Evidence mapPaperPMID 39344016Full record

ArticleEuropean journal of clinical investigation2025

A weekly 4-methylpyrazole treatment attenuates the development of non-obese metabolic dysfunction-associated steatotic liver disease (MASLD) in male mice: Role of JNK.

Katharina Burger, Finn Jung, Raphaela Staltner, Katja Csarmann, Kerstin Schweiger, Annette Brandt, Anja Baumann, Julia Scholda, Florian Kopp, Ina Bergheim

Abstract read
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Article in European journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Katharina BurgerDepartment of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, Austria.
Finn JungDepartment of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, Austria.
Raphaela StaltnerDepartment of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, Austria.
Katja CsarmannDepartment of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, Austria.
Kerstin SchweigerDepartment of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, Austria.
Annette BrandtDepartment of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, Austria.
Anja BaumannDepartment of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, Austria.
Julia ScholdaDepartment of Pharmaceutical Sciences, Clinical Pharmacy Group, University of Vienna, Vienna, Austria.
Florian KoppDepartment of Pharmaceutical Sciences, Clinical Pharmacy Group, University of Vienna, Vienna, Austria.
Ina BergheimDepartment of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, Austria.ORCID https://orcid.org/0000-0002-3356-4115

Funding

Austrian Science Fund P32164
6 · The paper itself

Abstract

background4-methylpyrazole (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-dependent signalling. Here, we determined if a treatment with 4MP once weekly affects the development of diet-induced non-obese metabolic dysfunction-associated steatotic liver disease (MASLD) in C57BL/6 mice.

methodsMale C57BL/6 mice (6-8 weeks old, n = 7-8/group) were pair-fed either a liquid control diet (C) or a liquid sucrose-, fat- and cholesterol-rich diet (SFC) for 8 weeks while being concomitantly treated with 4MP (50 mg/kg bw i.p.) or vehicle once a week. Liver damage, inflammatory markers and glucose tolerance were assessed. Moreover, in endotoxin-challenged J774A.1 cells pretreated with 4MP, pro-inflammatory markers were assessed.

resultsThe concomitant treatment of SFC-fed mice with 4MP attenuated the increase in JNK phosphorylation and pro-inflammatory markers like IFNγ, IL-6 and 3-nitrotyrosine protein adducts in liver tissue found in vehicle-treated SFC-fed mice, while not affecting impairments of glucose tolerance or the increase in portal endotoxin levels. Moreover, a pretreatment of endotoxin-stimulated J774A.1 cells with 4MP significantly attenuated the increases in JNK phosphorylation and pro-inflammatory mediators like IL-6 and Mcp1.

conclusionsTaken together, our results suggest that a treatment with 4MP once weekly attenuates the activation of JNK and dampens the development of non-obese MASLD in mice.

Indexed as

FomepizoleMice, Inbred C57BLNon-alcoholic Fatty Liver DiseaseAnimalsDiet, High-FatInterleukin-6LiverMaleMicePhosphorylationPyrazolesFomepizoleInterleukin-6Pyrazoles4‐methylpyrazolealcohol dehydrogenase inhibitorc‐Jun N‐terminal kinaseendotoxininflammation

Identifiers

PMID39344016
PMCPMC11628662

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.