Ischemic post-conditioning attenuates acute lung injury induced by intestinal ischemia–reperfusion in mice: role of Nrf2

Abstract

Intestinal ischemic post-conditioning (IPo) protects against lung injury induced by intestinal ischemia-reperfusion (IIR) partly through promotion of expression and function of heme oxygenase-1 (HO-1). NF-E2-related factor-2 (Nrf2) is a key transcription factor that interacts with HO-1 and regulates antioxidant defense. However, the role of Nrf2 in IPo protection of IIR-induced pulmonary injury is not completely understood. Here we show that IPo significantly attenuated IIR-induced lung injury and suppressed oxidative stress and systemic inflammatory responses. IPo also increased the expression of both Nrf2 and HO-1. Consistently, the beneficial effects of IPo were abolished by ATRA and Brusatol, potent inhibitors of Nrf2. Moreover, the Nrf2 agonist t-BHQ showed similar activity as IPo. Taken together, our data suggest that Nrf2 activity, along with HO-1, plays an important role in the protective effects of IPo against IIR-induced acute lung injury.

Ischemic Postconditioning Alleviates Intestinal Ischemia-Reperfusion Injury by Enhancing Autophagy and Suppressing Oxidative Stress through the Akt/GSK-3β/Nrf2 Pathway in Mice

“…This endogenous protective-adaptive intervention suppresses spontaneous Ca 2+ oscillations and inhibits mPTP opening [22], contributing to the maintenance of mitochondrial homeostasis, attenuation of oxidative stress, and alleviation of apoptosis [23]. IPO-induced protection against IR injury has been confirmed in multiple organs [11,19,22]. Consistent with these studies, we found that IPO markedly attenuated IIR injury as characterized by reduced histological damage and lower levels of serum biomarkers.…”

“…We previously demonstrated that IPO protects the intestine and remote organs from IIR injury [19,20]. In the present study, we demonstrated that IPO-induced autophagy had a crucial protective role against IIR injury.…”

“…The clip was removed gently 45 min later. IPO was implemented before reperfusion, which was performed by 3 cycles of 10 s reperfusion and ischemia at the initiation of reperfusion [19]. Shamoperated mice underwent the same surgical procedures without SMA occlusion.…”

Nrf2 Activation Induced by Sirt1 Ameliorates Acute Lung Injury After Intestinal Ischemia/Reperfusion Through NOX4-Mediated Gene Regulation

“…Nrf2 is also believed to protect a number of organs against IIR injury [22] including the lungs [23]. Furthermore, in several studies, the upregulation of Sirt1 has been found to activate Nrf2 [16, 17].…”

P-Kumari̇k Asi̇t, Renal İskemi̇ Reperfüzyon Kaynakli Akut Pulmoner Hasari Azaltir

“…2 İskemik akut böbrek hasarı, nadiren izole olarak ortaya çıkar ve çoğu zaman organ yetmezliklerine neden olur. Akciğer infl amasyonu, çoklu iskemi reperfüzyon hasarının neden olduğu en yaygın komplikasyondur [3][4][5] ve pulmoner yetmezlik akut böbrek hasarı ile ilişkili mortalitenin önde gelen nedenlerinden biridir. 6,7 Akut böbrek hasarı, kritik hastalarda sıklıkla akut akciğer hasarına yol açar.…”