Background: β-Hydroxybutyrate (BHB) is produced by
fatty acid oxidation in the liver under the fasting state and confirmed to play a cardioprotective role in
ischemia and hypertensive settings.
Doxorubicin (DOX) is an effective chemotherapeutic drug, but limited by serious irreversible
cardiotoxicity. However, whether BHB can protect from DOX-induced
cardiotoxicity remains unknown. Methods and Results: C57BL/6 mice were intraperitoneally injected with DOX to induce
cardiac toxicity and intragastrically administered into BHB for treatment. They were randomly divided into three groups, namely a
sham group (
Sham), a
doxorubicin group (DOX), and a doxorubicin+β-Hydroxybutyrate group (DOX + BHB). Echocardiography and pathological staining were performed to evaluate cardiac function and
fibrosis. H9c2 cardiomyocyte was treated with DOX or BHB for in vitro experiments. Cell apoptosis and ROS were determined by flow cytometry. BHB significantly restored DOX-induced cardiac function decline and partially prevented cardiac reverse remodeling, characterized by increased cell size and decreased
fibrosis. In vitro, BHB treatment decreased cellular injury and apoptosis. Also, BHB alleviated oxidative stress level and increased mitochondrial membrane potential. Conclusion: Our results suggested that BHB could protected from DOX-induced
cardiotoxicity by inhibiting cell apoptosis and oxidative stress and maintaining mitochondrial membrane integrity.