Potassium sorbate is widely used as a preservative in processed foods and beverages and is generally considered safe. However, emerging evidence suggests potential health risks with long-term or high-level exposure. A study published on November 23, 2025, in iMetaMed provides the first systematic evidence that this common additive can induce acute kidney injury through molecular mechanisms involving oxidative stress, inflammation, and dysregulated cell-to-cell communication.
The research team, led by scientists from Shanghai Jiao Tong University School of Medicine and Guangdong Medical University, applied a multi-disciplinary strategy to uncover how potassium sorbate damages renal tissue. They began by predicting potential targets using network toxicology, then validated interactions through molecular docking and dynamics simulations. Machine learning algorithms further prioritized key genes from clinical datasets.
Among the top candidates, amyloid precursor protein emerged as a central regulator. Single-cell RNA sequencing analysis of human kidney tissues revealed that APP mediates communication between endothelial cells and immune cells—such as monocytes and natural killer cells—through the APP-CD74 and APP-PTGER2 ligand-receptor pairs.
“This is the first time that APP has been implicated in potassium sorbate-induced kidney injury, and the first evidence that it facilitates endothelial-immune crosstalk in a toxicological context,” said corresponding author Dr. Meng-Yao Li. “Our findings provide a cellular mechanism that helps explain how a common food additive could trigger renal inflammation and functional decline.”
In vitro experiments using human renal tubular cells confirmed that potassium sorbate exposure significantly reduced cell viability, inhibited migration—a key repair process—and upregulated APP protein expression in a dose-dependent manner.
The study also identified other key targets, including MMP9 and SIRT1, and highlighted relevant pathways such as lipid metabolism, atherosclerosis, and the AGE-RAGE signaling cascade, which are known to be involved in kidney disease progression.
These findings not only advance the understanding of food additive safety but also establish a new methodology for evaluating environmental toxin risks using multi-optic and computational tools.
iMeta
Experimental study
Not applicable
Potassium Sorbate Triggers Kidney Injury via Dysregulated Intercellular Communication: A Study Combining Network Toxicology, Machine Learning, Molecular Docking, and Single-Cell RNA Sequencing
23-Nov-2025
The authors declare no conflicts of interest.