Evidence map›Paper›PMID 40862773›Full record

ArticleCells2025

Cilastatin Modulates DPEP1- and IQGAP1-Associated Neuro-Glio-Vascular Inflammation in Oxaliplatin-Induced Peripheral Neurotoxicity.

Rita Martín-Ramírez, María Ángeles González-Nicolás, Karen Álvarez-Tosco, Félix Machín, Julio Ávila, Manuel Morales, Alberto Lázaro, Pablo Martín-Vasallo

Abstract read
In one paragraph

Article in Cells, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Rita Martín-RamírezLaboratorio de Biología del Desarrollo, UD de Bioquímica y Biología Molecular, Universidad de La Laguna, 38206 San Cristóbal de La Laguna, Spain.ORCID 0000-0001-8170-2933
María Ángeles González-NicolásLaboratorio de Fisiopatología Renal, Departamento de Nefrología, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain.ORCID 0000-0002-3514-4616
Karen Álvarez-ToscoLaboratorio de Biología del Desarrollo, UD de Bioquímica y Biología Molecular, Universidad de La Laguna, 38206 San Cristóbal de La Laguna, Spain.ORCID 0000-0003-2504-554X
Félix MachínInstituto de Tecnologías Biomédicas, Universidad de La Laguna, 38071 San Cristóbal de La Laguna, Spain.ORCID 0000-0003-4559-7798
Julio ÁvilaLaboratorio de Biología del Desarrollo, UD de Bioquímica y Biología Molecular, Universidad de La Laguna, 38206 San Cristóbal de La Laguna, Spain.ORCID 0000-0001-5177-1188
Manuel MoralesInstituto de Tecnologías Biomédicas, Universidad de La Laguna, 38071 San Cristóbal de La Laguna, Spain.
Alberto LázaroLaboratorio de Fisiopatología Renal, Departamento de Nefrología, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain.ORCID 0000-0002-1095-679X
Pablo Martín-VasalloLaboratorio de Biología del Desarrollo, UD de Bioquímica y Biología Molecular, Universidad de La Laguna, 38206 San Cristóbal de La Laguna, Spain.ORCID 0000-0002-2220-5774

Funding

Fundación Canaria Instituto de Investigación Sanitaria de Canarias (FUNCANIS) PIFIISC22/34Fundación MAPFRE-Guanarteme OA21/110Gobierno de Canarias (cofounded by FEDER) ProID2020010073Instituto de Salud Carlos III-Fondo de Investigación en Salud ICI21/00111ISCIII-RICORS program to RICORS2040 (Kidney Disease) RD21/0005/0029ISCIII-RICORS program to RICORS2040-Renal RD24/0004/0023NextGenerationUE, Plan de Recuperación, Transformación y Resilencia), Comunidad de Madrid 2022/BMD-7223Spanish Ministry of Economy and Competitiveness PI20/01577Spanish Ministry of Science and Innovation CPP2022-009633Spanish Ministry of Science and Innovation (MCIN/AEI/10.13039/501100011033) PID2021-123716OB-I100
6 · The paper itself

Abstract

Oxaliplatin-induced peripheral neurotoxicity (OIPN) represents a major challenge in cancer therapy, characterized by dorsal root ganglia (DRG) inflammation and disruption of neuro-glio-vascular unit function. In this study, we investigated the involvement of the scaffold protein IQ Motif Containing GTPase Activating Protein 1 (IQGAP1) and dehydropeptidase-1 (DPEP1) in the DRG response to oxaliplatin (OxPt) and the modulatory effect of cilastatin. Behavioral assessment showed a robust nocifensive response to cold stimuli in OxPt-treated rats, attenuated by cilastatin co-treatment. Our confocal study revealed different cellular and subcellular expression patterns of IQGAP1 and DPEP1 in neurons, glia, and endothelial cells, where both signals overlap approximately one-third. OxPt enhanced cytosolic aggregation of IQGAP1 in neurons and upregulation of signal in glia, accompanied by co-expression of TNFα and IL-6, indicating involvement in the inflammatory process. DPEP1 showed altered subcellular distribution in OxPt-treated animals, suggesting a potential role in the inflammatory cascade. Notably, IQGAP1 expression was diminished in endothelial membranes under OxPt, while cilastatin preserved endothelial IQGAP1-CD31 colocalization, suggesting partial restoration of blood-nerve barrier integrity. These findings identify IQGAP1 and DPEP1 as key players in DRG inflammation and position cilastatin as a promising modulator of OIPN through neuro-glio-vascular stabilization.

Indexed as

CilastatinDipeptidasesNeuritisProtease Inhibitorsras GTPase-Activating ProteinsAnimalsAntineoplastic AgentsEndothelial CellsGanglia, SpinalGPI-Linked ProteinsMaleNeurogliaOxaliplatinRatsRats, WistarAntineoplastic AgentsCilastatindipeptidase 1DipeptidasesGPI-Linked ProteinsIQ motif containing GTPase activating protein 1OxaliplatinProtease Inhibitorsras GTPase-Activating Proteinsallodyniacilastatindehydropeptidase-1dorsal root ganglion (DRG)DRG-inflammationIQGAP1neurotoxicityoxaliplatinperipheral neuropathy

Identifiers

PMID40862773
PMCPMC12385093

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.