The protective role of IL-1Ra on intestinal ischemia reperfusion injury by anti-oxidative stress via Nrf2/HO-1 pathway in rat

Abstract

Background Intestinal ischemia reperfusion injury is a frequent clinical damage, in which the oxidative stress and inflammation play an important role. Interleukin-1 receptor antagonist (IL-1Ra) is a natural anti-inflammatory factor, however, its effect on intestinal ischemia reperfusion injury remains unclear. Methods The rat model of intestinal I/R was induced by occlusion (for 60 min) and reopening (for 60 min) of superior mesenteric artery. The rats were randomly divided into the following 5 groups: sham-operation(S), model (I/R),10 mg/kgIL-1Ra + I/R (C1),20 mg/kgIL-1Ra + I/R (C2), and30 mg/kgIL-1Ra + I/R (C3). Results In this study it was the first time to confirm that IL-1Ra had a significant protection against the intestinal ischemia reperfusion injury. IL-1Ra not only effectively inhibited the expression of inflammatory factors (such as IL-1β, IL-6 and TNF-α) and the activation of neutrophil in intestinal tissues, but also decreased the death of intestinal cells and the damages of intestinal tissues. Interestingly, besides anti-inflammation effect, it was also found that IL-1Ra possessed a significant inhibitory effect on the oxidative stress caused by ischemia/reperfusion injury. Furthermore, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1), and the phosphorylation level of Nrf2 were greatly promoted by IL-1Ra. At the same time, IL-1Ra inhibited the mitogen-activated protein kinase (MAPKs) pathway. Conclusion IL-1Ra had the protective effect against intestinal ischemia reperfusion injury, its mechanism included anti-inflammation and anti-oxidative stress in which the Nrf2/HO-1 pathway played an important role. The above-mentioned results may extend the clinical application of IL-1Ra in the treatment of intestinal ischemia reperfusion injury.

<p>Protective Effects of Chlorogenic Acid on Cerebral Ischemia/Reperfusion Injury Rats by Regulating Oxidative Stress-Related Nrf2 Pathway</p>

“…41 Previous studies have shown that IL-1Ra significantly inhibits CI/ R-induced oxidative stress by promoting the expression of Nrf2 and HO-1. 42 Similarly, this study found that Nrf2 pathway was inactivated in CI/R rats. Interestingly, CGA reactivated Nrf2 pathway and promoted Nrf2, HO-1 and NQO-1 expression, which further increased SOD activity and reduced MDA level.…”

Conditioned Medium from Human Amnion-Derived Mesenchymal Stromal/Stem Cells Attenuating the Effects of Cold Ischemia-Reperfusion Injury in an In Vitro Model Using Human Alveolar Epithelial Cells

“…Instead, encapsulated-hAMSCs only overproduced PIGF-1 significantly, while the expression of the other factors was comparable to that of 2D cultures. IL-1RA was shown to have protective effects through its anti-inflammatory and antioxidative mechanisms in an in vivo rat model of IRI [ 63 ], where IL-1RA not only effectively inhibited the expression of inflammatory factors, such as IL-1β, IL-6, and TNF-α, but it also decreased the death of damaged cells in intestinal tissues. It has been shown that both human and mouse pluripotent stem cells attenuate the apoptosis/necrosis and potentiate cell proliferation through different anti-inflammatory and growth factors, such as IL-10, FGF, EGF, and HGF [ 64 , 65 ].…”

<p>Rutaecarpine may improve neuronal injury, inhibits apoptosis, inflammation and oxidative stress by regulating the expression of ERK1/2 and Nrf2/HO-1 pathway in rats with cerebral ischemia-reperfusion injury</p>

“…Collectively, the repair effect of Rut on CI/R injury may be achieved by promoting the expression of CGRP and activation of Nrf2 pathway, and inhibiting the activation of ERK1/2 pathway.It has been reported that the Nrf2/HO-1 pathway has a significant protective effect on I/R injury 18. Jin et al found that IL-1ra inhibits oxidative stress and inflammation caused by I/R injury by promoting the expression of Nrf2 and HO-1 and the phosphorylation level of Nrf2 15. Similarly, Li et al found that icariside II can improve oxidative stress in brain tissue of rats with CIR injury by activating Nrf2/HO-1 pathway 16.…”

“…Nrf2/HO-1 is an important antioxidant system. The Nrf2/HO-1 pathway has been reported to play an important role in I/R injury 15. Activation of the Nrf2/HO-1 pathway attenuates oxidative stress and inflammation caused by I/R injury, restores neurological deficits and reduces cerebral infarction volume 16.…”