Losartan attenuates neuroinflammation and neuropathic pain in paclitaxel-induced peripheral neuropathy

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F20%3A00531073" target="_blank" >RIV/67985823:_____/20:00531073 - isvavai.cz</a>

Výsledek na webu

<a href="https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.15427" target="_blank" >https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.15427</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/jcmm.15427" target="_blank" >10.1111/jcmm.15427</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Losartan attenuates neuroinflammation and neuropathic pain in paclitaxel-induced peripheral neuropathy

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Losartan attenuates neuroinflammation and neuropathic pain in paclitaxel-induced peripheral neuropathy

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Cellular and Molecular Medicine

ISSN

1582-1838

e-ISSN

—

Svazek periodika

24

Číslo periodika v rámci svazku

14

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

7949-7958

Kód UT WoS článku

000536971900001

EID výsledku v databázi Scopus

2-s2.0-85085689929