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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 oxidative stress. The plasma level of MDA and tissue levels of GSH, SOD and CAT were analyzed. Values are the mean±s.e.m. of three independent experiments (n=9 mice per group). **P<0.01 vs sham-operated mice; #P<0.05, ##P<0.01 vs I/R mice. CAT, catalase; GSH, glutathione; MDA, malondialdehyde; SOD, superoxide dismutase.
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fig6: Effect of SPA0355 on I/R-induced oxidative stress. The plasma level of MDA and tissue levels of GSH, SOD and CAT were analyzed. Values are the mean±s.e.m. of three independent experiments (n=9 mice per group). **P<0.01 vs sham-operated mice; #P<0.05, ##P<0.01 vs I/R mice. CAT, catalase; GSH, glutathione; MDA, malondialdehyde; SOD, superoxide dismutase.

Mentions: The serum level of MDA, an indicator of oxidative damage, was also determined. As shown in Figure 6, I/R significantly increased the MDA content in liver tissues compared with the sham group. Consistent with this finding, I/R caused significant suppression of the hepatic antioxidant defense, as observed by a decrease in the glutathione level and in SOD and CAT enzyme activities. Pretreatment with SPA0355 reversed these changes caused by I/R; the serum level of MDA was significantly lower and hepatic levels of glutathione, SOD and CAT were significantly higher in the SPA0355 group than in the I/R group.


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 oxidative stress. The plasma level of MDA and tissue levels of GSH, SOD and CAT were analyzed. Values are the mean±s.e.m. of three independent experiments (n=9 mice per group). **P<0.01 vs sham-operated mice; #P<0.05, ##P<0.01 vs I/R mice. CAT, catalase; GSH, glutathione; MDA, malondialdehyde; SOD, superoxide dismutase.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: Effect of SPA0355 on I/R-induced oxidative stress. The plasma level of MDA and tissue levels of GSH, SOD and CAT were analyzed. Values are the mean±s.e.m. of three independent experiments (n=9 mice per group). **P<0.01 vs sham-operated mice; #P<0.05, ##P<0.01 vs I/R mice. CAT, catalase; GSH, glutathione; MDA, malondialdehyde; SOD, superoxide dismutase.
Mentions: The serum level of MDA, an indicator of oxidative damage, was also determined. As shown in Figure 6, I/R significantly increased the MDA content in liver tissues compared with the sham group. Consistent with this finding, I/R caused significant suppression of the hepatic antioxidant defense, as observed by a decrease in the glutathione level and in SOD and CAT enzyme activities. Pretreatment with SPA0355 reversed these changes caused by I/R; the serum level of MDA was significantly lower and hepatic levels of glutathione, SOD and CAT were significantly higher in the SPA0355 group than in the I/R group.

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