Integrated Bioinformatics Analysis of Amphotericin B Toxicity

Abstract

Amphotericin B is a broad-spectrum antifungal agent widely used for the prevention of severe and invasive fungal infections. Despite incredible antifungal activity, its scientific use is severely limited by extremely negative results, mainly nephrotoxicity Previous studies have proven that amphotericin B-precipitated toxicity is related to oxidative stress, inflammatory response, apoptosis, renal cell injury but toxicity-related genes and there interaction networks as well as molecular pathways in the pathogenesis involved in amphotericin B toxicity are incompletely understood.The aim of this study is to select toxicity-related genes associated with amphotericin B and monitor their molecular interactions and biological pathways using integrated bioinformatics procedures involving protein–protein interaction (PPI)network analysis and pathway enrichment evaluation .Bioinformatics analysis identified several toxicity-related genes thought to be involved in amphotericin B-induced cell injury. The PPI network assessment detected essential hub genes, including HOMOX 1, IL1B, TP53, CASP3, Clu, and NFKB1, which showed a high interaction area in the tested enrichment analysis. Those genes are involved in inflammatory response pathways, oxidative stress pathways, apoptosis, and signaling, with a strong association with inflammatory and apoptotic mechanisms that damage renal cells. This incorporated toxicogenomic and network pharmacology looks at important toxicity-related genes and molecular pathways in the pathogenesis involved in amphotericin B toxicity. The effects provide new insights into the molecular mechanisms underlying amphotericin B nephrotoxicity and may help to identify potential biomarkers and therapeutic targets to reduce drug-induced kidney injury.