Morphological and morphometric analysis of paclitaxel and docetaxel-induced peripheral neuropathy in rats.
The experimentally induced neurotoxic effects of paclitaxel and docetaxel have never been compared, since no animal models of docetaxel peripheral neurotoxicity have yet been reported. In this experiment, we examined the effect of the chronic administration of these two taxanes in the Wistar rat using neurophysiological, neuropathological and morphometrical methods. Our results showed that both paclitaxel and docetaxel induced a significant, equally severe and dose-dependent reduction in nerve conduction velocity. On the contrary, the morphometric examination demonstrated that the effect on the nerve fibres was more severe after paclitaxel administration when the same schedule was used. However, the overall severity of the pathological changes was milder than expected on the basis of the neurophysiological results. Our results support the hypothesis that taxanes (and particularly docetaxel) may exert their neurotoxic effect not only on the microtubular system of the peripheral nerves, but also on other less obvious targets.
Persohn
Elke
E
Novartis Pharma AG, Safety Profiling Assessment, Pathology, Basel, Switzerland.
Canta
Annalisa
A
Schoepfer
S
S
Traebert
Martin
M
Mueller
Lutz
L
Gilardini
Alessandra
A
Galbiati
Stefania
S
Nicolini
Gabriella
G
Scuteri
Arianna
A
Lanzani
Francesca
F
Giussani
Giuditta
G
Cavaletti
Guido
G
D000704:Analysis of Variance; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D000077143:Docetaxel; D005260:Female; D008870:Microtubules / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D020932:Nerve Growth Factor / Q000097:blood; D017239:Paclitaxel / Q000009:adverse effects*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D043823:Taxoids / Q000009:adverse effects*
D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D020932:Nerve Growth Factor; D017239:Paclitaxel