Beneficial role of oleuropein in sepsis-induced myocardial injury: possible involvement of GSK-3beta/NF-kB pathway
Xing, ConghuiXu, LiYao, Yingjie
Purpose The present study explored the potential therapeutic role of oleuropein in sepsis-induced heart injury along with the role of GSK-3beta/NF-kB signaling pathway. Methods Sepsis-induced myocardial injury was induced by cecal ligation and puncture (CLP) in rats. The cardiac injury was assessed by measuring the levels of cTnI and creatine kinase-MB (CK-MB). Sepsis-induced inflammation was assessed by measuring interleukin-6 (IL-6), IL-10 and HMGB1 levels. The different doses of oleuropein (5, 10, and 20 mg/kg) were given prior to CLP. Oleuropein (20 mg/kg) was administered after 6 hof CLP. The expressions of GSK-3beta, p-GSK-3beta (Ser9) and nuclear factor-B (NF-B) were measured in heart homogenates. Results Cecal ligation and puncture was associated with myocardial injury, an increase in IL-6, a decrease in IL-10 and an increase in HMGB1. Moreover, it decreased the ratio of p-GSK-3beta/GSK-3beta and increased the expression of p-NF-kB. Pretreatment with oleuropein attenuated CLP-induced myocardial injury and systemic inflammation in a dose-dependent manner. Administration of oleuropein after the onset of CLP also attenuated cardiac injury and inflammation. It also restored CLP-induced changes in the HMGB1 levels, the ratio of p-GSK-3beta/GSK-3beta and expression of p- NF-kB. Conclusions Oleuropein attenuates sepsis-induced systemic inflammation and myocardial injury by inhibiting NF-kB and GSK-3beta signaling.(AU)
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