Mechanistic insights into carvedilol's potential protection against doxorubicin-induced cardiotoxicity

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Elmorsy E.A.; Saber S.; Hamad R.S.; Abdel-Reheim M.A.; El-kott A.F.; AlShehri M.A.; Morsy K.; Negm S.; Youssef M.E.

Journal: European Journal of Pharmaceutical Sciences

Publisher: Elsevier B.V.

Publication Date: September 2024

Volume / Issue: Volume 200

Article No.: 106849

ISSN: 9280987

DOI: 10.1016/j.ejps.2024.106849

Scopus: View on Scopus

PubMed: 38992452

Document Type: Review

Access: All Open Access; Gold Open Access

Authors and Affiliations

Elmorsy E.A., Department of Pharmacology and Therapeutics, College of Medicine, Qassim University, Buraidah, 51452, Saudi Arabia, Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt; Saber S., Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, 11152, Egypt; Hamad R.S., Biological Sciences Department, College of Science, King Faisal University, Al Ahsa, 31982, Saudi Arabia, Central Laboratory, Theodor Bilharz Research Institute, Giza, 12411, Egypt; Abdel-Reheim M.A., Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Shaqra, 11961, Saudi Arabia, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni Suef, 62521, Egypt; El-kott A.F., Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia, Department of Zoology, Faculty of Science, Damanhour University, Egypt; AlShehri M.A., Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia; Morsy K., Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia, Department of Zoology, Faculty of Science, Cairo University, Cairo, Egypt; Negm S., Department of Life Sciences, College of Science and Art Mahyel Aseer, King Khalid University, Abha, 62529, Saudi Arabia; Youssef M.E., Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, 11152, Egypt

Abstract

Doxorubicin (DOX) is an anthracycline chemotherapy drug widely employed in the treatment of various cancers, known for its potent antineoplastic properties but often associated with dose-dependent cardiotoxicity, limiting its clinical use. This review explores the complex molecular details that determine the heart-protective effectiveness of carvedilol in relation to cardiotoxicity caused by DOX. The harmful effects of DOX on heart cells could include oxidative stress, DNA damage, iron imbalance, disruption of autophagy, calcium imbalance, apoptosis, dysregulation of topoisomerase 2-beta, arrhythmogenicity, and inflammatory responses. This review carefully reveals how carvedilol serves as a strong protective mechanism, strategically reducing each aspect of cardiac damage caused by DOX. Carvedilol's antioxidant capabilities involve neutralizing free radicals and adjusting crucial antioxidant enzymes. It skillfully manages iron balance, controls autophagy, and restores the calcium balance essential for cellular stability. Moreover, the anti-apoptotic effects of carvedilol are outlined through the adjustment of Bcl-2 family proteins and activation of the Akt signaling pathway. The medication also controls topoisomerase 2-beta and reduces the renin-angiotensin-aldosterone system, together offering a thorough defense against cardiotoxicity induced by DOX. These findings not only provide detailed understanding into the molecular mechanisms that coordinate heart protection by carvedilol but also offer considerable potential for the creation of targeted treatment strategies intended to relieve cardiotoxicity caused by chemotherapy. © 2024 The Author(s)

Keywords

Apoptosis; Cardiotoxicity; Carvedilol; Doxorubicin; Inflammation; Oxidative stress; Animals; Antibiotics, Antineoplastic; Carbazoles; Cardiotonic Agents; Humans; Propanolamines; anthracycline; calcium; DNA topoisomerase (ATP hydrolysing); iron; antineoplastic antibiotic; carbazole derivative; cardiotonic agent; propanolamine derivative; adverse drug reaction; Akt signaling; antiapoptotic activity; antineoplastic activity; autophagic cell death; autophagy (cellular); calcium balance; cancer inhibition; cardiac muscle cell; DNA damage; drug therapy; drug toxicity; heart injury; heart protection; human; male; mouse; nonhuman; pharmacokinetics; pharmacology; renin angiotensin aldosterone system; review; side effect; animal; drug effect; etiology; prevention and control

Citation Information

Scopus Citations: 17

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