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Updated: Jan 15, 2026

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Epigenetic Regulation of Manganese-Induced Hepatotoxicity Uncovering Histone Demethylation-Associated Gene Networks

Bing Yang1,2,3,4,5, Xiaofeng Li1,6

  • 1College of Animal Science, Anhui Science and Technology University, Fengyang, China.

Journal of Biochemical and Molecular Toxicology
|October 9, 2025
PubMed

Insights

Excessive manganese exposure causes liver damage. This study identifies key histone demethylation genes involved in manganese-induced liver toxicity, offering insights into disease mechanisms and potential therapeutic targets.

Area of Science:

  • Biochemistry
  • Toxicology
  • Epigenetics

Background:

  • Excessive manganese (Mn) exposure is linked to liver toxicity.
  • Histone demethylation, an epigenetic process, is implicated in liver disease.
  • The specific genes involved in Mn-induced hepatotoxicity via histone demethylation are not well understood.

Purpose of the Study:

  • To identify histone demethylation-associated genes differentially expressed in response to manganese exposure in the liver.
  • To elucidate the biological processes and pathways affected by these genes in Mn-induced hepatotoxicity.

Main Methods:

  • Analysis of gene expression data from liver samples exposed to manganese chloride (MnCl2) and control samples.
  • Identification of differentially expressed genes (DEGs) at different time points (Day 3 and Day 5).
  • Biological process and pathway enrichment analyses of overlapping DEGs.

Main Results:

  • 351 DEGs on Day 3 and 494 DEGs on Day 5 were identified.
  • 24 overlapping histone demethylation-associated DEGs were found across both time points.
  • These DEGs are associated with organ regeneration, cell proliferation, detoxification, bile transport, fatty acid metabolism, and pathways like IL-17 signaling and chemical carcinogenesis.

Conclusions:

  • Several histone demethylation-associated genes (e.g., CDKN1A, PPARA, CYP7A1, CAV1, GDF15, GRP) are significantly altered in Mn-induced hepatotoxicity.
  • These findings provide novel insights into the epigenetic mechanisms underlying manganese toxicity in the liver.
  • Identification of key genes may facilitate the development of targeted interventions for Mn-induced liver damage.
Keywords:
genehistone demethylationliver toxicitymanganesemechanisms

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