Naskali L, Oksanen H, Tähti H
Department of Biomedical Sciences, University of Tampere, Finland.
Neurotoxicology. 1994 Fall;15(3):609-12.
The aim of the study was to evaluate astrocytes in vitro as a model for studies of solvent neurotoxicity. Primary astrocyte cultures were established from newborn rat cerebella. The cells were cultured in the modified Minimum Essential Medium (MEM), and the neural membranes isolated from cultures were exposed to solvents in incubation mixtures containing different solvent concentrations (3, 6, and 9 mM) for one hour. The activity of membrane-bound total ATPase was determined after exposure to aromatic hydrocarbons (benzene, toluene, xylene, styrene and ethylbenzene), and to n-hexane and cyclohexane. The enzyme activities were decreased by aromatic hydrocarbons linearly according to the log dose and in order to the log lipid/water partition coefficients, benzene having the smallest and ethylbenzene the greatest effect in all concentrations studied. Cyclohexane caused much smaller enzyme inhibition (18% of control activity in 9 mM concentration) than ethylbenzene (67% in 9 mM), in spite of very similar partition coefficients. N-hexane had clearly slighter enzyme inhibiting effect than aromatic hydrocarbons, in spite of its markedly greater lipophilicity. In addition to lipophilicity, the structure of solvent molecule seems to be important when considering the CNS toxicity. These results suggest that organic solvents exert their toxic effects on CNS, at least in part, by disturbing ATPase-dependent astrocytic regulatory functions.
本研究的目的是评估体外培养的星形胶质细胞作为溶剂神经毒性研究模型的可行性。从新生大鼠小脑建立原代星形胶质细胞培养物。细胞在改良的最低必需培养基（MEM）中培养，从培养物中分离的神经膜在含有不同溶剂浓度（3、6和9 mM）的孵育混合物中暴露于溶剂1小时。在暴露于芳香烃（苯、甲苯、二甲苯、苯乙烯和乙苯）以及正己烷和环己烷后，测定膜结合总ATP酶的活性。芳香烃使酶活性根据对数剂量呈线性下降，并与对数脂/水分配系数相关，在所研究的所有浓度下，苯的影响最小，乙苯的影响最大。尽管环己烷和乙苯的分配系数非常相似，但环己烷引起的酶抑制作用（9 mM浓度下为对照活性的18%）远小于乙苯（9 mM浓度下为67%）。尽管正己烷的亲脂性明显更高，但其对酶的抑制作用明显小于芳香烃。在考虑中枢神经系统毒性时，除亲脂性外，溶剂分子的结构似乎也很重要。这些结果表明，有机溶剂至少部分通过干扰依赖ATP酶的星形胶质细胞调节功能对中枢神经系统产生毒性作用。
