Bradykinin-Potentiating Activity of a Gamma-Irradiated Bioactive Fraction Isolated from Scorpion ( Leiurus quinquestriat

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Bradykinin‑Potentiating Activity of a Gamma‑Irradiated Bioactive Fraction Isolated from Scorpion (Leiurus quinquestriatus) Venom in Rats with Doxorubicin‑Induced Acute Cardiotoxicity: Favorable Modulation of Oxidative Stress and Inflammatory, Fibrogenic and Apoptotic Pathways Lamiaa A. Ahmed1   · Fatma Y. Abdou2 · Abir A. El Fiky3 · Esmat A. Shaaban2 · Afaf A. Ain‑Shoka1 Received: 27 April 2020 / Accepted: 18 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Although doxorubicin (Dox) is a backbone of chemotherapy, the search for an effective and safe therapy to revoke Doxinduced 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. Keywords  Cardiotoxicity · Doxorubicin · Gamma irradiation · Scorpion venom

Introduction

Handling editor: Y. James Kang. * Lamiaa A. Ahmed [email protected] Fatma Y. Abdou [email protected] Abir A. El Fiky [email protected] Esmat A. Shaaban [email protected]

Peptides isolated from the venom of different animals can be highly selective, potent, and valuable therapeutics. The potential of venom-derived peptides to be used in therapies or cosmetics, therefore, is growing [1]. In 1960, Sergio 1



Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El Aini St., Cairo 11562, Egypt

2



Department of Drug Radiation Research, National Center for Radiation Research and Technology, Atomic Energy Authority, Nasr, Cairo, Egypt

3



ANDI Center of Excellence in Antivenom Research, Vacsera, Egypt

Afaf A. Ain‑Shoka [email protected]

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Cardiovascular