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ORAL PRESENTATION / TAM METİN SÖZLÜ SUNUM

INTRODUCTION

Cardiotoxicity is a term used to describe deleterious effects on the heart that may lead
to cardiomyopathies, including arrhythmia, myocardial infarction, and myocardial

hypertrophy. In animals, cardiotoxicity may result from exposure to various xenobiotic
compounds including cardiotoxic plant constituents, biotoxins, and mycotoxins. Additionally,

envenomation through bites or stings from other animals (e.g., snake envenomation or

arachnid toxins); chemotherapeutic agents, including antineoplastic drugs (such as
doxorubicin and cisplatin) and NSAIDs; and environmental contaminants, such as heavy
metals and persistent organic pollutants, have also been implicated as contributing factors

(Zoltani, 2018). Experimental evidence indicates that cardiomyocyte death or injury occurs

concurrently with the progression of cardiotoxicity, suggesting that xenobiotic-induced
cardiomyocyte loss may represent a central mechanism this pathology. The mechanisms by

which xenobiotics impair cardiac function are diverse, ranging from direct cytotoxic effects
on cardiomyocytes to alterations in ion channel activity and disruption of intracellular

signaling pathways. Therefore, targeting the specific molecular mechanisms and pathways
involved in xenobiotic-induced cardiotoxicity is essential to develop preventive strategies and

therapeutic interventions (Costa et al., 2013; Ma et al., 2020; Morelli et al., 2022).

Doxorubicin (DOX), a member of the anthracycline class of chemotherapeutic agents,
is highly effective against a wide range of cancers, including lung, breast, bladder, and

hematologic malignancies such as lymphomas and leukemia. Conversely, DOX can harm
healthy cells through mechanisms similar to those by which it exerts its cytotoxic effects on

cancer cells. However, its clinical application is limited by its well-documented cardiotoxicity
(Jones and Dass, 2022). The pathophysiology of DOX-induced cardiotoxicity involves various

factors and mechanisms, including oxidative stress, free radical formation, inflammatory
cytokine release, mitochondrial damage, intracellular iron accumulation, cellular calcium

overload, DNA and myocyte membrane injury, cell necrosis and apoptosis, and myofibrillar
disarray (Wang et al., 2021). This cardiotoxicity ultimately progresses to cardiomyopathy and

cardiac dysfunction. Therefore, enhancing antioxidant, anti-inflammatory, and anti-apoptotic

defenses may represent an effective strategy to mitigate DOX-induced cardiotoxicity (Tanwar
et al., 2025). Doxorubicin (5 µM) is widely used to establish a cardiotoxicity model in H9c2

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