# Subacute exposure to apigenin induces changes in protein synthesis in the liver of Swiss mice

**Authors:** Łukasz S. Jarosz, Katarzyna Socała, Katarzyna Michalak, Kamila Bulak, Artur Ciszewski, Agnieszka Marek, Zbigniew Grądzki, Piotr Wlaź, Edyta Kowalczuk-Vasilev, Anna Rysiak

PMC · DOI: 10.3389/fphys.2025.1576310 · Frontiers in Physiology · 2025-05-09

## TL;DR

This study shows that apigenin, a natural compound, causes minor liver cell changes and alters protein synthesis in mice without causing significant inflammation or weight changes.

## Contribution

The study identifies specific proteins upregulated in mice livers after apigenin exposure, suggesting functional changes without overt toxicity.

## Key findings

- Apigenin exposure leads to slight hepatocyte degeneration but no significant liver weight or cytokine changes.
- Proteomic analysis reveals increased synthesis of specific proteins like MAP2K19, GNMT, and EF2 in apigenin-treated mice.
- The observed liver changes may be self-limiting and part of regenerative processes rather than harmful toxicity.

## Abstract

Apigenin is a natural flavonoid with various pharmacological properties. Available data indicate that it affects the metabolic processes and protein profile of cells, including hepatocytes. However, there is speculation that the use of apigenin may have a hepatotoxic effect. The aim of the experiment was to assess the effect of apigenin administered intraperitoneally to mice on the concentrations of pro- and anti-inflammatory cytokines in the liver tissue and to analyse liver weight and morphological changes in the liver parenchyma. A proteomic analysis was also performed to examine differences in genes expression for specific proteins in liver cells. Adult male albino Swiss mice were divided into two groups and treated with either apigenin (50 mg/kg BW) – APG, or a vehicle (1% DMSO) – CONT, every 24 h for 14 days. The material for the study consisted of liver samples. Slight hepatocyte degeneration microscopically were demonstrated in most mice exposed to apigenin. No significant differences were observed in the absolute and relative weight of the liver or the concentrations of pro- and anti-inflammatory cytokines between the control and experimental group. The mass spectrometry results indicate significantly higher synthesis of the proteins MAP2K19, CEP69, GNMT, BPIFA3, SYT17, ANKRD1, GRHPR, CLEC1A and EF2 in the livers of mice from the APG group in comparison to CONT group. Exposure of mice to apigenin induces functional changes in the liver. In conjunction with the microscopical and proteomic analyses, this study may indicate that inflammatory changes developing in the liver could be self-limiting and subject to regenerative processes.

## Linked entities

- **Genes:** GNMT (glycine N-methyltransferase) [NCBI Gene 27232], BPIFA3 (BPI fold containing family A member 3) [NCBI Gene 128861], SYT17 (synaptotagmin 17) [NCBI Gene 51760], ANKRD1 (ankyrin repeat domain 1) [NCBI Gene 27063], GRHPR (glyoxylate and hydroxypyruvate reductase) [NCBI Gene 9380], CLEC1A (C-type lectin domain family 1 member A) [NCBI Gene 51267], EEF2 (eukaryotic translation elongation factor 2) [NCBI Gene 1938]
- **Chemicals:** apigenin (PubChem CID 5280443), DMSO (PubChem CID 679)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Bpifa3 (BPI fold containing family A, member 3) [NCBI Gene 73388] {aka 1700058C13Rik, Splunc3}, Syt17 (synaptotagmin XVII) [NCBI Gene 110058] {aka Bk, sytXVII}, Gnmt (glycine N-methyltransferase) [NCBI Gene 14711], Eef2 (eukaryotic translation elongation factor 2) [NCBI Gene 13629] {aka Ef-2}, Ankrd1 (ankyrin repeat domain 1) [NCBI Gene 107765] {aka Alrp, CARP, Crap, MARP1}, Grhpr (glyoxylate reductase/hydroxypyruvate reductase) [NCBI Gene 76238] {aka 1110059D05Rik, 6430629L09Rik, Glxr}, Clec1a (C-type lectin domain family 1, member a) [NCBI Gene 243653] {aka 5930406N14Rik}
- **Diseases:** hepatocyte degeneration (MESH:D009410), inflammatory (MESH:D007249)
- **Chemicals:** APG (-), flavonoid (MESH:D005419), DMSO (MESH:D004121), Apigenin (MESH:D047310)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12100293/full.md

## References

113 references — full list in the complete paper: https://tomesphere.com/paper/PMC12100293/full.md

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Source: https://tomesphere.com/paper/PMC12100293