A seleno-hormetine protects bone marrow hematopoietic cells against ionizing radiation-induced toxicities
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 de...
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| Veröffentlicht in: | PloS one 2019-04, Vol.14 (4), p.e0205626-e0205626 |
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| creator | Bartolini, Desirée Wang, Yanzhong Zhang, Jie Giustarini, Daniela Rossi, Ranieri Wang, Gavin Y Torquato, Pierangelo Townsend, Danyelle M Tew, Kenneth D Galli, Francesco |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0205626 |
| format | Article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0205626</identifier><identifier>PMID: 31034521</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Benzene Derivatives - chemistry ; Benzene Derivatives - pharmacology ; Bone marrow ; Cancer ; Cancer therapies ; Care and treatment ; Chemistry ; EDTA ; Gamma Rays - adverse effects ; Gene expression ; Genes ; Genetic aspects ; Glutathione ; Glutathione transferase ; Grants ; Health aspects ; Hematopoietic Stem Cells - metabolism ; Hematopoietic Stem Cells - pathology ; Hep G2 Cells ; Hepatocytes ; Humans ; In vivo methods and tests ; Ionizing radiation ; Laboratories ; Liver ; Liver cancer ; Male ; Medical research ; Metabolism ; Mice ; NF-E2-Related Factor 2 - metabolism ; Organic chemistry ; Organoselenium Compounds - chemistry ; Organoselenium Compounds - pharmacology ; Pharmaceutical sciences ; Pharmacology ; Pharmacy ; Prevention ; Properties (attributes) ; Radiation ; Radiation (Physics) ; Radiation damage ; Radiation effects ; Radiation exposure ; Radiation therapy ; Radiation-Protective Agents - chemistry ; Radiation-Protective Agents - pharmacology ; Selenium compounds ; Senescence ; Signal transduction ; Stem cells ; Stress response ; Systematic review ; Tissues ; Toxicity ; Transcription (Genetics) ; Transcription activation ; Transcription factors ; Transferases ; Wang, Kenneth</subject><ispartof>PloS one, 2019-04, Vol.14 (4), p.e0205626-e0205626</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Bartolini et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 Bartolini et al 2019 Bartolini et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-23691b32b327c83a7d077a04e03cdc5535bbaaf884799375c141cac609e0a32c3</citedby><cites>FETCH-LOGICAL-c692t-23691b32b327c83a7d077a04e03cdc5535bbaaf884799375c141cac609e0a32c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488049/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488049/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31034521$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Bunting, Kevin D.</contributor><creatorcontrib>Bartolini, Desirée</creatorcontrib><creatorcontrib>Wang, Yanzhong</creatorcontrib><creatorcontrib>Zhang, Jie</creatorcontrib><creatorcontrib>Giustarini, Daniela</creatorcontrib><creatorcontrib>Rossi, Ranieri</creatorcontrib><creatorcontrib>Wang, Gavin Y</creatorcontrib><creatorcontrib>Torquato, Pierangelo</creatorcontrib><creatorcontrib>Townsend, Danyelle M</creatorcontrib><creatorcontrib>Tew, Kenneth D</creatorcontrib><creatorcontrib>Galli, Francesco</creatorcontrib><title>A seleno-hormetine protects bone marrow hematopoietic cells against ionizing radiation-induced toxicities</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.</description><subject>Animals</subject><subject>Benzene Derivatives - chemistry</subject><subject>Benzene Derivatives - pharmacology</subject><subject>Bone marrow</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Chemistry</subject><subject>EDTA</subject><subject>Gamma Rays - adverse effects</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Glutathione</subject><subject>Glutathione transferase</subject><subject>Grants</subject><subject>Health aspects</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>Hematopoietic Stem Cells - pathology</subject><subject>Hep G2 Cells</subject><subject>Hepatocytes</subject><subject>Humans</subject><subject>In vivo methods and tests</subject><subject>Ionizing radiation</subject><subject>Laboratories</subject><subject>Liver</subject><subject>Liver cancer</subject><subject>Male</subject><subject>Medical research</subject><subject>Metabolism</subject><subject>Mice</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>Organic chemistry</subject><subject>Organoselenium Compounds - chemistry</subject><subject>Organoselenium Compounds - pharmacology</subject><subject>Pharmaceutical sciences</subject><subject>Pharmacology</subject><subject>Pharmacy</subject><subject>Prevention</subject><subject>Properties (attributes)</subject><subject>Radiation</subject><subject>Radiation (Physics)</subject><subject>Radiation damage</subject><subject>Radiation effects</subject><subject>Radiation exposure</subject><subject>Radiation therapy</subject><subject>Radiation-Protective Agents - chemistry</subject><subject>Radiation-Protective Agents - pharmacology</subject><subject>Selenium compounds</subject><subject>Senescence</subject><subject>Signal transduction</subject><subject>Stem cells</subject><subject>Stress response</subject><subject>Systematic review</subject><subject>Tissues</subject><subject>Toxicity</subject><subject>Transcription (Genetics)</subject><subject>Transcription activation</subject><subject>Transcription factors</subject><subject>Transferases</subject><subject>Wang, Kenneth</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk1uL1DAUx4so7rr6DUQLguhDx1x6SV-EYfEysLDg7TWcpqedLJ1kTFJd_fSmTneZyj5IArn9zv_knOQkyVNKVpRX9M2VHZ2BYbW3BleEkaJk5b3klNacZSUj_P7R_CR55P0VIQUXZfkwOeGU8Lxg9DTR69TjgMZmW-t2GLTBdO9sQBV82kTpdAfO2Z_pFncQ7N7qyKhU4TD4FHrQxodUW6N_a9OnDloNIS4zbdpRYZsGe62VDhr94-RBB4PHJ_N4lnx9_-7L-cfs4vLD5nx9kamyZiFjvKxpw1nslRIcqpZUFZAcCVetKgpeNA1AJ0Re1TWvCkVzqkCVpEYCnCl-ljw_6O4H6-WcJS8ZoxWpOaEiEpsD0Vq4knunY4i_pAUt_25Y10twMcoBZVNBdNmJglYiF03XUNHmTGHD2paXYvL2dvY2NjtsFZrgYFiILk-M3sre_pBlLgTJ6yjwahZw9vuIPsid9lN6waAdD_fOBc3FhL74B707upnqIQagTWejXzWJynUheF2wirBIre6gYmtxp1V8907H_YXB64VBZAJehx5G7-Xm86f_Zy-_LdmXR-wWYQhbb4dx-kV-CeYHUDnrvcPuNsmUyKkibrIhp4qQc0VEs2fHD3RrdFMC_A83VAc_</recordid><startdate>20190429</startdate><enddate>20190429</enddate><creator>Bartolini, Desirée</creator><creator>Wang, Yanzhong</creator><creator>Zhang, Jie</creator><creator>Giustarini, Daniela</creator><creator>Rossi, Ranieri</creator><creator>Wang, Gavin Y</creator><creator>Torquato, Pierangelo</creator><creator>Townsend, Danyelle M</creator><creator>Tew, Kenneth D</creator><creator>Galli, Francesco</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20190429</creationdate><title>A seleno-hormetine protects bone marrow hematopoietic cells against ionizing radiation-induced toxicities</title><author>Bartolini, Desirée ; Wang, Yanzhong ; Zhang, Jie ; Giustarini, Daniela ; Rossi, Ranieri ; Wang, Gavin Y ; Torquato, Pierangelo ; Townsend, Danyelle M ; Tew, Kenneth D ; Galli, Francesco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-23691b32b327c83a7d077a04e03cdc5535bbaaf884799375c141cac609e0a32c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Benzene Derivatives - 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31034521</pmid><doi>10.1371/journal.pone.0205626</doi><tpages>e0205626</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2019-04, Vol.14 (4), p.e0205626-e0205626 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2217093018 |
| source | MEDLINE; TestCollectionTL3OpenAccess; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Animals Benzene Derivatives - chemistry Benzene Derivatives - pharmacology Bone marrow Cancer Cancer therapies Care and treatment Chemistry EDTA Gamma Rays - adverse effects Gene expression Genes Genetic aspects Glutathione Glutathione transferase Grants Health aspects Hematopoietic Stem Cells - metabolism Hematopoietic Stem Cells - pathology Hep G2 Cells Hepatocytes Humans In vivo methods and tests Ionizing radiation Laboratories Liver Liver cancer Male Medical research Metabolism Mice NF-E2-Related Factor 2 - metabolism Organic chemistry Organoselenium Compounds - chemistry Organoselenium Compounds - pharmacology Pharmaceutical sciences Pharmacology Pharmacy Prevention Properties (attributes) Radiation Radiation (Physics) Radiation damage Radiation effects Radiation exposure Radiation therapy Radiation-Protective Agents - chemistry Radiation-Protective Agents - pharmacology Selenium compounds Senescence Signal transduction Stem cells Stress response Systematic review Tissues Toxicity Transcription (Genetics) Transcription activation Transcription factors Transferases Wang, Kenneth |
| title | A seleno-hormetine protects bone marrow hematopoietic cells against ionizing radiation-induced toxicities |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T08%3A30%3A05IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20seleno-hormetine%20protects%20bone%20marrow%20hematopoietic%20cells%20against%20ionizing%20radiation-induced%20toxicities&rft.jtitle=PloS%20one&rft.au=Bartolini,%20Desir%C3%A9e&rft.date=2019-04-29&rft.volume=14&rft.issue=4&rft.spage=e0205626&rft.epage=e0205626&rft.pages=e0205626-e0205626&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0205626&rft_dat=%3Cgale_plos_%3EA583952702%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2217093018&rft_id=info:pmid/31034521&rft_galeid=A583952702&rft_doaj_id=oai_doaj_org_article_b7a553f8517848bfb18d42ceb2dd368c&rfr_iscdi=true |