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Background and purpose <p>Alcoholic cardiomyopathy (ACM) is a serious complication of chronic and acute alcohol abuse that can progress to heart failure (HF). Currently, no curative drug exists for ACM, and heart transplantation remains the only definitive option. Although mineralocorticoid receptor (MR) antagonists (MRAs) are a cornerstone of HF management, their role in ethanol cardiotoxicity remains poorly defined. Because ethanol elevates aldosterone levels, targeting the aldosterone/MR axis may represent a promising therapeutic strategy. This study investigated the effects of finerenone, a next-generation non-steroidal MRA, in both <i>in vitro</i> and <i>in vivo</i> models of acute alcoholic myocardial injury.</p> Methods <p>H9c2 cardiomyocytes were exposed to ethanol with or without finerenone, and cell viability, apoptosis, mitochondrial dynamics, and proinflammatory signaling were assessed to evaluate cytoprotective effects. <i>In vivo</i>, a murine acute alcoholic myocardial injury model was generated by three days of ethanol exposure with concurrent finerenone administration. Circulating myocardial injury marker CK-MB was measured, and myocardial tissue was analyzed for MR/aldosterone levels, apoptosis, inflammation, macrophage infiltration, and mitochondrial fission/fusion dynamics.</p> Results <p>Finerenone attenuated ethanol-induced MR upregulation, apoptosis, mitochondrial fragmentation, and pro-inflammatory signaling in H9c2 cardiomyocytes. In mice, finerenone further reduced the ethanol-induced increase in serum CK-MB and attenuated ethanol-induced myocardial cell death and damage. Moreover, ethanol-induced myocardial inflammation, oxidative stress, and mitochondrial dysfunction were further reduced in this mouse model of ethanol cardiotoxicity following finerenone administration. Together, the non-steroidal MRA finerenone may attenuate acute ethanol-induced cardiotoxicity by regulating inflammatory pathways, oxidative stress, and mitochondrial function.</p> Conclusions and implications <p>Overall, these findings support the conclusion that the next-generation MRA finerenone attenuates acute ethanol-induced myocardial cell death, inflammation, oxidative stress, and mitochondrial dysfunction <i>in vitro</i> and <i>in vivo</i>. Finerenone may act as a novel protective agent against acute alcoholic myocardial injury in the future, but further clinical evidence is required to support this preclinical finding.</p> Graphical Abstract <p></p>

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Finerenone mitigates acute alcoholic myocardial injury by modulating inflammatory signaling, oxidative stress, and mitochondrial function

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月20日

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  • Ching-Han Liu,
  • Tian-Huei Chu,
  • Shih-Ming Yang,
  • Yi-Chen Wang,
  • Wen-Chin Lee,
  • Yi-Chen Chang,
  • Yao-Chang Chen,
  • Yi-Jen Chen,
  • Cheng-Chieh Fang,
  • Zhi-Hong Wen,
  • Chien-Wei Feng,
  • Hao-Ming Wu,
  • Po-Tseng Lee,
  • Nan-Chieh Huang,
  • Shih-Chung Huang

摘要

Background and purpose

Alcoholic cardiomyopathy (ACM) is a serious complication of chronic and acute alcohol abuse that can progress to heart failure (HF). Currently, no curative drug exists for ACM, and heart transplantation remains the only definitive option. Although mineralocorticoid receptor (MR) antagonists (MRAs) are a cornerstone of HF management, their role in ethanol cardiotoxicity remains poorly defined. Because ethanol elevates aldosterone levels, targeting the aldosterone/MR axis may represent a promising therapeutic strategy. This study investigated the effects of finerenone, a next-generation non-steroidal MRA, in both in vitro and in vivo models of acute alcoholic myocardial injury.

Methods

H9c2 cardiomyocytes were exposed to ethanol with or without finerenone, and cell viability, apoptosis, mitochondrial dynamics, and proinflammatory signaling were assessed to evaluate cytoprotective effects. In vivo, a murine acute alcoholic myocardial injury model was generated by three days of ethanol exposure with concurrent finerenone administration. Circulating myocardial injury marker CK-MB was measured, and myocardial tissue was analyzed for MR/aldosterone levels, apoptosis, inflammation, macrophage infiltration, and mitochondrial fission/fusion dynamics.

Results

Finerenone attenuated ethanol-induced MR upregulation, apoptosis, mitochondrial fragmentation, and pro-inflammatory signaling in H9c2 cardiomyocytes. In mice, finerenone further reduced the ethanol-induced increase in serum CK-MB and attenuated ethanol-induced myocardial cell death and damage. Moreover, ethanol-induced myocardial inflammation, oxidative stress, and mitochondrial dysfunction were further reduced in this mouse model of ethanol cardiotoxicity following finerenone administration. Together, the non-steroidal MRA finerenone may attenuate acute ethanol-induced cardiotoxicity by regulating inflammatory pathways, oxidative stress, and mitochondrial function.

Conclusions and implications

Overall, these findings support the conclusion that the next-generation MRA finerenone attenuates acute ethanol-induced myocardial cell death, inflammation, oxidative stress, and mitochondrial dysfunction in vitro and in vivo. Finerenone may act as a novel protective agent against acute alcoholic myocardial injury in the future, but further clinical evidence is required to support this preclinical finding.

Graphical Abstract