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

Abstract

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.

Nuclear and Radiological Emergencies: Biological Effects, Countermeasures and Biodosimetry

“…injected before or shortly after (+15 min) radiation exposure ( 60 Co, 9 Gy), enhance the survival of irradiated mice, but selenomethionine had lower toxicity [ 210 ]. Se treatment enhances Nrf2 transcription and upregulates the adaptive response to IR in bone marrow and hematopoietic precursors [ 211 ]. 3,3′-diselenodipropionic acid (DSePA) had maximum absorption in the lung, suppressed NF-kB/IL-17/G-CSF/neutrophil axis and significantly reduced infiltration of neutrophils and levels of IL1-β, ICAM-1, E-selectin, IL-17 and TGF-β in the bronchoalveolar fluid, prevented pneumonitis and increased survival of irradiated mice without affecting radiation sensitivity of tumors [ 212 ].…”

The Thiol-Modifier Effects of Organoselenium Compounds and Their Cytoprotective Actions in Neuronal Cells

“…Under normal conditions, Nrf2 is negatively regulated by Keap1. The oxidation of thiol bounds between Keap1 and Nrf2 leads to Nrf2 activation, stimulating the transcription of antioxidants elements [30,31]. In this context, we proposed to verify the ability of the prototype, (PhSe)2, to modulate antioxidant enzymes in HT22 cells, since in a previous study we demonstrated the effect of (PhSe)2 in activating the Nrf2 [10,15].…”

Synthesis of functionalised organochalcogenides and in vitro evaluation of their antioxidant activity

“…In summary, the organocalchogen compounds exert a significant antioxidant activity (p<0.05), presumably due to their GPX-like activity [5,41]. On the other hand, an effect on gene expression cannot be excluded, considering the long-term exposure to the studied compounds: modulation of the Nrf-2 antioxidant transcription factor has been recently reported for some selenium compounds [57]. The antioxidant effect was best detected when the concentration of ROS increased extensively within the cell, as it happens following H 2 O 2 exposure, and was persistent up to 2 h. Apparently, the behavior of the organo-tellurium and of the organo-selenium compounds was similar under the present experimental conditions.…”