{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:25:55Z","timestamp":1790508355975,"version":"4.1.0"},"reference-count":33,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Food and Chemical Toxicology"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1016\/j.fct.2025.115809","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:44:14Z","timestamp":1760661854000},"page":"115809","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"special_numbering":"C","title":["The synthetic cannabinoid CUMYL-4CN-BINACA induces hepatic injury in rats via oxidative stress, NF-\u03baB activation, Nrf2 suppression, EDEM-1, ER stress-mediated apoptotic pathways"],"prefix":"10.1016","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4039-3497","authenticated-orcid":false,"given":"Tuba","family":"Dogan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozkan","family":"Aksakal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1781-0323","authenticated-orcid":false,"given":"Omercan","family":"Alat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7473-2955","authenticated-orcid":false,"given":"Mesut B\u00fcnyami","family":"Halici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cihan","family":"Gur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.fct.2025.115809_bib1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-025-06355-5","article-title":"Vincamine induces cytoprotective autophagy via regulation of ampk\/mtor signaling pathway in gentamicin-induced hepatotoxicity and nephrotoxicity in rats","volume":"15","author":"Abouelhamd","year":"2025","journal-title":"Sci. Rep."},{"key":"10.1016\/j.fct.2025.115809_bib2","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0076-6879(84)05016-3","article-title":"[13] catalase in vitro","volume":"105","author":"Aebi","year":"1984","journal-title":"Methods Enzymol."},{"key":"10.1016\/j.fct.2025.115809_bib3","doi-asserted-by":"crossref","first-page":"E769","DOI":"10.1097\/MJT.0000000000001181","article-title":"Acute liver failure caused by synthetic Marijuana use","volume":"29","author":"Ahmed","year":"2022","journal-title":"Am. J. Therapeut."},{"key":"10.1016\/j.fct.2025.115809_bib4","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1002\/dta.2373","article-title":"Metabolism study for CUMYL-4CN-BINACA in human hepatocytes and authentic urine specimens: free cyanide is formed during the main metabolic pathway","volume":"10","author":"\u00c5strand","year":"2018","journal-title":"Drug Test. Anal."},{"key":"10.1016\/j.fct.2025.115809_bib5","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1093\/clinchem\/hvad210","article-title":"Exposure to synthetic psychoactive substances: a potential cause for increased human hepatotoxicity markers","volume":"70","author":"Balloni","year":"2024","journal-title":"Clin. Chem."},{"key":"10.1016\/j.fct.2025.115809_bib6","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/sms.12702","article-title":"An overview of technical considerations for Western blotting applications to physiological research","volume":"27","author":"Bass","year":"2017","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"10.1016\/j.fct.2025.115809_bib7","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.forsciint.2017.10.020","article-title":"Structural characterization of the new synthetic cannabinoids CUMYL-PINACA, 5F-CUMYL-PINACA, CUMYL-4CN-BINACA, 5F-CUMYL-P7AICA and CUMYL-4CN-B7AICA","volume":"281","author":"Bovens","year":"2017","journal-title":"Forensic Sci. Int."