Schwann cell mitochondrial alterations in peripheral nerves of rabbits treated with 2',3'-dideoxycytidine.
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.
Feldman
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Department of Investigative Toxicology, Hoffmann-La Roche Inc., Nutley, NJ 07110.
Anderson
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TD
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D000818:Animals; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D006801:Humans; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D009498:Neurotoxins / Q000633:toxicity*; D011817:Rabbits; D012016:Reference Values; D012583:Schwann Cells / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D013979:Tibial Nerve / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D016047:Zalcitabine / Q000633:toxicity*
D009498:Neurotoxins; D016047:Zalcitabine