9-Methoxy-N2-methylellipticinium acetate (MMEA) exhibits selective cytotoxicity towards glial-derived human brain tumor cell lines comprising the U.S. National Cancer Institute preclinical drug screen. Neurotoxic potential of MMEA has been demonstrated in an in vitro model employing sagittal slices of rat brain. Histochemical staining of rat brain slices for lactate dehydrogenase (LDH) activity revealed decreased staining intensity following incubation with increasing concentrations of MMEA (0.1-100 microM). Cytological evaluation of paraffin sections stained with Cresyl Fast Violet revealed neuronal damage delineated by cytoplasmic vacuolation, and distention and fraying of the plasma membrane. No glial or vascular pathology could be discerned. Autoradiography, following exposure to 14C-MMEA, revealed distinct labelling of the large neurons of the brain stem, neurons in the thalamus and pyramidal neurons of the hippocampus, indicating neuronal uptake of the drug.

译文

9-甲氧基-N2-甲基椭圆乙酸盐(MMEA)对包括美国国家癌症研究所临床前药物筛选的神经胶质来源的人脑肿瘤细胞系表现出选择性的细胞毒性。在使用大鼠脑矢状切片的体外模型中已证明了MMEA的神经毒性潜力。大鼠脑切片的乳酸脱氢酶(LDH)活性的组织化学染色显示,随着浓度增加的MMEA(0.1-100 microM)孵育后,染色强度降低。用Cresyl Fast Violet染色的石蜡切片的细胞学评估显示,神经元损伤由细胞质空泡,质膜​​的扩张和磨损所描绘。没有神经胶质或血管病理可以辨别。暴露于14C-MMEA的放射自显影显示大脑干的大型神经元,丘脑的神经元和海马的锥体神经元有明显的标记,表明该药物的神经元摄取。

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