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Updated: May 5, 2026

A High-throughput Assay for the Prediction of Chemical Toxicity by Automated Phenotypic Profiling of Caenorhabditis elegans
Published on: March 14, 2019
Food safety analysis: network toxicology, molecular docking, machine learning and single-cell analysis to interpret
Jingwei Li1, Hailong Yang1, Jingjia Yang2
1Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Background:
Sodium benzoate, a common food additive, has raised safety concerns despite its general recognition as safe. This study aimed to investigate the mechanisms of sodium benzoate-induced nephrotoxicity.
Method:
A network toxicology approach was used to identify key targets and core pathways involved in sodium benzoate nephrotoxicity. Molecular docking validated the binding affinity between these targets and sodium benzoate. Machine learning and single-cell analysis further explored the underlying mechanisms using dataset validation.
Result:
Protein-protein interaction (PPI) network analysis revealed five key targets with the lowest binding energies (Matrix metalloproteinase 2 (MMP2), Estrogen Receptor 1 (ESR1), Poly (ADP-ribose) polymerase 1 (PARP1), Prostaglandin-endoperoxide synthase 2 (PTGS2), Mitogen-activated protein kinase 14 (MAPK14)) as central to sodium benzoate-induced renal injury. Enrichment analysis indicated 'diabetic nephropathy' (DN) as the primary pathway. Machine learning and single-cell analysis confirmed PTGS2 as the dominant factor exerting nephrotoxicity among the key genes.
Conclusion:
This multi-method study uncovered potential mechanisms of sodium benzoate-induced renal injury, providing a basis for improving food safety evaluations.
Insights
Sodium benzoate, a food additive, can harm kidneys. This study identified key molecular targets and pathways, like diabetic nephropathy, involved in its toxicity, with PTGS2 being a major factor.
Area of Science:
- Toxicology
- Molecular Biology
- Computational Biology
Background:
- Sodium benzoate is a widely used food additive with established safety but emerging concerns.
- Investigating the specific mechanisms behind sodium benzoate-induced kidney damage is crucial for public health.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying sodium benzoate-induced nephrotoxicity.
- To identify key molecular targets and biological pathways implicated in renal injury caused by sodium benzoate.
Main Methods:
- Employed a network toxicology approach to identify critical targets and pathways.
- Utilized molecular docking to assess binding affinities of sodium benzoate to identified targets.
- Applied machine learning and single-cell analysis for in-depth mechanistic exploration and validation.
Main Results:
- Protein-protein interaction network analysis pinpointed MMP2, ESR1, PARP1, PTGS2, and MAPK14 as key targets in sodium benzoate nephrotoxicity.
- Pathway enrichment analysis identified diabetic nephropathy as a significantly affected pathway.
- Machine learning and single-cell data confirmed Prostaglandin-endoperoxide synthase 2 (PTGS2) as a dominant contributor to the observed kidney toxicity.
Conclusions:
- This study reveals potential molecular mechanisms of sodium benzoate-induced renal injury.
- Findings provide a foundation for enhanced food safety assessments regarding sodium benzoate consumption.
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