AdipoRon ameliorates chronic ethanol induced cardiac necroptosis by reducing ceramide mediated mtROS.

Chronic ethanol (EtOH) consumption has been widely recognized as a significant contributor to cardiotoxicity. However, no specific treatment is currently available to ameliorate chronic ethanol induced cardiotoxicity. Adiponectin receptor agonist AdipoRon exerts protective effects in multiple organs through alleviating lipotoxicity.

Chronic ethanol exposure induces cardiac fibroblast transdifferentiation via ceramide accumulation and oxidative stress.

Aims: Excessive alcohol consumption is associated with cardiac dysfunction and the development of myocardial fibrosis. In this study, we aimed to investigate the direct impacts of ethanol on myocardial fibroblasts and elucidate the underlying mechanism responsible for chronic ethanol-induced myocardial fibrosis.

Methods: Rat primary cardiac fibroblasts exposed to ethanol for 24 h and C57BL/6J mice fed on Lieber-DeCarli diet to establish an ethanol intoxication model in vitro and in vivo, respectively.

Inhibition of Ceramide Synthesis Attenuates Chronic Ethanol Induced Cardiotoxicity by Restoring Lysosomal Function and Reducing Necroptosis.

Aims: Chronic alcohol misuse could cause alcoholic cardiomyopathy (ACM), and the specific mechanisms remained largely unknown. In this study, we aimed to explore the effects of endogenous ceramides on chronic ethanol-induced myocardial injury or cell loss (e.g.