DOI: 10.1097/fjc.0000000000001480 ISSN:

Alpha-lipoic Acid Protects Against Chronic Alcohol Consumption-induced Cardiac Damage via the ALDH2-associated PINK/Parkin Pathway

Cheng Shen, Xueheng Chen, Yong Cao, Yanyan Du, Xuan Xu, Qingjing Wu, Lizhi Lin, Yiran Qin, Runqi Meng, Lijun Gan, Jinguo Zhang
  • Cardiology and Cardiovascular Medicine
  • Pharmacology


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. Here, we evaluated the role of α-LA in alcohol-induced cardiac damage by feeding mice a 4.8% (v/v) alcohol diet with or without α-LA for 6 w. Our results suggested that chronic alcohol consumption increased mortality, blood alcohol concentrations and serum aldehyde levels, but a-LA attenuated the elevations in mortality and aldehydes. Chronic alcohol intake also induced cardiac dysfunction, including enlarged left ventricles, reduced left ventricular ejection fraction, enhanced cardiomyocyte size and increased serum levels of brain natriuretic peptide (BNP), lactate dehydrogenase (LDH) and creatine kinase myocardial isoenzyme (CK-MB). Moreover, alcohol intake led to the accumulation of collagen fiber and mitochondrial dysfunction, the effects of which were alleviated by α-LA. In addition, α-LA intake also prevented the increase in reactive oxygen species (ROS) production and the decrease in mitochondrial number that were observed after alcohol consumption. Chronic alcohol exposure activated PINK1/Parkin-mediated mitophagy. These effects were diminished by α-LA intake via activation of aldehyde dehydrogenase 2 (ALDH2). Our data indicated that α-LA helps protect cardiac cells against the effects of chronic alcohol intake, likely by inhibiting PINK1/Parkin-related mitophagy via the activation of ALDH2.

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