title: Diazoxide attenuates ischemia/reperfusion injury via upregulation of heme oxygenase-1 after liver transplantation in rats.
abstract: OBJECTIVE
  To evaluate the effects of diazoxide on ischemia/reperfusion (I/R)-injured hepatocytes and further elucidate its underlying mechanisms.
  
  
  METHODS
  Male Sprague-Dawley rats were randomized (8 for donor and recipient per group) into five groups: I/R group (4 h of liver cold ischemia followed by 6 h of reperfusion); heme oxygenase-1 (HO-1) small interfering RNA (siRNA) group (injection of siRNA via donor portal vein 48 h prior to harvest); diazoxide (DZ) group (injection of DZ via donor portal vein 10 min prior to harvest); HO-1 siRNA + DZ group; and siRNA control group. Blood and liver samples were collected at 6 h after reperfusion. The mRNA expressions and protein levels of HO-1 were determined by reverse transcription polymerase chain reaction and Western blotting, and tissue morphology was examined by light and transmission electron microscopy. Serum transaminases level and cytokines concentration were also measured.
  
  
  RESULTS
  We observed that a significant reduction of HO-1 mRNA and protein levels in HO-1 siRNA and HO-1 siRNA + DZ group when compared with I/R group, while the increases were prominent in the DZ group. Light and transmission electron microscopy indicated severe disruption of tissue with lobular distortion and mitochondrial cristae damage in the HO-1 siRNA and HO-1 siRNA + DZ groups compared with DZ group. Serum alanine aminotransferase, aspartate transaminase, tumor necrosis factor-α and interleukin-6 levels increased in the HO-1 siRNA and HO-1 siRNA + DZ groups, and decreased in the DZ group.
  
  
  CONCLUSIONS
  The protective effect of DZ may be induced by upregulation of HO-1. By inhibiting expression of HO-1, this protection pretreated with DZ was abolished.
authors.affiliation: Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical College, Kunming 650032, Yunnan Province, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zeng
authors.forename: Han-Fei
authors.initials: HF
authors.lastname: Huang
authors.forename: Fei
authors.initials: F
authors.lastname: He
authors.forename: Lin-Xi
authors.initials: LX
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Chen
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D016207:Cytokines / Q000097:blood; D003981:Diazoxide / Q000494:pharmacology* / Q000627:therapeutic use; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000098:blood supply* / Q000473:pathology / Q000648:ultrastructure; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D046529:Microscopy, Electron, Transmission; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003981:Diazoxide