Recent progress in the role of endogenous metal ions in doxorubicin-induced cardiotoxicity

Ni Zhou; Shanshan Wei; Taoli Sun; Suifen Xie; Jian Liu; Wenqun Li; Bikui Zhang

doi:10.3389/fphar.2023.1292088

Recent progress in the role of endogenous metal ions in doxorubicin-induced cardiotoxicity

Front Pharmacol. 2023 Dec 8:14:1292088. doi: 10.3389/fphar.2023.1292088. eCollection 2023.

Authors

Ni Zhou^{1

2

3}, Shanshan Wei^{1

2}, Taoli Sun⁴, Suifen Xie^{1

2

3}, Jian Liu^{1

2}, Wenqun Li^{1

2}, Bikui Zhang^{1

2

3}

Affiliations

¹ Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Institute of Clinical Pharmacy, Central South University, Changsha, Hunan, China.
³ School of Pharmacy, Central South University, Changsha, Hunan, China.
⁴ School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, China.

Abstract

Doxorubicin is a widely used anticancer drug in clinical practice for the treatment of various human tumors. However, its administration is associated with cardiotoxicity. Administration of doxorubicin with low side effects for cancer treatment and prevention are, accordingly, urgently required. The human body harbors various endogenous metal ions that exert substantial influences. Consequently, extensive research has been conducted over several decades to investigate the potential of targeting endogenous metal ions to mitigate doxorubicin's side effects and impede tumor progression. In recent years, there has been a growing body of research indicating the potential efficacy of metal ion-associated therapeutic strategies in inhibiting doxorubicin-induced cardiotoxicity (DIC). These strategies offer a combination of favorable safety profiles and potential clinical utility. Alterations in intracellular levels of metal ions have been found to either facilitate or mitigate the development of DIC. For instance, ferroptosis, a cellular death mechanism, and metal ions such as copper, zinc, and calcium have been identified as significant contributors to DIC. This understanding can contribute to advancements in cancer treatment and provide valuable insights for mitigating the cardiotoxic effects of other therapeutic drugs. Furthermore, potential therapeutic strategies have been investigated to alleviate DIC in clinical settings. The ultimate goal is to improve the efficacy and safety of Dox and offer valuable insights for future research in this field.

Keywords: calcium; cardiotoxicity; copper; doxorubicin; iron; zinc.

Publication types

Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants of the National Natural Scientific Foundation of China (Nos 82173911 and 81973406), Fundamental Research Funds for the Central Universities of Central South University (No. 2023ZZTS0891), Hunan Provincial Natural Scientific Foundation (Nos 2023JJ30761 and 2023JJ30802), Scientific Research Project of Hunan Provincial Health and Family Planning Commission (No. 202113050843), and Research Project established by Chinese Pharmaceutical Association Hospital Pharmacy department (No. CPA-Z05-ZC-2021-002).