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

Abstract

The nuclear factor (NF)-κB and NOD-like receptor protein 3 (NLRP3) pathways promote inflammatory signaling that injures the kidneys, whereas the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway promotes anti-inflammatory signaling that inhibits oxidative damage. Penehyclidine hydrochloride (PHC) inhibits NF-κB and activates Nrf2 signaling. We investigated whether PHC induces communication between the Nrf2 and NF-κB/NLRP3 pathways, thereby protecting against renal ischemia/reperfusion (rI/R)-induced lung inflammation. Rat alveolar macrophages (NR8383 cells) were stimulated for 24 h with PHC with or without brusatol (a Nrf2 antagonist), after which they were treated for 4 h with tert-butyl hydroperoxide (10 mM). PHC Nrf2-dependently alleviated tert-butyl hydroperoxide-induced reactive oxygen species production in alveolar macrophages. Additionally, wild-type and Nrf2 −/− rats were each divided into four groups: (1) sham, (2) PHC (1 mg/kg), (3) rI/R and (4) rI/R + PHC (1 mg/kg). PHC markedly induced the Nrf2 and adenosine monophosphate-activated protein kinase pathways and suppressed rI/R-induced NF-κB and NLRP3 activation in the lungs. Nrf2 deficiency diminished the ability of PHC to ameliorate rI/R-induced histopathological alterations and reactive oxygen species release in the lungs; however, PHC inhibited NLRP3 signaling Nrf2-dependently, while it inhibited NF-κB signaling Nrf2-independently. Our findings demonstrate the beneficial effects of PHC on rI/R-induced lung inflammation.

Hypoxia-Inducible Factor-1: A Potential Target to Treat Acute Lung Injury

“…PHC can alleviate pulmonary capillary spasm, improve local microcirculation, reduce edema, and inhibit the production of inflammatory mediators [138,139]. Previous studies have found that PHC could reduce renal ischemia/reperfusion-induced ALI, inhibit inflammation through the NF-κB pathway, and improve the leakage of pulmonary blood vessels in lung tissue [140]. In addition, PHC has been suggested to ameliorate severe pancreatitis-related acute lung injury (PALI) by inhibiting the expression of inflammatory factors [141,142].…”

Effect of Adjunctive Acupuncture on Pain Relief Among Emergency Department Patients With Acute Renal Colic Due to Urolithiasis

“…Racanisodamine has been chosen as active control in several trials, and a response rate between 75.5% and 81.4% was found. 22,23 No additional intravenous fluid was administered in the first 60 minutes after acupuncture treatment.…”

Propofol ameliorates renal ischemia/reperfusion injury by enhancing macrophage M2 polarization through PPARγ/STAT3 signaling

“…Whereas perioperative interventions, such as ischemic preconditioning, fluid management, and intermittent hemodialysis may reduce rI/R injury and AKI development in selected surgical patients, pharmacological approaches have so far yielded disappointing or mixed results [7,8]. Therefore, numerous preclinical studies, including our own, continue to explore both the specific contribution of innate immunity and potential approaches to restrict the inflammatory response, attenuate oxidative damage, modulate autophagy, and stimulate angiogenesis in the setting of rI/R injury [9][10][11][12][13].…”