Synergistic Effect of Sodium Acetate and Sodium Butyrate in Ameliorating Ethanol-Induced Hepatic Inflammation Through Modulation of the NF-κB Signaling Pathway.

Authors

Manali Patel, Hiral Aghara, Prashsti Chadha, Harshrajsinh Solanki, Dhrubjyoti Sharma, Vijay Thiruvenkatam, Palash Mandal

Published in

Mediators of inflammation. Volume 2026. Issue 1. Pages e5835567.

Abstract

Chronic ethanol exposure activates inflammatory signaling pathways and inflicts hepatocellular damage, leading to alcohol-associated liver diseases (ALDs). ALD is one of the major causes of global burden, yet there are no FDA-approved treatment options available. This study evaluates the hepatoprotective effects of short-chain fatty acids (SCFAs), mainly sodium acetate (NaA) and sodium butyrate (NaB), against ethanol-induced inflammation and oxidative stress in both in vitro (Buffalo Rat Liver-3A [BRL3A]) and in vivo (male Wistar rats) models. The treatment of NaA and NaB and their combination was given to the cell lines where maximum viability was observed at concentrations of 1.5 mM, 5 mM, and 0.1 mM + 1 mM, respectively. Additionally, reactive oxygen species (ROS) and nuclear morphology were assessed by fluorescent staining. For in vivo samples, the hepatic injury was analyzed by serum biochemical markers. Furthermore, hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) staining were employed, which provided structural and immunological alterations in hepatic tissue. RT-qPCR profiled the expression levels of various pro-inflammatory and anti-inflammatory cytokines, as well as cytochrome P450 E1 (CYP2E1) and antioxidative stress markers. Moreover, enzyme-linked immunosorbent assay (ELISA) quantified the essential protein targets such as TNF-α, MCP-1, IL-1β, IL-6, HO-1, and Nrf2. The administration of NaA, NaB, and their combination resulted in reduced ROS levels and expression of pro-inflammatory cytokines, preserved nuclear integrity, and neutrophil infiltration. These findings were further confirmed by in silico analysis and conserved amino acid interactions, and the affinities of NaA and NaB for TNF-α and MCP-1 were observed as compared to established inhibitors or activators. This study is the first demonstration to report the synergistic effects of NaA and NaB on the feedback loop of the nuclear factor kappa B (NF-κB) signaling pathway, suggesting their potential as promising therapeutic candidates for alleviating alcohol-induced hepatic damage.

PMID:
42322178
Bibliographic data and abstract were imported from PubMed on 20 Jun 2026.

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