title: Isoflurane preconditioning at clinically relevant doses induce protective effects of heme oxygenase-1 on hepatic ischemia reperfusion in rats.
abstract: BACKGROUND
  Activation of heme oxygenase-1 (HO-1) has been proved to reduce damages to the liver in ischemia reperfusion injury. The objective of present study was to determine whether clinic relevant doses of isoflurane treatment could be sufficient to activate HO-1 inducing, which confers protective effect against hepatic ischemia-reperfusion injury.
  
  
  METHODS
  The hepatic artery and portal vein to the left and the median liver lobes of forty male Sprague-Dawley rats were occluded for 60 minutes. Reperfusion was allowed for 4 hours before the animal subjects were sacrificed. Six groups (n = 12) were included in the study. A negative control group received sham operation and positive control group a standard ischemia-reperfusion regimen. The third group was pretreated with isoflurane prior to the ischemia-reperfusion. The fourth group received an HO-1 inhibitor zinc protoporphyrin (Znpp) prior to the isoflurane pretreatment and the ischemia-reperfusion. The fifth group received Znpp alone before ischemia-reperfusion procedure, and the sixth group was administrated with a HO-1 inducer hemin prior to IR. HO-1 in the liver was measured using an enzymatic activity assay, a Western blot analysis, as well as immunohistochemical method. Extent of liver damage was estimated by determination of the serum transaminases, liver lipid peroxidation and hepatic histology. Infiltration of the liver by neutrophils was measured using a myeloperoxidase activity assay. TNFα mRNA in the liver was measured using RT-PCR.
  
  
  RESULTS
  Isoflurane pretreatment significantly attenuated the hepatic injuries and inflammatory responses caused by the ischemia reperfusion. Selectively inhibiting HO-1 with ZnPP completed blocked the protective effects of isoflurane. Inducing HO-1 with hemin alone produced protective effects similar in magnitude to that of isoflurane.
  
  
  CONCLUSIONS
  Clinic relevant doses of isoflurane attenuate ischemia reperfusion injury in rats by increasing the HO-1 expression and activity.
authors: Department of Anesthesia and Intensive Care, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai 200438, PR China.
authors: Xin
authors: X
authors: Lv
authors: Liqun
authors: L
authors: Yang
authors: Kunming
authors: K
authors: Tao
authors: Yantao
authors: Y
authors: Liu
authors: Tian
authors: T
authors: Yang
authors: Guozhong
authors: G
authors: Chen
authors: Weifeng
authors: W
authors: Yu
authors: Hao
authors: H
authors: Lv
authors: Feixiang
authors: F
authors: Wu
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology; D019194:Ischemic Preconditioning / Q000379:methods*; D007530:Isoflurane / Q000008:administration & dosage*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D000637:Transaminases / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D011524:Protoporphyrins; D014409:Tumor Necrosis Factor-alpha; C017803:zinc protoporphyrin; D006427:Hemin; D007530:Isoflurane; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D000637:Transaminases