RESUMEN

Antioxidants given concurrently with chemotherapy offer an effective strategy for reducing the negative effects of the drug. One remaining obstacle to the use of doxorubicin (DOX) in chemotherapy is cardiotoxicity. Using vitamin E (Vit. E) as a reference standard, our study focuses on the potential preventive benefits of oxyresveratrol (ORES) and/or dapagliflozin (DAPA) against DOX-induced cardiac injury. Acute cardiotoxicity was noticed after a single intravenous injection of a male rat's tail vein with 10 mg/kg of DOX. Oral doses of ORES (80 mg/kg), DAPA (10 mg/kg), and Vit. E (1 g/kg) were given, respectively. Pretreatment of animals with Vit. E, ORES and/or DAPA revealed a considerable alleviation of heart damage, as evidenced by histopathological change mitigation and a notable drop in serum AST, LDH, CK, CK-MB, and cardiac contents of MDA and NO2-. Also, serum TAC, tissue GSH, and SOD showed substantial increases. Additionally, tissue caspase-3, serum IL-6, and TNF-α were considerably reduced. Moreover, a downregulation in cardiac gene expression of ATG-5, Keap-1, and NF-κB in addition to an upregulation of Bcl-2 gene expression and HO-1, Nrf-2, and PPAR-γ protein expression clearly appeared. Ultimately, ORES and/or DAPA have an optimistic preventive action against severe heart deterioration caused by DOX.

Asunto(s)

Compuestos de Bencidrilo , Cardiotoxicidad , Caspasa 3 , Doxorrubicina , Glucósidos , Proteína 1 Asociada A ECH Tipo Kelch , Factor 2 Relacionado con NF-E2 , FN-kappa B , PPAR gamma , Animales , Glucósidos/farmacología , Masculino , Ratas , PPAR gamma/metabolismo , PPAR gamma/genética , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , FN-kappa B/metabolismo , FN-kappa B/genética , Compuestos de Bencidrilo/toxicidad , Cardiotoxicidad/prevención & control , Cardiotoxicidad/tratamiento farmacológico , Cardiotoxicidad/etiología , Doxorrubicina/toxicidad , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/genética , Caspasa 3/metabolismo , Caspasa 3/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Estilbenos/farmacología , Interleucina-6/metabolismo , Interleucina-6/genética , Hemo Oxigenasa (Desciclizante)/metabolismo , Hemo Oxigenasa (Desciclizante)/genética , Cardiotónicos/farmacología , Transducción de Señal/efectos de los fármacos , Modelos Animales de Enfermedad , Extractos Vegetales/farmacología , Ratas Wistar , Antioxidantes/farmacología