Number of the records: 1
Losartan attenuates neuroinflammation and neuropathic pain in paclitaxel-induced peripheral neuropathy
- 1.
SYSNO ASEP 0531073 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Losartan attenuates neuroinflammation and neuropathic pain in paclitaxel-induced peripheral neuropathy Author(s) Kalynovska, Nataliia (FGU-C) ORCID, RID
Diallo, Mickael (FGU-C) ORCID, RID
Sotáková-Kašparová, Dita (FGU-C) RID, ORCID, SAI
Paleček, Jiří (FGU-C) RID, ORCIDSource Title Journal of Cellular and Molecular Medicine. - : Wiley - ISSN 1582-1838
Roč. 24, č. 14 (2020), s. 7949-7958Number of pages 10 s. Language eng - English Country US - United States Keywords losartan ; macrophage ; neuroinflammation ; neuropathic pain ; paclitaxel Subject RIV FH - Neurology OECD category Neurosciences (including psychophysiology R&D Projects GA18-09853S GA ČR - Czech Science Foundation (CSF) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support FGU-C - RVO:67985823 UT WOS 000536971900001 EID SCOPUS 85085689929 DOI 10.1111/jcmm.15427 Annotation Paclitaxel-induced peripheral neuropathy (PIPN) is often associated with neuropathic pain and neuroinflammation in the central and peripheral nervous system. Antihypertensive drug losartan, an angiotensin II receptor type 1 (AT1R) blocker, was shown to have anti-inflammatory and neuroprotective effects in disease models, predominantly via activation of peroxisome proliferator-activated receptor gamma (PPAR gamma). Here, the effect of systemic losartan treatment (100 mg/kg/d) on mechanical allodynia and neuroinflammation was evaluated in rat PIPN model. The expression of pro-inflammatory markers protein and mRNA levels in dorsal root ganglia (DRGs) and spinal cord dorsal horn (SCDH) were measured with Western blot, ELISA and qPCR 10 and 21 days after PIPN induction. Losartan treatment attenuated mechanical allodynia significantly. Paclitaxel induced overexpression of C-C motif chemokine ligand 2 (CCL2), tumour necrosis alpha (TNF alpha) and interleukin-6 (IL-6) in DRGs, where the presence of macrophages was demonstrated. Neuroinflammatory changes in DRGs were accompanied with glial activation and pro-nociceptive modulators production in SCDH. Losartan significantly attenuated paclitaxel-induced neuroinflammatory changes and induced expression of pro-resolving markers (Arginase 1 and IL-10) indicating a possible shift in macrophage polarization. Considering the safety profile of losartan, acting also as partial PPAR gamma agonist, it may be considered as a novel treatment strategy for PIPN patients. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2021 Electronic address https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.15427
Number of the records: 1