CARBOPLATIN TOXIC EFFECTS ON THE PERIPHERAL NERVOUS-SYSTEM OF THE RAT

Background: The most striking of carboplatin's advantages (CBDCA) over cisplatin (CDDP) is its markedly reduced rate of neurotoxic effects. However, the use of CBDCA higher-intensity schedules and the associati on with other neurotoxic drugs in polychemotherapy may cause some conc ern about its safety with respect to peripheral nervous system damage. Materials and methods: Two different schedules of CBDCA administratio n (10 mg/kg and 15 mg/kg i.p. twice a week for nine times) were evalua ted in Wistar rats. Neurotoxicity was assessed for behavioral (tail-fl ick test), neurophysiological (nerve conduction velocity in the tail n erve), morphological, morphometrical and analytical effects. Results: CBDCA administration induced dose-dependent peripheral neurotoxicity. Pain perception and nerve conduction velocity in the tail were signifi cantly impaired, particularly after the high-dose treatment. The dorsa l root ganglia sensory neurons and, to a lesser extent, satellite cell s showed the same changes as those induced by CDDP, mainly affecting t he nucleus and nucleolus of ganglionic sensory neurons. Moreover, sign ificant amounts of platinum were detected in the dorsal root ganglia a nd kidney after CBDCA treatment. Conclusions: CBDCA is neurotoxic in o ur model, and the type of pathological changes it induces are so close ly similar to those caused by CDDP that it is probable that neurotoxic ity is induced in the two drugs by the same mechanism. This model can be used alone or in combination with other drugs to explore the effect of CBDCA on the peripheral nervous system.