RESUMEN
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.
Asunto(s)
Antineoplásicos/administración & dosificación , Compuestos Organoplatinos/administración & dosificación , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Animales , Antineoplásicos/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Potenciales Evocados Auditivos/efectos de los fármacos , Femenino , Inyecciones Intraperitoneales , Microscopía Electrónica , Conducción Nerviosa/efectos de los fármacos , Compuestos Organoplatinos/efectos adversos , Oxaliplatino , Enfermedades del Sistema Nervioso Periférico/patología , Platino (Metal)/análisis , Ratas , Ratas Wistar , Cola (estructura animal)/inervaciónRESUMEN
With the improved life expectation of beta -thalassemia major patients, new clinical problems, such as hearing damage, must be evaluated. Fifty-seven patients (32 F, 25 M; age range 17-32 years) have been studied to define risk factors for development of sensorineural hearing loss. All patients with beta -thalassemia major received daily chelation therapy with subcutaneous injection of desferrioxamine (30-50 mgkg(-1)per day). We performed an otological visit and pure tone audiometry as well as impedance; patients were followed for 3 years. Four patients with a conductive hearing loss were excluded; 66.6% had a normal audiogram; 22.8% had a slight sensorineural deficit (