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

Eur J Pharm Sci. 2024 Sep 1:200:106849. doi: 10.1016/j.ejps.2024.106849. Epub 2024 Jul 9.

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.

Keywords: Apoptosis; Cardiotoxicity; Carvedilol; Doxorubicin; Inflammation; Oxidative stress.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / adverse effects
  • Antibiotics, Antineoplastic / toxicity
  • Apoptosis / drug effects
  • Carbazoles / pharmacology
  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use
  • Cardiotoxicity* / etiology
  • Cardiotoxicity* / prevention & control
  • Carvedilol* / pharmacology
  • Carvedilol* / therapeutic use
  • Doxorubicin* / adverse effects
  • Doxorubicin* / toxicity
  • Humans
  • Oxidative Stress / drug effects
  • Propanolamines / pharmacology

Substances

  • Carvedilol
  • Doxorubicin
  • Antibiotics, Antineoplastic
  • Cardiotonic Agents
  • Carbazoles
  • Propanolamines