Abstract:
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.
摘要:
与化疗同时给予的抗氧化剂提供了减少药物负面影响的有效策略。在化疗中使用阿霉素(DOX)的一个剩余障碍是心脏毒性。使用维生素E(Vit。E)作为参考标准,我们的研究重点是氧化白藜芦醇(ORES)和/或达格列净(DAPA)对DOX诱导的心脏损伤的潜在预防作用.在雄性大鼠的尾静脉注射10mg/kg的DOX后,发现了急性心脏毒性。ORES的口服剂量(80mg/kg),DAPA(10mg/kg),和Vit。给予E(1g/kg),分别。用Vit预处理动物。E,ORES和/或DAPA揭示了心脏损伤的显著缓解,如组织病理学改变缓解和血清AST显著下降所证明,LDH,CK,CK-MB,心脏MDA和NO2-含量。此外,血清TAC,组织GSH,和SOD表现出显著的增加。此外,组织caspase-3,血清IL-6和TNF-α显着降低。此外,心脏ATG-5,Keap-1和NF-κB基因表达下调,Bcl-2基因表达上调,HO-1,Nrf-2和PPAR-γ蛋白表达上调。最终,ORES和/或DAPA对DOX引起的严重心脏恶化具有乐观的预防措施。