European Journal of Pharmaceutical Sciences 1 September 2024

Title	European Journal of Pharmaceutical Sciences 1 September 2024
Edition	1 September 2024
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ISBN/ISSN
Author(s)
Subject(s)	Doxorubicin Cardiotoxicity Inflammation
Classification
Series Title
GMD	Jurnal
Language	Indonesia
Publisher
Publishing Year	2024
Publishing Place
Collation
Abstract/Notes	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 effec- tiveness 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 de- fense against cardiotoxicity induced by DOX. These findings not only provide detailed understanding into the
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