RGD Reference Report - Remifentanil Ameliorates Liver Ischemia-Reperfusion Injury Through Inhibition of Interleukin-18 Signaling. - Rat Genome Database

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Remifentanil Ameliorates Liver Ischemia-Reperfusion Injury Through Inhibition of Interleukin-18 Signaling.

Authors: Liu, Xiaohua  Pan, Zhiying  Su, Diansan  Yang, Zhongwei  Zheng, Beijie  Wang, Xiangrui  Tian, Jie 
Citation: Liu X, etal., Transplantation. 2015 Oct;99(10):2109-17. doi: 10.1097/TP.0000000000000737.
RGD ID: 14696667
Pubmed: PMID:25919765   (View Abstract at PubMed)
DOI: DOI:10.1097/TP.0000000000000737   (Journal Full-text)


BACKGROUND: Hepatic injury induced by ischemia-reperfusion (I/R) after transplantation or lobectomy is a major clinical problem. The potential benefit of remifentanil in these hepatic surgeries remains unknown. The current study investigated whether remifentanil protects the liver against I/R injury in a rat model and whether the underlying mechanism involves the modulation of interleukin (IL)-18 signaling.
METHODS: Male Sprague-Dawley rats were subjected to 45 minutes of partial hepatic ischemia followed by 6 hours of reperfusion. Then, they received an intravenous saline or remifentanil (0.4, 2, or 10 μg/kg per minute) infusion from 30 minutes before ischemia until the end of ischemia with or without previous administration of naloxone, a nonselective opioid receptor antagonist. Serum aminotransferase, hepatic morphology, and hepatic neutrophil infiltration were analyzed. The expression of hepatic IL-18; IL-18-binding protein (BP); and key cytokines downstream of IL-18 signaling were measured.
RESULTS: Remifentanil significantly decreased serum aminotransferase levels and profoundly attenuated the liver histologic damages. Liver I/R injury increased the expression of both hepatic IL-18 and IL-18BP. Although remifentanil pretreatment significantly decreased I/R-induced IL-18 expression, it further upregulated IL-18BP levels in liver tissues. The I/R-induced increases of hepatic interferon-γ, tumor necrosis factor-α and IL-1β expression, and neutrophil infiltration were also significantly reduced by remifentanil. Naloxone inhibited the remifentanil-induced downregulation of IL-18, but not the elevation of IL-18BP, and significantly attenuated its protective effects on liver I/R injury.
CONCLUSIONS: Remifentanil protects the liver against I/R injury. Modulating the hepatic IL-18/IL-18BP balance and inhibiting IL-18 signaling mediate, at least in part, the hepatoprotective effects of remifentanil.




  
Object Symbol
Species
Term
Qualifier
Evidence
With
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Original Reference(s)
IL18HumanLiver Reperfusion Injury treatmentISOIl18 (Rattus norvegicus) RGD 
IL18BPHumanLiver Reperfusion Injury  ISOIl18bp (Rattus norvegicus)mRNA and protein:increased expression:liverRGD 
Il18RatLiver Reperfusion Injury treatmentIEP  RGD 
Il18MouseLiver Reperfusion Injury treatmentISOIl18 (Rattus norvegicus) RGD 
Il18bpRatLiver Reperfusion Injury  IEP mRNA and protein:increased expression:liverRGD 
Il18bpMouseLiver Reperfusion Injury  ISOIl18bp (Rattus norvegicus)mRNA and protein:increased expression:liverRGD 


Genes (Rattus norvegicus)
Il18  (interleukin 18) Il18bp  (interleukin 18 binding protein)

Genes (Mus musculus)
Il18  (interleukin 18) Il18bp  (interleukin 18 binding protein)

Genes (Homo sapiens)
IL18  (interleukin 18) IL18BP  (interleukin 18 binding protein)