Experimental peripheral neuropathy induced in adult rats by repeated intraperitoneal administration of taxol.
Taxol, a natural extract with antineoplastic properties, is known to be neurotoxic in humans. Its neurotoxicity after systemic administration, however, has never been studied in detail at the morphological level in humans and in animals. In this study we administered taxol intraperitoneally to female Wistar rats and we performed an extended neurophysiological and morphological examination of the peripheral nerves, dorsal root ganglia, spinal rootlets, and spinal cord. The results obtained in this experimental model indicate that taxol induces pathological changes mainly in the peripheral nerves, but they are present also in the ventral and dorsal spinal rootlets and spinal dorsal column fibers. The dorsal root ganglia and spinal cord neurons were, on the contrary, unaffected. The most impressive change induced by systemic taxol administration was intraaxonal neurotubule accumulation. Schwann cells showed signs of "activation" but clear demyelination was not observed. We conclude that with the use of this model it is possible to induce a peripheral neuropathy in the Wistar rat which resembles that reported in humans and which can, therefore, be used to better understand the basic mechanism(s) of taxol toxicity and to evaluate protective strategies in an attempt to reduce it.
Cavaletti
G
G
Institute of Human Anatomy, University of Milan, Italy.
Tredici
G
G
Braga
M
M
Tazzari
S
S
D000818:Animals; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology; D007274:Injections, Intraperitoneal; D008854:Microscopy, Electron; D009431:Neural Conduction / Q000187:drug effects; D009498:Neurotoxins / Q000008:administration & dosage / Q000633:toxicity*; D017239:Paclitaxel / Q000008:administration & dosage / Q000633:toxicity*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D010543:Peroneal Nerve / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012583:Schwann Cells / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013623:Tail / Q000294:innervation
D009498:Neurotoxins; D017239:Paclitaxel