Delayed functional recovery by vincristine after sciatic nerve crush injury: a mouse model of vincristine neurotoxicity.
Neuropathy is the dose-limiting side effect of vincristine (VCR) in cancer therapy. However, no simple experimental model has yet been reported. Here, we present a simple experimental model of VCR neurotoxicity using a mouse sciatic nerve crush model, which allows evaluation within a few weeks. VCR administered intravenously once on the day after the crush lesion caused a dose-dependent delay of the recovery of motor and sensory functions. The minimal dose required to cause the delay was 0.25 mg/kg, which corresponded to five times the usual clinical dose for man and was far less than the reported doses required to cause functional impairment in intact animals. The model would be useful not only for the development of new drugs but also for the estimation of the drug interactions in combination cancer therapy.
Nakamura
Y
Y
Department of Pharmacy, Branch Hospital, Faculty of Medicine, University of Tokyo, Mejirodai 3-28-6, Bunkyo-ku, 112-8688, Tokyo, Japan. starwards-tky@umin.ac.jp
Shimizu
H
H
Nishijima
C
C
Ueno
M
M
Arakawa
Y
Y
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D009409:Nerve Crush; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology; D012584:Sciatic Nerve / Q000187:drug effects* / Q000293:injuries / Q000502:physiology; D014750:Vincristine / Q000633:toxicity*
D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine