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

0531073 - FGÚ 2021 RIV US eng J - Journal Article
Kalynovska, Nataliia - Diallo, Mickael - Sotáková-Kašparová, Dita - Paleček, Jiří
Losartan attenuates neuroinflammation and neuropathic pain in paclitaxel-induced peripheral neuropathy.
Journal of Cellular and Molecular Medicine. Roč. 24, č. 14 (2020), s. 7949-7958. ISSN 1582-1838. E-ISSN 1582-4934
R&D Projects: GA ČR GA18-09853S; GA MŠMT(CZ) ED1.1.00/02.0109
Institutional support: RVO:67985823
Keywords : losartan * macrophage * neuroinflammation * neuropathic pain * paclitaxel
OECD category: Neurosciences (including psychophysiology
Impact factor: 5.310, year: 2020
Method of publishing: Open access
https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.15427

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.
Permanent Link: http://hdl.handle.net/11104/0309824