Limits...
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 - Exp. Mol. Med. (2014)

Bottom Line: Concomitantly, the expression of NF-κB target genes such as IL-1β, IL-6, TNF-α 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonbuk, Republic of Korea.

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

Show MeSH

Related in: MedlinePlus

Effect of SPA0355 on I/R-induced apoptosis. Liver tissues were retrieved 24 h after reperfusion and the expression levels of Bax, cleaved caspase-3 and Bcl-2 were examined by western blotting. Protein intensity was measured. Values are the mean±s.e.m. of three independent experiments (n=9 mice per group). **P<0.01 vs sham-operated mice; ##P<0.01 vs I/R mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4150932&req=5

fig3: Effect of SPA0355 on I/R-induced apoptosis. Liver tissues were retrieved 24 h after reperfusion and the expression levels of Bax, cleaved caspase-3 and Bcl-2 were examined by western blotting. Protein intensity was measured. Values are the mean±s.e.m. of three independent experiments (n=9 mice per group). **P<0.01 vs sham-operated mice; ##P<0.01 vs I/R mice.

Mentions: Although the major cause of cell death during hepatic I/R injury is necrosis, apoptotic cell death is also observed during the injury process.18 The number of apoptotic cells in I/R-injured liver tissues was determined by TUNEL staining. As shown in Figure 2c, the number of TUNEL-positive apoptotic cells was significantly higher in the I/R-injured mice compared with that in the sham group. This observation correlated with increased protein levels of proapoptotic Bax and cleaved caspase-3 and decreased protein level of antiapoptotic Bcl-2 (Figure 3). When mice were treated with SPA0355 before I/R injury, a significant reduction in apoptotic cells and concordant changes in apoptotic proteins were observed. Together, these results suggest that SPA0355 has protective effects against hepatic I/R injury.


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 - Exp. Mol. Med. (2014)

Effect of SPA0355 on I/R-induced apoptosis. Liver tissues were retrieved 24 h after reperfusion and the expression levels of Bax, cleaved caspase-3 and Bcl-2 were examined by western blotting. Protein intensity was measured. Values are the mean±s.e.m. of three independent experiments (n=9 mice per group). **P<0.01 vs sham-operated mice; ##P<0.01 vs I/R mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150932&req=5

fig3: Effect of SPA0355 on I/R-induced apoptosis. Liver tissues were retrieved 24 h after reperfusion and the expression levels of Bax, cleaved caspase-3 and Bcl-2 were examined by western blotting. Protein intensity was measured. Values are the mean±s.e.m. of three independent experiments (n=9 mice per group). **P<0.01 vs sham-operated mice; ##P<0.01 vs I/R mice.
Mentions: Although the major cause of cell death during hepatic I/R injury is necrosis, apoptotic cell death is also observed during the injury process.18 The number of apoptotic cells in I/R-injured liver tissues was determined by TUNEL staining. As shown in Figure 2c, the number of TUNEL-positive apoptotic cells was significantly higher in the I/R-injured mice compared with that in the sham group. This observation correlated with increased protein levels of proapoptotic Bax and cleaved caspase-3 and decreased protein level of antiapoptotic Bcl-2 (Figure 3). When mice were treated with SPA0355 before I/R injury, a significant reduction in apoptotic cells and concordant changes in apoptotic proteins were observed. Together, these results suggest that SPA0355 has protective effects against hepatic I/R injury.

Bottom Line: Concomitantly, the expression of NF-κB target genes such as IL-1β, IL-6, TNF-α 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonbuk, Republic of Korea.

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

Show MeSH
Related in: MedlinePlus