},{"issue":"4479","key":"10.1016\/j.fct.2025.115809_bib8","article-title":"PCV2 and PRV coinfection induces endoplasmic reticulum stress via PERK-eIF2\u03b1-ATF4-CHOP and IRE1-XBP1-EDEM pathways","volume":"23","author":"Chen","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.fct.2025.115809_bib9","doi-asserted-by":"crossref","first-page":"104374","DOI":"10.1016\/j.etap.2024.104374","article-title":"Investigation of the effects of crocin on inflammation, oxidative stress, apoptosis, NF-\u03baB, TLR-4 and Nrf-2\/HO-1 pathways in gentamicin-induced nephrotoxicity in rats","volume":"106","author":"Dogan","year":"2024","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"10.1016\/j.fct.2025.115809_bib10","doi-asserted-by":"crossref","first-page":"7643","DOI":"10.1007\/s00210-025-03824-6","article-title":"New insight on the acute CCl4-induced hepatotoxicity model in rats","volume":"398","author":"dos Anjos Melo","year":"2025","journal-title":"Naunyn-Schmiedebergs Arch Pharmacol"},{"key":"10.1016\/j.fct.2025.115809_bib11","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.toxrep.2020.02.014","article-title":"Safety assessment of a hemp extract using genotoxicity and oral repeat-dose toxicity studies in sprague-dawley rats","volume":"7","author":"Dziwenka","year":"2020","journal-title":"Toxicol. Rep."},{"key":"10.1016\/j.fct.2025.115809_bib12","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.1111\/jgh.16730","article-title":"Clinical guidance for cannabidiol-associated hepatotoxicity: a narrative review","volume":"39","author":"Eadie","year":"2024","journal-title":"J. Gastroenterol. Hepatol."},{"key":"10.1016\/j.fct.2025.115809_bib13","doi-asserted-by":"crossref","first-page":"115617","DOI":"10.1016\/j.fct.2025.115617","article-title":"Synthetic cannabinoid CUMYL-4CN-BINACA induces oxidative stress, ER stress, and apoptosis in brain and testicular tissues of male albino rats","volume":"204","author":"Eren Demir","year":"2025","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.fct.2025.115809_bib14","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.3390\/molecules24091694","article-title":"Hepatotoxicity of a cannabidiol-rich cannabis extract in the mouse model","volume":"24","author":"Ewing","year":"2019","journal-title":"Molecules"},{"key":"10.1016\/j.fct.2025.115809_bib15","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.apjtb.2017.06.013","article-title":"The protective effect of rutin and quercetin on 5-FU-induced hepatotoxicity in rats","volume":"7","author":"Gelen","year":"2017","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"10.1016\/j.fct.2025.115809_bib16","first-page":"404","article-title":"The protective effects of naringin against 5-fluorouracil-induced hepatotoxicity and nephrotoxicity in rats","volume":"21","author":"Gelen","year":"2018","journal-title":"Iran J. Basic Med. Sci."},{"key":"10.1016\/j.fct.2025.115809_bib17","doi-asserted-by":"crossref","first-page":"103240","DOI":"10.1016\/j.jksus.2024.103240","article-title":"Protective effects of cupressuflavone against doxorubicin-induced hepatic damage in rats","volume":"36","author":"Hayat","year":"2024","journal-title":"J. King Saud Univ. Sci."},{"key":"10.1016\/j.fct.2025.115809_bib18","doi-asserted-by":"crossref","first-page":"127445","DOI":"10.1016\/j.jtemb.2024.127445","article-title":"Ameliorative potential of eriocitrin against cadmium instigated hepatotoxicity in rats via regulating Nrf2\/keap1 pathway","volume":"84","author":"Hayat","year":"2024","journal-title":"J. Trace Elem. Med. Biol."},{"key":"10.1016\/j.fct.2025.115809_bib19","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s11419-023-00676-8","article-title":"Acute and subacute toxic effects of CUMYL-4CN-BINACA on male albino rats","volume":"42","author":"Lafzi","year":"2024","journal-title":"Forensic Toxicol."},{"key":"10.1016\/j.fct.2025.115809_bib20","doi-asserted-by":"crossref","first-page":"104593","DOI":"10.1016\/j.fbio.2024.104593","article-title":"Catechins counteracted hepatotoxicity induced by cadmium through Keap1-Nrf2 pathway regulation","volume":"61","author":"Lan","year":"2024","journal-title":"Food Biosci."