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Empagliflozin alleviates ethanol-induced cardiomyocyte injury through inhibition of mitochondrial apoptosis via a SIRT1/PTEN/Akt pathway.
- Source :
-
Clinical and experimental pharmacology & physiology [Clin Exp Pharmacol Physiol] 2021 Jun; Vol. 48 (6), pp. 837-845. Date of Electronic Publication: 2021 Feb 01. - Publication Year :
- 2021
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Abstract
- Ethanol-induced myocardial injury involves multiple pathophysiological processes including apoptosis. Empagliflozin (EMPA), is a novel hypoglycaemic drug which possesses multiple pharmacologically relevant protective effects, including anti-apoptotic, anti-inflammatory and antioxidant effects. However, whether EMPA treatment has a protective effect on ethanol-induced myocardial injury has not been assessed, to the best of our knowledge. Therefore, the aim of this study was to determine the effect of EMPA treatment on ethanol-induced myocardial injury and the underlying mechanism. An ethanol-induced myocardial injury model was established by culturing H9c2 cells treated with 200 mmol/L ethanol for 24 hours, and additional groups of ethanol treated cells were also treated with EMPA with or without SIRT1 inhibitors prior to ethanol treatment. Cell viability and apoptosis were assessed using a CCK-8 assay and flow cytometry, respectively. The expression of apoptosis-related proteins was assessed using western blotting. The results showed that EMPA pretreatment resulted in increased cell viability and a decrease in LDH activity. Moreover, EMPA pretreatment significantly reduced apoptosis of cardiomyocytes, and reduced the expression of cleaved caspase 3. Furthermore, EMPA increased the expression of SIRT1, increased the phosphorylation levels of Akt, and reduced the expression of PTEN. EMPA also reduced ethanol-induced mitochondrial apoptosis, increasing the Bcl-2/Bax ratio and the mitochondrial membrane potential. However, the cardioprotective effects of EMPA were abrogated when cells were pretreated with a SIRT1 inhibitor. In conclusion, EMPA can alleviate ethanol-induced myocardial injury by inhibiting mitochondrial apoptosis via the SIRT1/PTEN/Akt pathway. Therefore, EMPA may be a novel target for treatment of ethanol-induced myocardial injury.<br /> (© 2021 John Wiley & Sons Australia, Ltd.)
- Subjects :
- Animals
Rats
Cell Line
Cell Survival drug effects
Glucosides pharmacology
Myocytes, Cardiac drug effects
Myocytes, Cardiac metabolism
Myocytes, Cardiac pathology
PTEN Phosphohydrolase metabolism
Sirtuin 1 metabolism
Ethanol toxicity
Apoptosis drug effects
Proto-Oncogene Proteins c-akt metabolism
Signal Transduction drug effects
Benzhydryl Compounds pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1440-1681
- Volume :
- 48
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Clinical and experimental pharmacology & physiology
- Publication Type :
- Academic Journal
- Accession number :
- 33527532
- Full Text :
- https://doi.org/10.1111/1440-1681.13470