{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T13:00:25Z","timestamp":1773666025689,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T00:00:00Z","timestamp":1520380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004567","name":"Ministry of Education, Government of the People's Republic of Bangladesh","doi-asserted-by":"publisher","award":["NRF\u20102013R1A1A4A01010089"],"award-info":[{"award-number":["NRF\u20102013R1A1A4A01010089"]}],"id":[{"id":"10.13039\/501100004567","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Thioredoxin\u20101 (Trx\u20101) is a potent therapeutic agent against a variety of diseases because of its actions as an antioxidant and regulator of apoptosis. <jats:italic>N<\/jats:italic>\u2010acetyl\u2010p\u2010aminophenol (APAP), commonly known as acetaminophen, generates excessive oxidative stress and triggers hepatocyte cell death, exemplified by regulated necrosis. In the present study, we investigated whether APAP\u2010induced liver injury in a mouse model is associated with \u201cnecroptosis,\u201d and if pretreatment with recombinant Trx\u20101 prevents the hepatic injury caused by APAP overdose. We also explored the mechanism underlying the preventive action of Trx\u20101 against APAP\u2010induced hepatic injury. In a prevention study, C3H\/he mice received different doses (0, 10, 50 or 100\u00a0mg\u00a0kg<jats:sup>\u20131<\/jats:sup> body weight) of recombinant human Trx\u20101 intraperitoneally, followed by a single oral dose of 300\u00a0mg\u00a0kg<jats:sup>\u20131<\/jats:sup> of APAP. In this experimental paradigm, liver injury and lethality were markedly decreased in rhTrx\u20101\u2013pretreated mice. In survival experiments, mice received rhTrx\u20101 followed by oral administration of a lethal dose of APAP. APAP overdose caused a series of liver toxicity\u2010associated events, beginning with overexpression of c\u2010fos, excessive production of reactive oxygen species and reactive nitrogen species (RNS) and leading to decreased endogenous Trx\u20101 expression and activation of JNK signaling pathways. Pretreatment with rhTrx\u20101 inhibited all of these toxicological manifestations of APAP. In addition, rhTrx\u20101 significantly reduced the expression of RIP\u20103, a critical necrosome component. Taken together, our findings indicate that rhTrx\u20101 prevents APAP\u2010induced liver injury through multiple action mechanisms, including scavenging reactive oxygen species and reactive nitrogen species, restoring endogenous Trx\u20101 levels and inhibiting RIP\u20103 overexpression.<\/jats:p>","DOI":"10.1002\/jat.3609","type":"journal-article","created":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T04:22:50Z","timestamp":1520396570000},"page":"1008-1017","source":"Crossref","is-referenced-by-count":16,"title":["Exogenous recombinant human thioredoxin\u20101 prevents acetaminophen\u2010induced liver injury by scavenging oxidative stressors, restoring the thioredoxin\u20101 system and inhibiting receptor interacting protein\u20103 overexpression"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3943-7544","authenticated-orcid":false,"given":"Byung\u2010Woo","family":"Lee","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine and Institute of Veterinary Science Kangwon National University  1 Kangwondaehak\u2010gil Chuncheon Gangwon 24341 Republic of Korea"},{"name":"Biotoxtech Co.  53 Yeongudanji\u2010ro, Ochang\u2010eup, Cheongwon\u2010gu Cheongju\u2010si Chungcheongbuk\u2010do 28115 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byung\u2010Suk","family":"Jeon","sequence":"additional","affiliation":[{"name":"Biotoxtech Co.  53 Yeongudanji\u2010ro, Ochang\u2010eup, Cheongwon\u2010gu Cheongju\u2010si Chungcheongbuk\u2010do 28115 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4809-9903","authenticated-orcid":false,"given":"Byung\u2010Il","family":"Yoon","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine and Institute of Veterinary Science Kangwon National University  1 Kangwondaehak\u2010gil Chuncheon Gangwon 24341 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,3,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.2683"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbior.2016.05.001"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-9084(02)01374-3"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22837"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.5.1327"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.126"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/67.2.322"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708916200"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003412200"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMct0708278"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/53.2.467"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx9800349"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200209-982OC"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.3109\/03602532.2011.602688"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.31.12.1499"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx5000443"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.4322"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21926"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i42.7440"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.18.6638-6645.2000"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21175"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.223321.113"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.07.006"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.191498798"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5223(97)70393-3"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26547"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.075945"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2010.04.015"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.9.2596"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.134007"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2011.08.012"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.11.031"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/10715760701199618"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp400690v"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2970"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12329"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.11.030"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000102869.39150.23"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2014.01.005"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1200012109"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjat.3609","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.3609","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T16:29:40Z","timestamp":1760545780000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.3609"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,7]]},"references-count":40,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2018,7]]}},"alternative-id":["10.1002\/jat.3609"],"URL":"https:\/\/doi.org\/10.1002\/jat.3609","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,7]]}}}