Restoring the secretory function of irradiation-damaged salivary gland by administrating deferoxamine in mice
One of the major side effects of radiotherapy for treatments of the head and neck cancer is the radiation-induced dysfunction of salivary glands. The aim of the present study is to investigate the efficacy of deferoxamine (DFO) to restore the secretory function of radiation-damaged salivary glands i...
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| description | One of the major side effects of radiotherapy for treatments of the head and neck cancer is the radiation-induced dysfunction of salivary glands. The aim of the present study is to investigate the efficacy of deferoxamine (DFO) to restore the secretory function of radiation-damaged salivary glands in mice.
DFO (50 mg/kg/d) was administered intraperitoneally in C57BL/6 mice for 3 days before and/or after point-fixed irradiation (18 Gy) of submandibular glands. The total 55 mice were randomly divided into: (1) Normal group: mice received no treatment (n = 5); (2) Irradiation group (IR): mice only received irradiation (n = 5); (3) Pre-DFO group (D+IR) (n = 10); (4) Pre+Post DFO group (D+IR+D) (n = 10); (5) Post-DFO group (IR+D) (n = 10); (6) For each DFO-treated group, the mice were intraperitoneally injected with 0.1 ml sterilized water alone (by which DFO was dissolved) for 3 days before and/or after irradiation, and served as control. Sham1: Pre-sterilized water group (n = 5); sham2: Pre+Post sterilized water group (n = 5); sham3: Post-sterilized water group (n = 5). The salivary flow rate (SFR) was assessed at 30th, 60th and 90th day after irradiation, respectively. After 90 days, all mice were sacrificed and their submandibular glands were removed for further examinations.
The salivary glands showed remarkable dysfunction and tissue damage after irradiation. DFO restored SFR in the irradiated glands to a level comparable to that in normal glands and angiogenesis in damaged tissue was greatly increased. DFO also increased the expression levels of HIF-1α and VEGF while reduced apoptotic cells. Furthermore, Sca-1+cells were preserved in the salivary glands treated with DFO before IR.
Our results indicate DFO could prevent the radiation-induced dysfunction of salivary glands in mice. The mechanism of this protective effect may involve increased angiogenesis, reduced apoptosis of acinar cells and more preserved stem cells. |
| doi_str_mv | 10.1371/journal.pone.0113721 |
| format | Article |
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DFO (50 mg/kg/d) was administered intraperitoneally in C57BL/6 mice for 3 days before and/or after point-fixed irradiation (18 Gy) of submandibular glands. The total 55 mice were randomly divided into: (1) Normal group: mice received no treatment (n = 5); (2) Irradiation group (IR): mice only received irradiation (n = 5); (3) Pre-DFO group (D+IR) (n = 10); (4) Pre+Post DFO group (D+IR+D) (n = 10); (5) Post-DFO group (IR+D) (n = 10); (6) For each DFO-treated group, the mice were intraperitoneally injected with 0.1 ml sterilized water alone (by which DFO was dissolved) for 3 days before and/or after irradiation, and served as control. Sham1: Pre-sterilized water group (n = 5); sham2: Pre+Post sterilized water group (n = 5); sham3: Post-sterilized water group (n = 5). The salivary flow rate (SFR) was assessed at 30th, 60th and 90th day after irradiation, respectively. After 90 days, all mice were sacrificed and their submandibular glands were removed for further examinations.
The salivary glands showed remarkable dysfunction and tissue damage after irradiation. DFO restored SFR in the irradiated glands to a level comparable to that in normal glands and angiogenesis in damaged tissue was greatly increased. DFO also increased the expression levels of HIF-1α and VEGF while reduced apoptotic cells. Furthermore, Sca-1+cells were preserved in the salivary glands treated with DFO before IR.
