Bone marrow-derived mesenchymal stem cells ameliorate liver injury in a rat model of sepsis by activating Nrf2 signaling
Sepsis is a fatal condition that leads to serious systemic inflammation and multiple organ dysfunction syndromes. This study was designed to investigate the possible therapeutic effect of bone marrow-derived mesenchymal stem cells (BMSCs) on sepsis-induced liver injury. We also aimed to examine the...
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Veröffentlicht in: | Histochemistry and cell biology 2019-03, Vol.151 (3), p.249-262 |
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creator | Selim, Sally A. El-Baset, Samia A. Abd Kattaia, Asmaa A. A. Askar, Eman M. Elkader, Eman Abd |
description | Sepsis is a fatal condition that leads to serious systemic inflammation and multiple organ dysfunction syndromes. This study was designed to investigate the possible therapeutic effect of bone marrow-derived mesenchymal stem cells (BMSCs) on sepsis-induced liver injury. We also aimed to examine the role of Nrf2 activation in modulating the response to sepsis following BMSCs treatment. Twenty-four adult male albino rats were assigned to: control, lipopolysaccharide (LPS) and LPS-stem cell groups. Liver samples were processed for light and electron microscope examinations. Immunohistochemical localization of BAX, proliferating cell nuclear antigen and nuclear factor-erythroid 2-related factor 2 (Nrf2) was carried out. Liver homogenates were prepared for assessment of reduced glutathione, glutathione peroxidase, tumor necrosis factor-alpha and interleukin-6 and also real-time PCR analysis of Nrf2 expression. BMSCs treatment improved the histopathological changes of the liver, enhanced tissue regeneration and decreased apoptosis following sepsis. We reported highly significant enhancement in Nrf2 expressions at mRNA and protein levels in the LPS-stem cell group compared with the LPS group. The up regulation of Nrf2 was probably implicated in decreasing inflammatory cytokine levels and counteracting oxidative stress induced by sepsis. Thus, BMSCs therapies could be a viable approach to treat sepsis-induced liver damage by activating Nrf2 signaling. |
doi_str_mv | 10.1007/s00418-018-1731-4 |
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Abd ; Kattaia, Asmaa A. A. ; Askar, Eman M. ; Elkader, Eman Abd</creator><creatorcontrib>Selim, Sally A. ; El-Baset, Samia A. Abd ; Kattaia, Asmaa A. A. ; Askar, Eman M. ; Elkader, Eman Abd</creatorcontrib><description>Sepsis is a fatal condition that leads to serious systemic inflammation and multiple organ dysfunction syndromes. This study was designed to investigate the possible therapeutic effect of bone marrow-derived mesenchymal stem cells (BMSCs) on sepsis-induced liver injury. We also aimed to examine the role of Nrf2 activation in modulating the response to sepsis following BMSCs treatment. Twenty-four adult male albino rats were assigned to: control, lipopolysaccharide (LPS) and LPS-stem cell groups. Liver samples were processed for light and electron microscope examinations. Immunohistochemical localization of BAX, proliferating cell nuclear antigen and nuclear factor-erythroid 2-related factor 2 (Nrf2) was carried out. Liver homogenates were prepared for assessment of reduced glutathione, glutathione peroxidase, tumor necrosis factor-alpha and interleukin-6 and also real-time PCR analysis of Nrf2 expression. BMSCs treatment improved the histopathological changes of the liver, enhanced tissue regeneration and decreased apoptosis following sepsis. We reported highly significant enhancement in Nrf2 expressions at mRNA and protein levels in the LPS-stem cell group compared with the LPS group. The up regulation of Nrf2 was probably implicated in decreasing inflammatory cytokine levels and counteracting oxidative stress induced by sepsis. Thus, BMSCs therapies could be a viable approach to treat sepsis-induced liver damage by activating Nrf2 signaling.