},{"key":"10.1016\/j.fct.2025.115809_bib21","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/0006-291X(76)90747-6","article-title":"Glutathione peroxidase activity in selenium-deficient rat liver","volume":"71","author":"Lawrence","year":"1976","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.fct.2025.115809_bib22","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"10.1016\/j.fct.2025.115809_bib23","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin Phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.fct.2025.115809_bib24","doi-asserted-by":"crossref","first-page":"154213","DOI":"10.1016\/j.tox.2025.154213","article-title":"The synthetic cannabinoids ADB-FUBINACA and AMB-FUBINACA enhance in vitro neurodifferentiation of NG108-15 cells, along with PGC-1\u03b1 dysregulation and mitochondrial dysfunction","volume":"517","author":"Malheiro","year":"2025","journal-title":"Toxicology"},{"key":"10.1016\/j.fct.2025.115809_bib25","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.jhep.2013.03.032","article-title":"Cannabinoid signaling and liver therapeutics","volume":"59","author":"Mallat","year":"2013","journal-title":"J. Hepatol."},{"key":"10.1016\/j.fct.2025.115809_bib26","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1097\/MAJ.0000000000000466","article-title":"Synthetic cannabinoids","volume":"350","author":"Mills","year":"2015","journal-title":"Am. J. Med. Sci."},{"key":"10.1016\/j.fct.2025.115809_bib27","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","article-title":"Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction","volume":"95","author":"Ohkawa","year":"1979","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.fct.2025.115809_bib28","first-page":"216","article-title":"Silymarin ameliorates cisplatin-induced nephrotoxicity by downregulating TNF-\u03b1 and NF-kB and by upregulating IL-10","volume":"39","author":"Ozkok","year":"2022","journal-title":"Deneysel ve Klinik T\u0131p Dergisi"},{"key":"10.1016\/j.fct.2025.115809_bib33","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/0003-2697(68)90092-4","article-title":"Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman\u2019s reagent","volume":"25","author":"Sedlak","year":"1968","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.fct.2025.115809_bib29","doi-asserted-by":"crossref","first-page":"114590","DOI":"10.1016\/j.ecoenv.2023.114590","article-title":"Acetaminophen-induced hepatotoxicity predominantly via inhibiting Nrf2 antioxidative pathway and activating TLR4-NF-\u03baB-MAPK inflammatory response in mice","volume":"252","author":"Shen","year":"2023","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"10.1016\/j.fct.2025.115809_bib30","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1093\/clinchem\/34.3.497","article-title":"A simple method for clinical assay of superoxide dismutase","volume":"34","author":"Sun","year":"1988","journal-title":"Clin. Chem."},{"key":"10.1016\/j.fct.2025.115809_bib31","doi-asserted-by":"crossref","first-page":"828","DOI":"10.3390\/antiox10060828","article-title":"Keap1\/Nrf2 signaling pathway","volume":"10","author":"Sykiotis","year":"2021","journal-title":"Antioxidants"},{"key":"10.1016\/j.fct.2025.115809_bib32","doi-asserted-by":"crossref","first-page":"104783","DOI":"10.1016\/j.jff.2021.104783","article-title":"Antioxidant and hepatoprotective potential of sweet basil (Ocimum basilicum L.) extract in acetaminophen-induced hepatotoxicity in rats","volume":"87","author":"Teofilovi\u0107","year":"2021","journal-title":"J. Funct.Foods"}],"container-title":["Food and Chemical Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0278691525005770?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0278691525005770?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T21:19:07Z","timestamp":1769807947000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0278691525005770"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":33,"alternative-id":["S0278691525005770"],"URL":"https:\/\/doi.org\/10.1016\/j.fct.2025.115809","relation":{},"ISSN":["0278-6915"],"issn-type":[{"value":"0278-6915","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The synthetic cannabinoid CUMYL-4CN-BINACA induces hepatic injury in rats via oxidative stress, NF-\u03baB activation, Nrf2 suppression, EDEM-1, ER stress-mediated apoptotic pathways","name":"articletitle","label":"Article Title"},{"value":"Food and Chemical Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.fct.2025.115809","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"115809"}}