Effects of different schedules of oxaliplatin treatment on the peripheral nervous system of the rat

The aim of this study was to determine the influence of oxaliplatin schedul ing on the onset of peripheral neurotoxicity and ototoxicity in a rat model . Animals were treated with four different schedules of oxaliplatin using t wo cumulative doses (36 and 48 mg/kg intraperitoneally (i.p.)). The neuropa thological examination evidenced dorsal root ganglia (DRG) nucleolar, nucle ar and somatic size reduction with nucleolar segregation in the treated rat s. Sensory nerve conduction velocity (SNCV) was reduced after oxaliplatin t reatment, while the auditory pathway was unaffected. After treatment, plati num was detected in the kidney, DRG and sciatic nerve. After a 5-week follo w-up period, recovery of the pathological changes in the DRG and sciatic ne rves occurred, although platinum was still detectable in these tissues. The following conclusions may be drawn: the main targets of oxaliplatin neurot oxicity were the DRG; the shorter the interval between the injections, the higher the severity of peripheral neuropathy and this was also related to t he cumulative oxaliplatin dose; the peripheral neurotoxicity tended to be r eversible; ototoxicity was absent even with high cumulative doses of oxalip latin. (C) 2001 Elsevier Science Ltd. All rights reserved.