Effect of recombinant human nerve growth factor on cisplatin neurotoxicityin rats

In this study we evaluated the effect of recombinant human nerve growth fac tor (rhNGF) on cisplatin (CDDP)-induced sensory neuronopathy in an experime ntal 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 (ner ve conduction velocity in the tail) methods immediately after treatment and after a follow-up period of 6 weeks. Pathological and morphometrical exami nations of the dorsal root ganglia (DRG) and sciatic and saphenous nerves w ere 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 neuroprotectio n obtained with rhNGF treatment was not complete. At the follow-up examinat ion no differences between the three groups were observed in tail-flick tes t and nerve conduction velocity. We conclude that rhNGF, administered accor ding to the schedule used in this experiment, exerts a biologically signifi cant neuroprotective effect against CDDP peripheral neurotoxicity. (C) 1999 Academic Press.