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

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          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.

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          Most cited references45

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          Reactive species and antioxidants. Redox biology is a fundamental theme of aerobic life.

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            Superoxide radical and superoxide dismutases.

            O2- oxidizes the [4Fe-4S] clusters of dehydratases, such as aconitase, causing-inactivation and release of Fe(II), which may then reduce H2O2 to OH- +OH.. SODs inhibit such HO. production by scavengingO2-, but Cu, ZnSODs, by virtue of a nonspecific peroxidase activity, may peroxidize spin trapping agents and thus give the appearance of catalyzing OH. production from H2O2. There is a glycosylated, tetrameric Cu, ZnSOD in the extracellular space that binds to acidic glycosamino-glycans. It minimizes the reaction of O2- with NO. E. coli, and other gram negative microorganisms, contain a periplasmic Cu, ZnSOD that may serve to protect against extracellular O2-. Mn(III) complexes of multidentate macrocyclic nitrogenous ligands catalyze the dismutation of O2- and are being explored as potential pharmaceutical agents. SOD-null mutants have been prepared to reveal the biological effects of O2-. SodA, sodB E. coli exhibit dioxygen-dependent auxotrophies and enhanced mutagenesis, reflecting O2(-)-sensitive biosynthetic pathways and DNA damage. Yeast, lacking either Cu, ZnSOD or MnSOD, are oxygen intolerant, and the double mutant was hypermutable and defective in sporulation and exhibited requirements for methionine and lysine. A Cu, ZnSOD-null Drosophila exhibited a shortened lifespan.
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              The characterization of antioxidants.

              The role of antioxidants in nutrition is an area of increasing interest. Antioxidants are used (1) to prolong the shelf life and maintain the nutritional quality of lipid-containing foods, and (2) to modulate the consequences of oxidative damage in the human body. This review discusses what an antioxidant is and how the properties of antioxidants may be characterized.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Environ Res Public Health
                Int J Environ Res Public Health
                ijerph
                International Journal of Environmental Research and Public Health
                MDPI
                1661-7827
                1660-4601
                23 January 2017
                January 2017
                : 14
                : 1
                : 109
                Affiliations
                [1 ]Clinical Hospital Osijek, Josipa Huttlera 4, HR-31000 Osijek, Croatia; tomislavkizivat@ 123456gmail.com (T.K.); Ivana.Maric@ 123456mefos.hr (I.M.); robert.smolic@ 123456mefos.hr (R.S.); ibcurcic@ 123456mefos.hr (I.B.Č.); imihaljevic@ 123456mefos.hr (I.M.); avcev@ 123456mefos.hr (A.V.)
                [2 ]Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Cara Hadrijana 10, HR-3100 Osijek, Croatia; mtolusic@ 123456mefos.hr (M.T.L.); kunalucija@ 123456gmail.com (L.K.); atucak@ 123456mefos.hr (S.T.-Z.)
                Author notes
                [* ]Correspondence: martina.smolic@ 123456mefos.hr ; Tel.: +385-31-512800
                Article
                ijerph-14-00109
                10.3390/ijerph14010109
                5295359
                28125004
                440686a0-4c42-415f-a65a-d540baf9cca1
                © 2017 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 23 November 2016
                : 17 January 2017
                Categories
                Article

                Public health
                urolithiasis,vitamin e,l-arginine,madin-darby canine kidney cells,llc-pk1 cells
                Public health
                urolithiasis, vitamin e, l-arginine, madin-darby canine kidney cells, llc-pk1 cells

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