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.

• Authors: Xin Fan, Juan Du, Mao-Hua Wang, Jia-Man Li, Bo Yang, Ye Chen, Jun-Chao Dai, Chunxiang Zhang, Jun Zhou
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2019 Pg. 7857082 ( 2019) ISSN: 1942-0994 [Electronic] United States
• PMID: 31191804 (Publication Type: Journal Article)

Chemical References

• Antibodies, Neutralizing
• FNDC5 protein, rat
• Fibronectins
• Proto-Oncogene Proteins c-bcl-2
• Tumor Necrosis Factor-alpha
• Malondialdehyde
• Dexmedetomidine
• Aspartate Aminotransferases
• Alanine Transaminase

Topics

• Alanine Transaminase (metabolism)
• Animals
• Antibodies, Neutralizing (therapeutic use)
• Aspartate Aminotransferases (metabolism)
• Dexmedetomidine (therapeutic use)
• Fibronectins (antagonists & inhibitors, blood, metabolism)
• Intestines (drug effects, pathology)
• Ischemia (blood, drug therapy)
• Liver (drug effects, metabolism)
• Male
• Malondialdehyde (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (blood, drug therapy)
• Tumor Necrosis Factor-alpha (metabolism)