Our results indicate DFO could prevent the radiation-induced dysfunction of salivary glands in mice. The mechanism of this protective effect may involve increased angiogenesis, reduced apoptosis of acinar cells and more preserved stem cells.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0113721</identifier><identifier>PMID: 25427160</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acinar cells ; Angiogenesis ; Animals ; Apoptosis ; Apoptosis - drug effects ; Apoptosis - radiation effects ; Brain cancer ; Cancer ; Cancer therapies ; Cell cycle ; Deferoxamine ; Deferoxamine - therapeutic use ; Drug dosages ; Exocrine glands ; Flow velocity ; Glands ; Head & neck cancer ; Head and neck cancer ; Hospitals ; Iron ; Irradiation ; Kinases ; Laboratory animals ; Male ; Medical research ; Medicine ; Medicine and Health Sciences ; Mice ; Mice, Inbred C57BL ; Neuroblastoma ; Pharmaceutical sciences ; Radiation ; Radiation damage ; Radiation effects ; Radiation Injuries, Experimental - drug therapy ; Radiation Injuries, Experimental - pathology ; Radiation Injuries, Experimental - physiopathology ; Radiation therapy ; Recovery of function ; Salivary gland ; Salivary glands ; Salivary Glands - drug effects ; Salivary Glands - pathology ; Salivary Glands - physiopathology ; Salivary Glands - radiation effects ; Side effects ; Siderophores - therapeutic use ; Stem cell transplantation ; Stem cells ; Submandibular gland ; Tumors ; Vascular endothelial growth factor</subject><ispartof>PloS one, 2014-11, Vol.9 (11), p.e113721-e113721</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Zhang 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>2014 Zhang et al 2014 Zhang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-6903feeaa8b808554390036eb530745f0351acd09720dc9ce0da4de19c89b4ee3</citedby><cites>FETCH-LOGICAL-c758t-6903feeaa8b808554390036eb530745f0351acd09720dc9ce0da4de19c89b4ee3</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/PMC4245233/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245233/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25427160$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Junye</creatorcontrib><creatorcontrib>Cui, Lei</creatorcontrib><creatorcontrib>Xu, Minhua</creatorcontrib><creatorcontrib>Zheng, Yuanli</creatorcontrib><title>Restoring the secretory function of irradiation-damaged salivary gland by administrating deferoxamine in mice</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>One of the major side effects of radiotherapy for treatments of the head and neck cancer is the radiation-induced dysfunction of salivary glands. The aim of the present study is to investigate the efficacy of deferoxamine (DFO) to restore the secretory function of radiation-damaged salivary glands in mice.
DFO (50 mg/kg/d) was administered intraperitoneally in C57BL/6 mice for 3 days before and/or after point-fixed irradiation (18 Gy) of submandibular glands. The total 55 mice were randomly divided into: (1) Normal group: mice received no treatment (n = 5); (2) Irradiation group (IR): mice only received irradiation (n = 5); (3) Pre-DFO group (D+IR) (n = 10); (4) Pre+Post DFO group (D+IR+D) (n = 10); (5) Post-DFO group (IR+D) (n = 10); (6) For each DFO-treated group, the mice were intraperitoneally injected with 0.1 ml sterilized water alone (by which DFO was dissolved) for 3 days before and/or after irradiation, and served as control. Sham1: Pre-sterilized water group (n = 5); sham2: Pre+Post sterilized water group (n = 5); sham3: Post-sterilized water group (n = 5). The salivary flow rate (SFR) was assessed at 30th, 60th and 90th day after irradiation, respectively. After 90 days, all mice were sacrificed and their submandibular glands were removed for further examinations.
The salivary glands showed remarkable dysfunction and tissue damage after irradiation. DFO restored SFR in the irradiated glands to a level comparable to that in normal glands and angiogenesis in damaged tissue was greatly increased. DFO also increased the expression levels of HIF-1α and VEGF while reduced apoptotic cells. Furthermore, Sca-1+cells were preserved in the salivary glands treated with DFO before IR.
