SPA0355 attenuates ischemia/reperfusion-induced liver injury in mice

• Published in: Experimental & molecular medicine 2014, 46(0), , pp.1-8
• Main Authors: 배의진, 양재도, 가선오, 우성지, 이영래, 유희철, 조백환, 구정현, Hui-Yuan Zhao, 류재하, 이상명, 전라옥, 박병현
• Format: Article
• Language: English
• Subjects: 생화학
• ISSN: 1226-3613; 2092-6413

Hepatic ischemia/reperfusion (I/R) injury leads to oxidative stress and acute inflammatory responses that cause liver damage and have a considerable impact on the postoperative outcome. Much research has been performed to develop possible protective techniques. We aimed to investigate the efficacy of SPA0355, a synthetic thiourea analog, in an animal model of hepatic I/R injury. Male C57BL/6 mice underwent normothermic partial liver ischemia for 45 min followed by varying periods of reperfusion. The animals were divided into three groups: sham operated, I/R and SPA0355 pretreated. Pretreatment withSPA0355 protected against hepatic I/R injury, as indicated by the decreased levels of serum aminotransferase and reduced parenchymal necrosis and apoptosis. Liver synthetic function was also restored by SPA0355 as reflected by the prolonged prothrombin time. To gain insight into the mechanism involved in this protection, we measured the activity of nuclear factor-jB (NF-jB), which revealed that SPA0355 suppressed the nuclear translocation and DNA binding of NF-jB subunits. Concomitantly, the expression of NF-jB target genes such as IL-1b, IL-6, TNF-a and iNOS was significantly downregulated. Lastly, the liver antioxidant enzymes superoxide dismutase, catalase and glutathione were upregulated by SPA0355 treatment,which correlated with the reduction in serum malondialdehyde. Our results suggest that SPA0355 pretreatment prior to I/R injury could be an effective method to reduce liver damage. KCI Citation Count: 11