Nifurpirinol: A potent inducer of FSGS-like glomerular injury in transgenic zebrafish

Abstract

SummaryIdentifying effective drugs for focal segmental glomerulosclerosis (FSGS) treatment holds significant importance. Our high-content drug screening on zebrafish larvae relies on nitroreductase/metronidazole (NTR/MTZ)-induced podocyte ablation to generate FSGS-like injury. A crucial factor for successful drug screenings is minimizing variability in injury induction. For this, we introduce Nifurpirinol (NFP) as a more reliable prodrug for targeted podocyte depletion. NFP showed a 2.3-fold increase in efficiency at concentrations 1600-fold lower compared to MTZ-mediated injury induction. Integration into the screening workflow validated its suitability for the high-content drug screening. The presence of crucial FSGS hallmarks, including podocyte foot process effacement, proteinuria, and activation of parietal epithelial cells, was observed. In this study, we demonstrate that NFP serves as remarkably effective prodrug for inducing an FSGS-like phenotype in zebrafish larvae and proves to be well-suited for a high-content drug screening, aiding in the identification of potential candidates for FSGS treatment.