Evidence map›Paper›PMID 40493096›Full record

ArticleMolecular biology reports2025

Combined effects of IRAK inhibition and pioglitazone on hepatic inflammation and apoptosis in a mouse model of MASLD.

Hossein Fallah, Behnaz Danesh, Beydolah Shahouzehi

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Article in Molecular biology reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

3 authors.

Hossein FallahApplied Cellular and Molecular Research Center, Kerman University of Medical Sciences, Kerman, Iran.
Behnaz DaneshCardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.
Beydolah ShahouzehiGastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran. bshahouzehi@gmail.com.ORCID http://orcid.org/0000-0002-8758-6686

Funding

Student Research Committee, Kerman University of Medical Sciences 400000650
6 · The paper itself

Abstract

backgroundInflammation and apoptosis play crucial role in the progression of liver diseases. This study aimed to evaluate the effects of Interleukin-1 receptor-associated kinase inhibitor (IRAKi) in combination with pioglitazone on the expression of inflammatory and apoptotic markers in the liver of C57BL/6J mice subjected to a high-fat diet (HFD).

methodsMale C57BL/6J mice were divided into five groups: Control (normal diet, ND), HFD, HFD-IRAKi, HFD-pioglitazone (HFD-PIO), and HFD-IRAKi-PIO. All groups, except ND, were administered HFD for 12 weeks. Subsequently, IRAKi (2 mg/kg, intraperitoneally, three times per week) and pioglitazone (10 mg/kg, orally, daily) were administered for 14 days. Gene and protein expression levels were assessed using real-time PCR and western blot analysis.

resultsSeparate administration of IRAKi and pioglitazone significantly reduced the mRNA levels of inflammatory markers IL-1β, IL-6, TNF-α, and NF-κB (p < 0.001). Combined treatment with IRAKi and pioglitazone significantly reduced hepatic triglyceride (TG) and cholesterol content (p < 0.05) and attenuated expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, NF-κB) and apoptotic markers (cleaved-CASPASE3, Bax), while enhancing Il10 expression. These findings support the therapeutic potential of this combination in metabolic liver diseases such as MASLD.

conclusionCo-administration of IRAKi and PIO attenuated markers of inflammation and apoptosis. These findings highlight the potential of IRAKi and pioglitazone as therapeutic agents for metabolic and inflammatory liver diseases, warranting further clinical evaluation.

Indexed as

Interleukin-1 Receptor-Associated KinasesPioglitazoneAnimalsApoptosisDiet, High-FatDisease Models, AnimalInflammationLiverMaleMiceMice, Inbred C57BLNon-alcoholic Fatty Liver DiseaseInterleukin-1 Receptor-Associated KinasesPioglitazoneApoptosisFatty liverHigh-fat dietInflammationIRAKNF-κBPioglitazone

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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 OpenQuestion graph.