Irisin Contributes to the Hepatoprotection of Dexmedetomidine during Intestinal Ischemia/Reperfusion

Abstract

Intestinal ischemia/reperfusion (I/R), which is associated with high morbidity and mortality, is also accompanied with abnormal energy metabolism and liver injury. Irisin, a novel exercise-induced hormone, can regulate adipose browning and thermogenesis. The following study investigated the potential role of dexmedetomidine in liver injury during intestinal I/R in rats. Adult male Sprague–Dawley rats underwent occlusion of the superior mesenteric artery for 90 min followed by 2 h of reperfusion. Dexmedetomidine or irisin-neutralizing antibody was intravenously administered for 1 h before surgery. The results demonstrated that severe intestine and liver injuries occurred during intestinal I/R as evidenced by pathological scores and an apparent increase in serum diamine oxidase (DAO), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels. In addition, the hepatic irisin, cleaved caspase-3, Bax, and NLRP3 inflammasome components (including NLRP3, ASC, and caspase-1), protein expressions, apoptotic index, reactive oxygen species (ROS), malondialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor- (TNF-) α, and interleukin- (IL-) 6 levels increased; however, the serum irisin level and hepatic Bcl-2 protein expression and superoxide dismutase (SOD) activity decreased after intestinal I/R. Interestingly, dexmedetomidine could reduce the above listed changes and increase the irisin levels in plasma and the liver in I/R rats. Dexmedetomidine-mediated protective effects on liver injury and NLRP3 inflammasome activation during intestinal I/R were partially abrogated via irisin-neutralizing antibody treatment. The results suggest that irisin might contribute to the hepatoprotection of dexmedetomidine during intestinal ischemia/reperfusion.

Amelioration of Coagulation Disorders and Inflammation by Hydrogen-Rich Solution Reduces Intestinal Ischemia/Reperfusion Injury in Rats through NF-κB/NLRP3 Pathway

“…Intestinal I/R injury is associated with increases in luminal epithelial permeability and ingress of bacterial molecules (e.g., enterotoxin) or bacteria themselves which can result in systemic inflammatory responses, multiple organ failure, and even leading to death [1][2][3]. In the present study, Chiu's score, the W/D ratio of intestine, and serum DAO activities increased, indicating that intestinal I/R injury caused a great damage to the intestine, and the model was successfully established [4,6,22]. The present results also demonstrated that HRS could attenuate intestinal injury, as evidenced by Mediators of Inflammation the improved morphological changes and survival rate.…”

“…Intestinal I/R injury model was established as described previously [4,6]. Briefly, the rats were fasted for 12 h, with free access to drinking water before surgery.…”

“…It is hinted that NF-κB/NLRP3 pathway might be involved in intestinal I/R injury. The NLRP3 inflammasome was also shown to mediate hepatic injury induced by intestinal I/R [4]. Therefore, it can be concluded…”

“…Intestinal I/R injury potentially leads to a compromised mucosal barrier and increases intestinal permeability and translocation of intestinal bacteria. It also can release a great number of inflamma-tory mediators and cytokines into the blood, causing multiple organ failure [3][4][5][6][7].…”

Involvement of GPX4 in irisin's protection against ischemia reperfusion‐induced acute kidney injury

“…Recent studies have revealed that irisin improves mitochondrial function, reduces ROS production and provides organ protection in various diseases, including Alzheimer's disease, pancreatitis and I/R‐induced intestine, lungs, brain, heart, liver injury (Bi et al, 2020; Bi, Zhang, Ren, Du, Li, Wang, Wei, et al, 2019; Chen et al, 2017; Du et al, 2019; X. Fan, Du, et al, 2019; Lourenco et al, 2019; Ren et al, 2019, 2020; H. Wang et al, 2017).…”