</description><identifier>ISSN: 0948-6143</identifier><identifier>EISSN: 1432-119X</identifier><identifier>DOI: 10.1007/s00418-018-1731-4</identifier><identifier>PMID: 30250973</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Apoptosis ; BAX protein ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Bone marrow ; Cell Biology ; Developmental Biology ; Glutathione peroxidase ; Hepatocytes ; Inflammation ; Interleukin 6 ; Lipopolysaccharides ; Liver ; Localization ; Mesenchymal stem cells ; Mesenchyme ; mRNA ; Original Paper ; Oxidative stress ; Proliferating cell nuclear antigen ; Regeneration ; Rodents ; Sepsis ; Stem cell transplantation ; Stem cells ; Tumor necrosis factor-α</subject><ispartof>Histochemistry and cell biology, 2019-03, Vol.151 (3), p.249-262</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2018</rights><rights>Histochemistry and Cell Biology is a copyright of Springer, (2018). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-48faf3e8bb22b39032c1215a56dd219ed8e767d73473805a707dac5000ac4e193</citedby><cites>FETCH-LOGICAL-c372t-48faf3e8bb22b39032c1215a56dd219ed8e767d73473805a707dac5000ac4e193</cites><orcidid>0000-0002-7188-0100</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00418-018-1731-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00418-018-1731-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,782,786,27931,27932,41495,42564,51326</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30250973$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Selim, Sally A.</creatorcontrib><creatorcontrib>El-Baset, Samia A. Abd</creatorcontrib><creatorcontrib>Kattaia, Asmaa A. A.</creatorcontrib><creatorcontrib>Askar, Eman M.</creatorcontrib><creatorcontrib>Elkader, Eman Abd</creatorcontrib><title>Bone marrow-derived mesenchymal stem cells ameliorate liver injury in a rat model of sepsis by activating Nrf2 signaling</title><title>Histochemistry and cell biology</title><addtitle>Histochem Cell Biol</addtitle><addtitle>Histochem Cell Biol</addtitle><description>Sepsis is a fatal condition that leads to serious systemic inflammation and multiple organ dysfunction syndromes. This study was designed to investigate the possible therapeutic effect of bone marrow-derived mesenchymal stem cells (BMSCs) on sepsis-induced liver injury. We also aimed to examine the role of Nrf2 activation in modulating the response to sepsis following BMSCs treatment. Twenty-four adult male albino rats were assigned to: control, lipopolysaccharide (LPS) and LPS-stem cell groups. Liver samples were processed for light and electron microscope examinations. Immunohistochemical localization of BAX, proliferating cell nuclear antigen and nuclear factor-erythroid 2-related factor 2 (Nrf2) was carried out. Liver homogenates were prepared for assessment of reduced glutathione, glutathione peroxidase, tumor necrosis factor-alpha and interleukin-6 and also real-time PCR analysis of Nrf2 expression. BMSCs treatment improved the histopathological changes of the liver, enhanced tissue regeneration and decreased apoptosis following sepsis. We reported highly significant enhancement in Nrf2 expressions at mRNA and protein levels in the LPS-stem cell group compared with the LPS group. The up regulation of Nrf2 was probably implicated in decreasing inflammatory cytokine levels and counteracting oxidative stress induced by sepsis. Thus, BMSCs therapies could be a viable approach to treat sepsis-induced liver damage by activating Nrf2 signaling.</description><subject>Apoptosis</subject><subject>BAX protein</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Bone marrow</subject><subject>Cell Biology</subject><subject>Developmental Biology</subject><subject>Glutathione peroxidase</subject><subject>Hepatocytes</subject><subject>Inflammation</subject><subject>Interleukin 6</subject><subject>Lipopolysaccharides</subject><subject>Liver</subject><subject>Localization</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchyme</subject><subject>mRNA</subject><subject>Original Paper</subject><subject>Oxidative stress</subject><subject>Proliferating cell nuclear antigen</subject><subject>Regeneration</subject><subject>Rodents</subject><subject>Sepsis</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Tumor necrosis factor-α</subject><issn>0948-6143</issn><issn>1432-119X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kU1v1DAQhq0KRJfCD-ilssSFS2DGTtbJsVR8SRVcqNSb5cSTxask3nqSwv57vGwpEhIHa-SZZ96x5xXiHOENApi3DFBiXUA-aDQW5YlYYalVgdjcPhEraMq6WOfMqXjOvAXAqlHqmTjVoCpojF6Jn-_iRHJ0KcUfhacU7snLkZim7vt-dIPkmUbZ0TCwdCMNISY3kxwyl2SYtkva5yCdzGk5Rk-DjL1k2nFg2e6l6-Zw7-YwbeSX1CvJYTO5IV9fiKe9G5hePsQzcfPh_berT8X114-fry6vi04bNRdl3bteU922SrW6Aa06VFi5au29woZ8TWZtvNGl0TVUzoDxrqsAwHUlYaPPxOuj7i7Fu4V4tmPgw3_cRHFhqzDrNQbXOqOv_kG3cUn5ub8p1HVVI2QKj1SXInOi3u5SyAvcWwR7sMUebbHZFnuwxZa55-JBeWlH8o8df3zIgDoCnEvThtLf0f9X_QUgFJfr</recordid><startdate>20190301</startdate><enddate>20190301</enddate><creator>Selim, Sally A.