EXPERIMENTAL PERIPHERAL NEUROPATHY INDUCED IN ADULT-RATS BY REPEATED INTRAPERITONEAL ADMINISTRATION OF TAXOL

Taxol, a natural extract with antineoplastic properties, is known to b e neurotoxic in humans. Its neurotoxicity after systemic administratio n, however, has never been studied in detail at the morphological leve l in humans and in animals. In this study we administered taxol intrap eritoneally to female Wistar rats and we performed an extended neuroph ysiological and morphological examination of the peripheral nerves, do rsal root ganglia, spinal rootlets, and spinal cord. The results obtai ned in this experimental model indicate that taxol induces pathologica l changes mainly in the peripheral nerves, but they are present also i n the ventral and dorsal spinal rootlets and spinal dorsal column fibe rs. The dorsal root ganglia and spinal cord neurons were, on the contr ary, 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 observ ed. We conclude that with the use of this model it is possible to indu ce a peripheral neuropathy in the Wistar rat which resembles that repo rted in humans and which can, therefore, be used to better understand the basic mechanism(s) of taxol toxicity and to evaluate protective st rategies in an attempt to reduce it. (C) 1995 Academic Press, Inc.