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Losartan attenuates neuroinflammation and neuropathic pain in paclitaxel-induced peripheral neuropathy
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SYSNO ASEP 0531073 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Losartan attenuates neuroinflammation and neuropathic pain in paclitaxel-induced peripheral neuropathy Tvůrce(i) 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, ORCIDZdroj.dok. Journal of Cellular and Molecular Medicine. - : Wiley - ISSN 1582-1838
Roč. 24, č. 14 (2020), s. 7949-7958Poč.str. 10 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova losartan ; macrophage ; neuroinflammation ; neuropathic pain ; paclitaxel Vědní obor RIV FH - Neurologie, neurochirurgie, neurovědy Obor OECD Neurosciences (including psychophysiology CEP GA18-09853S GA ČR - Grantová agentura ČR ED1.1.00/02.0109 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora FGU-C - RVO:67985823 UT WOS 000536971900001 EID SCOPUS 85085689929 DOI 10.1111/jcmm.15427 Anotace 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. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2021 Elektronická adresa https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.15427
Počet záznamů: 1