ABSTRACT
The article "Effect and mechanism of propofol in hepatic ischemia/reperfusion injury of rat, by L. Wei, W.-Y. Chen, T. Hu, Y.-X. Tang, B.-B. Pan, M. Jin, G.-Y. Kong, published in Eur Rev Med Pharmacol Sci 2017; 21 (15): 3516-3522-PMID: 28829487" has been withdrawn from the authors due to some technical reasons in the preparation of figures. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/13224.
ABSTRACT
OBJECTIVE: Hepatic ischemia/reperfusion (I/R) injury remains to be one of the most common clinical diseases. This study aimed to explore the potential effect and mechanism of propofol in protecting rat liver from I/R injury. MATERIALS AND METHODS: The hepatic I/R model was established in Sprague-Dawley (SD) rats by perfusing the liver with heparinized cold saline through the portal vein for 20 min. The rats were then received a 100 mg/kg/d propofol administration for the continuously 10 days. The hepatic function indexes of ALT, AST, and GGT were detected by ELISA. The apoptosis of hepatic cells was assessed by TUNEL analysis, and Bax and Bcl-2 expression changes were detected by qRT-PCR and Western blotting. In addition, serum pro-inflammatory factors and the signaling pathway-related protein expressions were detected. RESULTS: Propofol markedly attenuated the increases of ALT, AST, and GGT induced by I/R. Propofol reduced I/R-induced apoptosis and pro-inflammatory factors secretion. Furthermore, propofol could promote the expression of phosphorylated (p)-AKT and inhibited the expression of p-mTOR. CONCLUSIONS: Propofol protects hepatic I/R injury partly by reducing apoptosis and reducing the release of pro-inflammatory cytokines, which is possibly involved in the modulation of the PI3K/AKT/mTOR signaling pathway. All these data suggest that propofol may play certain positive roles in protecting the liver from I/R injury.
Subject(s)
Liver Diseases/drug therapy , Liver/drug effects , Propofol/pharmacology , Reperfusion Injury/drug therapy , Animals , Apoptosis/drug effects , Hepatocytes/drug effects , In Situ Nick-End Labeling , Liver Diseases/metabolism , Male , Phosphatidylinositol 3-Kinases/metabolism , Phosphorylation/drug effects , Protective Agents/pharmacology , Rats , Rats, Sprague-Dawley , Reperfusion Injury/metabolism , Signal Transduction/drug effectsABSTRACT
Expression of inducible nitric oxide synthase (iNOS) protein was studied in the brain after intracerebroventricular injections of interferon (IFN)-gamma, and IFN-gamma combined with lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-alpha, compared to ovalbumin as control. Wild-type mice and mice with targeted deletion of the IFN-gamma receptor gene were used. Findings based on iNOS immunoreactivity were evaluated at 1, 2, 4 and 7 days post-injection, using also quantitative image analysis and double labeling with glial cell markers. IFN-gamma administration induced iNOS immmunostaining in activated microglia and macrophages in the parenchyma surrounding the ventricular system, several cortical fields and fiber tracts. IFN-gamma-elicited iNOS immunoreactivity was down-regulated after 1 day. The number of iNOS-immunopositive cells was significantly enhanced by co-administration of LPS or TNF-alpha; IFN-gamma+TNF-alpha injections also resulted in longer persistence of iNOS immunoreactivity. No immunopositive cells were seen in the brain of IFN-gamma receptor knockout mice after IFN-gamma administration; very few immunostained macrophages were detected in these cases, mostly around the injection needle track, after co-administration of LPS or TNF-alpha. Western blot analysis confirmed a marked iNOS induction in the brain of wild-type mice 24 h after IFN-gamma+LPS injections. The findings show that inflammatory mediators circulating in the cerebrospinal fluid induce in vivo iNOS in the brain with topographical selectivity and temporal regulation. The data also demonstrate that the signaling cascade activated by IFN-gamma binding to its receptor is critical for iNOS induction, and the synergistic action of LPS and TNF-alpha as iNOS inducers in brain cells is largely mediated by the receptor-regulated action of IFN-gamma.
