## 1 Introduction  
Anthracycllines rank as some of the most potent chemotherapy drugs, crucial for treating a range of adult cancers such as breast cancer, sarcomas, and lymphomas. Their anticancer efficacy is due in part to their ability to intercalate into nuclear DNA, inhibit topoisomerase II, and generate reactive oxygen species (ROS), leading to widespread cellular damage including DNA, mitochondria, and cell membranes, and triggering apoptosis in cardiomyocytesocytes [1]. Despite their efficacy, the clinical application of anthracyclines is curtailed by cardiotoxicity that is proportional to the dose administered, with lower doses potentially compromising the response to cancer treatment.  
Apoptosis of cardiomyocytes is a critical aspect of the cardiac damage induced by anthracyclines. Recent studies underline the significant role of this apoptosis in the development of drug-induced cardiomyopathy [2; 3; 4]. To counteract the oxidative stress provoked by anthracycline medications, the use of antioxidants, whether natural or synthetic, has been proposed. Agents like N-acetylcysteine, berberine, and silymarin have shown promise in biochemically and histologically preventing doxorubicin-induced cardiotoxicity in rat models [5; 6; 7]. Similarly, melatonin has been observed to safeguard heart tissue from epirubicin-induced toxicity [8].  
Hesperetin (HSP) is a flavanone, a type of flavonoid, which is a class of compounds with antioxidant effects found naturally in a variety of plants. HSP is particularly abundant in citrus fruits and is the predominant flavanone in oranges and lemons. It is the aglycone form of hesperidin, which means that hesperidin is hesperidin without its sugar part. HSP, like other flavonoids, is known for its potential health benefits. It has been studied for its antioxidant properties, which can help to protect cells from damage caused by free radicals [9; 10; 11]. This action is the basis for its potential role in reducing inflammation and fighting against various diseases, including cancer and cardiovascular diseases.  
HSP is known for its broad range of pharmacological benefits, including its role as an antioxidant [9; 10; 12], anti-inflammatory [13], anticarcinogenic [14], and neuroprotective [15; 16] agent. While prior research has shown that HSP can mitigate the cardiotoxicity induced by doxorubicin by reducing oxidative stress [17], the specific effects of HSP on cardiomyocyte apoptosis and desmin integrity in the context of epirubicin-induced damage have not yet been explored.  
The study hypothesizes that HSP has cardioprotective properties capable of reducing the cardiotoxic effects of epirubicin (Epi), a chemotherapeutic agent known for induction apoptosis in cardiomyocytes, leading to cardiomyopathy. Through histopathological analysis, along with immunofluorescence, immunohistochemistry, and transmission electron microscopy (TEM), the study aims to evaluate whether HSP treatment preserves cardiac morphology, modulates the expression of apoptosis-regulating Bcl-2 family proteins, and maintains mitochondrial and DNA integrity in cardiac cells. This histopathological approach seeks to establish the efficacy of HSP in preventing the characteristic cardiac damage associated with Epi exposure.