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Published on: April 2, 2017
SPA0355 attenuates ischemia/reperfusion-induced liver injury in mice
Ui-Jin Bae1, Jae Do Yang2, Sun-O Ka1
1Department 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.
Insights
SPA0355, a synthetic thiourea analog, effectively protects against liver damage from hepatic ischemia/reperfusion (I/R) injury. It reduces inflammation and oxidative stress by inhibiting NF-κB activation and boosting antioxidant enzymes.
Area of Science:
- Hepatology
- Immunology
- Pharmacology
Background:
- Hepatic ischemia/reperfusion (I/R) injury causes significant liver damage via oxidative stress and inflammation, impacting patient outcomes.
- Developing effective protective strategies against I/R injury is crucial for improving surgical results.
Purpose of the Study:
- To evaluate the protective efficacy of SPA0355, a synthetic thiourea analog, against hepatic I/R injury in a mouse model.
- To elucidate the underlying mechanisms of SPA0355-mediated protection.
Main Methods:
- Male C57BL/6 mice underwent partial liver ischemia followed by reperfusion.
- Animals were grouped into sham, I/R, and SPA0355 pretreated groups.
- Assessed liver damage markers, liver synthetic function, NF-κB activity, inflammatory gene expression, and antioxidant enzyme levels.
Main Results:
- SPA0355 pretreatment significantly reduced serum aminotransferase levels, parenchymal necrosis, and apoptosis.
- Liver synthetic function improved, indicated by prolonged prothrombin time.
- SPA0355 suppressed NF-κB activation, downregulated inflammatory genes (IL-1β, IL-6, TNF-α, iNOS), and upregulated antioxidant enzymes (superoxide dismutase, catalase, glutathione), reducing malondialdehyde.
Conclusions:
- SPA0355 demonstrates significant hepatoprotective effects against I/R injury.
- The protective mechanism involves the inhibition of NF-κB signaling and enhancement of the antioxidant defense system.
- SPA0355 is a promising therapeutic agent for mitigating liver damage in hepatic I/R injury.
