Exp Mol Med.  2014 Aug;46(8):e109. 10.1038/emm.2014.48.

SPA0355 attenuates ischemia/reperfusion-induced liver injury in mice

• Bae UJ
• Yang JD
• Ka SO
• Koo JH
• Woo SJ
• Lee YR
• Yu HC
• Cho BH
• Zhao HY
• Ryu JH
• Lee SM
• Jeon R
• Park BH

• KMID: 2155374
• DOI: http://doi.org/10.1038/emm.2014.48

Abstract

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 with SPA0355 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-kappaB (NF-kappaB), which revealed that SPA0355 suppressed the nuclear translocation and DNA binding of NF-kappaB subunits. Concomitantly, the expression of NF-kappaB target genes such as IL-1beta, IL-6, TNF-alpha 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.

MeSH Terms

Animals
Anti-Inflammatory Agents/*therapeutic use
Benzoxazines/*therapeutic use
Liver/*drug effects/immunology/*injuries/pathology
Male
Mice, Inbred C57BL
NF-kappa B/immunology
Reperfusion Injury/*drug therapy/immunology/pathology
Signal Transduction/drug effects
Thiourea/*analogs & derivatives/therapeutic use
Anti-Inflammatory Agents
Benzoxazines
NF-kappa B
Thiourea