Isoeugenol Attenuates Oxalate-Induced Renal Injury and Inhibits Glycolate Oxidase: A Natural Strategy Against Nephrolithiasis

Abstract

Isoeugenol (2-methoyxy-4-propenyl-phenol), a natural derivative of eugenol found in plants, essential oils, coffee, and wine, known for its antioxidant, anti-inflammatory, and enzyme-inhibitory properties. With the increasing prevalence of calcium oxalate kidney stones— driven by hyperoxaluria, poor dietary habits, and dehydration—novel, effective treatments are urgently needed. Using NRK-52E renal tubular epithelial cells, we investigated the cytoprotective effects of isoeugenol against oxalate-induced injury. Isoeugenol exhibited no cytotoxicity at concentrations up to 100 µM and significantly improved cell viability in a dose-dependent manner, with viability increasing from 43.79% in oxalate-treated cells to 80.29% at 100 µM. The compound also markedly reduced lactate dehydrogenase release and nitric oxide levels, enhancing membrane integrity and reducing oxidative stress.
Additionally, molecular docking studies demonstrated a strong binding affinity between isoeugenol and glycolate oxidase, implicating a potential mechanism for lowering oxalate synthesis. Collectively, these findings position isoeugenol as a promising, natural, and cost- effective candidate for preventing and managing calcium oxalate urolithiasis, and they underscore the need for further research into its therapeutic applications.