Protective effect of CDDO-imidazolide against intestinal ischemia/reperfusion injury in mice

Abstract

Intestinal ischemia/reperfusion (I/R) is life-threatening and challenging in clinical practice. CDDO-imidazolide (CDDO-Im) is therapeutic in alleviating I/R injury. Nevertheless, there is a lack of investigation on the effects of CDDO-Im on intestinal I/R. Mice were randomly divided into four groups: (a) the sham group, (b) the CDDO-Im group, (c) the I/R group, and (d) the I/R + CDDO-Im group. Intestinal I/R was performed by clamping arteria mesenteric anterior for 45 min, followed by 24 h reperfusion. In addition, Kaplan–Meier method and the log-rank test were used to compare the survival rates among groups by observing for 24 h. Intestinal I/R in model group demonstrated severe injury of the intestinal mucosa, lung, kidney, and liver. The intestinal mucosal damage and intestinal barrier dysfunction were obviously attenuated in CDDO-Im-treated group compared with the model group. Also, preconditioning with CDDO-Im reduced pulmonary, hepatic and renal damage, and decreased oxidative stress (malondialdehyde (MDA), superoxide dismutase (SOD), and NO) and pro-inflammatory responses (tumor necrosis factor (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6)) following I/R injury. Furthermore, we also observed that these protective properties of CDDO-Im were accomplished by the activation of nuclear factor E2-related factor 2 (Nrf2) signaling pathway and upregulation of its downstream antioxidant genes, including heme oxygenase (HO-1), NQO-1, and glutamate–cysteine ligase regulatory subunit (GCLM). Our data suggest that CDDO-Im exerts a beneficial effect on intestinal I/R-associated mucosal barrier dysfunction and distant organ injuries.