The mechanism of synergistic effect by non-neurotoxic substance on 2,5-Hexanedione induced neuorotoxicity

非神经毒性物质对2,5-己二酮致神经毒性的协同作用机制已按原研究计划完成。2,5-苯并地酮与甲乙基酮、丙酮或甲苯一起皮下注射。测定血清、胆汁、尿液、粪便、肝脏、肺、肾脏、脑和坐骨神经中2,5-己二酮的浓度，并根据测定的浓度计算2,5-己二酮的药代动力学。同时检测肝、肺细胞色素p450酶的活性。综上所述，甲乙基酮、丙酮和甲苯联合注射会影响2,5-己二酮的药代动力学，表明联合注射组的2,5-己二酮清除率降低。结果这些药代动力学变化表明2,5-己二酮在脑和神经中的浓度升高，这些升高可能是甲基乙基酮和丙酮协同作用于2,5-己二酮引起的神经毒性的关键作用。此外，共同治疗组的清除率降低是假定的结果。从抑制肝脏细胞色素p450酶的活性。本研究的部分结果已发表在《职业健康杂志》、《职业与环境健康国际成就》和《神经化学研究》上。

The mechanism of synergistic effect by non-neurotoxic substances on 2,5-hexandinone induced neurotoxicity' has been finished according to the original study plan. 2,5-bexandinone along or combined with methyl ethyl ketone, acetone, or toluene were subcutaneously injected to groups of rat. Concentrations 2,5-hexandinone in serum, bile, urine, feces, liver, lunge, kidney, brain and sciatic nerve were measured, and according to the concentrations determined, the 2,5-hexandinone pharmacokinetics were calculated. In the same time, activities of the cytochrome p450 enzymes in the liver and lung were also detected. Based on these results, the pharmacokinetics of 2,5-hexanedione can be influenced by combined injections of methyl ethyl ketone, acetone, and toluene indicated by the decreases of 2,5-hexandinone clearance in the co-treated groups. Results from these pharmacokinetics changes, the concentrations of 2,5-hexandinone in brain and nerve were increased, and these increases can be supposed to play a key role for the synergistic effect of methyl ethyl ketone and acetone on the neurotoxicity induced by 2, 5-hexandinone. Furthermore, the clearance decreases in the co-treated groups is supposed result. from the inhibition of the cytochrome p450 enzymes activity in the liver. Parts of the results in the present study have been published in the Journal of Occupational Health, International Achieves of Occupational and Environmental Health, and Neurochemical Research.