Feldman D, Anderson T D
Department of Investigative Toxicology, Hoffmann-La Roche Inc., Nutley, NJ 07110.
Acta Neuropathol. 1994;87(1):71-80. doi: 10.1007/BF00386256.
2',3'-Dideoxycytidine (ddC) is a nucleoside analogue and reverse-transcriptase inhibitor that is approved for treatment of AIDS patients. A rabbit model of ddC neurotoxicity was developed to help understand the dose-limiting clinical neurotoxicity of ddC. Rabbits with a myelinopathy resulting from treatment with ddC exhibited mitochondrial alterations in Schwann cells of sciatic and tibial nerves and dorsal root ganglia. These changes were initially evident after 16 weeks of oral treatment with 35 mg/kg per day of ddC and were positively correlated with myelin pathology in individual animals. Cup-shaped mitochondria were frequently observed; when these mitochondria occurred in multiple concentric arrays or at various angles to one another, different profiles were formed depending on the plane of section. An increased number of mitochondrial cristae assumed a tubular configuration. It is suggested that the complex aggregations of mitochondria seen in this experiment are an adaptive response to altered mitochondrial function caused by treatment with ddC.
2',3'-双脱氧胞苷（ddC）是一种核苷类似物和逆转录酶抑制剂，已被批准用于治疗艾滋病患者。为了帮助理解ddC的剂量限制性临床神经毒性，建立了ddC神经毒性的兔模型。用ddC治疗导致髓鞘病的兔子，其坐骨神经、胫神经和背根神经节的施万细胞中线粒体发生改变。这些变化在每天口服35mg/kg ddC 16周后最初明显，并且与个体动物的髓鞘病理呈正相关。经常观察到杯状线粒体；当这些线粒体以多个同心阵列或彼此成不同角度出现时，根据切片平面会形成不同的形态。线粒体嵴数量增加呈管状结构。有人认为，本实验中看到的线粒体复杂聚集是对ddC治疗引起的线粒体功能改变的一种适应性反应。
