{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T01:55:02Z","timestamp":1780451702499,"version":"3.54.1"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,9,29]],"date-time":"2024-09-29T00:00:00Z","timestamp":1727568000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P32164"],"award-info":[{"award-number":["P32164"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>4\u2010methylpyrazole (4MP, fomepizole) is a competitive inhibitor of alcohol dehydrogenase (ADH) preventing the metabolism of ethylene glycol and methanol, respectively, into their toxic metabolites. 4MP seems also to possess a potential in the treatment of intoxication from other substance, for example, acetaminophen, and to modulate JNK\u2010dependent signalling. Here, we determined if a treatment with 4MP once weekly affects the development of diet\u2010induced non\u2010obese metabolic dysfunction\u2010associated steatotic liver disease (MASLD) in C57BL\/6 mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male C57BL\/6 mice (6\u20138\u2009weeks old, <jats:italic>n<\/jats:italic>\u2009=\u20097\u20108\/group) were pair\u2010fed either a liquid control diet (C) or a liquid sucrose\u2010, fat\u2010 and cholesterol\u2010rich diet (SFC) for 8\u2009weeks while being concomitantly treated with 4MP (50\u2009mg\/kg bw i.p.) or vehicle once a week. Liver damage, inflammatory markers and glucose tolerance were assessed. Moreover, in endotoxin\u2010challenged J774A.1 cells pretreated with 4MP, pro\u2010inflammatory markers were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The concomitant treatment of SFC\u2010fed mice with 4MP attenuated the increase in JNK phosphorylation and pro\u2010inflammatory markers like IFN\u03b3, IL\u20106 and 3\u2010nitrotyrosine protein adducts in liver tissue found in vehicle\u2010treated SFC\u2010fed mice, while not affecting impairments of glucose tolerance or the increase in portal endotoxin levels. Moreover, a pretreatment of endotoxin\u2010stimulated J774A.1 cells with 4MP significantly attenuated the increases in JNK phosphorylation and pro\u2010inflammatory mediators like IL\u20106 and <jats:italic>Mcp1<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Taken together, our results suggest that a treatment with 4MP once weekly attenuates the activation of JNK and dampens the development of non\u2010obese MASLD in mice.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.14320","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T04:08:38Z","timestamp":1727669318000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A weekly 4\u2010methylpyrazole treatment attenuates the development of non\u2010obese metabolic dysfunction\u2010associated steatotic liver disease (<scp>MASLD<\/scp>) in male mice: Role of 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