Effect of the chronic combined administration of cisplatin and paclitaxel in a rat model of peripheral neurotoxicity.
We have characterised for the first time the general and neurological side effects experienced when using a series of chronic non-lethal cisplatin + paclitaxel schedules in Wistar rats, selected according to our previous experience and the animals' maximum tolerated dose. At the pathological level, the use of combination schedules was definitely more toxic at the kidney and sternal bone marrow level than the single-agent schedules. At the neurophysiological examination based on the assessment of the nerve conduction velocity measurement in the tail nerve, we identified only one combination schedule that was more neurotoxic than the similar schedules based on single-agent administration. This observation was confirmed by the neuropathological examination performed on the sciatic nerve, dorsal root ganglia, ventral and dorsal roots. Our study supports the hypothesis that the general and, to a lesser extent, neurological effects of a combination of cisplatin and paclitaxel are different from those of the administration of both drugs as single agents. We believe that these models may be useful for testing neuroprotective strategies.
Carozzi
Valentina
V
Department of Neuroscience and Biomedical Technologies, University of Milan Bicocca, Via Cadore 48, 20052 Monza (MI), Italy.
Chiorazzi
Alessia
A
Canta
Annalisa
A
Oggioni
Norberto
N
Gilardini
Alessandra
A
Rodriguez-Menendez
Virginia
V
Avezza
Federica
F
Crippa
Luca
L
Ceresa
Cecilia
C
Nicolini
Gabriella
G
Bossi
Mario
M
Cavaletti
Guido
G
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000633:toxicity*; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000633:toxicity; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015431:Weight Loss / Q000187:drug effects
D017239:Paclitaxel; D002945:Cisplatin