Gut metabolite Urolithin A mitigates ionizing radiation‐induced intestinal damage
Ionizing radiation (IR)‐induced intestinal damage is the major and common injury of patients receiving radiotherapy. Urolithin A (UroA) is a metabolite of the intestinal flora of ellagitannin, a compound found in fruits and nuts such as pomegranates, strawberries and walnuts. UroA shows the immunomo...
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| Veröffentlicht in: | Journal of cellular and molecular medicine 2021-11, Vol.25 (21), p.10306-10312 |
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| creator | Zhang, Yuanyang Dong, Yinping Lu, Ping Wang, Xinyue Li, Wenxuan Dong, Hui Fan, Saijun Li, Deguan |
| description | Ionizing radiation (IR)‐induced intestinal damage is the major and common injury of patients receiving radiotherapy. Urolithin A (UroA) is a metabolite of the intestinal flora of ellagitannin, a compound found in fruits and nuts such as pomegranates, strawberries and walnuts. UroA shows the immunomodulatory and anti‐inflammatory capacity in various metabolic diseases. To evaluate the radioprotective effects, UroA(0.4, 2 and 10 mg/kg) were intraperitoneally injected to C57BL/6 male mice 48, 24, 1 h prior to and 24 h after 9.0Gy TBI. The results showed that UroA markedly upregulated the survival of irradiated mice, especially at concentration of 2 mg/kg. UroA improved the intestine morphology architecture and the regeneration ability of enterocytes in irradiated mice. Then, UroA significantly decreased the apoptosis of enterocytes induced by radiation. Additionally, 16S rRNA sequencing analysis showed the effect of UroA is associated with the recovery of the IR‐induced intestinal microbacteria profile changes in mice. Therefore, our results determinated UroA could be developed as a potential candidate for radiomitigators in radiotherapy and accidental nuclear exposure. And the beneficial functions of UroA might be associated with the inhibition of p53‐mediated apoptosis and remodelling of the gut microbes. |
| doi_str_mv | 10.1111/jcmm.16951 |
| format | Article |
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Urolithin A (UroA) is a metabolite of the intestinal flora of ellagitannin, a compound found in fruits and nuts such as pomegranates, strawberries and walnuts. UroA shows the immunomodulatory and anti‐inflammatory capacity in various metabolic diseases. To evaluate the radioprotective effects, UroA(0.4, 2 and 10 mg/kg) were intraperitoneally injected to C57BL/6 male mice 48, 24, 1 h prior to and 24 h after 9.0Gy TBI. The results showed that UroA markedly upregulated the survival of irradiated mice, especially at concentration of 2 mg/kg. UroA improved the intestine morphology architecture and the regeneration ability of enterocytes in irradiated mice. Then, UroA significantly decreased the apoptosis of enterocytes induced by radiation. Additionally, 16S rRNA sequencing analysis showed the effect of UroA is associated with the recovery of the IR‐induced intestinal microbacteria profile changes in mice. Therefore, our results determinated UroA could be developed as a potential candidate for radiomitigators in radiotherapy and accidental nuclear exposure. And the beneficial functions of UroA might be associated with the inhibition of p53‐mediated apoptosis and remodelling of the gut microbes.</description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/jcmm.16951</identifier><identifier>PMID: 34595829</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Animals ; Antioxidants ; Apoptosis ; Apoptosis - drug effects ; Apoptosis - radiation effects ; Cancer ; Confidence intervals ; Coumarins - metabolism ; Coumarins - pharmacology ; Digestive system ; DNA Damage - drug effects ; DNA Damage - radiation effects ; Enterocytes ; Gastrointestinal Microbiome - drug effects ; Gastrointestinal Microbiome - radiation effects ; Gastrointestinal tract ; Gastrointestinal Tract - drug effects ; Gastrointestinal Tract - pathology ; Gastrointestinal Tract - radiation effects ; gut microbes ; Immunomodulation ; Inflammation ; Intestinal microflora ; Intestinal Mucosa - drug effects ; Intestinal Mucosa - pathology ; Intestinal Mucosa - radiation effects ; Intestine ; Ionizing radiation ; Melatonin ; Metabolic disorders ; Metabolites ; Mice ; Microbiota ; Morphology ; Radiation Dosage ; radiation enteritis ; Radiation therapy ; Radiation, Ionizing ; Radiation-Protective Agents - pharmacology ; rRNA 16S ; Sequence analysis ; Short Communication ; Short Communications ; Small intestine ; UroA</subject><ispartof>Journal of cellular and molecular medicine, 2021-11, Vol.25 (21), p.10306-10312</ispartof><rights>2021 The Authors. published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.</rights><rights>2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.</rights><rights>2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4481-356b6fbe2ce230f4d42f6e7cd4f8e8d6c89319006598baf197b7da024162b6713</citedby><cites>FETCH-LOGICAL-c4481-356b6fbe2ce230f4d42f6e7cd4f8e8d6c89319006598baf197b7da024162b6713</cites><orcidid>0000-0002-3832-8621</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8572803/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8572803/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34595829$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Yuanyang</creatorcontrib><creatorcontrib>Dong, Yinping</creatorcontrib><creatorcontrib>Lu, Ping</creatorcontrib><creatorcontrib>Wang, Xinyue</creatorcontrib><creatorcontrib>Li, Wenxuan</creatorcontrib><creatorcontrib>Dong, Hui</creatorcontrib><creatorcontrib>Fan, Saijun</creatorcontrib><creatorcontrib>Li, Deguan</creatorcontrib><title>Gut metabolite Urolithin A mitigates ionizing