{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T23:38:10Z","timestamp":1788910690544,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005047","name":"Natural Science Foundation of Liaoning Province","doi-asserted-by":"publisher","award":["201602223, 2019\u2010ZD\u20100652"],"award-info":[{"award-number":["201602223, 2019\u2010ZD\u20100652"]}],"id":[{"id":"10.13039\/501100005047","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Severe acetaminophen (APAP)\u2010induced hepatic damage is the second most common cause for hepatic transplantation. Clinically, hepatic damage caused by APAP is treated using <jats:italic>N<\/jats:italic>\u2010acetyl\u2010L\u2010cysteine, which can induce numerous side effects. Naringin, a bioflavonoid abundant in grapefruit and other citrus fruits, displays marked antiinflammatory and antioxidant activities. Herein, we aimed to investigate the potential mechanism underlying naringin\u2010mediated protection against APAP\u2010induced acute hepatotoxicity. We observed that naringin afforded protection against APAP\u2010induced acute liver failure in mice. Importantly, pretreatment with naringin before APAP administration further increased antioxidant enzyme expression, inhibited the production of proinflammatory cytokines, and activated apoptotic pathways. Furthermore, we observed that the protective effect was associated with the upregulation of cation transport regulator\u2010like protein 2 (CHAC2) and nuclear factor erythroid derived\u20102\u2010related factor 2 (Nrf2). Notably, CHAC2 knockdown inhibited Nrf2 activation and naringin\u2010mediated antioxidant, antiinflammatory, and antiapoptotic effects in APAP\u2010induced liver injury. Likewise, si\u2010Nrf2 blocked the protective effect of naringin against APAP\u2010induced liver injury. Collectively, our results indicate that naringin may be a potent CHAC2 activator, alleviating APAP\u2010induced hepatitis via CHAC2\u2010mediated activation of the Nrf2 pathway. These data provide new insights into mechanisms through which CHAC2 regulates APAP\u2010induced liver injury by targeting Nrf2, which should be considered a novel therapeutic target.<\/jats:p>","DOI":"10.1002\/tox.23487","type":"journal-article","created":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T13:09:10Z","timestamp":1645189750000},"page":"1332-1342","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Naringin alleviates a<scp>cetaminophen\u2010induced<\/scp> acute liver injury by activating Nrf2 via <scp>CHAC2<\/scp> upregulation"],"prefix":"10.1002","volume":"37","author":[{"given":"Xiaohan","family":"Zhai","sequence":"first","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiantian","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy 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