L-Carvone as a Metabolic Enzyme Modulator in Doxorubicin Toxicity Induced Rat Tissue: A Combined Computational and Cardiac Slice Study

Cardiac hypertrophy and Heart failure are frequently caused by essential dysfunction, including deficiencies in tricarboxylic acid cycle (TCA) enzymes and redox state imbalances. The well-known cardiotoxic effects of doxorubicin (DOX), a frequently used chemotherapeutic drug, are mostly ascribed to its disruption of metabolic enzymes and consequent rise in reactive oxygen species (ROS). Mentha spicata L., is the source of L-Carvone, a monoterpenoid molecule with anti-inflammatory, antioxidant, and calcium-regulatory qualities. To assess the effectiveness of L-Carvone in reducing DOX-induced metabolic dysfunction, this work proposes an integrated approach that combines in situ experimental validation using rat heart slices with in silico kinetic modelling. We examined the effects of normal; DOX and DOX treated with L-Carvone circumstances on three important TCA cycle enzymes: Isocitrate dehydrogenase (IDH), Succinate dehydrogenase (SDH), and Malate dehydrogenase (MDH). Within a brief time frame, L-Carvone significantly restored enzymatic activity which may balance the NAD⁺/NADH redox ratio according to simulations and experimental experiments. Our results show strong proof that L-Carvone modulates TCA cycle key enzymes quickly and effectively, potentially providing treatment for chemotherapy-induced cardiomyopathy.