Abstract
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.