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Cardioprotective Effect of Tangeretin by Inhibiting PTEN/AKT/mTOR Axis in Experimental Sepsis-Induced Myocardial Dysfunction.
- Source :
-
Molecules (Basel, Switzerland) [Molecules] 2020 Nov 29; Vol. 25 (23). Date of Electronic Publication: 2020 Nov 29. - Publication Year :
- 2020
-
Abstract
- Sepsis aggregates undesirable immune response causing depression of ventricular myocardium and diastolic dysfunction. This present study examined the effect of a plant-derived flavone tangeretin (TG) on autophagy and reduction in myocardial dysfunction. The sepsis was induced by cecum ligation and puncture (CLP) in male Sprague-Dawley rats. Abnormal changes were seen in the heart after the sepsis induction. These abnormalities were analyzed based on the cardiac markers, namely Cardiac myosin light chain-1 (cMLC1) and Cardiac troponin I (cTnl), echocardiography, and plasma parameters, like Lactate dehydrogenase (LDH) and Creatinine kinase (CK). Microanatomy of the heart was studied using hematoxylin and eosin stained histopathological samples of cardiac tissue. Western blot technique was used to detect the nature and extent of protein with the amount of a specific RNA (gene expression) in the cardiac homogenate. Oxidative damage was analyzed using redox marker, reduced glutathione. This study successfully showed that TG attenuated sepsis-induced myocardial dysfunction by inhibiting myocardial autophagy via silencing the Phosphatase and tensin homolog (PTEN) expression and acting on the AKT/mTOR pathway. The present findings supported that TG is a novel cardioprotective therapeutic target for sepsis induced myocardial dysfunction.
- Subjects :
- Animals
Autophagy drug effects
Cardiomyopathies blood
Cardiomyopathies etiology
Cardiotonic Agents administration & dosage
Cecum injuries
Cell Death drug effects
Disease Models, Animal
Flavones administration & dosage
Glutathione drug effects
Glutathione metabolism
Heart drug effects
Ligation methods
Male
Myocardium pathology
Myocardium ultrastructure
NLR Family, Pyrin Domain-Containing 3 Protein drug effects
Protein Carbonylation drug effects
Punctures methods
Rats, Sprague-Dawley
STAT3 Transcription Factor drug effects
Sepsis metabolism
Tyrosine analogs & derivatives
Tyrosine drug effects
Cardiomyopathies drug therapy
Cardiotonic Agents pharmacology
Flavones pharmacology
PTEN Phosphohydrolase metabolism
Proto-Oncogene Proteins c-akt metabolism
Sepsis complications
TOR Serine-Threonine Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1420-3049
- Volume :
- 25
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Molecules (Basel, Switzerland)
- Publication Type :
- Academic Journal
- Accession number :
- 33260422
- Full Text :
- https://doi.org/10.3390/molecules25235622