Cilastatin Modulates DPEP1- and IQGAP1-Associated Neuro-Glio-Vascular Inflammation in Oxaliplatin-Induced Peripheral Neurotoxicity
Abstract
1. Introduction
2. Materials and Methods
2.1. Subjects
2.2. Animal Models
2.2.1. OxPt-Induced Neuropathic Allodynia Animal Model
2.2.2. Allodynia Test
2.3. Antibodies
2.4. Western Blot
2.5. Immunohistochemistry
2.6. Confocal Analysis
2.7. Image Quantitative Analysis
2.8. Image Qualitative and Semi-Quantitative Analysis
2.9. Statistical Analysis
3. Results
3.1. Differential Nocifensive Response to Allodynia Among Controls, OxPt-, and Cilastatin-Treated Rats
3.2. Tissue-Specific Expression Patterns of DPEP1 and IQGAP1 by Western Blot Reveal the Need for Cellular-Level Analysis in Peripheral Neuropathy
3.3. Immunohistochemical-Confocal Localization of DPEP1 and IQGAP1 in DRG from OxPt- and Cilastatin-Treated Rats
3.4. IQGAP1 Expression in Glial Cells in DRGs from OxPt- and Cilastatin-Treated Rats
3.5. IQGAP1 Expression in Endothelial Cells of DRG
3.6. IQGAP1 in the Short-Time DRG Inflammation Response to OxPt Chemotherapy
4. Discussions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CD31 | Cluster of differentiation 31 (also known as platelet endothelial cell adhesion molecule) |
CIL | Cilastatin |
CIPN | Chemotherapy-induced peripheral neuropathy |
CZI | Carl Zeiss Image Data File |
DPEP1 | Dehydropeptidase-1 |
DRG | Dorsal root ganglion |
GFAP | Glial fibrillary acidic protein |
GPI | Glycosylphosphatidylinositol |
GSH | Glutathione |
IL-6 | Interlukin 6 |
IQGAP1 | IQ motif-containing GTPase-activating protein 1 |
LIF | Leica Image Format |
MAP2 | Microtubule-associated protein 2 |
OIPN | Oxaliplatin-induced peripheral neuropathy |
OxPt | Oxaliplatin |
PCC | Pearson correlation coefficient |
PFA | Paraformaldehyde |
ROS | Reactive oxygen species |
SEM | Standard error of the mean |
TBS | Tris-buffered saline |
TNFα | Tumor Necrosis Factor-alpha |
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Primary Antibodies | |||||
---|---|---|---|---|---|
Target | Host/Class | Dilution | Source | Cat.# | |
Anti-DPEP1 | Rabbit polyclonal | 1:100 | Martín-Vasallo/Ávila [16] | DPEP1C | |
Anti-IQGAP1 | Rabbit polyclonal | 1:500 | Millipore-Sigma Darmstadt, Germany | ABT186 | |
Anti-IQGAP1 | Mouse monoclonal | 1:100 | Santa Cruz Biotechnology Dallas, TX, USA | sc-376021 | |
Anti-MAP2 | Mouse monoclonal | 1:500 | Merck-Millipore | MAB378 | |
Anti-GFAP | Mouse monoclonal | 1:100 | Santa Cruz Biotechnology Dallas, TX, USA | sc-33673 | |
Anti-CD31 | Mouse monoclonal | 1:150 | Santa Cruz Biotechnology Dallas, TX, USA | sc-376764 | |
Anti-TNFα | Mouse monoclonal | 1:150 | Santa Cruz Biotechnology Dallas, TX, USA | sc-52B83 | |
Anti-IL-6 | Mouse monoclonal | 1:200 | Santa Cruz Biotechnology Dallas, TX, USA | sc-28343 | |
Anti-Laminin | Mouse monoclonal | 1:200 | Santa Cruz Biotechnology Dallas, TX, USA | sc-365962 | |
Anti-α-Actin | Mouse monoclonal | 1:60,000 | Sigma Aldrich/Merck Millipore Saint Louis, MO, USA/Darmstadt, Germany | A5441 | |
Secondary antibodies | |||||
Target | Conjugation | Host/Class | Dilution | Source | Cat.# |
Rabbit IgG | FITC | Goat polyclonal | 1:200 | Sigma-Aldrich Saint Louis, MO, USA | F9887 |
Mouse IgG | DyLight®650 | Goat polyclonal | 1:100 | Abcam Cambridge, UK | ab97018 |
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Martín-Ramírez, R.; González-Nicolás, M.Á.; Álvarez-Tosco, K.; Machín, F.; Ávila, J.; Morales, M.; Lázaro, A.; Martín-Vasallo, P. Cilastatin Modulates DPEP1- and IQGAP1-Associated Neuro-Glio-Vascular Inflammation in Oxaliplatin-Induced Peripheral Neurotoxicity. Cells 2025, 14, 1294. https://doi.org/10.3390/cells14161294
Martín-Ramírez R, González-Nicolás MÁ, Álvarez-Tosco K, Machín F, Ávila J, Morales M, Lázaro A, Martín-Vasallo P. Cilastatin Modulates DPEP1- and IQGAP1-Associated Neuro-Glio-Vascular Inflammation in Oxaliplatin-Induced Peripheral Neurotoxicity. Cells. 2025; 14(16):1294. https://doi.org/10.3390/cells14161294
Chicago/Turabian StyleMartín-Ramírez, Rita, María Ángeles González-Nicolás, Karen Álvarez-Tosco, Félix Machín, Julio Ávila, Manuel Morales, Alberto Lázaro, and Pablo Martín-Vasallo. 2025. "Cilastatin Modulates DPEP1- and IQGAP1-Associated Neuro-Glio-Vascular Inflammation in Oxaliplatin-Induced Peripheral Neurotoxicity" Cells 14, no. 16: 1294. https://doi.org/10.3390/cells14161294
APA StyleMartín-Ramírez, R., González-Nicolás, M. Á., Álvarez-Tosco, K., Machín, F., Ávila, J., Morales, M., Lázaro, A., & Martín-Vasallo, P. (2025). Cilastatin Modulates DPEP1- and IQGAP1-Associated Neuro-Glio-Vascular Inflammation in Oxaliplatin-Induced Peripheral Neurotoxicity. Cells, 14(16), 1294. https://doi.org/10.3390/cells14161294