Prevention of ochratoxin A‐induced oxidative stress‐mediated apoptotic processes and impairment of embryonic development in mouse blastocysts by liquiritigenin
Ochratoxin A (OTA), a mycotoxin constituent of a range of food commodities, including coffee, wine, beer, grains, and spices, exerts toxicological and pathological effects in vivo, such as nephrotoxicity, hepatotoxicity, and immunotoxicity. In a previous report, we highlighted the potential of OTA t...
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Veröffentlicht in: | Environmental toxicology 2019-05, Vol.34 (5), p.573-584 |
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description | Ochratoxin A (OTA), a mycotoxin constituent of a range of food commodities, including coffee, wine, beer, grains, and spices, exerts toxicological and pathological effects in vivo, such as nephrotoxicity, hepatotoxicity, and immunotoxicity. In a previous report, we highlighted the potential of OTA to induce apoptosis via reactive oxygen species (ROS) generation in mouse blastocysts that led to impaired preimplantation and postimplantation embryo development in vitro and in vivo. Here, we have shown that liquiritigenin (LQ), a type of flavonoid isolated from Glycyrrhiza radix, effectively protects against OTA‐mediated apoptosis and inhibition of cell proliferation in mouse blastocysts. Preincubation of blastocysts with LQ clearly prevented OTA‐triggered impairment of preimplantation and postimplantation embryonic development and fetal weight loss, both in vitro and in vivo. Detailed investigation of regulatory mechanisms revealed that OTA mediated apoptosis and embryotoxicity through ROS generation, loss of mitochondrial membrane potential (MMP), and activation of caspase‐9 and caspase‐3, which were effectively prevented by LQ. The embryotoxic effects of OTA were further validated in an animal model in vivo. Intravenous injection of dams with OTA (3 mg/kg/day) led to apoptosis of blastocysts, impairment of embryonic development from zygote to blastocyst stage and decrease in day 18 fetal weight. Notably, preinjection of dams with LQ (5 mg/kg/day) effectively prevented OTA‐induced apoptosis and toxic effects on embryo development. Our collective results clearly demonstrate that OTA exposure via injection has the potential to damage preimplantation and postimplantation embryonic development against which LQ has a protective effect. |
doi_str_mv | 10.1002/tox.22724 |
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In a previous report, we highlighted the potential of OTA to induce apoptosis via reactive oxygen species (ROS) generation in mouse blastocysts that led to impaired preimplantation and postimplantation embryo development in vitro and in vivo. Here, we have shown that liquiritigenin (LQ), a type of flavonoid isolated from Glycyrrhiza radix, effectively protects against OTA‐mediated apoptosis and inhibition of cell proliferation in mouse blastocysts. Preincubation of blastocysts with LQ clearly prevented OTA‐triggered impairment of preimplantation and postimplantation embryonic development and fetal weight loss, both in vitro and in vivo. Detailed investigation of regulatory mechanisms revealed that OTA mediated apoptosis and embryotoxicity through ROS generation, loss of mitochondrial membrane potential (MMP), and activation of caspase‐9 and caspase‐3, which were effectively prevented by LQ. The embryotoxic effects of OTA were further validated in an animal model in vivo. Intravenous injection of dams with OTA (3 mg/kg/day) led to apoptosis of blastocysts, impairment of embryonic development from zygote to blastocyst stage and decrease in day 18 fetal weight. Notably, preinjection of dams with LQ (5 mg/kg/day) effectively prevented OTA‐induced apoptosis and toxic effects on embryo development. Our collective results clearly demonstrate that OTA exposure via injection has the potential to damage preimplantation and postimplantation embryonic development against which LQ has a protective effect.</description><identifier>ISSN: 1520-4081</identifier><identifier>EISSN: 1522-7278</identifier><identifier>DOI: 10.1002/tox.22724</identifier><identifier>PMID: 30698892</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Animal embryos ; Animal models ; Animals ; Apoptosis ; Apoptosis - drug effects ; Beer ; Biocompatibility ; Blastocyst - drug effects ; Blastocyst - metabolism ; Blastocyst - pathology ; Blastocysts ; Body weight loss ; Caspase ; Cell proliferation ; Cell Proliferation - drug effects ; Coffee ; Commodities ; Dams ; Embryogenesis ; Embryonic development ; Embryonic Development - drug effects ; Embryonic growth stage ; Embryos ; Female ; Fetuses ; Flavanones - pharmacology ; Hepatotoxicity ; Immunotoxicity ; Impairment ; In vivo methods and tests ; Injection ; Intravenous administration ; Liquiritigenin ; Membrane potential ; Membrane Potential, Mitochondrial - drug effects ; Mice ; Mitochondria ; Mycotoxins ; Ochratoxin A ; Ochratoxins - toxicity ; Oxidative stress ; Oxidative Stress - drug effects ; Pathological effects ; Pregnancy ; Proliferation ; Protective Agents - pharmacology ; Reactive oxygen species ; Regulatory mechanisms (biology) ; Spices ; Toxicology ; Weight ; Weight loss ; Wine ; Zygotes</subject><ispartof>Environmental toxicology, 2019-05, Vol.34 (5), p.573-584</ispartof><rights>2019 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3904-6aa9aa3cc1e13885a64153d4f98f3ea97aeba28d57d34a32aa5055d884e97cc03</citedby><cites>FETCH-LOGICAL-c3904-6aa9aa3cc1e13885a64153d4f98f3ea97aeba28d57d34a32aa5055d884e97cc03</cites><orcidid>0000-0002-9999-0731</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Ftox.22724$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Ftox.22724$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30698892$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huang, Chien‐Hsun</creatorcontrib><creatorcontrib>Wang, Fu‐Ting</creatorcontrib><creatorcontrib>Chan, Wen‐Hsiung</creatorcontrib><title>Prevention of ochratoxin A‐induced oxidative stress‐mediated apoptotic processes and impairment of embryonic development in mouse blastocysts by liquiritigenin</title><title>Environmental toxicology</title><addtitle>Environ Toxicol</addtitle><description>Ochratoxin A (OTA), a mycotoxin constituent of a range of food commodities, including coffee, wine, beer, grains, and spices, exerts toxicological and pathological effects in vivo, such as nephrotoxicity, hepatotoxicity, and immunotoxicity. In a previous report, we highlighted the potential of OTA to induce apoptosis via reactive oxygen species (ROS) generation in mouse blastocysts that led to impaired preimplantation and postimplantation embryo development in vitro and in vivo. Here, we have shown that liquiritigenin (LQ), a type of flavonoid isolated from Glycyrrhiza radix, effectively protects against OTA‐mediated apoptosis and inhibition of cell proliferation in mouse blastocysts. Preincubation of blastocysts with LQ clearly prevented OTA‐triggered impairment of preimplantation and postimplantation embryonic development and fetal weight loss, both in vitro and in vivo. Detailed investigation of regulatory mechanisms revealed that OTA mediated apoptosis and embryotoxicity through ROS generation, loss of mitochondrial membrane potential (MMP), and activation of caspase‐9 and caspase‐3, which were effectively prevented by LQ. The embryotoxic effects of OTA were further validated in an animal model in vivo. Intravenous injection of dams with OTA (3 mg/kg/day) led to apoptosis of blastocysts, impairment of embryonic development from zygote to blastocyst stage and decrease in day 18 fetal weight. Notably, preinjection of dams with LQ (5 mg/kg/day) effectively prevented OTA‐induced apoptosis and toxic effects on embryo development. Our collective results clearly demonstrate that OTA exposure via injection has the potential to damage preimplantation and postimplantation embryonic development against which LQ has a protective effect.</description><subject>Animal embryos</subject><subject>Animal models</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Beer</subject><subject>Biocompatibility</subject><subject>Blastocyst - drug effects</subject><subject>Blastocyst - metabolism</subject><subject>Blastocyst - pathology</subject><subject>Blastocysts</subject><subject>Body weight loss</subject><subject>Caspase</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Coffee</subject><subject>Commodities</subject><subject>Dams</subject><subject>Embryogenesis</subject><subject>Embryonic development</subject><subject>Embryonic Development - drug effects</subject><subject>Embryonic growth stage</subject><subject>Embryos</subject><subject>Female</subject><subject>Fetuses</subject><subject>Flavanones - pharmacology</subject><subject>Hepatotoxicity</subject><subject>Immunotoxicity</subject><subject>Impairment</subject><subject>In vivo methods and tests</subject><subject>Injection</subject><subject>Intravenous administration</subject><subject>Liquiritigenin</subject><subject>Membrane potential</subject><subject>Membrane Potential, Mitochondrial - drug effects</subject><subject>Mice</subject><subject>Mitochondria</subject><subject>Mycotoxins</subject><subject>Ochratoxin A</subject><subject>Ochratoxins - toxicity</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Pathological effects</subject><subject>Pregnancy</subject><subject>Proliferation</subject><subject>Protective Agents - pharmacology</subject><subject>Reactive oxygen species</subject><subject>Regulatory mechanisms (biology)</subject><subject>Spices</subject><subject>Toxicology</subject><subject>Weight</subject><subject>Weight loss</subject><subject>Wine</subject><subject>Zygotes</subject><issn>1520-4081</issn><issn>1522-7278</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kUtu1jAURi0Eog8YsAFkiRGDtI4fiT2sKl5SpTIoErPoxr4BV0mc2k5LZiyBPbAzVlL3_wszRrb8HZ0rf5eQVzU7qRnjpzn8OOG85fIJOawV51XLW_10d2eVZLo-IEcpXTPGTKOa5-RAsMZobfgh-f054i3O2YeZhoEG-z1C0fmZnv35-cvPbrXoaHlwkP0t0pQjplSiCZ2HXDJYwpJD9pYuMdgSYqIwO-qnBXycivtBjFMftzAXypV5Y1h2QRkzhTUh7UdIOdgt5UT7jY7-ZvXRZ_8NZz-_IM8GGBO-fDyPyZf3767OP1YXlx8-nZ9dVFYYJqsGwAAIa2ushdYKGlkr4eRg9CAQTAvYA9dOtU5IEBxAMaWc1hJNay0Tx-TN3ls-crNiyt11WONcRnacMylN2yhTqLd7ysaQUsShW6KfIG5dzbqHdXSlv263jsK-fjSufSnsH_m3_wKc7oE7P-L2f1N3dfl1r7wH2JGb7w</recordid><startdate>201905</startdate><enddate>201905</enddate><creator>Huang, Chien‐Hsun</creator><creator>Wang, Fu‐Ting</creator><creator>Chan, Wen‐Hsiung</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</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>7QH</scope><scope>7ST</scope><scope>7TN</scope><scope>7U7</scope><scope>7UA</scope><scope>C1K</scope><scope>F1W</scope><scope>H97</scope><scope>K9.</scope><scope>L.G</scope><scope>M7N</scope><scope>SOI</scope><orcidid>https://orcid.org/0000-0002-9999-0731</orcidid></search><sort><creationdate>201905</creationdate><title>Prevention of ochratoxin A‐induced oxidative stress‐mediated apoptotic processes and impairment of embryonic development in mouse blastocysts by liquiritigenin</title><author>Huang, Chien‐Hsun ; Wang, Fu‐Ting ; Chan, Wen‐Hsiung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3904-6aa9aa3cc1e13885a64153d4f98f3ea97aeba28d57d34a32aa5055d884e97cc03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animal embryos</topic><topic>Animal models</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Beer</topic><topic>Biocompatibility</topic><topic>Blastocyst - drug effects</topic><topic>Blastocyst - metabolism</topic><topic>Blastocyst - pathology</topic><topic>Blastocysts</topic><topic>Body weight loss</topic><topic>Caspase</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>Coffee</topic><topic>Commodities</topic><topic>Dams</topic><topic>Embryogenesis</topic><topic>Embryonic development</topic><topic>Embryonic Development - drug effects</topic><topic>Embryonic growth stage</topic><topic>Embryos</topic><topic>Female</topic><topic>Fetuses</topic><topic>Flavanones - pharmacology</topic><topic>Hepatotoxicity</topic><topic>Immunotoxicity</topic><topic>Impairment</topic><topic>In vivo methods and tests</topic><topic>Injection</topic><topic>Intravenous administration</topic><topic>Liquiritigenin</topic><topic>Membrane potential</topic><topic>Membrane Potential, Mitochondrial - drug effects</topic><topic>Mice</topic><topic>Mitochondria</topic><topic>Mycotoxins</topic><topic>Ochratoxin A</topic><topic>Ochratoxins - toxicity</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Pathological effects</topic><topic>Pregnancy</topic><topic>Proliferation</topic><topic>Protective Agents - pharmacology</topic><topic>Reactive oxygen species</topic><topic>Regulatory mechanisms (biology)</topic><topic>Spices</topic><topic>Toxicology</topic><topic>Weight</topic><topic>Weight