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Transcriptomics and metabolomics revealed the molecular mechanism of the toxic effect of mancozeb on liver of mice

Mancozeb (MCZ), a broad-spectrum fungicide, has been widely used in crops (tomatoes and potatoes) in the past few decades, resulting in its bioaccumulation in the food web. However, the mechanism of MCZ on liver injury has not been reported yet. This study combined transcriptomics and metabolomics t...

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Published in:Ecotoxicology and environmental safety 2022-09, Vol.243, p.114003-114003, Article 114003
Main Authors: Zhang, Yan, Bao, Jialu, Gong, Xincheng, Shi, Wanyu, Liu, Tao, Wang, Xiaodan
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description Mancozeb (MCZ), a broad-spectrum fungicide, has been widely used in crops (tomatoes and potatoes) in the past few decades, resulting in its bioaccumulation in the food web. However, the mechanism of MCZ on liver injury has not been reported yet. This study combined transcriptomics and metabolomics to explore the potential mechanism of MCZ on liver injury. MCZ group was given 100 mg/kg MCZ every day, and the C group was given 0.2 mL of deionized water every day. One hundred mg/kg MCZ led to unclear hepatocyte structure and hemorrhagic inflammatory cell infiltration. Transcriptomics and metabolomics analyses showed that the MCZ group resulted in 326 differentially expressed genes (DEGs) and 179 differential metabolites. Joint analysis showed that DEGs and differential metabolites were mainly enriched in the adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway. We found that MCZ could increase the content of reactive oxygen species (ROS) and reduce the activities of superoxide dismutase (SOD) and catalase (CAT). The contents of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) in the liver decreased significantly, and the state of DNA methylation was significantly higher than the control (C) group (p 
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However, the mechanism of MCZ on liver injury has not been reported yet. This study combined transcriptomics and metabolomics to explore the potential mechanism of MCZ on liver injury. MCZ group was given 100 mg/kg MCZ every day, and the C group was given 0.2 mL of deionized water every day. One hundred mg/kg MCZ led to unclear hepatocyte structure and hemorrhagic inflammatory cell infiltration. Transcriptomics and metabolomics analyses showed that the MCZ group resulted in 326 differentially expressed genes (DEGs) and 179 differential metabolites. Joint analysis showed that DEGs and differential metabolites were mainly enriched in the adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway. We found that MCZ could increase the content of reactive oxygen species (ROS) and reduce the activities of superoxide dismutase (SOD) and catalase (CAT). The contents of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) in the liver decreased significantly, and the state of DNA methylation was significantly higher than the control (C) group (p &lt; 0.05). Our results suggest that AMPK and mitogen‑activated protein kinase (MAPK) signaling pathways play an important role in MCZ-induced liver injury and are the key mechanisms for understanding the hepatotoxicity of MCZ. •Mancozeb induced hepatotoxicity in mice.•The mechanism of mancozeb liver injury was analyzed by transcriptomics and metabonomics.•The liver injury induced by mancozeb is related to apoptosis and chemical carcinogenesis.•MAPK pathway plays a role in apoptosis and carcinogenesis.</description><identifier>ISSN: 0147-6513</identifier><identifier>EISSN: 1090-2414</identifier><identifier>DOI: 10.1016/j.ecoenv.2022.114003</identifier><language>eng</language><publisher>Elsevier Inc</publisher><subject>Liver ; Mancozeb ; Metabonomics ; Transcriptomics</subject><ispartof>Ecotoxicology and environmental safety, 2022-09, Vol.243, p.114003-114003, Article 114003</ispartof><rights>2022 The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-ca184b62e98817bfc52aa3f167b3ac1a0156f396b8a5ee7d760acd7805ecd4b13</citedby><cites>FETCH-LOGICAL-c451t-ca184b62e98817bfc52aa3f167b3ac1a0156f396b8a5ee7d760acd7805ecd4b13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0147651322008430$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3549,27924,27925,45780</link.rule.ids></links><search><creatorcontrib>Zhang, Yan</creatorcontrib><creatorcontrib>Bao, Jialu</creatorcontrib><creatorcontrib>Gong, Xincheng</creatorcontrib><creatorcontrib>Shi, Wanyu</creatorcontrib><creatorcontrib>Liu, Tao</creatorcontrib><creatorcontrib>Wang, Xiaodan</creatorcontrib><title>Transcriptomics and metabolomics revealed the molecular mechanism of the toxic effect of mancozeb on liver of mice</title><title>Ecotoxicology and environmental safety</title><description>Mancozeb (MCZ), a broad-spectrum fungicide, has been widely used in crops (tomatoes and potatoes) in the past few decades, resulting in its bioaccumulation in the food web. 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The contents of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) in the liver decreased significantly, and the state of DNA methylation was significantly higher than the control (C) group (p &lt; 0.05). Our results suggest that AMPK and mitogen‑activated protein kinase (MAPK) signaling pathways play an important role in MCZ-induced liver injury and are the key mechanisms for understanding the hepatotoxicity of MCZ. •Mancozeb induced hepatotoxicity in mice.•The mechanism of mancozeb liver injury was analyzed by transcriptomics and metabonomics.•The liver injury induced by mancozeb is related to apoptosis and chemical carcinogenesis.•MAPK pathway plays a role in apoptosis and carcinogenesis.</description><subject>Liver</subject><subject>Mancozeb</subject><subject>Metabonomics</subject><subject>Transcriptomics</subject><issn>0147-6513</issn><issn>1090-2414</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNp9kUFv1DAQha0KJJbCP-CQI5csHtuxvRckVEGpVIlLOVuTyaT1Kom3dnYF_PpmN4gjJ0vPb74ZvSfEB5BbkGA_7bdMiafTVkmltgBGSn0lNiB3slYGzCuxkWBcbRvQb8TbUvZyccim2Yj8kHEqlONhTmOkUuHUVSPP2KZhFTKfGAfuqvmJqzENTMcB8-KhJ5xiGavUX77m9CtSxX3PNJ-1ESdKf7it0lQN8cT5Ikbid-J1j0Ph93_fa_Hz29eHm-_1_Y_bu5sv9zWZBuaaELxpreKd9-DanhqFqHuwrtVIgBIa2-udbT02zK5zViJ1zsuGqTMt6Gtxt3K7hPtwyHHE_DskjOEipPwYMM-RBg7OYqud65dQvGkufK08aQtKee3PrI8r65DT85HLHMZYiIcBJ07HEpSTzsLOKbdYzWqlnErJ3P9bDTKc6wr7sNYVznWFta5l7PM6xkskp8g5FIo8EXcxL4kuN8f_A14AcmWgYg</recordid><startdate>20220915</startdate><enddate>20220915</enddate><creator>Zhang, Yan</creator><creator>Bao, Jialu</creator><creator>Gong, Xincheng</creator><creator>Shi, Wanyu</creator><creator>Liu, Tao</creator><creator>Wang, Xiaodan</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>DOA</scope></search><sort><creationdate>20220915</creationdate><title>Transcriptomics and metabolomics revealed the molecular mechanism of the toxic effect of mancozeb on liver of mice</title><author>Zhang, Yan ; Bao, Jialu ; Gong, Xincheng ; Shi, Wanyu ; Liu, Tao ; Wang, Xiaodan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-ca184b62e98817bfc52aa3f167b3ac1a0156f396b8a5ee7d760acd7805ecd4b13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Liver</topic><topic>Mancozeb</topic><topic>Metabonomics</topic><topic>Transcriptomics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Yan</creatorcontrib><creatorcontrib>Bao, Jialu</creatorcontrib><creatorcontrib>Gong, Xincheng</creatorcontrib><creatorcontrib>Shi, Wanyu</creatorcontrib><creatorcontrib>Liu, Tao</creatorcontrib><creatorcontrib>Wang, Xiaodan</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Ecotoxicology and environmental safety</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Yan</au><au>Bao, Jialu</au><au>Gong, Xincheng</au><au>Shi, Wanyu</au><au>Liu, Tao</au><au>Wang, Xiaodan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcriptomics and metabolomics revealed the molecular mechanism of the toxic effect of mancozeb on liver of mice</atitle><jtitle>Ecotoxicology and environmental safety</jtitle><date>2022-09-15</date><risdate>2022</risdate><volume>243</volume><spage>114003</spage><epage>114003</epage><pages>114003-114003</pages><artnum>114003</artnum><issn>0147-6513</issn><eissn>1090-2414</eissn><abstract>Mancozeb (MCZ), a broad-spectrum fungicide, has been widely used in crops (tomatoes and potatoes) in the past few decades, resulting in its bioaccumulation in the food web. However, the mechanism of MCZ on liver injury has not been reported yet. This study combined transcriptomics and metabolomics to explore the potential mechanism of MCZ on liver injury. MCZ group was given 100 mg/kg MCZ every day, and the C group was given 0.2 mL of deionized water every day. One hundred mg/kg MCZ led to unclear hepatocyte structure and hemorrhagic inflammatory cell infiltration. Transcriptomics and metabolomics analyses showed that the MCZ group resulted in 326 differentially expressed genes (DEGs) and 179 differential metabolites. Joint analysis showed that DEGs and differential metabolites were mainly enriched in the adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway. We found that MCZ could increase the content of reactive oxygen species (ROS) and reduce the activities of superoxide dismutase (SOD) and catalase (CAT). The contents of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) in the liver decreased significantly, and the state of DNA methylation was significantly higher than the control (C) group (p &lt; 0.05). Our results suggest that AMPK and mitogen‑activated protein kinase (MAPK) signaling pathways play an important role in MCZ-induced liver injury and are the key mechanisms for understanding the hepatotoxicity of MCZ. •Mancozeb induced hepatotoxicity in mice.•The mechanism of mancozeb liver injury was analyzed by transcriptomics and metabonomics.•The liver injury induced by mancozeb is related to apoptosis and chemical carcinogenesis.•MAPK pathway plays a role in apoptosis and carcinogenesis.</abstract><pub>Elsevier Inc</pub><doi>10.1016/j.ecoenv.2022.114003</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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subjects Liver
Mancozeb
Metabonomics
Transcriptomics
title Transcriptomics and metabolomics revealed the molecular mechanism of the toxic effect of mancozeb on liver of mice
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