The Effects of Two Anesthetics, Propofol and Sevoflurane, on Liver Ischemia/Reperfusion Injury.
BACKGROUND
Propofol and sevoflurane are widely used in clinical anesthesia, and both have been reported to exert a protective effect in organ ischemia/reperfusion (IR). This study aims to investigate and compare the effects of propofol and sevoflurane on liver ischemia/reperfusion and the precise molecular mechanism.


METHODS
Rats were randomized into four groups: the sham group, I/R group, propofol treatment group (infused with 1% propofol at 500 μg· kg-1· min-1), and sevoflurane treatment group (infused with 3% (2 L/min) sevoflurane). The liver ischemia/reperfusion model was used to evaluate the hepatoprotective effect on ischemic injury. Liver enzyme leakage, liver cytokines and histopathological examination were used to evaluate the extent of hepatic ischemia/reperfusion injury. Oxidative stress was investigated by evaluating the levels of Malondialdehyde(MDA), Superoxide Dismutase(SOD) and NO. The terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling (TUNEL) assay and western blot were applied to detect apoptosis in the ischemic liver tissue and its mechanism.


RESULTS
Both propofol and sevoflurane attenuated the extent of hepatic ischemia/reperfusion injury which is evident from the hisopathological studies and alterations in liver enzymes such as AST and LDH by inhibiting Nuclear factor kappa B (NFx03BA;B) activation and subsequent alterations in inflammatory cytokines interleukin-1(IL-1), interleukin-6(IL-6), tumor necrosis factor-alpha (TNF-α) and increased IL10 release. Propofol exhibited a similar protective effect and a lower IL-1 release, while sevoflurane decreased TNF-α leakage more significantly. Meanwhile, oxidative stress was attenuated by reduced MDA and NO and elevated SOD release. The expression of antiapoptotic protein Bcl-2 and Bcl-xl were enhanced while that of apoptotic protein Bax and Bak were reduced by both propofol and sevoflurane to regulate hepatic apoptosis. In addition, propofol downregulated the phosphorylation of AKT and Bad protein, while sevoflurane downregulated the phosphorylation of p38. In addition, Both the treatments had no effect on the expression of AKT, Bad and p38.


CONCLUSIONS
Both propofol and sevoflurane can protect the liver from ischemia/reperfusion injury by modulating the inflammatory responses reducing oxidative stress and liver apoptosis.
Zhijie
Z
Xu
Jingui
J
Yu
Jianbo
J
Wu
Feng
F
Qi
Huanliang
H
Wang
Zhigang
Z
Wang
Zhou
Z
Wang
D000818:Animals; D004195:Disease Models, Animal; D007375:Interleukin-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008099:Liver / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008738:Methyl Ethers / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D000077149:Sevoflurane; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D007375:Interleukin-1; D015850:Interleukin-6; D008738:Methyl Ethers; D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D000077149:Sevoflurane; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D048051:p38 Mitogen-Activated Protein Kinases; D015742:Propofol