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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

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Abstract

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.

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All data generated or analyzed during this study are included in this published article.

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Acknowledgements

The authors are thankful to the Faculty of Pharmacy, Cairo University, and the Atomic Energy Authority for cooperation. The authors are also grateful to Prof. Dr. Ahmed Othman, Faculty of Veterinary Medicine, Cairo University, for his efforts in the histopathological examinations.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

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

    Lamiaa A. Ahmed & Afaf A. Ain-Shoka

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

    Fatma Y. Abdou & Esmat A. Shaaban

  3. ANDI Center of Excellence in Antivenom Research, Vacsera, Egypt

    Abir A. El Fiky

Authors
  1. Lamiaa A. Ahmed
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  2. Fatma Y. Abdou
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  3. Abir A. El Fiky
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  4. Esmat A. Shaaban
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  5. Afaf A. Ain-Shoka
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Contributions

LAA, FYA and AAA conceived and designed research. LAA, FYA and AAE conducted experiments. LAA, EAS and FYA analyzed data. LAA and FYA wrote the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Lamiaa A. Ahmed.

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Conflict of interest

The authors report no conflict of interest.

Ethical Approval

All procedures performed in this study were conducted in accordance with the regulations approved by the Ethics Committee at Faculty of Pharmacy, Cairo University (permit number:1776). The investigation complied with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85-23, revised 2011).

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Ahmed, L.A., Abdou, F.Y., El Fiky, A.A. et al. 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. Cardiovasc Toxicol 21, 127–141 (2021). https://doi.org/10.1007/s12012-020-09602-5

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  • DOI: https://doi.org/10.1007/s12012-020-09602-5

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