Key result
Empagliflozin (10 mg/kg/day) significantly attenuated adverse left ventricular remodeling, preserved LVEF, and prevented ER stress and apoptosis in rats with doxorubicin-induced cardiotoxicity.
Why the study?
Doxorubicin causes severe cardiotoxicity and strategies to prevent it remain limited, prompting evaluation of empagliflozin's potential to prevent and treat doxorubicin-induced cardiomyopathy in vivo.
Does empagliflozin prevent doxorubicin-induced cardiomyopathy and endoplasmic reticulum stress in rats?
Does empagliflozin prevent doxorubicin-induced cardiomyopathy and endoplasmic reticulum stress in rats?
In a rat model, empagliflozin mitigated doxorubicin-induced cardiotoxicity by preserving LVEF and reducing endoplasmic reticulum stress and apoptosis.
Should not change clinical practice for doxorubicin cardiotoxicity; leaves open SGLT2i prevention hypothesis pending human trials.
Although Doxorubicin (Dox) is an effective anticancer drug, it can cause severe cardiotoxicity. While several mechanisms have been proposed to explain Dox-induced cardiomyopathy (DIC), strategies to prevent it remain limited. In previous research on isolated cardiomyocytes, we identified that Empagliflozin (EMPA), an antidiabetic drug, mitigated Dox-induced ER stress and apoptosis. In this in vivo study using rats, we further investigated EMPA's potential in preventing and treating DIC. Rats administered a cumulative dose of 15 mg/kg Dox exhibited significant cardiovascular damage, including left ventricular cavity dilation, decreased left ventricular ejection fraction (LVEF), ER dilation, mitochondrial defects and vacuole formation. These structural changes were linked to the activation of ER-stress pathways (PERK, IRE1 and ATF6) and upregulation of apoptotic proteins initiated by ER stress. When EMPA (10 mg/kg/day) was administered either prophylactically or concurrently with Dox, it significantly attenuated adverse LV remodelling and preserved LVEF. Additionally, EMPA prevented ER stress and subsequent apoptosis in the myocardium of the Dox + EMPA-treated group. These findings suggest that EMPA offers cardioprotective benefits in DIC, likely through the inhibition of ER-stress-induced myocardial injury.
No takes yet. Share an insight, caveat, or question.
Malik et al. (2026) studied Doxorubicin-induced cardiotoxicity. Empagliflozin vs. Doxorubicin alone was evaluated on Left ventricular remodeling, LVEF, and ER stress. Empagliflozin (10 mg/kg/day) significantly attenuated adverse left ventricular remodeling, preserved LVEF, and prevented ER stress and apoptosis in rats with doxorubicin-induced cardiotoxicity.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: