{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:57:14Z","timestamp":1786978634513,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T00:00:00Z","timestamp":1678147200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hexavalent chromium Cr (VI) is a primary human carcinogen with damaging toxic effects on multiple organs. Cr (VI) exposure can induce hepatotoxicity through oxidative stress, but its exact mechanism of action was still unclear. In our study, a model of acute Cr (VI) induced liver injury was established by exposing mice to different concentrations (0, 40, 80, and 160\u2009mg\/kg) of Cr (VI); RNA\u2010seq was used to characterize changes in liver tissue transcriptome of C57BL\/6 mice after exposing to 160\u2009mg\/kg\u2009Bw of Cr (VI). Changes in liver tissue structures, proteins, and genes were observed by hematoxylin and eosin (H&amp;E), western blot, immunohistochemistry and RT\u2010PCR. After Cr (VI) exposure, abnormal liver tissue structure, hepatocyte injury, and hepatic inflammatory response were observed in mice in a dose\u2010dependent manner. RNA\u2010seq transcriptome results indicated that oxidative stress, apoptosis, and inflammatory response pathways were increased after Cr (VI) exposure; KEGG pathway analysis found that activation of NF\u2010\u03baB signaling pathway was significantly upregulated. Consistent with the RNA\u2010seq results, immunohistochemistry showed that Cr (VI) exposure resulted in infiltrating of Kupffer cells and neutrophils, increasing expression of inflammatory factors (TNF\u2010\u03b1, IL\u20106, IL\u20101\u03b2), and activating of NF\u2010\u03baB signaling pathways (p\u2010IKK\u03b1\/\u03b2 and p\u2010p65). However, ROS inhibitor, N\u2010acetyl\u2010L\u2010cysteine (NAC), could reduce infiltration of Kupffer cells and neutrophils and expression of inflammatory factors. Besides, NAC could inhibit NF\u2010\u03baB signaling pathway activation, and alleviate Cr (VI)\u2010induced liver tissue damage. Our findings strongly suggested that inhibition of ROS by NAC might help in the development of new strategies for Cr (VI)\u2010associated liver fibrosis. Our findings revealed for the first time that Cr (VI) induced liver tissue damage through the inflammatory response mediated by the NF\u2010\u03baB signaling pathway, and inhibition of ROS by NAC might help in the development of new strategies for Cr (VI)\u2010associated hepatotoxicity.<\/jats:p>","DOI":"10.1002\/tox.23769","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T05:24:49Z","timestamp":1678166689000},"page":"1361-1371","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Role of\n                    <scp>NF\u2010\u03baB<\/scp>\n                    signaling pathway in hexavalent chromium\u2010induced hepatotoxicity"],"prefix":"10.1002","volume":"38","author":[{"given":"Jiayuan","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Pathology Affiliated Hospital of Shaoxing University  Shaoxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merveille Chancelle","family":"Kom","sequence":"additional","affiliation":[{"name":"School of Life Science Shaoxing University  Shaoxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huarong","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Life and Environmental Science Hangzhou Normal University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoquan","family":"Fu","sequence":"additional","affiliation":[{"name":"School of Life Science Shaoxing University  Shaoxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixia","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Life Science Shaoxing University  Shaoxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Life Science Shaoxing University  Shaoxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxin","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Life Science Shaoxing University  Shaoxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2395-8284","authenticated-orcid":false,"given":"Junyan","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Life Science Shaoxing University  Shaoxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifang","family":"Jin","sequence":"additional","affiliation":[{"name":"School of Life Science Shaoxing University  Shaoxing China"},{"name":"Shaoxing Academy of Biomedicine of Zhejiang Sci\u2010Tech University  Shaoxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.5004\/dwt.2017.20322"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jenvman.2022.115356"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx200251t"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113119"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40726-016-0044-2"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/782493"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12995-017-0161-x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2021.04.002"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2020.188450"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2021.103725"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2016.01.057"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3965"},{"issue":"2","key":"e_1_2_8_14_1","article-title":"The double face of metals: the intriguing case of chromium","volume":"11","author":"Genchi G","year":"2021","journal-title":"Appl Sci\u2010Basel"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtemb.2012.04.016"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2021.112320"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1159\/000495713"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxrep.2015.03.013"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2013.04.012"},{"key":"e_1_2_8_20_1","article-title":"Cr(VI) induces ROS\u2010mediated mitochondrial\u2010dependent apoptosis in neuronal cells via the activation of Akt\/ERK\/AMPK signaling pathway","volume":"65","author":"Fu SC","year":"2020","journal-title":"Toxicol In Vitro"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2020.08.012"},{"issue":"1","key":"e_1_2_8_22_1","first-page":"1004","article-title":"Role of NF\u2010\u03baB signaling pathway and oxidative stress in liver inflammation","volume":"1","author":"Vysakh A","year":"2016","journal-title":"Austin Hepatol"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.0900715"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2016.02.008"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1177\/0960327116680275"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-12-86"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.16031"},{"issue":"9","key":"e_1_2_8_28_1","volume":"9","author":"Lee YH","year":"2014","journal-title":"PLoS One"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/sigtrans.2017.23"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-016-0901-2"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28433"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2017.03.003"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2021.112614"}],"container-title":["Environmental Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/tox.23769","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/tox.23769","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/tox.23769","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T10:16:17Z","timestamp":1764238577000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/tox.23769"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,7]]},"references-count":32,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1002\/tox.23769"],"URL":"https:\/\/doi.org\/10.1002\/tox.23769","archive":["Portico"],"relation":{},"ISSN":["1520-4081","1522-7278"],"issn-type":[{"value":"1520-4081","type":"print"},{"value":"1522-7278","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,7]]},"assertion":[{"value":"2022-08-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}