# Evaluation of Metabolic Characteristics Induced by Deoxynivalenol in 3D4/21 Cells

**Authors:** Yu Han, Bo Yu, Wenao Weng, Liangyu Shi, Jing Zhang

PMC · DOI: 10.3390/ani15152324 · Animals : an Open Access Journal from MDPI · 2025-08-07

## TL;DR

This study explores how the mycotoxin deoxynivalenol affects metabolism in pig immune cells, identifying key metabolic changes that could help reduce its harmful effects.

## Contribution

The study reveals novel metabolic pathways affected by deoxynivalenol in porcine macrophages, linking them to immunotoxicity through integrated metabolomic and transcriptomic analysis.

## Key findings

- DON reduced cell viability in a concentration- and time-dependent manner in 3D4/21 cells.
- 127 differential metabolites were identified, primarily affecting purine, glutathione, and arginine–proline metabolism.
- Metabolic changes were confirmed to play key roles in DON-induced immunotoxicity through integration with transcriptomic data.

## Abstract

Deoxynivalenol (DON) is a common mycotoxin that weakens immune function in pigs. However, its effects on cellular metabolism remain unclear. This study employs porcine alveolar macrophages (3D4/21 cells) to investigate DON-induced metabolic alterations using non-targeted metabolomics. MTT assays showed DON reduced cell viability in a concentration- and time-dependent manner. Metabolomic analysis identified 127 differential metabolites, revealing distinct metabolic profiles between control and DON-treated cells. These changes mainly affected purine metabolism, glutathione metabolism, and arginine–proline metabolism. Integration with transcriptomics data confirmed these pathways are important for DON-induced immunotoxicity. The study provides new insights into DON-induced metabolic reprogramming in immune cells and identifies candidate targets for alleviating mycotoxin-driven immunosuppression in swine.

Deoxynivalenol (DON) is a common mycotoxin that causes immunosuppression in pigs. Its effects on cellular metabolism remain unclear. In this study, we investigate DON-induced metabolic alterations in porcine alveolar macrophage cell line 3D4/21 using non-targeted metabolomics. MTT assays showed DON reduced cell viability in a concentration- and time-dependent manner. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) revealed distinct metabolic profiles between control and DON-treated groups. Metabolomic analysis identified 127 differential metabolites (VIP > 1, p < 0.05), primarily in purine metabolism, glutathione metabolism, and arginine–proline metabolism. Integration with transcriptomic data confirmed that these pathways play key roles in DON-induced immunotoxicity. Specifically, changes in purine metabolism suggested disrupted nucleotide synthesis and energy balance, while glutathione depletion indicated weakened antioxidant defense. These findings provided a systems biology perspective on DON’s metabolic reprogramming of immune cells and identified potential therapeutic targets to reduce mycotoxin-related immunosuppression in swine.

## Linked entities

- **Chemicals:** Deoxynivalenol (PubChem CID 40024), glutathione (PubChem CID 124886)
- **Species:** Sus scrofa (taxon 9823)

## Full-text entities

- **Chemicals:** proline (MESH:D011392), purine (MESH:C030985), arginine (MESH:D001120), MTT (MESH:C070243), glutathione (MESH:D005978), DON (MESH:C007262)
- **Species:** Sus scrofa (pig, species) [taxon 9823]
- **Cell lines:** 3D4/21 — Sus scrofa (Pig), Transformed cell line (CVCL_0F14)

## Full text

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## Figures

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## References

50 references — full list in the complete paper: https://tomesphere.com/paper/PMC12345648/full.md

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Source: https://tomesphere.com/paper/PMC12345648