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Updated: Jun 13, 2025
Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity
Published on: April 26, 2012
Dorsal root ganglion inflammation by oxaliplatin toxicity: DPEP1 as possible target for peripheral neuropathy
Karen Álvarez-Tosco1,2,3, Rebeca González-Fernández1,4, María Ángeles González-Nicolás5,6
1Laboratorio de Biología del Desarrollo, UD de Bioquímica y Biología Molecular, Universidad de La Laguna, San Cristóbal de La Laguna, Spain.
Background:
Peripheral neuropathy (PN) constitutes a dose-limiting side effect of oxaliplatin chemotherapy that often compromises the efficacy of antineoplastic treatments. Sensory neurons damage in dorsal root ganglia (DRG) are the cellular substrate of PN complex molecular origin. Dehydropeptidase-1 (DPEP1) inhibitors have shown to avoid platin-induced nephrotoxicity without compromising its anticancer efficiency. The objective of this study was to describe DPEP1 expression in rat DRG in health and in early stages of oxaliplatin toxicity. To this end, we produced and characterized anti-DPEP1 polyclonal antibodies and used them to define the expression, and cellular and subcellular localization of DPEP1 by immunohistochemical confocal microscopy studies in healthy controls and short term (six days) oxaliplatin treated rats.
Results:
DPEP1 is expressed mostly in neurons and in glia, and to a lesser extent in endothelial cells. Rats undergoing oxaliplatin treatment developed allodynia. TNF-𝛼 expression in DRG revealed a pattern of focal and at different intensity levels of neural cell inflammatory damage, accompanied by slight variations in DPEP1 expression in endothelial cells and in nuclei of neurons.
Conclusions:
DPEP1 is expressed in neurons, glia and endothelial cells of DRG. Oxaliplatin caused allodynia in rats and increased TNF-α expression in DRG neurons. The expression of DPEP1 in neurons and other cells of DRG suggest this protein as a novel strategic molecular target in the prevention of oxaliplatin-induced acute neurotoxicity.
Insights
Dehydropeptidase-1 (DPEP1) is found in rat dorsal root ganglia (DRG) neurons and cells. Inhibiting DPEP1 may prevent oxaliplatin-induced neurotoxicity, a common chemotherapy side effect.
Area of Science:
- Neuroscience
- Oncology
- Pharmacology
Background:
- Peripheral neuropathy (PN) is a dose-limiting side effect of oxaliplatin chemotherapy.
- Damage to sensory neurons in dorsal root ganglia (DRG) underlies PN.
- Dehydropeptidase-1 (DPEP1) inhibitors may prevent platinum-induced nephrotoxicity without reducing anticancer efficacy.
Purpose of the Study:
- To investigate DPEP1 expression in rat DRG under healthy conditions and early oxaliplatin toxicity.
- To characterize the cellular and subcellular localization of DPEP1 in DRG.
Main Methods:
- Production and characterization of anti-DPEP1 polyclonal antibodies.
- Immunohistochemical confocal microscopy to analyze DPEP1 expression in rat DRG.
- Assessment of oxaliplatin-induced allodynia and TNF-α expression.
Main Results:
- DPEP1 expression was observed in neurons, glia, and endothelial cells of DRG.
- Oxaliplatin treatment induced allodynia and increased TNF-α expression in DRG.
- Slight variations in DPEP1 expression were noted in endothelial cells and neuronal nuclei during oxaliplatin toxicity.
Conclusions:
- DPEP1 is present in multiple cell types within the DRG.
- Oxaliplatin induces neurotoxicity, evidenced by allodynia and inflammation.
- DPEP1 represents a potential molecular target for preventing oxaliplatin-induced neurotoxicity.
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