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PLoS One. 2019 Apr 29;14(4):e0205626. doi: 10.1371/journal.pone.0205626. eCollection 2019.

A seleno-hormetine protects bone marrow hematopoietic cells against ionizing radiation-induced toxicities.

Author information

1
Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy.
2
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, United States of America.
3
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, United States of America.
4
Department of Biotechnology Chemistry and Pharmacy, University of Siena, Siena, Italy.

Abstract

2,2'-diselenyldibenzoic acid (DSBA) is a chemical probe produced to explore the pharmacological properties of diphenyldiselenide-derived agents with seleno-hormetic activity undergoing preclinical development. The present study was designed to verify in vivo the drug's properties and to determine mechanistically how these may mediate the protection of tissues against stress conditions, exemplified by ionizing radiation induced damage in mouse bone marrow. In murine bone marrow hematopoietic cells, the drug initiated the activation of the Nrf2 transcription factor resulting in enhanced expression of downstream stress response genes. This type of response was confirmed in human liver cells and included enhanced expression of glutathione S-transferases (GST), important in the metabolism and pharmacological function of seleno-compounds. In C57 BL/6 mice, DSBA prevented the suppression of bone marrow hematopoietic cells caused by ionizing radiation exposure. Such in vivo prevention effects were associated with Nrf2 pathway activation in both bone marrow cells and liver tissue. These findings demonstrated for the first time the pharmacological properties of DSBA in vivo, suggesting a practical application for this type of Se-hormetic molecules as a radioprotective and/or prevention agents in cancer treatments.

Conflict of interest statement

The authors have declared that no competing interests exist.

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