Myclobutanil worsens nonalcoholic fatty liver disease: An in vitro study of toxicity and apoptosis on HepG2 cells
•Hepatic toxicity of myclobutanil exacerbates fatty acid-induced steatosis.•Myclobutanil reduces viability of HepG2 cells to
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| Veröffentlicht in: | Toxicology letters 2016-11, Vol.262, p.100-104 |
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| creator | Stellavato, Antonietta Lamberti, Monica Pirozzi, Anna Virginia Adriana de Novellis, Francesca Schiraldi, Chiara |
| description | •Hepatic toxicity of myclobutanil exacerbates fatty acid-induced steatosis.•Myclobutanil reduces viability of HepG2 cells to |
| doi_str_mv | 10.1016/j.toxlet.2016.09.013 |
| format | Article |
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Myclobutanil is a conazole class fungicide widely used as an agrichemical. It is approved for use on fruit, vegetables and seed commodities in the EU and elsewhere to control fungi such as Ascomycetes, Fungi Imperfecti and, Basidiomycetes. Its widespread use has raised the issue of possible health risks for agrarian communities and the general population, which can be exposed to residues present in food and drinking water. The toxicities identified include adverse effects on liver and kidney and on the development of male reproductive organs. Since the liver is the first-line organ in the defense against xenobiotics, toxic effects on hepatic metabolism cause degeneration, necrosis, and tissue hypertrophy. Therefore, we investigated myclobutanil’s effects on the human liver cell line HepG2. We found that myclobutanil increases the amount of fatty acids in these hepatic cells, as evaluated with Oil Red O staining, and progressively reduces cell viability from 1ppm to 500ppm. Analysis of biomarkers such as Bcl-xL/Bak and Mcl-1/Bak confirmed activation of cell death pathways at low doses. Therefore, myclobutanil may play an important role in the pathogenesis and progression of chronic hepatocellular diseases in humans.</description><identifier>ISSN: 0378-4274</identifier><identifier>EISSN: 1879-3169</identifier><identifier>DOI: 10.1016/j.toxlet.2016.09.013</identifier><identifier>PMID: 27693777</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Apoptosis - drug effects ; Ascomycetes ; Basidiomycetes ; bcl-2 Homologous Antagonist-Killer Protein - metabolism ; bcl-X Protein - metabolism ; Cell Death - drug effects ; Commodities ; Conazole fungicide ; Cytochromes c - metabolism ; Drinking water ; Fatty Acids - metabolism ; Fungi ; Fungicides ; Fungicides, Industrial - toxicity ; Hep G2 Cells ; Hepatocytes - drug effects ; Hepatoxicity ; HepG2 cells ; Humans ; L-Lactate Dehydrogenase - metabolism ; Lipid Metabolism - drug effects ; Liver ; Myclobutanil ; Myeloid Cell Leukemia Sequence 1 Protein - metabolism ; Nitriles - toxicity ; Non-alcoholic Fatty Liver Disease - chemically induced ; Non-alcoholic Fatty Liver Disease - pathology ; Nonalcoholic fatty liver disease ; Organs ; Toxicity ; Toxicology ; Triazoles - toxicity</subject><ispartof>Toxicology letters, 2016-11, Vol.262, p.100-104</ispartof><rights>2016 Elsevier Ireland Ltd</rights><rights>Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-f1e5a385ed89dcb3479b38f1820a27fdfeb9bd3502a61c0f624fe64ee96f48a3</citedby><cites>FETCH-LOGICAL-c428t-f1e5a385ed89dcb3479b38f1820a27fdfeb9bd3502a61c0f624fe64ee96f48a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.toxlet.2016.09.013$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27693777$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stellavato, Antonietta</creatorcontrib><creatorcontrib>Lamberti, Monica</creatorcontrib><creatorcontrib>Pirozzi, Anna Virginia Adriana</creatorcontrib><creatorcontrib>de Novellis, Francesca</creatorcontrib><creatorcontrib>Schiraldi, Chiara</creatorcontrib><title>Myclobutanil worsens nonalcoholic fatty liver disease: An in vitro study of toxicity and apoptosis on HepG2 cells</title><title>Toxicology letters</title><addtitle>Toxicol Lett</addtitle><description>•Hepatic toxicity of myclobutanil exacerbates fatty acid-induced steatosis.•Myclobutanil reduces viability of HepG2 cells to <50% at 100ppm and to <10% at 500ppm.•Myclobutanil modifies the function of enzymes such LDH and cytochrome c.•Analysis of biomarkers such as Bcl-xL/Bak and Mcl-1/Bak confirmed activation of cell death pathways at low doses of myclobutanil.
Myclobutanil is a conazole class fungicide widely used as an agrichemical. It is approved for use on fruit, vegetables and seed commodities in the EU and elsewhere to control fungi such as Ascomycetes, Fungi Imperfecti and, Basidiomycetes. Its widespread use has raised the issue of possible health risks for agrarian communities and the general population, which can be exposed to residues present in food and drinking water. The toxicities identified include adverse effects on liver and kidney and on the development of male reproductive organs. Since the liver is the first-line organ in the defense against xenobiotics, toxic effects on hepatic metabolism cause degeneration, necrosis, and tissue hypertrophy. Therefore, we investigated myclobutanil’s effects on the human liver cell line HepG2. We found that myclobutanil increases the amount of fatty acids in these hepatic cells, as evaluated with Oil Red O staining, and progressively reduces cell viability from 1ppm to 500ppm. Analysis of biomarkers such as Bcl-xL/Bak and Mcl-1/Bak confirmed activation of cell death pathways at low doses. Therefore, myclobutanil may play an important role in the pathogenesis and progression of chronic hepatocellular diseases in humans.</description><subject>Apoptosis - drug effects</subject><subject>Ascomycetes</subject><subject>Basidiomycetes</subject><subject>bcl-2 Homologous Antagonist-Killer Protein - metabolism</subject><subject>bcl-X Protein - metabolism</subject><subject>Cell Death - drug effects</subject><subject>Commodities</subject><subject>Conazole fungicide</subject><subject>Cytochromes c - metabolism</subject><subject>Drinking water</subject><subject>Fatty Acids - metabolism</subject><subject>Fungi</subject><subject>Fungicides</subject><subject>Fungicides, Industrial - toxicity</subject><subject>Hep G2 Cells</subject><subject>Hepatocytes - drug effects</subject><subject>Hepatoxicity</subject><subject>HepG2 cells</subject><subject>Humans</subject><subject>L-Lactate Dehydrogenase - metabolism</subject><subject>Lipid Metabolism - drug effects</subject><subject>Liver</subject><subject>Myclobutanil</subject><subject>Myeloid Cell Leukemia Sequence 1 Protein - metabolism</subject><subject>Nitriles - toxicity</subject><subject>Non-alcoholic Fatty Liver Disease - chemically induced</subject><subject>Non-alcoholic Fatty Liver Disease - pathology</subject><subject>Nonalcoholic fatty liver disease</subject><subject>Organs</subject><subject>Toxicity</subject><subject>Toxicology</subject><subject>Triazoles - toxicity</subject><issn>0378-4274</issn><issn>1879-3169</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1r3DAQhkVoSTZp_0EpOvZiVx-2JfVQCCEfhZRecheyNKJavJIjydvuv6-XTXosPQ0DzzszzIPQB0paSujwedvW9HuC2rK1a4lqCeVnaEOlUA2ng3qDNoQL2XRMdBfospQtIWTohv4cXTAxKC6E2KDn7wc7pXGpJoYJ_0q5QCw4pmgmm36mKVjsTa0HPIU9ZOxCAVPgC76OOES8DzUnXOriDjh5vB4UbFhhEx02c5prKqHgFPEDzPcMW5im8g699WYq8P6lXqGnu9unm4fm8cf9t5vrx8Z2TNbGU-gNlz04qZwdeSfUyKWnkhHDhHceRjU63hNmBmqJH1jnYegA1OA7afgV-nQaO-f0vECpehfK8QATIS1FU9n3XFDG5H-gXHCmiOhXtDuhNqdSMng957Az-aAp0UcteqtPWvRRiyZKr1rW2MeXDcu4A_c39OphBb6eAFg_sg-QdbEBogUXMtiqXQr_3vAHjJSiXg</recordid><startdate>20161116</startdate><enddate>20161116</enddate><creator>Stellavato, Antonietta</creator><creator>Lamberti, Monica</creator><creator>Pirozzi, Anna Virginia Adriana</creator><creator>de Novellis, Francesca</creator><creator>Schiraldi, Chiara</creator><general>Elsevier B.V</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>7U7</scope><scope>C1K</scope><scope>8FD</scope><scope>FR3</scope><scope>KR7</scope></search><sort><creationdate>20161116</creationdate><title>Myclobutanil worsens nonalcoholic fatty liver disease: An in vitro study of toxicity and apoptosis on HepG2 cells</title><author>Stellavato, Antonietta ; Lamberti, Monica ; Pirozzi, Anna Virginia Adriana ; de Novellis, Francesca ; Schiraldi, Chiara</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c428t-f1e5a385ed89dcb3479b38f1820a27fdfeb9bd3502a61c0f624fe64ee96f48a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Apoptosis - drug effects</topic><topic>Ascomycetes</topic><topic>Basidiomycetes</topic><topic>bcl-2 Homologous Antagonist-Killer Protein - metabolism</topic><topic>bcl-X Protein - metabolism</topic><topic>Cell Death - drug effects</topic><topic>Commodities</topic><topic>Conazole fungicide</topic><topic>Cytochromes c - metabolism</topic><topic>Drinking water</topic><topic>Fatty Acids - metabolism</topic><topic>Fungi</topic><topic>Fungicides</topic><topic>Fungicides, Industrial - toxicity</topic><topic>Hep G2 Cells</topic><topic>Hepatocytes - drug effects</topic><topic>Hepatoxicity</topic><topic>HepG2 cells</topic><topic>Humans</topic><topic>L-Lactate Dehydrogenase - metabolism</topic><topic>Lipid Metabolism - drug effects</topic><topic>Liver</topic><topic>Myclobutanil</topic><topic>Myeloid Cell Leukemia Sequence 1 Protein - metabolism</topic><topic>Nitriles - toxicity</topic><topic>Non-alcoholic Fatty Liver Disease - chemically induced</topic><topic>Non-alcoholic Fatty Liver Disease - pathology</topic><topic>Nonalcoholic fatty liver disease</topic><topic>Organs</topic><topic>Toxicity</topic><topic>Toxicology</topic><topic>Triazoles - toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stellavato, Antonietta</creatorcontrib><creatorcontrib>Lamberti, Monica</creatorcontrib><creatorcontrib>Pirozzi, Anna Virginia Adriana</creatorcontrib><creatorcontrib>de Novellis, Francesca</creatorcontrib><creatorcontrib>Schiraldi, Chiara</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Civil Engineering Abstracts</collection><jtitle>Toxicology letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stellavato, Antonietta</au><au>Lamberti, Monica</au><au>Pirozzi, Anna Virginia Adriana</au><au>de Novellis, Francesca</au><au>Schiraldi, Chiara</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Myclobutanil worsens nonalcoholic fatty liver disease: An in vitro study of toxicity and apoptosis on HepG2 cells</atitle><jtitle>Toxicology letters</jtitle><addtitle>Toxicol Lett</addtitle><date>2016-11-16</date><risdate>2016</risdate><volume>262</volume><spage>100</spage><epage>104</epage><pages>100-104</pages><issn>0378-4274</issn><eissn>1879-3169</eissn><abstract>•Hepatic toxicity of myclobutanil exacerbates fatty acid-induced steatosis.•Myclobutanil reduces viability of HepG2 cells to <50% at 100ppm and to <10% at 500ppm.•Myclobutanil modifies the function of enzymes such LDH and cytochrome c.•Analysis of biomarkers such as Bcl-xL/Bak and Mcl-1/Bak confirmed activation of cell death pathways at low doses of myclobutanil.
Myclobutanil is a conazole class fungicide widely used as an agrichemical. It is approved for use on fruit, vegetables and seed commodities in the EU and elsewhere to control fungi such as Ascomycetes, Fungi Imperfecti and, Basidiomycetes. Its widespread use has raised the issue of possible health risks for agrarian communities and the general population, which can be exposed to residues present in food and drinking water. The toxicities identified include adverse effects on liver and kidney and on the development of male reproductive organs. Since the liver is the first-line organ in the defense against xenobiotics, toxic effects on hepatic metabolism cause degeneration, necrosis, and tissue hypertrophy. Therefore, we investigated myclobutanil’s effects on the human liver cell line HepG2. We found that myclobutanil increases the amount of fatty acids in these hepatic cells, as evaluated with Oil Red O staining, and progressively reduces cell viability from 1ppm to 500ppm. Analysis of biomarkers such as Bcl-xL/Bak and Mcl-1/Bak confirmed activation of cell death pathways at low doses. Therefore, myclobutanil may play an important role in the pathogenesis and progression of chronic hepatocellular diseases in humans.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>27693777</pmid><doi>10.1016/j.toxlet.2016.09.013</doi><tpages>5</tpages></addata></record> |
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| ispartof | Toxicology letters, 2016-11, Vol.262, p.100-104 |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Apoptosis - drug effects Ascomycetes Basidiomycetes bcl-2 Homologous Antagonist-Killer Protein - metabolism bcl-X Protein - metabolism Cell Death - drug effects Commodities Conazole fungicide Cytochromes c - metabolism Drinking water Fatty Acids - metabolism Fungi Fungicides Fungicides, Industrial - toxicity Hep G2 Cells Hepatocytes - drug effects Hepatoxicity HepG2 cells Humans L-Lactate Dehydrogenase - metabolism Lipid Metabolism - drug effects Liver Myclobutanil Myeloid Cell Leukemia Sequence 1 Protein - metabolism Nitriles - toxicity Non-alcoholic Fatty Liver Disease - chemically induced Non-alcoholic Fatty Liver Disease - pathology Nonalcoholic fatty liver disease Organs Toxicity Toxicology Triazoles - toxicity |
| title | Myclobutanil worsens nonalcoholic fatty liver disease: An in vitro study of toxicity and apoptosis on HepG2 cells |
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