{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T04:06:16Z","timestamp":1780459576344,"version":"3.54.1"},"reference-count":83,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005289","name":"Provincial Secretariat for Higher Education and Scientific Research, Autonomous Province of Vojvodina","doi-asserted-by":"publisher","award":["003864121 2025 09418 003 000 000 001"],"award-info":[{"award-number":["003864121 2025 09418 003 000 000 001"]}],"id":[{"id":"10.13039\/501100005289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Carnosine is widely recognized for its antioxidant and cytoprotective properties and is being increasingly used in dietary supplements. However, its effects in drug-induced liver injury remain insufficiently studied. This study aimed to investigate and compare the hepatoprotective and antioxidative effects of pure carnosine and an antioxidant-enriched commercial carnosine supplement in a murine model of paracetamol-induced hepatotoxicity. Adult male Swiss Webster mice were pretreated orally for seven days with carnosine or a commercial carnosine supplement prior to a single hepatotoxic dose of paracetamol. The serum biochemical parameters, hepatic oxidative stress markers, histopathology, and immunohistochemical expression of CYP2E1, COX-2, and Iba1 were evaluated 24 h after paracetamol administration. Paracetamol increased serum aminotransferases, lipid peroxidation, CYP2E1 expression, and histological liver injury. Pure carnosine pretreatment tended to exacerbate biochemical liver injury, whereas the commercial supplement attenuated lipid peroxidation, preserved bilirubin levels, and reduced histological damage. Both formulations decreased CYP2E1 expression and were associated with less necrosis and COX-2 immunoreactivity compared with paracetamol alone. Antioxidant enzyme activities and macrophage markers showed no consistent intergroup differences. These findings indicate that carnosine may not consistently exert hepatoprotective effects in acute drug-induced liver injury and that accompanying antioxidants may critically modify its biological actions.<\/jats:p>","DOI":"10.3390\/cimb48060581","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T02:37:26Z","timestamp":1780454246000},"page":"581","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Varied Effects of Carnosine and an Antioxidant-Enriched Carnosine Supplement in Paracetamol-Induced Hepatotoxicity Model in Mice"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7186-3212","authenticated-orcid":false,"given":"Dragana","family":"Zaklan","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9229-4867","authenticated-orcid":false,"given":"Nikola","family":"Marti\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6810-9190","authenticated-orcid":false,"given":"Bojana","family":"Andreji\u0107 Vi\u0161nji\u0107","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9560-7176","authenticated-orcid":false,"given":"Milana","family":"Bosanac","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2605-7913","authenticated-orcid":false,"given":"Sne\u017eana","family":"Had\u017eistevi\u0107","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Faculty of Medicine, University of Pristina in Kosovska Mitrovica, 38220 Kosovska Mitrovica, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandar","family":"Ra\u0161kovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9444-5830","authenticated-orcid":false,"given":"Neboj\u0161a","family":"Pavlovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nrendo.2016.54","article-title":"Dietary supplements and disease prevention\u2014A global overview","volume":"12","author":"Rautiainen","year":"2016","journal-title":"Nat. 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