Thaliporphine preserves cardiac function of endotoxemic rabbits by both directly and indirectly attenuating NFκB signaling pathway

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Abstract

Cardiac depression in sepsis is associated with the increased morbidity and mortality. Although myofilaments damage, autonomic dysfunction, and apoptosis play roles in sepsis-induced myocardial dysfunction, the underlying mechanism is not clear. All of these possible factors are related to NFkappaB signaling, which plays the main role in sepsis signaling. Thaliporphine was determined to possess anti-inflammatory and cardioprotective activity by suppressing NFkappaB signaling in rodents. The purpose of this study is to further prove this protective effect in larger septic animals, and try to find the underlying mechanisms. The systolic and diastolic functions were evaluated in vivo by pressure-volume analysis at different preloads. Both preload-dependent and -independent hemodynamic parameters were performed. Inflammatory factors of whole blood and serum samples were analyzed. Several sepsis-related signaling pathways were also determined at protein level. Changes detected by conductance catheter showed Thaliporphine could recover impaired left ventricular systolic function after 4 hours LPS injection. It could also reverse the LPS induced steeper EDPVR and gentler ESPVR, thus improve Ees, Ea, and PRSW. Thaliporphine may exert this protective effect by decreasing TNFalpha and caspase3 dependent cell apoptosis, which was consistent with the decreased serum cTnI and LDH concentration. Thaliporphine could protect sepsis-associated myocardial dysfunction in both preload-dependent and -independent ways. It may exert these protective effects by both increase of "good"-PI3K/Akt/mTOR and decrease of "bad"-p38/NFkappaB pathways, which followed by diminishing TNFalpha and caspase3 dependent cell apoptosis.

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Lee, A. S., Chen, W. P., Kuo, Y. L., Ho, Y. J., Lee, S. S., & Su, M. J. (2012). Thaliporphine preserves cardiac function of endotoxemic rabbits by both directly and indirectly attenuating NFκB signaling pathway. PLoS ONE, 7(6). https://doi.org/10.1371/journal.pone.0039174

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