Lipoxin A4 ameliorates renal ischaemia–reperfusion‐induced acute lung injury in rats

Abstract

Lipoxin A4 (LA4), a bioactive product of arachidonic acid, has been shown to exert strong anti-inflammatory activity. By contrast, the anti-inflammatory action of LA4 in a renal ischaemia-reperfusion (RIR)-mediated acute lung inflammation (ALI) model and the potential pathogenesis of the condition is still unclear. The aim of the current research was to investigate the effect of LA4 on RIR-induced ALI. The rat ALI model was induced by RIR. LA4 was injected via the tail vein immediately after RIR. The results indicate that LA4 markedly inhibits inflammatory cells infiltration, attenuates myeloperoxidase activity, and reduces the concentration of inflammatory mediators and Toll-like receptor 4 (TLR4) in RIR-induced ALI. Furthermore, LA4 suppressed nuclear factor kappa B (NF-κB) p65 and mitogen-activated protein kinase (MAPK) activation. The protective effect of LA4 in RIR-stimulated ALI was reversed by BOC-2 (an antagonist of the LA4 receptor). These results indicate that LA4 exerts powerful anti-inflammatory functions in RIR-induced ALI by attenuating TLR4 expression via MAPK and NF-κB signalling. Accordingly, LA4 might be an underlying treatment drug for RIR-induced ALI.

Lipoxin A4 inhibits UV radiation-induced skin inflammation and oxidative stress in mice

“…IL-10 and TGF-b) [11]. Moreover, the treatment with LXA 4 reduced spinal cord cell apoptosis, and ameliorates ischemia/reperfusion induced spinal cord injury in rabbits through its anti-apoptotic and antioxidant activities [23].…”

“…Pro-resolution-inducing agents can induce remission and restore normal physiological function of the target tissues [18]. LXA 4 limits inflammation and induces resolution in varied models of disease such as inflammatory bowel disease [18], rheumatoid arthritis [19], Alzheimer's disease [20], asthma [21,22], ischemia [13,23] and atherosclerosis [24]. Furthermore, up-regulation of LXA 4 promotes the resolution of phorbol myristate acetate (PMA)induced acute skin inflammation [25].…”

Lipoxin A4 protects primary spinal cord neurons from Erastin‐induced ferroptosis by activating the Akt/Nrf2/HO‐1 signaling pathway

“…For example, LXA4 treatment effectively represses microglial activation and inflammatory response, ultimately attenuating neuropathic pain in mouse and rat models of SCI [ 16 ]. LXA4 ameliorates neurological function and reduces cell apoptosis and oxidative stress in a rabbit model of ischemia–reperfusion‐induced SCI [ 17 ]. LXA4 exerts an anti‐inflammatory function in a rat model of noncompressive disk herniation by suppressing activation of NLRP3 inflammasome via the c‐Jun NH2‐terminal kinase 1/beclin‐1/class III phosphatidylinositol‐3‐kinase signaling pathway [ 18 ].…”

Penehyclidine hydrochloride inhibits renal ischemia/reperfusion-induced acute lung injury by activating the Nrf2 pathway

“…Continuous and unrestrained inflammatory responses are associated with rI/R-induced lung inflammation and oxidative stress [ 29 – 31 , 41 ]. Upon rI/R, increased pro-inflammatory cell infiltration and molecule production elevate ROS generation, thus inducing further inflammatory responses that damage pulmonary structures [ 31 ].…”

“…Renal ischemia/reperfusion (rI/R)-induced lung inflammation, a major disease with limited remedies and high lethality, is strongly dependent on oxidative stress and inflammatory responses [ 28 – 31 ]. We previously explored the detrimental effects of NF-κB, mitogen-activated protein kinase, toll-like receptor 4 and NLRP3 and the protective functions of HO-1 in rI/R-induced lung inflammation [ 29 – 31 ]. Penehyclidine hydrochloride (PHC, Figure 1A ), an intravenous anesthetic with sedative and analgesic properties, is an effective NF-κB inhibitor and Nrf2 activator that can suppress caspase-3 activation and apoptosis [ 32 – 35 ].…”