Editorial Comment to renal tubular epithelial cell injury and oxidative stress induce calcium oxalate crystal formation in mouse kidney

Reactive oxygen and nitrogen species play significant regulatory roles. They normally occur at steady state levels and are generated when needed. In various pathological conditions, however, there is uncontrolled generation of the reactive oxygen or nitrogen species and/or a reduction in the endogenous antioxidant capacity leading to the development of oxidative stress. Both animal model and tissue culture studies have provided evidence for the production of oxidative stress (OS) when cells are exposed to high oxalate and/or calcium oxalate crystals.1,2 Recent studies have also provided evidence for the development of OS in the kidneys of stone patients. Mitochondria are generally the most common source of superoxide and hydrogen peroxide in most cells and tissues. However, membrane-associated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is also a major source of reactive oxygen species (ROS) in the kidneys, particularly in the presence of angiotensin II. According to a number of experimental studies, it is also a likely source of Ox-induced superoxide production. Angiotensin II is implicated in causing oxidative stress by stimulating membrane bound NAD(P)H oxidase leading to increased generation of superoxide. Administration of angiotensin II type 1 receptor blockers3 or angiotensin converting enzyme inhibitors to hyperoxaluric rats produced significant reduction in hyperoxaluria-induced production of renal lipid peroxides. These treatments additionally produced a reduction in Transforming growth factor beta (TGF-β) expression in the kidneys. TGF- β participates in ROS production through the activation of NADPH oxidase. In tissue culture studies Ox-induced injury of NRK52E cells was significantly reduced in the presence of NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI).4,5 In this study the authors induced hyperoxaluria by the administration of glyoxylate, provided green tea as an antioxidant and investigated the development of oxidative stress and the production of CaOx nephrolithiasis. As expected and shown in earlier studies, hyperoxaluria developed quickly, was associated with the renal epithelial injury and later resulted in crystal deposition. Injury was associated with oxidative stress. Mitochondria appeared damaged even before renal crystal deposition and has been previously implicated as being involved in the development of oxidative stress. However there is no indication that NADPH oxidase was not involved and was not the first to respond. In conclusion, oxidative stress from excess oxalate ion plays an important role in early stage calcium oxalate crystal formation in renal tubules. I hope, in future, many studies on this area will be able to reveal the full pathogenesis of urolithiasis.