Effective Protection Against Alcohol-Related Cardiac Damage: Dapagliflozin

Chronic alcohol consumption causes serious damage to the liver and cardiovascular system and leads to neoplastic lesions in various organs such as the esophagus, liver, and breast. In our study, we evaluated the protective effects of standard and high doses of dapagliflozin against alcohol-related cardiac damage by utilizing its anti-inflammatory, anti-fibrotic, and anti-cardiac remodeling effects with biochemical and pathological parameters. Twenty male and twenty female Sprague-Dawley rats were used in the experiments. The animals were randomly divided into 5 groups, with 4 males and 4 females in each group. The experimental groups (ALCOHOL, ALCOHOL+DAP, and ALCOHOL+hDAP groups) were given 20% ethyl alcohol intraperitoneally (i.p.) once daily for 28 days. Dapagliflozin (DAP, ALCOHOL+DAP, and ALCOHOL+hDAP groups) and saline solution (CONT and ALCOHOL groups) were administered orally via gavage (o.g.). In the hearts of animals exposed to alcohol, cardiomyocyte hypertrophy, irregular myofiber arrangement, widespread or focal infiltration of inflammatory cells such as neutrophils and lymphocytes, and marked cytoplasmic vacuolization were observed. Treatment with high-dose dapagliflozin alleviated these structural changes. Alcohol caused significant proximal tubular damage. High-dose dapagliflozin resulted in a greater reduction in alcohol-induced renal damage. Although standard dose dapagliflozin improved alcohol-induced impaired Caspas-3, Cytokeratin 18-M30, Cytokeratin 18-M65, TAS, TOS, OSI, MDA, IL-1β, TNF-α, HsCRP, Endothelin-1, IMA, total thiol, native thiol, and disulfide levels, high dose dapagliflozin provided significant improvements (p<0.001). This study suggests that high-dose dapagliflozin (3 mg/kg) may have the potential to regulate mitochondrial function and thiol/disulfide balance in alcohol-related heart damage by inhibiting fibrosis, hypertrophy, apoptosis, inflammation, and oxidative stress through various mechanisms.