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-己二酮神经毒性的协同作用机制

• 批准号: 09670362
• 负责人: MISUMI Junichi
• 金额: $ 1.73万
• 依托单位: Oita Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670362/
• 关键词: Neurotoxicity; Diabetes mellitus; 2,5-Hexanedione; Motor nerve conduction velocity; Glucose; Sorbitol; Fructose; Myo-inositol; Neurotoxicity,; Diabetes mellitus,; 2,5-Hexanedione,; Motor nerve conduction velocity,; Glucose,; Sorbitol,; Fruct

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.

非神经毒性物质对2，5-己二酮神经毒性的协同作用机制研究已按原研究计划完成。将2，5-苯并地孕酮沿着或与甲基乙基酮、丙酮或甲苯组合皮下注射到各组大鼠中。测定血清、胆汁、尿液、粪便、肝、肺、肾、脑和坐骨神经中2，5-己二烯酮的浓度，并根据测定的浓度计算2，5-己二烯酮的药代动力学。同时测定了肝、肺组织细胞色素p450酶的活性。基于这些结果，甲乙酮、丙酮和甲苯联合注射可影响2，5-己二酮的药代动力学，这通过联合给药组中2，5-己二酮清除率的降低来表明。结果2，5-己啶酮在大鼠脑和神经组织中的浓度升高，这可能是甲乙酮和丙酮协同对抗2，5-己啶酮神经毒性的重要机制。此外，联合给药组中的清除率降低是假定的结果。抑制肝脏中的细胞色素P450酶活性。本研究的部分结果已发表在《职业健康杂志》、《国际职业与环境健康成就》和《神经化学研究》上。

项目成果

JUNICHI MISUMI: "Effects of methyl ethyl ketone,acetone,or toinene coadministration on 2,5-hexanedione concentration in the aclatic nerve,serum,and urine of rats" International Achieves of Occupational and Environmental Health. 71. 236-244 (1998)

JUNICHI MISUMI：“甲基乙基酮、丙酮或甲苯烯共同给药对大鼠无运动神经、血清和尿液中 2,5-己二酮浓度的影响”国际职业和环境健康成就。

JUNICHI MISUMI: "Relationship Between 2,5-Hexanedion Concentrations in Nerve, Serum, and Urine Alone or Under Co-Treatment with Different Doses of Methyl Ethyl Ketone, Acetone, and toluene" Neurochemical research. 23-6. 837-843 (1998)

JUNICHI MISUMI：“单独或在不同剂量的甲基乙基酮、丙酮和甲苯共同治疗下，神经、血清和尿液中 2,5-己二酮浓度之间的关系”神经化学研究。

JUNICHI MISUMI: "Relationship Between 2,5-Hexanedione Concentrations in Nerve,Serum,and Urine Alone or Under Co-Treatment with Different Doses of Methyl Ethyl Ketone,Acetone,and Toluene" Neurochemical research. 23(6). 837-843 (1998)

JUNICHI MISUMI：“单独或在不同剂量的甲基乙基酮、丙酮和甲苯共同治疗下，神经、血清和尿液中 2,5-己二酮浓度之间的关系”神经化学研究。

JUNICHI MISUMI: "Effects of methyl ethyl ketone, acetone, or Toluene coadministration on 2,5Hexanedione concentration in the sciatic nerve, serum, and urine of rats" International Achieves of Occupational and Environmental Health. 71. 236-244 (1998)

JUNICHI MISUMI：“甲基乙基酮、丙酮或甲苯共同给药对大鼠坐骨神经、血清和尿液中 2,5 己二酮浓度的影响”国际职业和环境健康成就。

JUNICHI MISUMI: "Electrophysiological and Biochemical Effects of Exposure to 2,5-Hexanedione on Peripheral Nerve in Experimental Diabetic Rats" Journal of Occupational Health. 40. 148-158 (1998)

JUNICHI MISUMI：“暴露于 2,5-己二酮对实验糖尿病大鼠周围神经的电生理和生化影响”职业健康杂志。