Abstract
Purpose: To evaluate the effect of epigallocatechin gallate (EGCG) on sepsis-induced liver injury in a rat model of sepsis established by cercal ligation and puncture (CLP). Methods: Male Wistar rats were randomly divided into 6 groups (n = 12): normal control, sepsis, dexamethasone (5 mg/kg), low-dose EGCG (12.5 mg/kg), medium-dose EGCG (25 mg/kg), and highdose EGCG (50 mg/kg) groups. Dexamethasone and EGCG were given once daily. Survival rates following CLP were recorded. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured to evaluate liver function. Tumor necrosis factor-α (TNF-α) and interleukin (IL)-10 were determined by ELISA. Superoxide dismutase (SOD) and levels of glutathione (GSH) and malondialdehyde (MDA) were assayed to evaluate oxidative stress. Protein and mRNA expression levels of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor (Nrf2) were measured by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Results: Survival rates were significantly (p < 0.05) increased by EGCG (83.3 %) when compared to the untreated sepsis group (33.3 %) or dexamethasone-treated sepsis group (41.7 %). The increase in survival rates was associated with significant decreases in AST, ALT, MDA, and TNF-α, and significant elevations in SOD, GSH, and IL-10. QRT-PCR and Western blotting data indicate that there was increase in hepatic expression of Nrf-2 and HO-1 of EGCG-treated sepsis rats, relative to the untreated sepsis group. Conclusion: These results suggest that EGCG treatment reduces sepsis-induced liver injury and improves the survival rate of rats with polymicrobial sepsis by reducing oxidative stress via regulation of Nrf2/HO-1 signaling. These findings highlight the promising potential of EGCG for the treatment of sepsis. Keywords: Epigallocatechin gallate, Cecal ligation and puncture (CLP), Sepsis, Liver injury, Oxidative stress, Inflammation
Highlights
Sepsis is often the main cause of death in a surgical intensive care unit (ICU), and is still a worldwide challenge [1]
Survival of normal control rats was 100 % (12/12), whereas the survival of untreated septic rats decreased to 33.3 % (4/12) at 72 h after Cecal ligation and puncture (CLP)
Dexamethasone treatment had no significant effects on survival rate when compared with untreated rats after CLP (p > 0.05)
Summary
Sepsis is often the main cause of death in a surgical intensive care unit (ICU), and is still a worldwide challenge [1]. Accumulating evidence demonstrate that severe oxidative stress is present in patients with sepsis, due to overload of reactive oxygen species (ROS) and inadequate anti-oxidative defenses [7]. In sepsis situations, it is important to overcome oxidative stress and the resulting disease progression using antioxidants. The protective role of EGCG against oxidative stress and liver injury in rats subjected to CLP-induced sepsis was investigated. Cecum was moved but was not ligated or punctured. Blood samples and liver tissues were obtained from rats with CLP and normal control rats. Liver tissue samples were collected at different time-points after CLP, and homogenized separately. The SOD activity in the liver tissue was measured using the method described previously [15].
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