Neurotoxicology
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Paclitaxel, which is known to induce peripheral neuropathy in humans, was administered to BDF1 mice, and a neuropathological examination was then conducted. Paclitaxel was administered at a dose of 30 mg/kg once or several times at different intervals, 3 times, every 3 hours (q3hx3), every day (q1dx3), every 2 days (q2dx3) and 4 times, once a week (q7dx4). The spinal cord, spinal ganglion and peripheral nerves (sciatic and tibial) were then processed for neuropathological examination following perfusion of the anesthetized mice. ⋯ The severity of the degeneration was as follows: q2dx3>q1dx3>q3hx3 and q7dx4. The degeneration in the mice treated on q3hx3 and q7dx4 was very slight, but it was clear that paclitaxel also induced degeneration on these schedules. These results suggest that paclitaxel induces a predominantly sensory neuropathy in mice and the severity is obviously dependent on the treatment schedule.
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Vincristine is an effective chemotherapeutic agent for a variety of human neoplasms, but has dose-limiting neurotoxicity. Since laboratory rodents have proven to be refractive in such neurotoxicological studies, we conducted a neuropathological and behavioral assessment in rabbits treated with vincristine at doses known to be both chemotherapeutically effective and neurotoxic in humans. Rabbits (Kbl: NZW) were given vincristine intravenously at doses of 0 (saline), 200, 250 or 300 microg/kg once a week for 6 weeks, 500 microg/kg once a week for 3 weeks, or a single 500 microg/kg administration. ⋯ These alterations were observed even after a single dose of 500 microg/kg. In the group given weekly doses of 500 microg/kg, neuronal chromatolysis was also found in the spinal cord. These results suggest the rabbit is responsive to vincristine neurotoxicity producing a predominantly sensory neuropathy and confirming earlier studies.