Influence of cisplatin on the sensitivity of the rat sciatic nerve to local hyperthermia.
The influence of cisplatin on the sensitivity of the rat sciatic nerve to local hyperthermia was investigated. Rats received 1.7 mg/kg cisplatin i.p., twice a week for 6 weeks, up to a cumulative dose of 20.4 mg/kg. After termination of cisplatin treatment, a 5 mm segment of the nerve was locally heated at a temperature of 45 degrees C (5-30 min). Loss of motor function was assessed by means of the toe-spreading test, 24 h post heating. The calculated ED50 for control nerves was significantly (p < 0.01) larger than the ED50 for cisplatin treated rats; 16.3 +/- 1.1 min vs. 10.9 +/- 1.1 min. This indicates that nerves from cisplatin treated rats were more sensitive to heat than nerves from control rats (dose modifying factor = 1.5 +/- 0.2). Histopathological investigation of nerves after heat alone or after heat preceded by cisplatin confirmed these differences and showed that edema, vascular damage and axonal degenerative changes of axons and myelin sheaths occurred at lower heat doses when compared to control nerves. Recovery studies showed that cisplatin treatment before hyperthermia caused a delay in recovery from motor function loss of about 6 days. Cisplatin treatment after hyperthermia had no influence on recovery from motor function loss.
Department of Radiotherapy, University of Amsterdam, Academish Medisch Centrum, The Netherlands.
J F
JF
Hoogeveen
A H
AH
Van Der Kracht
J
J
Wondergem
D
D
Gonzalez Gonzalez
J
J
Haveman
D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006979:Hyperthermia, Induced / Q000009:adverse effects*; D007677:Kidney Function Tests; D010523:Peripheral Nervous System Diseases / Q000209:etiology* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects*; D015431:Weight Loss / Q000187:drug effects
D002945:Cisplatin