Morphological and electrophysiological study of the effects of cisplatin and ORG.2766 on rat spinal ganglion neurons.
Eleven- to 12-wk-old rats were treated twice a week with cisplatin/saline or with cisplatin plus ORG.2766 during 12.5 wk. Cisplatin and ORG.2766 were administered at a final concentration of 0.04 mg/ml (i.p.) and 10 micrograms/ml (s.c.), respectively. Control animals were treated with saline. In this period the cisplatin-treated animals developed a peripheral neuropathy resulting in impairment of sensory functions. Estimates of the motor (MNCV) and sensory (SNCV) nerve conduction velocity were made after 0, 7.5, 10, and 12.5 wk. It appeared that the MNCV of the control, cisplatin-, and cisplatin plus ORG.2766-treated rats increased from 50 to 59 m/s. In contrast, the SNCV of the cisplatin-treated rats decreased significantly (P less than 0.001) from 63 to 56 m/s, whereas that of the control animals increased from 62 to 84 m/s. Rats which received cisplatin plus ORG.2766 showed an increase in SNCV up to control levels. After 12.5 wk the animals were perfused with a mixture of 1% paraformaldehyde and 1.25% glutaraldehyde in 0.05 M phosphate buffer. At the level of L5 and L6, 5 mm of spinal cord tissue and three dorsal root ganglia were removed and processed for electron microscopy. With the point-counting method the volume fraction (v/v) of somata and myelin in spinal ganglia was estimated. No significant change in the volume fraction of somata of the control (0.42), cisplatin (0.33)-, and cisplatin plus ORG.2766 (0.39)-treated rats was found. The same held true for the volume fraction of myelin of the control (0.53), cisplatin (0.59)-, and cisplatin plus ORG.2766 (0.58)-treated rats. In addition, the number of lysosomes per 100 microns 2 was estimated in spinal ganglion neurons and in spinal cord motor neurons of a total of 120 randomly chosen neurons. It was found that the number of lysosomes in the spinal ganglion neurons of the control animals was lower (10 per 100 microns 2) than in cisplatin-treated (30 per 100 microns 2) and in cisplatin plus ORG.2766-treated rats (28 per 100 microns 2) (P less than 0.05). No difference was observed in the number of lysosomes between cisplatin- and cisplatin plus ORG.2766-treated rats. The number of lysosomes in spinal cord tissue of cisplatin-treated rats (2.4 per 100 microns 2) did not differ from controls (0.1 per 100 microns 2) and from cisplatin plus ORG.2766-treated rats (0.8 per 100 microns 2).(ABSTRACT TRUNCATED AT 400 WORDS)
Müller
L J
LJ
Department of Biology, Vrije Universiteit, Amsterdam, The Netherlands.
Gerritsen van der Hoop
R
R
Moorer-van Delft
C M
CM
Gispen
W H
WH
Roubos
E W
EW
D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001369:Axons / Q000187:drug effects / Q000648:ultrastructure; D002466:Cell Nucleolus / Q000187:drug effects / Q000648:ultrastructure; D002945:Cisplatin / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D008247:Lysosomes / Q000187:drug effects / Q000648:ultrastructure; D008854:Microscopy, Electron; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012584:Sciatic Nerve / Q000187:drug effects* / Q000502:physiology
D000927:Anticonvulsants; D010446:Peptide Fragments; C013765:Org 2766; D000324:Adrenocorticotropic Hormone; D002945:Cisplatin