Protective effect of amifostine against cisplatin-induced motor neuropathy in rat.
Cisplatin (CDDP) is a potent anticancer drug. Neurotoxicity is one of the most important dose-limiting toxicity of CDDP. We investigated the role of amifostine in the protection against CDDP-induced neurotoxicity especially on the motor nerves. All experiments were conducted on female Wistar albino rats. Animals were randomly assigned to two groups, each including six rats. Group A received CDDP plus amifostine and Group B received CDDP only. Electroneurography (ENG) was carried out in the beginning and at the end of 7 wk; then, the rats were sacrificed and the sciatic nerve was removed for histopathological examination. The mean initial latency was 2.4667 msn for group A and 2.44833 msn for group B. After 7 wk of treatment, the latency was 2.9167 for group A and 2.6333 for group B. The difference in latencies was not statistically significant. The amplitude was 11.7853 mV and 13.533 mV for groups A and B, respectively. After 7 wk of treatment, the amplitude was 9.400 mV and 9.000 mV, respectively. The decrease of amplitude in compound muscle action potential (CMAP) was 20% in the amifostine group and the decrease was 33% in the untreated group. The mean area of the CMAP in group A was 9.400 mVsn initially and 9.666 mVsn at the end of the treatment; there was a 0.3% increase despite CDDP treatment. In group B, the mean area of the CMAP was 13.816 mVsn initially and 11.857 mVsn at the end of the treatment; this corresponded to a statistically significant 14% decrease as a result of CDDP treatment. The ENG and histopathological studies showed that at the given dose and schedule CDDP-induced motor neuropathy and amifostine reduced this neuropathy both by protection of the amplitude and area of the CMAP in ENG studies and by sparing a larger number of nerve fibers.
Yalcin
Suayib
S
Institute of Oncology, School of Medicine, Department of Histology, Hacettepe University, Sihhiye, 06100 Ankara, Turkey. syalcin@hacettepe.edu.tr
Nurlu
Gulay
G
Orhan
Bülent
B
Zeybek
Dilara
D
Müftüoğlu
Sevda
S
Sarer
Banu
B
Yildirim
Berna Akkuş
BA
Cetin
Eren
E
D004999:Amifostine / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D005260:Female; D016472:Motor Neuron Disease / Q000139:chemically induced* / Q000517:prevention & control; D009046:Motor Neurons / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D004999:Amifostine; D002945:Cisplatin