PBAT-modified starch blended film extract induces in vitro toxicity in L-02 cells: induction of oxidative stress, inflammation, and modulation of AMPK pathway.
Chunhong LiuXueman XiaoYifeng RangWeiye LiHuiying HuangGenghua OuChunhong LiuPublished in: Drug and chemical toxicology (2024)
PBAT-modified starch blended film are thermoplastic biodegradable materials with good properties and a wide range of applications. In this study, L-02 cells were used as an in vitro toxicity evaluation system for risk assessment of PBAT-modified starch films with migration studies obtained in different food simulants. Determination of total migration and organic matter revealed that the results were in accordance with the standard except for the total organic matter under 95% (v/v) ethanol food simulant which exceeded the standard. The CCK-8 assay showed that these compounds affect the cell viability of L-02 cells. It was observed that the compounds made the cells express increased AST, ALT, TNF-α, IL-6, IL-1β, and ROS, and decreased SOD, GSH, and ATP. In addition, we explored the effect of migration in PBAT-modified starch composites on protein and gene expression levels in L-02 cells using a transcriptomic approach and found that the AMPK signaling pathway was affected. The expression of AMPK signaling pathway-related proteins was detected by Western Blot, and the expression levels of p-AMPK/AMPK were found to be upregulated, and those of p-mTOR/mTOR, SIRT1, PGC-1α, NRF1 and TFAM were downregulated. The above data suggest that the compounds migrating into the PBAT-modified starch film when exposed to food may induce oxidative stress and inflammation in hepatocytes, and may cause damage to hepatocytes through the AMPK pathway.
Keyphrases
- oxidative stress
- induced apoptosis
- signaling pathway
- gene expression
- skeletal muscle
- cell cycle arrest
- risk assessment
- endoplasmic reticulum stress
- ischemia reperfusion injury
- organic matter
- epithelial mesenchymal transition
- cell proliferation
- human health
- mass spectrometry
- dna methylation
- small molecule
- artificial intelligence
- binding protein
- south africa
- liver injury
- machine learning
- big data
- electronic health record
- ionic liquid