Open AccessA seleno-hormetine protects bone marrow hematopoietic cells against ionizing radiation-induced toxicities
Author(s) -
Desirée Bartolini,
Yanzhong Wang,
Jie Zhang,
Daniela Giustarini,
Ranieri Rossi,
Gavin Y. Wang,
Pierangelo Torquato,
Danyelle M. Townsend,
Kenneth D. Tew,
Francesco Galli
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0205626
Subject(s) - bone marrow , in vivo , haematopoiesis , ionizing radiation , cancer research , pharmacology , chemistry , glutathione , hormesis , biology , microbiology and biotechnology , oxidative stress , stem cell , immunology , biochemistry , enzyme , irradiation , physics , nuclear physics
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.