Abstract
BackgroundActivation 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.MethodsThe 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.ResultsIsoflurane 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.ConclusionsClinic relevant doses of isoflurane attenuate ischemia reperfusion injury in rats by increasing the HO-1 expression and activity.
Highlights
Activation of heme oxygenase-1 (HO-1) has been proved to reduce damages to the liver in ischemia reperfusion injury
We found that increased HO-1 activity and expression by isoflurane was associated with lower levels of aminotransferases and TNFa mRNA, decreased lipid peroxidation and myeloperoxidase activity in the liver
The effects of isoflurane on all measures of liver damage were completely abolished by zinc protoporphyrin (Znpp), which strongly suggested that the protective effects of isoflurane were mediated by an increase in HO-1 activity and expression
Summary
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 ischemiareperfusion injury. The heme oxygenase (HO) has been shown to limit reperfusion injury after experimental systemic and regional hepatic ischemia[1]. Schmidt et al.[11] have confirmed that pretreatment with isoflurane (ISO) induces hepatic HO-1 expression and thereby protects rat lives from IR injury. Whether shorter time intervals or lower concentrations of ISO treatment could be sufficient to activate HO-1 and confer protective effect still needs to be evaluated
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