{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T23:18:55Z","timestamp":1778541535379,"version":"3.51.4"},"reference-count":57,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,1]],"date-time":"2020-03-01T00:00:00Z","timestamp":1583020800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2018M3A7B4071233, NRF-2019R1I1A3A01058584"],"award-info":[{"award-number":["NRF-2018M3A7B4071233, NRF-2019R1I1A3A01058584"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Age is a risk factor for drug-induced liver injury (DILI). However, there is a limited understanding of pediatric DILI. Here, 2-week-old weaning and 8-week-old adult male ICR mice were intraperitoneally injected with CCl4 (0.1 mmol\/kg equal to 15.4 mg\/kg) to comparatively evaluate the time-dependent liver damage and cellular events. CCl4 significantly enhanced the serum alanine aminotransferase\/aspartate aminotransferase levels and hepatic centrilobular necrosis in the weaning mice, whereas it induced mild liver injury in the adult mice. CCl4-treated weaning mice exhibited higher hepatic levels of pro-apoptotic proteins (Bax, cleaved caspase-3, -7, and -9), activated MAPKs (p-JNK and p-Erk), and endoplasmic reticulum stress indicators (ATF6 and CHOP) and lower hepatic anti-apoptotic Bcl-2 levels than the adult mice. The weaning mice exhibited enhanced basal hepatic glutathione (GSH) levels due to high glutamate cysteine ligase (GCL) and low anti-cysteine dioxygenase (CDO) enzyme levels. However, CCl4 markedly reduced the hepatic GSH levels only in the weaning mice. Furthermore, higher hepatic levels of oxidative stress-induced malondialdehyde, 4-hydroxynonenal, nitrotyrosine-protein adducts, and oxidized proteins were observed in CCl4-treated weaning mice than in CCl4-treated adult mice. The enhanced levels of hepatic cytochrome P450 (CYP) 2E1 and CYP3A, and decreased hepatic GSH S-transferase (GST)-\u03c0 and GSH reductase (GR) levels in the weaning mice may contribute to their enhanced susceptibility to liver damage.<\/jats:p>","DOI":"10.3390\/antiox9030201","type":"journal-article","created":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T04:16:16Z","timestamp":1583122576000},"page":"201","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Weaning Mice and Adult Mice Exhibit Differential Carbon Tetrachloride-Induced Acute Hepatotoxicity"],"prefix":"10.3390","volume":"9","author":[{"given":"Tae Bin","family":"Jeong","sequence":"first","affiliation":[{"name":"College of Pharmacy, Pusan National University, Busan 46241, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doyoung","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94158, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung Won","family":"Son","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Pusan National University, Busan 46241, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sou Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Pusan National University, Busan 46241, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun-Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min-Soo","family":"Seo","sequence":"additional","affiliation":[{"name":"Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kil Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea"},{"name":"College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-Suk","family":"Jung","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Pusan National University, Busan 46241, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/B978-0-12-415813-9.00003-9","article-title":"Metabolism of xenobiotics of human environments","volume":"112","author":"Croom","year":"2012","journal-title":"Prog. 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