Toxic effects and molecular mechanism of doxorubicin on different organs – an update

Abstract

Doxorubicin is an extensively used anti-neoplastic drug used for solid and hematogenous cancer since the 1950s, and its usage is limited due to its toxic effects upon various organs. The main reason behind the toxicity is the production of free radicals. It is evident that the first and foremost organ affected by the doxorubicin is the heart, and further, it causes toxic effects in hepatic, kidney, reproductive organs, adipose tissue, and brain. This review aims to bring up recent findings on the molecular mechanisms underlying doxorubicin-induced toxicity among different organs via the regulation of various signaling and biochemical events.

Highlights

• The review focuses on the multiorgan toxicity due to doxorubicin treatment explained among various animal models and cell lines.

• The heart has been reported as the primary organ, which is highly vulnerable to doxorubicin therapy through multiple pathways, eventually emanating cardiotoxicity.

• Apart from the heart, the mechanisms underlying multiorgan toxicity, which include liver, kidney, adipose tissue, reproductive systems of both male and female, and the nervous system were also affected during the doxorubicin therapy.

• The most common mechanism of toxicity among all the organs includes imbalances in the redox potential of the cell due to the free radicals produced during the metabolism of doxorubicin treatment.

• Besides the use of doxorubicin for malignancies, the patients are prone to developing serious side effects at an off-target site.

Keywords:

• Doxorubicin
• cardiotoxicity
• hepatotoxicity
• nephrotoxicity
• reproductive toxicity
• neurotoxicity
• adipose tissue toxicity

Acknowledgements

The authors thank the VIT, Vellore, Tamil Nadu, India, for supporting this work. The author Kaviyarasi Renu is grateful to ICMR for providing financial assistance in the form of a Senior Research Fellowship (SRF).

Disclosure statement

The authors declare that there is no conflict of interest.

Additional information

Funding

This work was supported by the "VIT SEED GRANT" and ICMR-National Task Force Project [F. no. 5/7/482/2010-RBMH&CH].