rhGGF2 protects against cisplatin-induced neuropathy in the rat.
In many patients treated with cisplatin a peripheral sensory neuropathy develops. This side-effect is considered dose-limiting, and therefore restricts the total dose of cisplatin that can be administered. Recent in vitro and in vivo studies suggest that recombinant human Glial Growth Factor 2 (rhGGF2) has neuroprotective effects. This prompted us to investigate in a rat model whether rhGGF2 ameliorates cisplatin neuropathy. A total of 48 rats were randomly divided into four groups of 12 rats each. Three groups received cisplatin and were treated with either 0.1 mg/kg rhGGF2, 0.3 mg/kg rhGGF2 or placebo. The fourth group (saline/placebo) served as age-matched controls. In the cisplatin/placebo treated rats a neuropathy developed, as determined by measurements of the nerve conduction velocity (NCV). Treatment with rhGGF2 dose-dependently protected against the neuropathy. Histological examination and morphometric analysis revealed that rhGGF2 also protects against cisplatin-induced changes in the morphology and size of DRG satellite cell nuclei. In a control study rhGGF2 did not affect normal NCV development. We conclude that rhGGF2 treatment is of benefit in the treatment of cisplatin neuropathy in the rat.
ter Laak
M P
MP
Rudolf Magnus Institute for Neurosciences, Department of Medical Pharmacology, Utrecht University, Utrecht, The Netherlands.
Hamers
F P
FP
Kirk
C J
CJ
Gispen
W H
WH
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000009:adverse effects*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins; D009431:Neural Conduction / Q000502:physiology; D020890:Neuregulin-1 / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009836:Oligodendroglia / Q000473:pathology / Q000502:physiology; D010525:Peripheral Nerves / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology
D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; D018696:Neuroprotective Agents; C490580:Nrg1 protein, rat; D011994:Recombinant Proteins; D002945:Cisplatin