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2022-11-11

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cc-by-nc-nd (c) Aina Calls et al., 2022
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/222872

A transient inflammatory response contributes to oxaliplatin neurotoxicity in mice

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Objectives Peripheral neuropathy is a relevant dose-limiting adverse event that can affect up to 90% of oncologic patients with colorectal cancer receiving oxaliplatin treatment. The severity of neurotoxicity often leads to dose reduction or even premature cessation of chemotherapy. Unfortunately, the limited knowledge about the molecular mechanisms related to oxaliplatin neurotoxicity leads to a lack of effective treatments to prevent the development of this clinical condition. In this context, the present work aimed to determine the exact molecular mechanisms involved in the development of oxaliplatin neurotoxicity in a murine model to try to find new therapeutical targets. Methods By single-cell RNA sequencing (scRNA-seq), we studied the transcriptomic profile of sensory neurons and satellite glial cells (SGC) of the Dorsal Root Ganglia (DRG) from a well-characterized mouse model of oxaliplatin neurotoxicity. Results Analysis of scRNA-seq data pointed to modulation of inflammatory processes in response to oxaliplatin treatment. In this line, we observed increased levels of NF-kB p65 protein, pro-inflammatory cytokines, and immune cell infiltration in DRGs and peripheral nerves of oxaliplatin-treated mice, which was accompanied by mechanical allodynia and decrease in sensory nerve amplitudes. Interpretation Our data show that, in addition to the well-described DNA damage, oxaliplatin neurotoxicity is related to an exacerbated pro-inflammatory response in DRG and peripheral nerves, and open new insights in the development of anti-inflammatory strategies as a treatment for preventing peripheral neuropathy induced by oxaliplatin.

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Matèries

Neurotoxicologia, Càncer colorectal, Neuropaties perifèriques

Matèries (anglès)

Neurotoxicology, Colorectal cancer, Peripheral neuropathies

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Articles publicats en revistes (Genètica, Microbiologia i Estadística)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

CALLS, Aina, TORRES-ESPIN, Abel, TORMO, Marc, MARTÍNEZ-ESCARDÓ, Laura, BONET, Núria, CASALS LÓPEZ, Ferran, NAVARRO, Xavier, YUSTE, Victor j., UDINA, Esther, BRUNA, Jordi. A transient inflammatory response contributes to oxaliplatin neurotoxicity in mice. _Annals of Clinical and Translational Neurology_. 2022. Vol. 9, núm. 12, pàgs. 1985-1998. [consulta: 24 de novembre de 2025]. ISSN: 2328-9503. [Disponible a: https://hdl.handle.net/2445/222872]

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