Mg132 Alleviates Liver Injury Induced By Intestinal Ischemia/reperfusion In Rats: Involvement Of The AhR And NfκB Pathways

Background: MG132 is a potent antioxidant and has been reported to play a protective role in ischemia/reperfusion (I/R) of many organs. Recent studies have shown that the Aryl hydrocarbon receptor (AhR) may play a beneficial role in I/R of many organs and an AhR agonist has been implicated in an anti-inflammatory role. MG132 might be function as an AhR agonist through proteasome inhibition, possibly through the inhibition of NFκB. Herein, we hypothesized that MG132 may play a protective role in liver injury induced by intestinal I/R and we analyzed the expression behavior of AhR and NFκB to determine whether the two factors play a role in intestinal I/R.Objective: To explore the role of AhR pathway in intestinal ischemia/reperfus- ion of rats. To determine the effects of MG132 on expression of AhR, cyp1a2, NFκB and ICAM-1 etc.Methods: Thirty-two Sprague-Dawley rats were divided into four groups: control, I/R, control+MG132, MG132 Pretreatment. The IR and MG132 Pretreatment groups were subjected to mesenteric arterial ischemia for 1 hour and reperfusion for 3 hours. The control and control+MG132 groups underwent surgical preparation including isolation of the superior mesenteric artery (SMA) without occlusion. The control+MG132 and MG132 Pretreatment groups were subjected to intraperitoneal administration of 0.5 mg/kg MG132 30 min before surgery. We collected serum specimens to measure TNF-α, IL-6, liver tissue levels of malondialdehyde (MDA), AhR and cyp1a2; NFκB, IκBαand ICAM-1 were also tested. Histological changes of liver and intestine were subsequently evaluated.Results: Compared to the control group, significant increases in MDA, NFκB and ICAM-1 levels were accompanied by decreases in AhR, cyp1a2 and IκBαexpression in the liver in the IR group, which is consistent with liver and intestinal tissue injury. MG132 blocked the alterations of the indicators above. There were no changes in the control+MG132 group compared to the control group in the indicators above.Conclusions: This study demonstrated that MG132 has a significant effect on protection against liver injury induced by intestinal I/R, which may be due to modulation of the AhR and NFκB pathways.