{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T07:51:46Z","timestamp":1781769106661,"version":"3.54.5"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T00:00:00Z","timestamp":1644883200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08DK098623"],"award-info":[{"award-number":["K08DK098623"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R03EB015955\u201001"],"award-info":[{"award-number":["R03EB015955\u201001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aspenjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Parenter Enteral Nutr"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Parenteral nutrition (PN) remains a critical therapeutic option in patients who cannot tolerate enteral feeding. However, although lifesaving, PN is associated with significant side effects, including liver injury, the etiology of which is multifactorial. Carbamazepine (CBZ), an antiepileptic medication, is known to modulate hepatic fibrosis and hepatocellular injury in a variety of liver diseases. We hypothesized that CBZ could prevent PN\u2010associated liver disease (PNALD), which we tested by using our novel ambulatory PN piglet model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Piglets were fitted with jugular catheters and infusion pumps for PN and randomized to enteral nutrition (<jats:italic>n<\/jats:italic>\u2009=\u20097), PN (<jats:italic>n<\/jats:italic>\u2009=\u20096), or PN with parenteral CBZ (<jats:italic>n<\/jats:italic>\u2009=\u20096) for 2 weeks. Serum and liver tissue were analyzed via light microscopy, quantification of serum liver injury markers, Ki67 and cytokeratin\u20107 indexing, and real\u2010time quantitative polymerase chain reaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PN\u2010fed piglets in our model developed manifestations of PNALD\u2014particularly, increased serum bilirubin, gamma\u2010glutamyltransferase, liver cholestasis, and Ki67 expression compared with that of EN\u2010fed animals (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.03). CBZ therapy in PN\u2010fed animals led to a significant reduction in these markers of injury (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). Investigation into the mechanism of these therapeutic effects revealed increased expression of sterol regulatory element\u2010binding protein 1 (SREBP\u20101), peroxisome proliferator\u2010activated receptor alpha (PPAR\u2010\u03b1), and fatty acid binding protein (FABP) in PN\u2010fed animals receiving CBZ (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.03). Further investigation revealed increased LC3 expression and decreased lysosomal\u2010associated membrane protein (LAMP1) expression with CBZ (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.03).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CBZ administration mitigates PNALD severity, suggesting a novel therapeutic strategy targeting PN\u2010associated side effects, and may present a paradigm change to current treatment options.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jpen.2330","type":"journal-article","created":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T05:29:24Z","timestamp":1643002164000},"page":"1384-1392","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Carbamazepine mitigates parenteral nutrition\u2013associated liver disease in a novel ambulatory piglet model"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2505-8108","authenticated-orcid":false,"given":"Eric","family":"Song","sequence":"first","affiliation":[{"name":"Department of Pediatrics Saint Louis University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aakash","family":"Nagarapu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Saint Louis University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"van Nispen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Saint Louis University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Saint Louis University School of Medicine St. Louis Missouri 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