Ahmed Lamiaa A, Abdou Fatma Y, El Fiky Abir A, Shaaban Esmat A, Ain-Shoka Afaf A
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El Aini St., Cairo, 11562, Egypt.
Department of Drug Radiation Research, National Center for Radiation Research and Technology, Atomic Energy Authority, Nasr, Cairo, Egypt.
Cardiovasc Toxicol. 2021 Feb;21(2):127-141. doi: 10.1007/s12012-020-09602-5. Epub 2020 Aug 29.
Although doxorubicin (Dox) is a backbone of chemotherapy, the search for an effective and safe therapy to revoke Dox-induced acute cardiotoxicity remains a critical matter in cardiology and oncology. The current study was the first to explore the probable protective effects of native and gamma-irradiated fractions with bradykinin-potentiating activity (BPA) isolated from scorpion (Leiurus quinquestriatus) venom against Dox-induced acute cardiotoxicity in rats. Native or irradiated fractions (1 μg/g) were administered intraperitoneally (i.p.) twice per week for 3 weeks, and Dox (15 mg/kg, i.p.) was administered on day 21 at 1 h after the last native or irradiated fraction treatment. Electrocardiographic (ECG) aberrations were ameliorated in the Dox-treated rats pretreated with the native fraction, and the irradiated fraction provided greater amelioration of ECG changes than that of the native fraction. The group pretreated with native protein with BPA also exhibited significant improvements in the levels of oxidative stress-related, inflammatory, angiogenic, fibrogenic, and apoptotic markers compared with those of the Dox group. Notably, the irradiated fraction restored these biomarkers to their normal levels. Additionally, the irradiated fraction ameliorated Dox-induced histological changes and alleviated the severity of cardiac injury to a greater extent than that of the native fraction. In conclusion, the gamma-irradiated detoxified fraction of scorpion venom elicited a better cardioprotective effect than that of the native fraction against Dox-induced acute cardiotoxicity in rats.
尽管阿霉素（Dox）是化疗的主要药物，但寻找一种有效且安全的疗法来消除Dox诱导的急性心脏毒性仍是心脏病学和肿瘤学中的关键问题。本研究首次探讨了从蝎子（Leiurus quinquestriatus）毒液中分离出的具有缓激肽增强活性（BPA）的天然及γ射线辐照组分对大鼠Dox诱导的急性心脏毒性的潜在保护作用。天然或辐照组分（1μg/g）每周腹腔注射（i.p.）两次，共3周，在第21天最后一次天然或辐照组分处理后1小时腹腔注射Dox（15mg/kg，i.p.）。用天然组分预处理的Dox处理大鼠的心电图（ECG）异常得到改善，且辐照组分对ECG变化的改善程度大于天然组分。与Dox组相比，用具有BPA的天然蛋白预处理的组在氧化应激相关、炎症、血管生成、纤维化和凋亡标志物水平上也有显著改善。值得注意的是，辐照组分将这些生物标志物恢复到正常水平。此外，辐照组分改善了Dox诱导的组织学变化，并在更大程度上减轻了心脏损伤的严重程度，优于天然组分。总之，蝎子毒液经γ射线辐照的解毒组分对大鼠Dox诱导的急性心脏毒性的心脏保护作用优于天然组分。
