Cisplatin-induced peripheral neuropathy: neuroprotection by erythropoietin without affecting tumour growth.
This study examined the dose-dependent efficacy of erythropoietin (EPO) for preventing and/or treating cisplatin (CDDP) induced peripheral neurotoxicity (CINP), and its influence on tumour treatment and growth. Rats received eight intraperitoneal (ip) injections of 2 mg/kg CDDP twice weekly. EPO co-administered (50 or 10 microg/kg ip, three times/week) had a dose-dependent effect, partially preventing CINP, but 0.5 microg/kg ip was not effective. The neuroprotective effect lasted at least 5 weeks after the last dose of EPO and CDDP. In addition, EPO (50 microg/kg ip three times/week) after the last injection of CDDP still induced a significant recovery of CINP. In a separate experiment in rats bearing mammary carcinoma EPO treatment (50 microg/kg ip) given concurrently with CDDP (1.0 and 1.5 mg/kg twice a week for four weeks) was neuroprotective without influencing the effectiveness of the treatment or tumour growth. EPO thus appears to be an effective neuroprotectant that does not interfere with tumour treatment.
Bianchi
Roberto
R
Mario Negri Institute of Pharmacological Research, Milan, Italy.
Gilardini
Alessandra
A
Rodriguez-Menendez
Virginia
V
Oggioni
Norberto
N
Canta
Annalisa
A
Colombo
Tina
T
De Michele
Giulia
G
Martone
Sara
S
Sfacteria
Alessandra
A
Piedemonte
Giuseppe
G
Grasso
Giovanni
G
Beccaglia
Patrizia
P
Ghezzi
Pietro
P
D'Incalci
Maurizio
M
Lauria
Giuseppe
G
Cavaletti
Guido
G
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006400:Hematocrit; D006614:Hindlimb; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D009431:Neural Conduction / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D004921:Erythropoietin; D002945:Cisplatin