Gracillin Protects Liver Ischemia-Reperfusion Injury from Oxidative Stress-Induced Apoptosis.

PURPOSE: To explore the therapeutic effects of gracillin on liver ischemia-reperfusion (IR) injury.

METHODS

The effects of gracillin on mouse liver function were evaluated by pathological analysis and measurement of serum biochemical indicators including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH). In addition, apoptosis-related gene expression levels were assessed using quantitative real-time PCR and western blotting. The following oxidative stress related indices were detected by reactive oxygen species (ROS) content, malondialdehyde (MDA) content, and glutathione peroxidase (GSH-Px) activity, and superoxide dismutase (SOD) content. An H2O2-mediated oxidative stress model was developed to test the therapeutic effects of gracillin. The Akt inhibitors LY294002 was used to explore the role of the Akt/GSK3β signaling pathway in gracillin-induced protective effects.

RESULTS

Gracillin protected against IR-induced liver dysfunction. Gracillin pretreatment significantly inhibited pathological liver damages and decreased serum ALT, AST, ALP, and LDH levels. Gracillin pretreatment increased the mRNA and protein levels of anti-apoptotic factor Bcl-2, while reducing those of pro-apoptotic factor Bax mRNA and protein levels. Additionally, H2O2-induced the oxidative stress and H2O2-enhanced hepatocyte apoptosis were markedly inhibited by gracillin pretreatment. Mechanistically, gracillin pretreatment activated the Akt/GSK3β signaling pathway. Inhibition of the Akt/GSK3β signaling pathway reversed the protective effects induced by gracillin.

CONCLUSION

These results provide evidences that gracillin exerts beneficial effects against liver dysfunction during liver IR. The mechanisms underlying the beneficial effects may be suppression of oxidative stress and apoptosis via the Akt/GSK3β signaling pathway activation. These results suggest that a potential therapeutic role for gracillin in protecting against liver IR injury.