Effect of recombinant human nerve growth factor on cisplatin neurotoxicity in rats.
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.
Tredici
G
G
L.I.T.A., Università di Milano, Segrate, Italy.
Braga
M
M
Nicolini
G
G
Miloso
M
M
Marmiroli
P
P
Schenone
A
A
Nobbio
L
L
Frattola
L
L
Cavaletti
G
G
D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D006801:Humans; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009431:Neural Conduction / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity*; D010146:Pain / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D012584:Sciatic Nerve / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D013997:Time Factors
D009414:Nerve Growth Factors; D009498:Neurotoxins; D011994:Recombinant Proteins; D002945:Cisplatin