Our results indicate DFO could prevent the radiation-induced dysfunction of salivary glands in mice. The mechanism of this protective effect may involve increased angiogenesis, reduced apoptosis of acinar cells and more preserved stem cells.</description><subject>Acinar cells</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - radiation effects</subject><subject>Brain cancer</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Cell cycle</subject><subject>Deferoxamine</subject><subject>Deferoxamine - therapeutic use</subject><subject>Drug dosages</subject><subject>Exocrine glands</subject><subject>Flow velocity</subject><subject>Glands</subject><subject>Head & neck cancer</subject><subject>Head and neck cancer</subject><subject>Hospitals</subject><subject>Iron</subject><subject>Irradiation</subject><subject>Kinases</subject><subject>Laboratory animals</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Neuroblastoma</subject><subject>Pharmaceutical sciences</subject><subject>Radiation</subject><subject>Radiation damage</subject><subject>Radiation effects</subject><subject>Radiation Injuries, Experimental - drug therapy</subject><subject>Radiation Injuries, Experimental - pathology</subject><subject>Radiation Injuries, Experimental - physiopathology</subject><subject>Radiation therapy</subject><subject>Recovery of function</subject><subject>Salivary gland</subject><subject>Salivary glands</subject><subject>Salivary Glands - drug effects</subject><subject>Salivary Glands - pathology</subject><subject>Salivary Glands - physiopathology</subject><subject>Salivary Glands - radiation effects</subject><subject>Side effects</subject><subject>Siderophores - therapeutic use</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Submandibular gland</subject><subject>Tumors</subject><subject>Vascular endothelial growth factor</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9tq3DAQhk1padK0b1BaQ6G0F7vVyQfdFEJI24VAID3cCq009mqxrY1kh-TtM-46YV1yUQy2ZvzNP9KMJkneUrKkvKBftn4InW6WO9_BklD0MfosOaaSs0XOCH9-sD5KXsW4JSTjZZ6_TI5YJlhBc3KctFcQex9cV6f9BtIIJgDad2k1dKZ3vkt9lboQtHV6NBdWt7oGm0bduBuNYN3ozqbru1Tb1nUu9gFBlLNQQfC3Gp2Qui5tnYHXyYtKNxHeTN-T5Pe3819nPxYXl99XZ6cXC1NkZb_IJeEVgNbluiRllgkuCeE5rDNOCpFVhGdUG0tkwYg10gCxWlig0pRyLQD4SfJ-r7trfFRTpaKiOSuZKIqcIrHaE9brrdoF1-JZlNdO_XX4UCsdemcaUITkYAqQVmgQjJZlRmgu8ZVBjmaFWl-nbMO6BWugwxo0M9H5n85tVO1vlGAiY5yjwKdJIPjrARuiWhcNNFhZ8MN-32WJfRz3_eEf9OnTTVSt8QCuqzzmNaOoOhW0KCSTcky7fILCxwI2C69V5dA_C_g8C0Cmh9u-1kOMavXz6v_Zyz9z9uMBuwHd9Jvom2G8cHEOij1ogo8xQPVYZErUOBUP1VDjVKhpKjDs3WGDHoMexoDfA8SUCCY</recordid><startdate>20141126</startdate><enddate>20141126</enddate><creator>Zhang, Junye</creator><creator>Cui, Lei</creator><creator>Xu, Minhua</creator><creator>Zheng, Yuanli</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>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20141126</creationdate><title>Restoring the secretory function of irradiation-damaged salivary gland by administrating deferoxamine in mice</title><author>Zhang, Junye ; Cui, Lei ; Xu, Minhua ; Zheng, Yuanli</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-6903feeaa8b808554390036eb530745f0351acd09720dc9ce0da4de19c89b4ee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Acinar cells</topic><topic>Angiogenesis</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - radiation effects</topic><topic>Brain cancer</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Cell cycle</topic><topic>Deferoxamine</topic><topic>Deferoxamine - therapeutic use</topic><topic>Drug dosages</topic><topic>Exocrine glands</topic><topic>Flow velocity</topic><topic>Glands</topic><topic>Head & neck cancer</topic><topic>Head and neck cancer</topic><topic>Hospitals</topic><topic>Iron</topic><topic>Irradiation</topic><topic>Kinases</topic><topic>Laboratory animals</topic><topic>Male</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Neuroblastoma</topic><topic>Pharmaceutical sciences</topic><topic>Radiation</topic><topic>Radiation damage</topic><topic>Radiation effects</topic><topic>Radiation Injuries, Experimental - drug therapy</topic><topic>Radiation Injuries, Experimental - pathology</topic><topic>Radiation Injuries, Experimental - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Junye</au><au>Cui, Lei</au><au>Xu, Minhua</au><au>Zheng, Yuanli</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Restoring the secretory function of irradiation-damaged salivary gland by administrating deferoxamine in mice</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-11-26</date><risdate>2014</risdate><volume>9</volume><issue>11</issue><spage>e113721</spage><epage>e113721</epage><pages>e113721-e113721</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>One of the major side effects of radiotherapy for treatments of the head and neck cancer is the radiation-induced dysfunction of salivary glands. The aim of the present study is to investigate the efficacy of deferoxamine (DFO) to restore the secretory function of radiation-damaged salivary glands in mice.
