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Biofactors. 2019 Oct 16. doi: 10.1002/biof.1578. [Epub ahead of print]

Nrf2-modulation by seleno-hormetic agents and its potential for radiation protection.

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Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy.
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina.
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina.


The trace element selenium (Se) is an essential component of selenoproteins and plays a critical role in redox signaling via regulating the activity of selenoenzymes such as thioredoxin reductase-1 and glutathione peroxidases. Se compounds and its metabolites possess a wide range of biological functions including anticancer and cytoprotection effects, modulation of hormetic genes and antioxidant enzyme activities. Radiation-induced injury of normal tissues is a significant side effect for cancer patients who receive radiotherapy in the clinic and the development of new and effective radioprotectors is an important goal of research. Others and we have shown that seleno-compounds have the potential to protect ionizing radiation-induced toxicities in various tissues and cells both in in vitro and in vivo studies. In this review, we discuss the potential utilization of Se compounds with redox-dependent hormetic activity as novel radio-protective agents to alleviate radiation toxicity. The cellular and molecular mechanisms underlying the radioprotection effects of these seleno-hormetic agents are also discussed. These include Nrf2 transcription factor modulation and the consequent upregulation of the adaptive stress response to IR in bone marrow stem cells and hematopoietic precursors.


Nrf2; free radicals; glutathione; glutathione S-transferase; ionizing radiations; oxidant stress; selenium; seleno-hormesis


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