ligand binding for nicotinic acetylcholine receptor. These results suggest that exposure to various doses of PB, alone and in combination with DEET and permethrin, leads to sensorimotor deficits and differential alterations of the cholinergic system in the CNS.
部署在海湾战争（PGW）中的军事人员接触到了多种化学物质，包括溴化吡啶斯的明（PB）、避蚊胺（DEET）和氯菊酯。我们研究了这些化学物质单独或联合使用时，对雄性斯普拉格-道利大鼠感觉运动性能和胆碱能系统的剂量反应效应。动物每天经皮给予避蚊胺和/或氯菊酯，持续60天，并在最后15天给予PB（灌胃）。在开始给予避蚊胺和氯菊酯治疗后的第60天评估神经行为表现。在最后一次治疗24小时后处死大鼠进行生化评估。与对照组相比，单独使用PB，或与避蚊胺联合使用，或与避蚊胺和氯菊酯联合使用，均导致横梁行走评分降低和横梁行走时间延长。单独使用PB，或与避蚊胺、氯菊酯联合使用，或与避蚊胺和氯菊酯联合使用，均会导致斜面性能和前爪握力受损。所有剂量的单独PB均轻微抑制血浆丁酰胆碱酯酶活性，而PB与避蚊胺或氯菊酯联合使用则会增加其活性。所有剂量的避蚊胺或氯菊酯联合使用后，脑干乙酰胆碱酯酶（AChE）活性显著增加，而小脑在PB/避蚊胺/氯菊酯联合使用后AChE活性显著增加。同时接触PB、避蚊胺和氯菊酯会导致中脑AChE显著抑制。所有剂量的单独PB或与避蚊胺和氯菊酯联合使用均会增加皮质中m2毒蕈碱型乙酰胆碱受体的配体结合。此外，PB和避蚊胺一起使用，或PB、避蚊胺和氯菊酯联合使用会显著增加烟碱型乙酰胆碱受体的配体结合。这些结果表明，接触不同剂量的PB，单独或与避蚊胺和氯菊酯联合使用，会导致感觉运动缺陷和中枢神经系统胆碱能系统的不同改变。
Zotero 插件