Biomarkers of apoptosis and endoplasmic reticulum stress in cardiomyocytes of rats under chronic ethanol consumption and germanium-nicotinic acid complex administration

Abstract

Chronic ethanol consumption is associated with a range of harmful effects on different systems of the body, including the heart. Coordination complexes of bioactive compounds based on non-toxic metals are attracting interest in biomedical research due to their potential therapeutic properties. The study aimed to evaluate the influence of the germanium-nicotinic acid complex (MIGU-1) on apoptosis and endoplasmic reticulum (ER) stress indicators in the myocardium of rats under chronic alcohol exposure. Female Wistar rats were divided into three groups of 6 animals each: intact animals; rats that received 20% ethanol as the sole source of liquid for 110 days; animals with chronic consumption of 20% ethanol, which from the 90th day until the end of the experiment were intraperitoneally administered MIGU-1 solution (10 mg/kg/day). Biomarkers related to apoptosis, ER stress autophagy were assessed by Western blot analysis. It was shown that chronic ethanol consumption significantly activated apoptotic pathways in rat myocardium tissue, evidenced by increased levels of cleaved caspase-3 and BAX proteins alongside Beclin-1 level elevation, indicating enhanced autophagy. A significant decrease in the content of the protein IRE1 and its phosphorylated form in myocardial with no changes in GRP78 protein level was detected. Treatment with MIGU-1 resulted in both ethanol-induced apoptosis reduction and ER stress attenuation in cardiomyocytes with the level of Beclin-1 and GRP78 proteins remaining unchanged. Our findings demonstrate that the MIGU-1 complex promotes cardiomyocyte survival by balancing apoptosis and unfolded protein response, thus preventing alcohol-related cardiac injury.