Peripheral neuropathy induced by 2',3'-dideoxycytidine

A rabbit model of 2',3'-dideoxycytidine neurotoxicity

T. D. Anderson, A. Davidovich, R. Arceo, C. Brosnan, Joseph C. Arezzo, H. Schaumburg

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

The nucleoside analog 2',3'-dideoxycytidine (ddC) is a potent inhibitor of the reverse transcriptase of human immunodeficiency virus and a DNA chain terminator. In clinical trials in patients with acquired immunodeficiency syndrome, ddC treatment has been associated with a dose-limiting and dose- dependent, painful, sensorimotor peripheral neuropathy. In search of an animal model for ddC-induced neurotoxicity we studied 36 New Zealand White rabbits (3 males/3 females/group) given 0, 10, 50, 100, 150, or 250 mg/kg/day of ddC, by oral intubation, for 13 or 18 weeks. Rabbits in the 150 and 250 mg/kg/day groups were sacrificed at 13 weeks because of hematopoietic toxicity. After 16 weeks, rabbits in the 50 and 100 mg/kg/day groups showed hindlimb paresis and/or gait abnormalities. Nerve conduction velocities and amplitudes in the 100 mg/kg/day rabbits were reduced by 30 to 50%. The most prominent pathologic changes in peripheral nerve and ventral roots of ddC- treated rabbits were (a) myelin splitting and intramyelinic edema, (b) demyelination and remyelination of axons, and (c) axonal loss. Treatment- related histologic lesions were not observed in spinal cord, brain, or retina. The pathology in these ddC-treated rabbits is consistent with a peripheral myelinopathy and axonopathy. This represents the first clinical, electrophysiologic, and pathologic description of an animal model of a peripheral neuropathy induced by a nucleoside analog.

Original languageEnglish (US)
Pages (from-to)63-74
Number of pages12
JournalLaboratory Investigation
Volume66
Issue number1
StatePublished - 1992
Externally publishedYes

Fingerprint

Zalcitabine
Peripheral Nervous System Diseases
Rabbits
Nucleosides
Animal Models
HIV Reverse Transcriptase
Spinal Nerve Roots
Neural Conduction
Demyelinating Diseases
Paresis
Hindlimb
Myelin Sheath
Gait
Peripheral Nerves
Intubation
Axons
Retina
Edema
Spinal Cord
Acquired Immunodeficiency Syndrome

Keywords

  • Axonopathy
  • Myelinopathy
  • Nucleoside

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Anderson, T. D., Davidovich, A., Arceo, R., Brosnan, C., Arezzo, J. C., & Schaumburg, H. (1992). Peripheral neuropathy induced by 2',3'-dideoxycytidine: A rabbit model of 2',3'-dideoxycytidine neurotoxicity. Laboratory Investigation, 66(1), 63-74.

Peripheral neuropathy induced by 2',3'-dideoxycytidine : A rabbit model of 2',3'-dideoxycytidine neurotoxicity. / Anderson, T. D.; Davidovich, A.; Arceo, R.; Brosnan, C.; Arezzo, Joseph C.; Schaumburg, H.

In: Laboratory Investigation, Vol. 66, No. 1, 1992, p. 63-74.

Research output: Contribution to journalArticle

Anderson, TD, Davidovich, A, Arceo, R, Brosnan, C, Arezzo, JC & Schaumburg, H 1992, 'Peripheral neuropathy induced by 2',3'-dideoxycytidine: A rabbit model of 2',3'-dideoxycytidine neurotoxicity', Laboratory Investigation, vol. 66, no. 1, pp. 63-74.
Anderson, T. D. ; Davidovich, A. ; Arceo, R. ; Brosnan, C. ; Arezzo, Joseph C. ; Schaumburg, H. / Peripheral neuropathy induced by 2',3'-dideoxycytidine : A rabbit model of 2',3'-dideoxycytidine neurotoxicity. In: Laboratory Investigation. 1992 ; Vol. 66, No. 1. pp. 63-74.
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