Thaliporphine Preserves Cardiac Function of Endotoxemic Rabbits by Both Directly and Indirectly Attenuating NFκB Signaling Pathway
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 NFκB sign...
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| Format: | Online |
| Language: | English |
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Public Library of Science
2012
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382609/ |
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pubmed-33826092012-07-03 Thaliporphine Preserves Cardiac Function of Endotoxemic Rabbits by Both Directly and Indirectly Attenuating NFκB Signaling Pathway Lee, A. S. Chen, W. P. Kuo, Y. L. Ho, Y. J. Lee, S. S. Su, M. J. Research Article 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 NFκB signaling, which plays the main role in sepsis signaling. Thaliporphine was determined to possess anti-inflammatory and cardioprotective activity by suppressing NFκB 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 TNFα 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/NFκB pathways, which followed by diminishing TNFα and caspase3 dependent cell apoptosis. Public Library of Science 2012-06-25 /pmc/articles/PMC3382609/ /pubmed/22761733 http://dx.doi.org/10.1371/journal.pone.0039174 Text en Lee et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Lee, A. S. Chen, W. P. Kuo, Y. L. Ho, Y. J. Lee, S. S. Su, M. J. |
| spellingShingle |
Lee, A. S. Chen, W. P. Kuo, Y. L. Ho, Y. J. Lee, S. S. Su, M. J. Thaliporphine Preserves Cardiac Function of Endotoxemic Rabbits by Both Directly and Indirectly Attenuating NFκB Signaling Pathway |
| author_facet |
Lee, A. S. Chen, W. P. Kuo, Y. L. Ho, Y. J. Lee, S. S. Su, M. J. |
| author_sort |
Lee, A. S. |
| title |
Thaliporphine Preserves Cardiac Function of Endotoxemic Rabbits by Both Directly and Indirectly Attenuating NFκB Signaling Pathway |
| title_short |
Thaliporphine Preserves Cardiac Function of Endotoxemic Rabbits by Both Directly and Indirectly Attenuating NFκB Signaling Pathway |
| title_full |
Thaliporphine Preserves Cardiac Function of Endotoxemic Rabbits by Both Directly and Indirectly Attenuating NFκB Signaling Pathway |
| title_fullStr |
Thaliporphine Preserves Cardiac Function of Endotoxemic Rabbits by Both Directly and Indirectly Attenuating NFκB Signaling Pathway |
| title_full_unstemmed |
Thaliporphine Preserves Cardiac Function of Endotoxemic Rabbits by Both Directly and Indirectly Attenuating NFκB Signaling Pathway |
| title_sort |
thaliporphine preserves cardiac function of endotoxemic rabbits by both directly and indirectly attenuating nfκb signaling pathway |
| description |
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 NFκB signaling, which plays the main role in sepsis signaling. Thaliporphine was determined to possess anti-inflammatory and cardioprotective activity by suppressing NFκB 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 TNFα 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/NFκB pathways, which followed by diminishing TNFα and caspase3 dependent cell apoptosis. |
| publisher |
Public Library of Science |
| publishDate |
2012 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382609/ |
| _version_ |
1611538922592010240 |