Possible Cardio-protective Effects of TND1128 and Omega-3 Fatty Acids Against Daunorubicin-Induced Cardiotoxicity in Male Wistar Rats: A Comparative In Vivo Study

Abstract

Background: Daunorubicin, an anthracycline antibiotic widely used in chemotherapy, is limited due to its dose-dependent cardiotoxicity. Omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) provide cardioprotective benefits through reducing oxidative damage, suppressing inflammatory markers and enhancing antioxidant defenses. TND1128, a novel 5-deazaflavin derivative with mitochondrial-targeted redox activity, has been studied in hepatic and neuronal oxidative stress models, but its cardioprotective potential remains unexplored. This study aimed to evaluate the efficacy of Omega-3 and TND1128 in preventing daunorubicin-induced cardiotoxicity. Methods: Thirty-six male Wistar rats were randomized into six groups: Group Ӏ received corn oil; Group ӀӀ received daunorubicin (12 mg/kg i.p., last 3 days; cumulative dose 36 mg/kg); Group III received omega-3 (600 mg/kg/day, orally, 14 days); Group ӀV received omega-3 (600 mg/kg/day, by oral gavage,14 days)+daunorubicin (12 mg/kg i.p., last 3 days); Group V received TND1128 (10 mg/kg/day, by oral gavage, 14 days), and group VI received TND1128 (10 mg/kg/day, by oral gavage,14 days)+daunorubicin (12 mg/kg i.p., last 3 days). Cardiac injury indicators, oxidative stress markers, inflammation mediators, apoptotic signaling components (caspase-3), and histopathological analysis were assessed. Results: Both interventions significantly attenuated daunorubicin-induced biochemical, molecular, and histological alterations (P<0.01). TND1128 showed greater efficacy in reducing apoptosis and inflammation compared to omega-3 fatty acids, highlighting its potential as an adjunct therapy in anthracycline-based regimens. Conclusion: Omega-3 fatty acids and TND1128 significantly protected against daunorubicin-induced cardiotoxicity by improving oxidative stress, inflammation, apoptosis, and myocardial integrity. TND1128 provided superior protection, supporting its potential as an adjunct therapeutic strategy in anthracycline chemotherapies.