Abstract
The short- and long-term side effects of chemotherapy limit the maximum therapeutic dose and impair quality of life of survivors. Injury to normal tissues, especially chemotherapy-induced cardiomyopathy, is an unintended outcome that presents devastating health impacts. Approximately half of the drugs approved by the Food and Drug Administration for cancer treatment are associated with the generation of reactive oxygen species, and Doxorubicin (Dox) is one of them. Dox undergoes redox cycling by involving its quinone structure in the production of superoxide free radicals, which are thought to be instrumental to the role it plays in cardiomyopathy. Dox-induced protein oxidation changes protein function, translocation, and aggregation that are toxic to cells. To maintain cellular homeostasis, oxidized proteins can be degraded intracellularly by ubiquitin-proteasome pathway or by autophagy, depending on the redox status of the cell. Alternatively, the cell can remove oxidized proteins by releasing extracellular vesicles (EVs), which can be transferred to neighboring or distant cells, thereby instigating an intercellular oxidative stress response. In this article, we discuss the role of EVs in oxidative stress response, the potential of EVs as sensitive biomarkers of oxidative stress, and the role of superoxide dismutase in attenuating EV-associated oxidative stress response resulting from chemotherapy.
Document Type
Review
Publication Date
9-28-2017
Digital Object Identifier (DOI)
https://doi.org/10.3390/antiox6040075
Funding Information
This study was supported by the National Institutes of Health (R01 CA139843) and the Royal Thai Government Scholarship (Ministry of Science and Technology).
Repository Citation
Yarana, Chontida and St. Clair, Daret K., "Chemotherapy-Induced Tissue Injury: An Insight into the Role of Extracellular Vesicles-Mediated Oxidative Stress Responses" (2017). Toxicology and Cancer Biology Faculty Publications. 62.
https://uknowledge.uky.edu/toxicology_facpub/62
Notes/Citation Information
Published in Antioxidants, v. 6, issue 4, 75, p. 1-17.
© 2017 by the authors. Licensee MDPI, Basel, Switzerland.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).