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.
Highlights
Intestinal ischemia–reperfusion (I/R) is a common pathophysiological phenomenon commonly present in various kinds of life-threatening conditions, such as cardiopulmonary bypass, vascular embolism, and small bowel transplantation [1,2,3,4,5]
Dexmedetomidine Improved the Intestinal and Hepatic Pathological Injury. These findings suggested that dexmedetomidine could significantly protect rats against intestinal I/R
The results of correlation analyses demonstrated that lower plasma irisin levels were associated with more serious liver damage and higher levels of hepatic proinflammatory cytokines in rats with intestinal I/R
Summary
Intestinal ischemia–reperfusion (I/R) is a common pathophysiological phenomenon commonly present in various kinds of life-threatening conditions, such as cardiopulmonary bypass, vascular embolism, and small bowel transplantation [1,2,3,4,5]. The excessive generation of reactive oxygen species (ROS), cytokine/chemokine generation, activated complement, and neutrophil activation is all involved in injury to remote organs following intestinal I/R [1, 6]. Those cause liver cell edema, bacterial and Oxidative Medicine and Cellular Longevity inflammatory cell infiltration, and significant increases in the levels of oxygen-free radicals and lipid peroxidation products in the liver tissue [9, 11]. The mechanism of intestinal I/R-induced liver injury has not yet been fully elucidated
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