Effect of recombinant human nerve growth factor on cisplatin neurotoxicity in rats

Exp Neurol. 1999 Oct;159(2):551-8. doi: 10.1006/exnr.1999.7174.

Abstract

In this study we evaluated the effect of recombinant human nerve growth factor (rhNGF) on cisplatin (CDDP)-induced sensory neuronopathy in an experimental paradigm in the rat. Young adult female Wistar rats were treated with CDDP (2 mg/kg ip twice weekly for nine times) alone or in combination with rhNGF (1 mg/kg sc on alternate days). The effect of CDDP +/- NGF treatment was evaluated with behavioral (tail-flick test) and neurophysiological (nerve conduction velocity in the tail) methods immediately after treatment and after a follow-up period of 6 weeks. Pathological and morphometrical examinations of the dorsal root ganglia (DRG) and sciatic and saphenous nerves were also performed. rhNGF treatment induced a significant reduction in the CDDP-induced decrease in nerve conduction velocity (P < 0.05), and this was associated with a significant protection against the decrease in somatic (P < 0.05), nuclear (P < 0.05), and nucleolar size (P < 0.01) caused by CDDP treatment. However, for each of the parameters examined the neuroprotection obtained with rhNGF treatment was not complete. At the follow-up examination no differences between the three groups were observed in tail-flick test and nerve conduction velocity. We conclude that rhNGF, administered according to the schedule used in this experiment, exerts a biologically significant neuroprotective effect against CDDP peripheral neurotoxicity.

MeSH terms

  • Animals
  • Cisplatin / toxicity*
  • Female
  • Ganglia, Spinal / drug effects*
  • Ganglia, Spinal / pathology
  • Ganglia, Spinal / physiology
  • Humans
  • Nerve Growth Factors / pharmacology*
  • Neural Conduction / drug effects*
  • Neurotoxins / toxicity*
  • Pain / physiopathology
  • Rats
  • Rats, Wistar
  • Recombinant Proteins / pharmacology
  • Sciatic Nerve / drug effects*
  • Sciatic Nerve / pathology
  • Sciatic Nerve / physiology
  • Time Factors

Substances

  • Nerve Growth Factors
  • Neurotoxins
  • Recombinant Proteins
  • Cisplatin