title: Propofol attenuated acute kidney injury after orthotopic liver transplantation via inhibiting gap junction composed of connexin 32.
abstract: BACKGROUND
  Postliver transplantation acute kidney injury (AKI) severely affects patient survival, whereas the mechanism is unclear and effective therapy is lacking. The authors postulated that reperfusion induced enhancement of connexin32 (Cx32) gap junction plays a critical role in mediating postliver transplantation AKI and that pretreatment/precondition with the anesthetic propofol, known to inhibit gap junction, can confer effective protection.
  
  
  METHODS
  Male Sprague-Dawley rats underwent autologous orthotopic liver transplantation (AOLT) in the absence or presence of treatments with the selective Cx32 inhibitor, 2-aminoethoxydiphenyl borate or propofol (50 mg/kg) (n = 8 per group). Also, kidney tubular epithelial (NRK-52E) cells were subjected to hypoxia-reoxygenation and the function of Cx32 was manipulated by three distinct mechanisms: cell culture in different density; pretreatment with Cx32 inhibitors or enhancer; Cx32 gene knock-down (n = 4 to 5).
  
  
  RESULTS
  AOLT resulted in significant increases of renal Cx32 protein expression and gap junction, which were coincident with increases in oxidative stress and impairment in renal function and tissue injury as compared to sham group. Similarly, hypoxia-reoxygenation resulted in significant cellular injury manifested as reduced cell growth and increased lactate dehydrogenase release, which was significantly attenuated by Cx32 gene knock-down but exacerbated by Cx32 enhancement. Propofol inhibited Cx32 function and attenuated post-AOLT AKI. In NRK-52E cells, propofol reduced posthypoxic reactive oxygen species production and attenuated cellular injury, and the cellular protective effects of propofol were reinforced by Cx32 inhibition but cancelled by Cx32 enhancement.
  
  
  CONCLUSIONS
  Cx32 plays a critical role in AOLT-induced AKI and that inhibition of Cx32 function may represent a new and major mechanism whereby propofol reduces oxidative stress and subsequently attenuates post-AOLT AKI.
authors.affiliation: From the Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China (C.L., D.Y., X.L., W.Y., G.L., X.C., Z.H.); and Department of Anesthesiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China (H.L., M.G.I., Z.X.).
authors.forename: Chenfang
authors.initials: C
authors.lastname: Luo
authors.forename: Dongdong
authors.initials: D
authors.lastname: Yuan
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Li
authors.forename: Weifeng
authors.initials: W
authors.lastname: Yao
authors.forename: Gangjian
authors.initials: G
authors.lastname: Luo
authors.forename: Xinjin
authors.initials: X
authors.lastname: Chi
authors.forename: Haobo
authors.initials: H
authors.lastname: Li
authors.forename: Michael G
authors.initials: MG
authors.lastname: Irwin
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Xia
authors.forename: Ziqing
authors.initials: Z
authors.lastname: Hei
mesh_terms: D058186:Acute Kidney Injury / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D018686:Anesthetics, Intravenous / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D017630:Connexins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D017629:Gap Junctions / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D016031:Liver Transplantation / Q000009:adverse effects* / Q000379:methods; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011183:Postoperative Complications / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D015742:Propofol / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097002:Gap Junction beta-1 Protein
chemical_list: D018686:Anesthetics, Intravenous; D017630:Connexins; D015742:Propofol; D000097002:Gap Junction beta-1 Protein