Paclitaxel-induced peripheral neuropathy (PIPN) and neuropathic pain are dose-limiting side effects of anticancer treatment, which are poorly managed by existing treatments and usually result in premature cessation of chemotherapy treatment. Considering the safety profile of losartan, acting also as partial PPARОі agonist, it may be considered as a novel treatment strategy for PIPN patients. 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. Neuroinflammatory changes in DRGs were accompanied with glial activation and pro-nociceptive modulators production in SCDH. Paclitaxel induced overexpression of C-C motif chemokine ligand 2 (CCL2), tumour necrosis alpha (TNFО±) and interleukin-6 (IL-6) in DRGs, where the presence of macrophages was demonstrated. Losartan treatment attenuated mechanical allodynia significantly.

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 21В days after PIPN induction. Here, the effect of systemic losartan treatment (100В mg/kg/d) on mechanical allodynia and neuroinflammation was evaluated in rat PIPN model. 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 (PPARОі). Paclitaxel-induced peripheral neuropathy (PIPN) is often associated with neuropathic pain and neuroinflammation in the central and peripheral nervous system.

Aida kasparova