Novel xanthine oxidase-based cell model using HK-2 cell for screening antihyperuricemic functional compounds

Abstract

Hyperuricemia is a metabolic disease caused by disorders of purine metabolism, the prevalence of which has increased worldwide. Here, a cell model for high uric acid production was established in vitro employing cultured human kidney cells (HK-2 cells), and its molecular basis was analyzed using gene expression profile. High performance liquid chromatography (HPLC) was used to monitor the content of metabolites in cell culture media. Adenosine addition was found to induce HK-2 cells to produce uric acid precursors (inosine and hypoxanthine). Furthermore, the cell model was verified by confirming the antihyperuricemic effect of the widely used antihyperuricemic drugs allopurinol, probenecid, and febuxostat, as well as reported bioactive peptides and amino acids, encompassing glutathione, tryptophan and carnosine, which significantly reduced uric acid production in the HK-2 cells (p < 0.05). RNA-Seq technology was used to perform a wide transcriptome analysis of the hyperuricemic cell model, and the results demonstrated that it has the potential to be used as a rapid and valid in vitro model to screen antihyperuricemic compounds that mimics in vivo cell growth patterns.