DFO (50 mg/kg/d) was administered intraperitoneally in C57BL/6 mice for 3 days before and/or after point-fixed irradiation (18 Gy) of submandibular glands. The total 55 mice were randomly divided into: (1) Normal group: mice received no treatment (n = 5); (2) Irradiation group (IR): mice only received irradiation (n = 5); (3) Pre-DFO group (D+IR) (n = 10); (4) Pre+Post DFO group (D+IR+D) (n = 10); (5) Post-DFO group (IR+D) (n = 10); (6) For each DFO-treated group, the mice were intraperitoneally injected with 0.1 ml sterilized water alone (by which DFO was dissolved) for 3 days before and/or after irradiation, and served as control. Sham1: Pre-sterilized water group (n = 5); sham2: Pre+Post sterilized water group (n = 5); sham3: Post-sterilized water group (n = 5). The salivary flow rate (SFR) was assessed at 30th, 60th and 90th day after irradiation, respectively. After 90 days, all mice were sacrificed and their submandibular glands were removed for further examinations.
The salivary glands showed remarkable dysfunction and tissue damage after irradiation. DFO restored SFR in the irradiated glands to a level comparable to that in normal glands and angiogenesis in damaged tissue was greatly increased. DFO also increased the expression levels of HIF-1α and VEGF while reduced apoptotic cells. Furthermore, Sca-1+cells were preserved in the salivary glands treated with DFO before IR.
Our results indicate DFO could prevent the radiation-induced dysfunction of salivary glands in mice. The mechanism of this protective effect may involve increased angiogenesis, reduced apoptosis of acinar cells and more preserved stem cells.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25427160</pmid><doi>10.1371/journal.pone.0113721</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1628247761 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Acinar cells Angiogenesis Animals Apoptosis Apoptosis - drug effects Apoptosis - radiation effects Brain cancer Cancer Cancer therapies Cell cycle Deferoxamine Deferoxamine - therapeutic use Drug dosages Exocrine glands Flow velocity Glands Head & neck cancer Head and neck cancer Hospitals Iron Irradiation Kinases Laboratory animals Male Medical research Medicine Medicine and Health Sciences Mice Mice, Inbred C57BL Neuroblastoma Pharmaceutical sciences Radiation Radiation damage Radiation effects Radiation Injuries, Experimental - drug therapy Radiation Injuries, Experimental - pathology Radiation Injuries, Experimental - physiopathology Radiation therapy Recovery of function Salivary gland Salivary glands Salivary Glands - drug effects Salivary Glands - pathology Salivary Glands - physiopathology Salivary Glands - radiation effects Side effects Siderophores - therapeutic use Stem cell transplantation Stem cells Submandibular gland Tumors Vascular endothelial growth factor |
| title | Restoring the secretory function of irradiation-damaged salivary gland by administrating deferoxamine in mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T23%3A18%3A18IST&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=Restoring%20the%20secretory%20function%20of%20irradiation-damaged%20salivary%20gland%20by%20administrating%20deferoxamine%20in%20mice&rft.jtitle=PloS%20one&rft.au=Zhang,%20Junye&rft.date=2014-11-26&rft.volume=9&rft.issue=11&rft.spage=e113721&rft.epage=e113721&rft.pages=e113721-e113721&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0113721&rft_dat=%3Cgale_plos_%3EA417792993%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=1628247761&rft_id=info:pmid/25427160&rft_galeid=A417792993&rft_doaj_id=oai_doaj_org_article_006ec7e9d4ae42188501695015e6218f&rfr_iscdi=true |