loss</topic><topic>Wine</topic><topic>Zygotes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huang, Chien‐Hsun</creatorcontrib><creatorcontrib>Wang, Fu‐Ting</creatorcontrib><creatorcontrib>Chan, Wen‐Hsiung</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aqualine</collection><collection>Environment Abstracts</collection><collection>Oceanic Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Water Resources Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Environment Abstracts</collection><jtitle>Environmental toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huang, Chien‐Hsun</au><au>Wang, Fu‐Ting</au><au>Chan, Wen‐Hsiung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prevention of ochratoxin A‐induced oxidative stress‐mediated apoptotic processes and impairment of embryonic development in mouse blastocysts by liquiritigenin</atitle><jtitle>Environmental toxicology</jtitle><addtitle>Environ Toxicol</addtitle><date>2019-05</date><risdate>2019</risdate><volume>34</volume><issue>5</issue><spage>573</spage><epage>584</epage><pages>573-584</pages><issn>1520-4081</issn><eissn>1522-7278</eissn><abstract>Ochratoxin A (OTA), a mycotoxin constituent of a range of food commodities, including coffee, wine, beer, grains, and spices, exerts toxicological and pathological effects in vivo, such as nephrotoxicity, hepatotoxicity, and immunotoxicity. In a previous report, we highlighted the potential of OTA to induce apoptosis via reactive oxygen species (ROS) generation in mouse blastocysts that led to impaired preimplantation and postimplantation embryo development in vitro and in vivo. Here, we have shown that liquiritigenin (LQ), a type of flavonoid isolated from Glycyrrhiza radix, effectively protects against OTA‐mediated apoptosis and inhibition of cell proliferation in mouse blastocysts. Preincubation of blastocysts with LQ clearly prevented OTA‐triggered impairment of preimplantation and postimplantation embryonic development and fetal weight loss, both in vitro and in vivo. Detailed investigation of regulatory mechanisms revealed that OTA mediated apoptosis and embryotoxicity through ROS generation, loss of mitochondrial membrane potential (MMP), and activation of caspase‐9 and caspase‐3, which were effectively prevented by LQ. The embryotoxic effects of OTA were further validated in an animal model in vivo. Intravenous injection of dams with OTA (3 mg/kg/day) led to apoptosis of blastocysts, impairment of embryonic development from zygote to blastocyst stage and decrease in day 18 fetal weight. Notably, preinjection of dams with LQ (5 mg/kg/day) effectively prevented OTA‐induced apoptosis and toxic effects on embryo development. Our collective results clearly demonstrate that OTA exposure via injection has the potential to damage preimplantation and postimplantation embryonic development against which LQ has a protective effect.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>30698892</pmid><doi>10.1002/tox.22724</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-9999-0731</orcidid></addata></record> |
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subjects | Animal embryos Animal models Animals Apoptosis Apoptosis - drug effects Beer Biocompatibility Blastocyst - drug effects Blastocyst - metabolism Blastocyst - pathology Blastocysts Body weight loss Caspase Cell proliferation Cell Proliferation - drug effects Coffee Commodities Dams Embryogenesis Embryonic development Embryonic Development - drug effects Embryonic growth stage Embryos Female Fetuses Flavanones - pharmacology Hepatotoxicity Immunotoxicity Impairment In vivo methods and tests Injection Intravenous administration Liquiritigenin Membrane potential Membrane Potential, Mitochondrial - drug effects Mice Mitochondria Mycotoxins Ochratoxin A Ochratoxins - toxicity Oxidative stress Oxidative Stress - drug effects Pathological effects Pregnancy Proliferation Protective Agents - pharmacology Reactive oxygen species Regulatory mechanisms (biology) Spices Toxicology Weight Weight loss Wine Zygotes |
title | Prevention of ochratoxin A‐induced oxidative stress‐mediated apoptotic processes and impairment of embryonic development in mouse blastocysts by liquiritigenin |
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