New Treatment for the Cognitive and Emotional Deficits Linked with Paclitaxel-Induced Peripheral Neuropathy in Mice
Martínez-Martel, Ignacio (Universitat Autònoma de Barcelona. Institut de Neurociències)
Bai, Xue (Universitat Autònoma de Barcelona. Institut de Neurociències)
Batallé Melgarejo, Gerard (Universitat Autònoma de Barcelona. Institut de Neurociències)
Pol, Olga (Universitat Autònoma de Barcelona. Institut de Neurociències)

Data:	2022
Resum:	Chemotherapy-provoked peripheral neuropathy and its linked comorbidities severely reduce the quality of a patient's life. Its therapy is not completely resolved and has become an important clinical challenge. The protective actions of molecular hydrogen (H) in many neurological disorders have been described, but its effects on memory and the emotional deficits accompanying neuropathic pain induced by chemotherapy remain unknown. In this study, using male mice injected with paclitaxel (PTX), we examined the effects of systemic treatment with hydrogen-rich water (HRW) in: (i) the mechanical and thermal allodynia provoked by PTX and the pathways involved; (ii) the memory deficits, anxiety- and depressive-like behaviors associated with PTX-induced peripheral neuropathy (PIPN); and (iii) the plasticity (p-extracellular signal-regulated protein kinase; p-ERK ½), nociceptive (p-protein kinase B, p-Akt), inflammatory (p-nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha; p-IKBα), and oxidative (4-hydroxynonenal: 4-HNE) alterations provoked by PIPN in the prefrontal cortex (PFC). The results revealed: (1) the antiallodynic actions of HRW administered at one or two times per day during 7 and 3 consecutive days; (2) the participation of Kv7 potassium channels and the Nrf2-heme oxygenase 1-NAD(P)H: quinone oxidoreductase 1 pathway in the painkiller effects of HRW; (3) the inhibition of memory deficits and the anxiodepressive-like behaviors related with PIPN induced by HRW; and (4) the normalization of p-ERK ½, p-Akt and 4-HNE up-regulation and the activation of antioxidant enzymes produced by this treatment in PFC. This study proposes HRW as a possible effective and safe therapy for PIPN and its associated cognitive and emotional deficits.
Ajuts:	Instituto de Salud Carlos III PI18/00645 Instituto de Salud Carlos III PI21/00592
Nota:	This work was supported by Ministerio de Ciencia, Innovación y Universidades, Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea [Grants: PI18/00645 and PI21/00592] and CERCA Programme/Generalitat de Catalunya.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Antioxidants, Vol. 11 Núm. 12 (december 2022) , p. 2387, ISSN 2076-3921

DOI: 10.3390/antiox11122387
PMID: 36552595

17 p, 13.9 MB

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