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 scheduling on the onset of peripheral neurotoxicity and ototoxicity in a rat model. Animals were treated with four different schedules of oxaliplatin using two cumulative doses (36 and 48 mg/kg intraperitoneally (i.p.)). The neuropathological examination evidenced dorsal root ganglia (DRG) nucleolar, nuclear and somatic size reduction with nucleolar segregation in the treated rats. Sensory nerve conduction velocity (SNCV) was reduced after oxaliplatin treatment, while the auditory pathway was unaffected. After treatment, platinum was detected in the kidney, DRG and sciatic nerve. After a 5-week follow-up period, recovery of the pathological changes in the DRG and sciatic nerves occurred, although platinum was still detectable in these tissues. The following conclusions may be drawn: the main targets of oxaliplatin neurotoxicity were the DRG; the shorter the interval between the injections, the higher the severity of peripheral neuropathy and this was also related to the cumulative oxaliplatin dose; the peripheral neurotoxicity tended to be reversible; ototoxicity was absent even with high cumulative doses of oxaliplatin.
Cavaletti
G
G
Clinica Neurologica, A.O.S. Gerardo, Monza, Italy. guido.cavaletti@unimi.it
Tredici
G
G
Petruccioli
M G
MG
Dondè
E
E
Tredici
P
P
Marmiroli
P
P
Minoia
C
C
Ronchi
A
A
Bayssas
M
M
Etienne
G G
GG
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D005260:Female; D007274:Injections, Intraperitoneal; D008854:Microscopy, Electron; D009431:Neural Conduction / Q000187:drug effects; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000077150:Oxaliplatin; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D010984:Platinum / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013623:Tail / Q000294:innervation
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D010984:Platinum