Related Experiment Video
Updated: Feb 2, 2026
Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Published on: January 7, 2019
Monomethyl fumarate alleviates sepsis-induced hepatic dysfunction by regulating TLR-4/NF-κB signalling pathway
Armin Azadkhah Shalmani1, Mohammad Hossein Ghahremani1, Fereshteh Jeivad1
1Toxicology and Poisoning Research Centre, Tehran University of Medical Sciences, Tehran, Iran; Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Aims:
Sepsis is a potentially fatal illness that can lead to impairment of multiple organs such as liver. The condition is deeply associated with oxidative stress and inflammation. Monomethyl fumarate (MMF) has manifested antioxidant and immunomodulatory properties. The aim of current study was to evaluate protective effects of MMF in sepsis-induced hepatic dysfunction.
Main Methods:
Sepsis was induced by cecal ligation and puncture (CLP). Wistar rats were assigned to one of sham, CLP, CLP + dexamethasone (as positive control of inflammation) and CLP + MMF groups. Levels of serum IL-1β, IL-6, IL-10, AST, ALT and γ‑GT were quantified. Furthermore, Hepatic levels of GSH and MDA and mRNA expression of TNF and NFKBIA along with hepatic protein level of TLR-4 were assessed. Also, histopathological study of liver was carried out to evaluate hepatic injuries.
Key Findings:
Septic rats demonstrated risen levels of IL-1β, IL-6, IL-10, AST, ALT and γ‑GT, while treatment with dexamethasone or MMF attenuated these levels. Moreover, enhancements in protein level of TLR-4 and mRNA levels of TNF and NFKBIA were observed in CLP rats. These elevations were mitigated in CLP-induced rats that were treated with either dexamethasone or MMF. Treatment with dexamethasone or MMF also shifted sepsis-induced disturbance in the levels of GSH and MDA towards sham levels. Hepato-protective effects of dexamethasone and MMF were further confirmed by histopathological observations.
Significance:
Our findings imply that MMF alleviates sepsis-induced hepatic dysfunction by mitigating the inflammatory and oxidative state and this effect is at least partly mediated by the inhibition of TLR-4/NF-κB signalling pathway.
Insights
Monomethyl fumarate (MMF) protects the liver from sepsis-induced damage by reducing inflammation and oxidative stress. This study shows MMF
Area of Science:
- Hepatology
- Immunology
- Pharmacology
Background:
- Sepsis can cause severe liver dysfunction due to oxidative stress and inflammation.
- Monomethyl fumarate (MMF) exhibits antioxidant and immunomodulatory properties.
- MMF's potential protective effects against sepsis-induced liver injury warrant investigation.
Purpose of the Study:
- To evaluate the protective effects of Monomethyl fumarate (MMF) in a rat model of sepsis-induced hepatic dysfunction.
- To assess MMF's impact on inflammatory markers, oxidative stress indicators, and liver enzymes in sepsis.
- To investigate the underlying molecular mechanisms, including the TLR-4/NF-κB pathway.
Main Methods:
- Sepsis was induced in Wistar rats using cecal ligation and puncture (CLP).
- Groups included sham, CLP, CLP + dexamethasone, and CLP + MMF.
- Assessed serum cytokines (IL-1β, IL-6, IL-10), liver enzymes (AST, ALT, γ-GT), oxidative stress markers (GSH, MDA), and gene/protein expression (TNF, NFKBIA, TLR-4). Histopathology was performed.
Main Results:
- Sepsis increased inflammatory cytokines, liver enzymes, TLR-4, TNF, and NFKBIA, while decreasing GSH and increasing MDA.
- MMF treatment significantly attenuated these sepsis-induced changes, similar to dexamethasone.
- Histopathological analysis confirmed the hepatoprotective effects of MMF.
Conclusions:
- MMF alleviates sepsis-induced hepatic dysfunction by reducing inflammation and oxidative stress.
- The protective mechanism of MMF involves the inhibition of the TLR-4/NF-κB signaling pathway.
- MMF demonstrates potential as a therapeutic agent for sepsis-related liver injury.
Related Concept Videos
02:26NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
03:14Notch Signaling Pathway
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
02:33Hedgehog Signaling Pathway
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:41Non-Canonical Wnt Signaling Pathways
02:54Canonical Wnt Signaling Pathway