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Circulating nerve growth factor level changes during oxaliplatin treatment-induced neurotoxicity in the rat
G Cavaletti1, M G Petruccioli, P Marmiroli
1Dipartimento di Neuroscienze e Tecnologie Biomediche, Università di Milano Bicocca, Monza, Italy. guido.cavaletti@unimib.it
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.
Materials And 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.
Conclusion:
This specific association between neurological impairment and NGF modulation indicates that NGF impairment has a role in the neurotoxicity of oxaliplatin.
Insights
Oxaliplatin treatment can cause nerve damage. This study found that reduced nerve growth factor (NGF) levels are linked to oxaliplatin-induced sensory neuronopathy in rats.
Area of Science:
- Neuroscience
- Pharmacology
- Oncology
Background:
- Oxaliplatin is a chemotherapy drug known to cause neurotoxicity.
- The exact causes of oxaliplatin-induced sensory neuronopathy remain unclear.
- Neuronal growth factors, or neurotrophins, may play a role in this condition.
Purpose of the Study:
- To investigate the potential involvement of neurotrophins in oxaliplatin-induced sensory neuronopathy.
- To explore the relationship between oxaliplatin treatment and nerve growth factor (NGF) levels.
Main Methods:
- A rat model was used with two different doses of oxaliplatin administered intravenously.
- Neurophysiological and pathological assessments evaluated neurotoxicity.
- Serum neurotrophin levels were quantified using enzyme-linked immunosorbent assay (ELISA).
Main Results:
- Oxaliplatin treatment induced neurophysiological and neuropathological changes consistent with human chronic effects.
- These changes included reversible sensory impairment due to dorsal root ganglia neuron damage.
- A significant, dose-dependent reduction in circulating nerve growth factor (NGF) levels was observed, normalizing post-recovery.
Conclusions:
- The observed association between neurological impairment and NGF modulation suggests a role for NGF in oxaliplatin neurotoxicity.
- NGF impairment is implicated as a contributing factor to oxaliplatin-induced nerve damage.