A toxicological report on drug-induced toxicity evaluation: integrated preclinical findings from in vitro and in vivo studies to human risk prediction and lethal outcomes, including teratogenic effects and mortality

Abstract Anthracyclines, potent chemotherapeutic agents derived from Streptomyces species, play a pivotal role in the treatment of various malignancies, particularly haematologic and solid tumors in humans. Despite their efficacy, their clinical utility is hampered by dose-dependent, irreversible chronic cardiotoxicity, which contributes to rising morbidity and mortality among cancer survivors. This is a limitation and drawback of anthracycline drugs, which constrain their therapeutic potency, clinical effectiveness, pharmacological activity and therapeutic impact. Compromised pharmacodynamic efficacy compromises patient safety and poses significant obstacles to achieving remission, thereby affecting patient tolerability and increasing risk. Type-1 anthracycline-induced cardiotoxicity (AIC) involves progressive cardiomyocyte loss and heart failure, presenting a serious challenge in cardio-oncology. Recent advances have elucidated molecular mechanisms underpinning AIC, including topoisomerase II inhibition, oxidative stress (reactive oxygen species generation), and mitochondrial dysfunction, enabling targeted research and precision-based interventions. It elucidates advanced translational toxicology by enabling mitochondrial-targeted drug-induced cardiotoxicity, resulting in mitochondrial dysfunction offering precision-based cardiac function studies and optimising patient-specific clinical outcomes as study results. Using cardiac magnetic resonance and magnetic resonance spectroscopy (MRS) imaging techniques, the study further highlighted how advancements in emerging technology play a pivotal role in cardiac function studies. Over and above that, a detailed dissection with a thorough examination of the heart and its muscles through autopsy and histological analysis of cardiac tissue under the microscope revealed significant, substantial histopathological evidence, confirming the cardiotoxic effects. Anthracycline-associated cardiac complications with other agents encompass concerns such as: bradycardia, tachyarrhythmias, blocks in the heart’s electrical signals, reduced blood flow to the heart muscle (myocardial ischaemia) and frequent hypotension.