Toxic effects of 5-hydroxymethylfurfural on intestinal epithelial cell and its impact on the expression of MAPK pathway-related genes
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Dongying Qin1, Xunlin Chen1, Keyan Pan1
1Scientific Research Base of Tea Comprehensive Utilization Technology Integration of Ministry of Agriculture and Rural Affairs, Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou 510642, China.
Abstract:
5-Hydroxymethylfurfural (5-HMF), a common by-product of thermal-processed foods, poses a potential risk of intestinal toxicity upon ingestion. However, its underlying toxic mechanisms remain incompletely understood. In this study, we investigated the effects and potential molecular pathways of 5-HMF using normal human intestinal epithelial cells (HIEC-6). The results showed that 5-HMF inhibited the proliferation of HIEC-6 cells in a concentration-dependent manner and induced apoptosis possibly through both the death receptor and mitochondrial pathways, as evidenced by increased activities of caspase-8 and caspase-9.5-HMF increased intracellular reactive oxygen species (ROS) levels by 1.42 to 2.12 fold, disrupted antioxidant enzymes activities, and increased malondialdehyde content, indicating oxidative damage. Meanwhile, 5-HMF upregulated the mRNA expression of the pro-inflammatory cytokines TNF-α and IL-6 and downregulated the mRNA and protein expression of key tight junction proteins ZO-1, Occludin and Claudin-1, indicating promotion of inflammation and impairment of epithelial barrier. 5-HMF also altered the mRNA expression of MAPK pathway-associated genes and NF-κB, indicating a possible correlation between this signaling cascade and the toxic effects of 5-HMF. Collectively, these findings provide a theoretical foundation for the risk assessment of dietary 5-HMF exposure and for future mechanistic studies on the role of MAPK signaling in 5-HMF-induced intestinal toxicity.
Insights
5-Hydroxymethylfurfural (5-HMF) in food causes intestinal cell damage by inhibiting growth, inducing apoptosis, and increasing oxidative stress. It also promotes inflammation and weakens the gut barrier, potentially via the MAPK pathway.
Area of Science:
- Food Science
- Toxicology
- Cell Biology
Background:
- 5-Hydroxymethylfurfural (5-HMF) is a thermal processing food by-product.
- Its intestinal toxicity mechanisms are not fully understood.
Purpose of the Study:
- Investigate 5-HMF effects on human intestinal cells (HIEC-6).
- Elucidate potential molecular pathways of 5-HMF toxicity.
Main Methods:
- Cell proliferation assays.
- Apoptosis assays (caspase activity).
- Oxidative stress markers (ROS, MDA).
- Gene/protein expression analysis (cytokines, tight junction proteins, MAPK, NF-κB).
Main Results:
- 5-HMF inhibited HIEC-6 cell proliferation and induced apoptosis.
- Increased oxidative stress (ROS, MDA) and disrupted antioxidant enzymes.
- Promoted inflammation (TNF-α, IL-6) and impaired epithelial barrier (ZO-1, Occludin, Claudin-1).
- Altered MAPK and NF-κB pathway gene expression.
Conclusions:
- 5-HMF induces intestinal toxicity via apoptosis, oxidative stress, inflammation, and barrier dysfunction.
- The MAPK signaling pathway may be involved in 5-HMF toxicity.
- Findings support risk assessment for dietary 5-HMF exposure.
