Circulating nerve growth factor level changes during oxaliplatin treatment-induced neurotoxicity in the rat.
BACKGROUND
Oxaliplatin neurotoxicity represents a clinically-relevant problem and its etio-pathogenesis is still unknown. We explored the possible role of some neuronal growth factors ("neurotrophins") during the course of oxaliplatin sensory neuronopathy.


METHODS
In our rat model two different doses of oxaliplatin were used (2 and 3 mg/kg i.v. twice weekly for 9 times). The neurotoxicity of the treatment was assessed with neurophysiological and pathological methods and serum neurotrophin levels were measured by ELISA.


RESULTS
Both oxaliplatin-treated groups showed the neurophysiological and neuropathological changes which mimic the chronic effects of oxaliplatin administration in humans, e.g. reversible sensory impairment due to dorsal root ganglia neuron damage. These changes were associated with a significant and dose-dependent reduction only in the circulating level of nerve growth factor (NGF), which returned to normal values after neurophysiological and pathological recovery.


CONCLUSIONS
This specific association between neurological impairment and NGF modulation indicates that NGF impairment has a role in the neurotoxicity of oxaliplatin.
Cavaletti
G
G
Dipartimento di Neuroscienze e Tecnologie Biomediche, Università di Milano Bicocca, Monza, Italy. guido.cavaletti@unimib.it
Petruccioli
M G
MG
Marmiroli
P
P
Rigolio
R
R
Galbiati
S
S
Zoia
C
C
Ferrarese
C
C
Tagliabue
E
E
Dolci
C
C
Bayssas
M
M
Griffon Etienne
G
G
Tredici
G
G
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology; D009414:Nerve Growth Factors / Q000097:blood*; D009431:Neural Conduction / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009944:Organoplatinum Compounds / Q000633:toxicity*; D000077150:Oxaliplatin; D010523:Peripheral Nervous System Diseases / Q000097:blood* / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology; D013623:Tail / Q000294:innervation
D000970:Antineoplastic Agents; D009414:Nerve Growth Factors; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin