{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T02:43:54Z","timestamp":1787971434071,"version":"build-2784847793"},"reference-count":89,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T00:00:00Z","timestamp":1696896000000},"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":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Acetaminophen (APAP) in high doses causes acute liver injury and acute liver failure. Ethyl gallate (EG) is a natural polyphenol, possessing antioxidant, anti\u2010inflammatory, and anti\u2010microbial properties. Therefore, in this study, we evaluated the protective role of EG against APAP\u2010induced acute liver injury in mice. Acute liver injury was induced by a single dose of APAP (400\u2009mg\/kg.,\u2009i.p.). In separate groups, EG (10\u2009mg\/kg), EG (20\u2009mg\/kg), and <jats:italic>N<\/jats:italic>\u2010acetylcysteine (NAC; 1200\u2009mg\/kg., i.p.) were administered concurrently with APAP. The mice were sacrificed after 24\u2009h of treatment. Liver marker enzymes of hepatotoxicity, antioxidant markers, inflammatory markers, and histopathological studies were done. APAP administration caused a significant elevation of marker enzymes of hepatotoxicity and lipid peroxidation. APAP administration also decreased enzymic and nonenzymic antioxidants. Acute APAP intoxication induced nuclear factor \u03ba B, tumor necrosis factor\u2010\u03b1, interleukin\u20101, p65, and p52 and downregulated I\u03baB gene expressions. Our histopathological studies have confirmed the presence of centrilobular necrosis, 24\u2009h after APAP intoxication. All the above abnormalities were significantly inhibited in groups of mice that were concurrently administered with APAP\u2009+\u2009EG and APAP\u2009+\u2009NAC. Our in silico analysis further confirms that hydroxyl groups of EG interact with the above inflammatory proteins at the 3,4,5\u2010trihydroxybenzoic acid region. These effects of EG against APAP\u2010induced acute liver injury could be attributed to its antioxidative, free radical scavenging, and anti\u2010inflammatory potentials. Therefore, this study suggests that EG can be an efficient therapeutic approach to protect the liver from APAP intoxication.<\/jats:p>","DOI":"10.1111\/cbdd.14369","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T04:28:48Z","timestamp":1697084928000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Ethyl gallate concurrent administration protects against acetaminophen\u2010induced acute liver injury in mice: An in vivo and in silico approach"],"prefix":"10.1111","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5068-2383","authenticated-orcid":false,"given":"Devaraj","family":"Ezhilarasan","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Hepatology and Molecular Medicine Lab, Saveetha Dental College Saveetha Institute of Medical and Technical Sciences Chennai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik","family":"Shree\u00a0Harini","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Hepatology and Molecular Medicine Lab, Saveetha Dental College Saveetha Institute of Medical and Technical Sciences Chennai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munusamy","family":"Karthick","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Hepatology and Molecular Medicine Lab, Saveetha Dental College Saveetha Institute of Medical and Technical Sciences Chennai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrabose","family":"Selvaraj","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Hepatology and Molecular Medicine Lab, Saveetha Dental College Saveetha Institute of Medical and Technical Sciences Chennai India"},{"name":"Laboratory for Artificial Intelligence and Molecular Modelling, Center for Global Health Research Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences Chennai India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2672.1998.00363.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-021-03211-z"},{"issue":"4","key":"e_1_2_8_4_1","first-page":"439","article-title":"Gallic acid protects the liver in rats against injuries induced by transient ischemia\u2010reperfusion through regulating microRNAs expressions","volume":"22","author":"Akbari G.","year":"2019","journal-title":"Iranian Journal of Basic Medical Sciences"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fsi.2021.12.044"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.09.014"},{"issue":"12","key":"e_1_2_8_7_1","first-page":"503","article-title":"Inhibition by galloylglucose (GG6\u201010) of tumor invasion through extracellular matrix and gelatinase\u2010mediated degradation of type IV collagens by metastatic tumor cells","volume":"8","author":"Ata N.","year":"1996","journal-title":"Oncology Research"},{"key":"e_1_2_8_8_1","first-page":"49","volume-title":"Manual of histological techniques","author":"Bancroft J. D.","year":"1984"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)62062-0"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1208937"},{"key":"e_1_2_8_11_1","first-page":"882","article-title":"Improved method for the determination of blood glutathione","volume":"61","author":"Beutler E.","year":"1963","journal-title":"The Journal of Laboratory and Clinical Medicine"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12010-023-04430-z"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2021.10.035"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0405-305"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.04.024"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2018.01.007"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-019-0382-z"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/1682743"},{"key":"e_1_2_8_19_1","first-page":"73","article-title":"Drug\u2010induced liver injury","volume":"6","author":"David S.","year":"2010","journal-title":"US Gastroenterology & Hepatology Review"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(59)90090-6"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.02.014"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajg.2018.03.002"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.22697"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apha.2018.12.004"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2014-0214-RA"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.23478"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094557"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxrep.2020.12.010"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v12.i11.949"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)42083-8"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.3109\/03602532.2011.602688"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfg181"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3841.2011.02243.x"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22137071"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114320"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.09.008"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-014-3293-9"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/CNQ.0000000000000409"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12042"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2017.06.002"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1177\/0960327120961158"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8TX00185E"},{"issue":"9","key":"e_1_2_8_43_1","first-page":"5597","article-title":"Corilagin reduces acetaminophen\u2010induced hepatotoxicity through MAPK and NF\u2010\u03baB signaling pathway in a mouse model","volume":"12","author":"Liu F. C.","year":"2020","journal-title":"American Journal of Translational Research"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2021.03.158"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1974.tb03714.x"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2005.06.035"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0000000000000150"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfm165"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2012.05.018"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)83745-6"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20170316"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1177\/0023677215570992"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-230X-10-34"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(79)90738-3"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0032-1328062"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.13261"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1081300"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-019-01777-x"},{"issue":"5","key":"e_1_2_8_59_1","first-page":"391","article-title":"Paracetamol poisoning. Prevention of liver damage","volume":"8","author":"Prescott L. F.","year":"1979","journal-title":"Medecine & Chirurgie Digestives"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-1679919"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.6197"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1211\/jpp.62.05.0012"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/28.1.56"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.179.4073.588"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22179371"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1093\/jpp\/rgaa048"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1080\/003655299750025949"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1093\/bfgp\/elac046"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2019.113643"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.2.549-555.2005"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(72)90132-7"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwab021"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198812153192401"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-991511"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i46.8459"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24061186"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.17.9.5386"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2017.09.019"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)91385-8"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23116049"},{"issue":"3","key":"e_1_2_8_81_1","first-page":"881","article-title":"Ubiquitination regulation of inflammatory responses through NF\u2010\u03baB pathway","volume":"10","author":"Wu Y.","year":"2018","journal-title":"American Journal of Translational Research"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphs.2022.01.012"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.04.019"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2017.05.001"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc7782"},{"issue":"2","key":"e_1_2_8_86_1","first-page":"131","article-title":"Acetaminophen\u2010induced hepatotoxicity: A comprehensive update","volume":"4","author":"Yoon E.","year":"2016","journal-title":"Journal of Clinical and Translational Hepatology"},{"issue":"6","key":"e_1_2_8_87_1","first-page":"1221","article-title":"Induction of apoptosis by gallic acid in human stomach cancer KATO III and colon adenocarcinoma COLO 205 cell lines","volume":"7","author":"Yoshioka K.","year":"2000","journal-title":"Oncology Reports"},{"key":"e_1_2_8_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2020.108578"},{"key":"e_1_2_8_89_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2017.22"},{"key":"e_1_2_8_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2009.02.059"}],"container-title":["Chemical Biology &amp; Drug Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.14369","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,16]],"date-time":"2024-11-16T06:19:45Z","timestamp":1731737985000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cbdd.14369"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,10]]},"references-count":89,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1111\/cbdd.14369"],"URL":"https:\/\/doi.org\/10.1111\/cbdd.14369","archive":["Portico"],"relation":{},"ISSN":["1747-0277","1747-0285"],"issn-type":[{"value":"1747-0277","type":"print"},{"value":"1747-0285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,10]]},"assertion":[{"value":"2023-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14369"}}