Antioxidant Pre-Treatment Reduces the Toxic Effects of Oxalate on Renal Epithelial Cells in a Cell Culture Model of Urolithiasis

Abstract

Urolithiasis is characterized by the formation and retention of solid crystals within the urinary tract. Kidney stones are mostly composed of calcium oxalate, which predominantly generates free radicals that are toxic to renal tubular cells. The aim of the study is to explore possible effects of antioxidant pre-treatment on inhibition of oxidative stress. Three cell lines were used as in vitro model of urolithiasis: MDCK I, MDCK II and LLC-PK1. Oxidative stress was induced by exposure of cells to sodium oxalate in concentration of 8 mM. In order to prevent oxidative stress, cells were pre-treated with three different concentrations of l-arginine and vitamin E. Oxidative stress was evaluated by determining the expression of superoxide dismutase (SOD), osteopontin (OPN), and by the concentration of glutathione (GSH). In all three cell lines, pre-treatment of antioxidants increased cell survival. Positive correlation of SOD and OPN expression as well as GSH concentration was observed in all groups of cells. Our results indicate that an antioxidant pre-treatment with l-arginine and vitamin E is able to hamper oxalate-induced oxidative stress in kidney epithelial cells and as such could play a role in prevention of urolithiasis.

Antiurolithiatic effects of pentacyclic triterpenes: The distance traveled from therapeutic aspects

“…Therefore, a reduction in renal oxidative stress might also be an effective therapeutic approach for managing . If there is a deficiency in SOD, superoxides will react with nitric oxide (NO) to produce peroxynitrite that can damage DNA, lipids, and proteins (Kizivat et al, 2017). Renal exposure to…”

“…Continuous and unabated oxidative stress can prompt inflammation (Ci et al, 2017). Antioxidants avert kidney stone formation by increasing renal epithelial cell survival by increasing SOD expression and GSH concentration (Kizivat et al, 2017). These agents may diminish membrane injury, thus preventing retention of CaOx and subsequently maintain a strategic distance from calculi formation (Grases et al, 2009).…”

Metabolism oxalic acid: failure causes and consequences of molecular-biochemical factors for the formation of oxalate-induced diseases

“…Також було показано, що взаємодія епітеліальних клітин з ЩК стимулює експресію остеопонтіна, котрий відіграє важливу роль у формуванні ниркових каменів [73]. Однак не тільки ОС, але й нітрозативний стрес може впливати на утворення сечових каменів шляхом нітрування глікопротеїну Tamm-Horsfall (уромодулін), що може сприяти підвищенню ризику кристалізації сечі [74].…”

Renal Benefits of SGLT 2 Inhibitors and GLP-1 Receptor Agonists: Evidence Supporting a Paradigm Shift in the Medical Management of Type 2 Diabetes

“…Inflammation and chronic high levels of circulating glucose and its end metabolites are main causes of tissue damage in DM by, among other, creating high levels of oxidative and nitrosative stress in kidneys [20,21]. The effects of oxidative stress in other renal diseases like urolithiasis have been described [22]. High production of ROS and nitrosative species (NS) can cause damage to nuclear and mitochondrial DNA, induce apoptosis, and cause endoplasmic reticulum stress, and with this playing a role in cell death pathways such as apoptosis and necrosis in key cell types such as podocytes [20].…”