</creator><creator>El-Baset, Samia A. 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Abd ; Kattaia, Asmaa A. A. ; Askar, Eman M. ; Elkader, Eman Abd</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-48faf3e8bb22b39032c1215a56dd219ed8e767d73473805a707dac5000ac4e193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Apoptosis</topic><topic>BAX protein</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Bone marrow</topic><topic>Cell Biology</topic><topic>Developmental Biology</topic><topic>Glutathione peroxidase</topic><topic>Hepatocytes</topic><topic>Inflammation</topic><topic>Interleukin 6</topic><topic>Lipopolysaccharides</topic><topic>Liver</topic><topic>Localization</topic><topic>Mesenchymal stem cells</topic><topic>Mesenchyme</topic><topic>mRNA</topic><topic>Original Paper</topic><topic>Oxidative stress</topic><topic>Proliferating cell nuclear antigen</topic><topic>Regeneration</topic><topic>Rodents</topic><topic>Sepsis</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Tumor necrosis factor-α</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Selim, Sally A.</creatorcontrib><creatorcontrib>El-Baset, Samia A. 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Abd</au><au>Kattaia, Asmaa A. A.</au><au>Askar, Eman M.</au><au>Elkader, Eman Abd</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bone marrow-derived mesenchymal stem cells ameliorate liver injury in a rat model of sepsis by activating Nrf2 signaling</atitle><jtitle>Histochemistry and cell biology</jtitle><stitle>Histochem Cell Biol</stitle><addtitle>Histochem Cell Biol</addtitle><date>2019-03-01</date><risdate>2019</risdate><volume>151</volume><issue>3</issue><spage>249</spage><epage>262</epage><pages>249-262</pages><issn>0948-6143</issn><eissn>1432-119X</eissn><abstract>Sepsis is a fatal condition that leads to serious systemic inflammation and multiple organ dysfunction syndromes. This study was designed to investigate the possible therapeutic effect of bone marrow-derived mesenchymal stem cells (BMSCs) on sepsis-induced liver injury. We also aimed to examine the role of Nrf2 activation in modulating the response to sepsis following BMSCs treatment. Twenty-four adult male albino rats were assigned to: control, lipopolysaccharide (LPS) and LPS-stem cell groups. Liver samples were processed for light and electron microscope examinations. Immunohistochemical localization of BAX, proliferating cell nuclear antigen and nuclear factor-erythroid 2-related factor 2 (Nrf2) was carried out. Liver homogenates were prepared for assessment of reduced glutathione, glutathione peroxidase, tumor necrosis factor-alpha and interleukin-6 and also real-time PCR analysis of Nrf2 expression. BMSCs treatment improved the histopathological changes of the liver, enhanced tissue regeneration and decreased apoptosis following sepsis. We reported highly significant enhancement in Nrf2 expressions at mRNA and protein levels in the LPS-stem cell group compared with the LPS group. The up regulation of Nrf2 was probably implicated in decreasing inflammatory cytokine levels and counteracting oxidative stress induced by sepsis. Thus, BMSCs therapies could be a viable approach to treat sepsis-induced liver damage by activating Nrf2 signaling.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>30250973</pmid><doi>10.1007/s00418-018-1731-4</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-7188-0100</orcidid></addata></record> |
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subjects | Apoptosis BAX protein Biochemistry Biomedical and Life Sciences Biomedicine Bone marrow Cell Biology Developmental Biology Glutathione peroxidase Hepatocytes Inflammation Interleukin 6 Lipopolysaccharides Liver Localization Mesenchymal stem cells Mesenchyme mRNA Original Paper Oxidative stress Proliferating cell nuclear antigen Regeneration Rodents Sepsis Stem cell transplantation Stem cells Tumor necrosis factor-α |
title | Bone marrow-derived mesenchymal stem cells ameliorate liver injury in a rat model of sepsis by activating Nrf2 signaling |
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