radiation‐induced intestinal damage</title><title>Journal of cellular and molecular medicine</title><addtitle>J Cell Mol Med</addtitle><description>Ionizing radiation (IR)‐induced intestinal damage is the major and common injury of patients receiving radiotherapy. Urolithin A (UroA) is a metabolite of the intestinal flora of ellagitannin, a compound found in fruits and nuts such as pomegranates, strawberries and walnuts. UroA shows the immunomodulatory and anti‐inflammatory capacity in various metabolic diseases. To evaluate the radioprotective effects, UroA(0.4, 2 and 10 mg/kg) were intraperitoneally injected to C57BL/6 male mice 48, 24, 1 h prior to and 24 h after 9.0Gy TBI. The results showed that UroA markedly upregulated the survival of irradiated mice, especially at concentration of 2 mg/kg. UroA improved the intestine morphology architecture and the regeneration ability of enterocytes in irradiated mice. Then, UroA significantly decreased the apoptosis of enterocytes induced by radiation. Additionally, 16S rRNA sequencing analysis showed the effect of UroA is associated with the recovery of the IR‐induced intestinal microbacteria profile changes in mice. Therefore, our results determinated UroA could be developed as a potential candidate for radiomitigators in radiotherapy and accidental nuclear exposure. And the beneficial functions of UroA might be associated with the inhibition of p53‐mediated apoptosis and remodelling of the gut microbes.</description><subject>Animals</subject><subject>Antioxidants</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - radiation effects</subject><subject>Cancer</subject><subject>Confidence intervals</subject><subject>Coumarins - metabolism</subject><subject>Coumarins - pharmacology</subject><subject>Digestive system</subject><subject>DNA Damage - drug effects</subject><subject>DNA Damage - radiation effects</subject><subject>Enterocytes</subject><subject>Gastrointestinal Microbiome - drug effects</subject><subject>Gastrointestinal Microbiome - radiation effects</subject><subject>Gastrointestinal tract</subject><subject>Gastrointestinal Tract - drug effects</subject><subject>Gastrointestinal Tract - pathology</subject><subject>Gastrointestinal Tract - radiation effects</subject><subject>gut microbes</subject><subject>Immunomodulation</subject><subject>Inflammation</subject><subject>Intestinal microflora</subject><subject>Intestinal Mucosa - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cellular and molecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Yuanyang</au><au>Dong, Yinping</au><au>Lu, Ping</au><au>Wang, Xinyue</au><au>Li, Wenxuan</au><au>Dong, Hui</au><au>Fan, Saijun</au><au>Li, Deguan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gut metabolite Urolithin A mitigates ionizing radiation‐induced intestinal damage</atitle><jtitle>Journal of cellular and molecular medicine</jtitle><addtitle>J Cell Mol Med</addtitle><date>2021-11</date><risdate>2021</risdate><volume>25</volume><issue>21</issue><spage>10306</spage><epage>10312</epage><pages>10306-10312</pages><issn>1582-1838</issn><eissn>1582-4934</eissn><abstract>Ionizing radiation (IR)‐induced intestinal damage is the major and common injury of patients receiving radiotherapy. Urolithin A (UroA) is a metabolite of the intestinal flora of ellagitannin, a compound found in fruits and nuts such as pomegranates, strawberries and walnuts. UroA shows the immunomodulatory and anti‐inflammatory capacity in various metabolic diseases. To evaluate the radioprotective effects, UroA(0.4, 2 and 10 mg/kg) were intraperitoneally injected to C57BL/6 male mice 48, 24, 1 h prior to and 24 h after 9.0Gy TBI. The results showed that UroA markedly upregulated the survival of irradiated mice, especially at concentration of 2 mg/kg. UroA improved the intestine morphology architecture and the regeneration ability of enterocytes in irradiated mice. Then, UroA significantly decreased the apoptosis of enterocytes induced by radiation. Additionally, 16S rRNA sequencing analysis showed the effect of UroA is associated with the recovery of the IR‐induced intestinal microbacteria profile changes in mice. Therefore, our results determinated UroA could be developed as a potential candidate for radiomitigators in radiotherapy and accidental nuclear exposure. And the beneficial functions of UroA might be associated with the inhibition of p53‐mediated apoptosis and remodelling of the gut microbes.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>34595829</pmid><doi>10.1111/jcmm.16951</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-3832-8621</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antioxidants Apoptosis Apoptosis - drug effects Apoptosis - radiation effects Cancer Confidence intervals Coumarins - metabolism Coumarins - pharmacology Digestive system DNA Damage - drug effects DNA Damage - radiation effects Enterocytes Gastrointestinal Microbiome - drug effects Gastrointestinal Microbiome - radiation effects Gastrointestinal tract Gastrointestinal Tract - drug effects Gastrointestinal Tract - pathology Gastrointestinal Tract - radiation effects gut microbes Immunomodulation Inflammation Intestinal microflora Intestinal Mucosa - drug effects Intestinal Mucosa - pathology Intestinal Mucosa - radiation effects Intestine Ionizing radiation Melatonin Metabolic disorders Metabolites Mice Microbiota Morphology Radiation Dosage radiation enteritis Radiation therapy Radiation, Ionizing Radiation-Protective Agents - pharmacology rRNA 16S Sequence analysis Short Communication Short Communications Small intestine UroA |
| title | Gut metabolite Urolithin A mitigates ionizing radiation‐induced intestinal damage |
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