Exploring Esculetin's Protective Role: Countering Doxorubicin-Induced Oxidative Stress in Rat Heart
2024
Hamid Ceylan | Habibe Karadaş | Hilal Tosun | Murat Isıyel | Esra Nur Yeşilkent | Medine Sibel Karağaç | Neslihan Öztürk | Yeliz Demir
Doxorubicin (DOX) and other anthracyclines are potent chemotherapy drugs used against cancer; however, their clinical application is linked to significant and potentially life-threatening cardiotoxicity. Despite extensive research over many years, the available treatment choices are still constrained. DOX is typically believed to primarily affect mitochondria, and the characteristic feature of DOX-induced cardiotoxicity is mitochondrial dysfunction. In this study was designed to explore the protective effects of esculetin against DOX-induced cardiotoxicity in Sprague-Dawley rats, considering its known properties. Cardiotoxicity was induced by administering DOX via intraperitoneal injection at a weekly dosage of 5 mg/kg body weight for two consecutive weeks. Rats receiving DOX injections were simultaneously supplemented with esculetin at doses of 50 and 100 mg/kg body weight through intraperitoneal administration over the same period. The investigation, oxidative stress enzymes in heart tissue employed biochemical and molecular methods. Enzyme activities and expression levels of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were assessed in heart tissues.Intoxication with DOX resulted in a reduction in antioxidant status, affecting CAT and GPx and SOD. Both enzyme activity and mRNA expression decreased in the DOX group. There was an increase in DOX and esculetin combined groups. The present study proposes that DOX-induced detrimental effects on heart tissue are potentially mitigated by esculetin via modulation of oxidative stress.
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