Background: Metformin, a first-line oral anti-diabetic drug, has recently been reported to exert protective effect on various cardiovascular diseases. However, the potential role of metformin in ethanol-induced cardiomyocyte injury is still unknown. Therefore, this study was aimed to investigate the effect of metformin on ethanol-induced cardiomyocyte injury and its underlying mechanism.
Methods And Results: H9c2 cardiomyocytes were exposed to ethanol for 24 h to establish an ethanol-induced cardiomyocyte injury model, and followed by treatment with metformin in the presence or absence of Lapatinib (an ErbB2 inhibition). CCK8 and LDH assays demonstrated that metformin improved cell viability in cardiomyocytes exposed to ethanol. Furthermore, metformin suppressed cardiomyocyte apoptosis and reduced the expressions of apoptosis-related proteins (Bax and C-CAS-3). In addition, our results showed that metformin activated the AKT/Nrf2 pathway, and then promoted Nrf2 nuclear translocation and the transcription of its downstream antioxidant genes (HO-1, CAT and SOD2), thereby inhibiting oxidative stress. Interestingly, we found that ErbB2 protein expression was significantly inhibited in ethanol-treated cardiomyocytes, which was markedly reversed by metformin. In contrast, Lapatinib largely abrogated the activation of AKT/Nrf2 signaling by metformin, accompanied by the increases in oxidative stress and cardiomyocyte apoptosis, indicating that metformin prevented ethanol-induced cardiomyocyte injury in an ErbB2-dependent manner.
Conclusion: In summary, our study provides the first evidence that metformin protects cardiomyocyte against ethanol-induced oxidative stress and apoptosis by activating ErbB2-mediated AKT/Nrf2 signaling. Thus, metformin may be a potential novel treatment approach for alcoholic cardiomyopathy.
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http://dx.doi.org/10.1007/s11033-023-08310-x | DOI Listing |
Alcohol Clin Exp Res (Hoboken)
July 2024
Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA.
Background: Current research on ethanol-induced cardiovascular anomalies has focused on left ventricular (LV) function and blood pressure. To extend this area of research, we sought to determine whether ethanol-induced alterations in the structure and function of the right cardiac ventricle (RV) and pulmonary artery (PA) lead to pulmonary arterial hypertension (PAH).
Methods: Two groups of male Sprague-Dawley rats received a balanced liquid diet containing 5% ethanol (w/v) or a pair-fed isocaloric liquid diet for 8 weeks.
Cell Stress Chaperones
June 2024
Department of Toxicology and Nutrition, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China; Department of Nutrition, Qilu Hospital of Shandong University, Jinan, China. Electronic address:
Acta Biochim Biophys Sin (Shanghai)
December 2023
Department of Cardiology and Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Binge drinking exerts cardiac toxicity through various mechanisms, including oxidative stress and inflammation. NLRP3 inflammasomes possess both pro- and anti-inflammatory properties, although the role of NLRP3 in ethanol-induced cardiotoxicity remains unknown. This study is designed to examine the role of NLRP3 inflammasome in acute ethanol cardiotoxicity and the underlying mechanisms of action.
View Article and Find Full Text PDFJ Cardiovasc Pharmacol
November 2023
Department of Cardiology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China.
Chronic alcohol intake contributes to high mortality rates due to ethanol-induced cardiac hypertrophy and contractile dysfunction, which are accompanied by increased oxidative stress and disrupted mitophagy. Alpha-lipoic acid (α-LA), a well-known antioxidant, has been shown to protect against cardiac hypertrophy and inflammation. However, little is known about its role and mechanism in the treatment of alcoholic cardiomyopathy.
View Article and Find Full Text PDFMol Biol Rep
April 2023
Department of Pharmacy, Ningbo first Hospital, 315010, Ningbo, People's Republic of China.
Background: Metformin, a first-line oral anti-diabetic drug, has recently been reported to exert protective effect on various cardiovascular diseases. However, the potential role of metformin in ethanol-induced cardiomyocyte injury is still unknown. Therefore, this study was aimed to investigate the effect of metformin on ethanol-induced cardiomyocyte injury and its underlying mechanism.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!