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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.

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Effect of SPA0355 on I/R-induced neutrophil infiltration. MPO activity was determined as an index of neutrophil infiltration after 24 h reperfusion. 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.
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fig4: Effect of SPA0355 on I/R-induced neutrophil infiltration. MPO activity was determined as an index of neutrophil infiltration after 24 h reperfusion. 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: MPO, an enzyme that is predominantly stored in azurophilic neutrophil granules, was used to quantify neutrophil infiltration in the liver. After 24 h of reperfusion, MPO activity increased markedly in the I/R-injured mice compared with the sham group (Figure 4). Consistent with the observed decrease in liver damage, the MPO activity of mice that were pretreated with 5 μgkg−1 SPA0355 was 48.5% of that in the vehicle group. These results suggest that suppression of neutrophil infiltration by SPA0355 may further contribute to protection against 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 neutrophil infiltration. MPO activity was determined as an index of neutrophil infiltration after 24 h reperfusion. 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

fig4: Effect of SPA0355 on I/R-induced neutrophil infiltration. MPO activity was determined as an index of neutrophil infiltration after 24 h reperfusion. 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: MPO, an enzyme that is predominantly stored in azurophilic neutrophil granules, was used to quantify neutrophil infiltration in the liver. After 24 h of reperfusion, MPO activity increased markedly in the I/R-injured mice compared with the sham group (Figure 4). Consistent with the observed decrease in liver damage, the MPO activity of mice that were pretreated with 5 μgkg−1 SPA0355 was 48.5% of that in the vehicle group. These results suggest that suppression of neutrophil infiltration by SPA0355 may further contribute to protection against 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