L-Carvone restored activity of key TCA cycle enzymes to approximately 86-91% of control within 5 minutes in doxorubicin-injured rat cardiac tissue slices.
Does L-Carvone improve TCA cycle enzyme activity in doxorubicin-induced cardiotoxicity in rat heart slices?
L-Carvone rapidly restores key TCA cycle enzyme activities in doxorubicin-treated rat heart slices, suggesting potential as a metabolic modulator for chemotherapy-induced cardiotoxicity.
Effect estimate: Enzymatic activity restored to approximately 86-91% of control levels with L-Carvone at 5 minutes compared to ~40-50% activity with doxorubicin alone
Absolute Event Rate: 86% vs 100%
p-value: p=<0.05
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.
Nagarajan et al. (Mon,) conducted a other in Adult male Wistar rats (10-12 weeks old, 250-300 g) with cardiac tissue exposed ex vivo to doxorubicin-induced cardiotoxicity (n=18). L-Carvone vs. Doxorubicin 10 µM alone and control buffer only was evaluated on Enzymatic activity of TCA cycle key enzymes (Isocitrate dehydrogenase, Succinate dehydrogenase, Malate dehydrogenase) in cardiac tissue slices (Enzymatic activity restored to approximately 86-91% of control levels with L-Carvone at 5 minutes compared to ~40-50% activity with doxorubicin alone, p=<0.05). L-Carvone restored activity of key TCA cycle enzymes to approximately 86-91% of control within 5 minutes in doxorubicin-injured rat cardiac tissue slices.