Free Radical Scavengers, Catalase and Superoxide Dismutase Provide Protection From Oxalate-Associated Injury to LLC-Pk1 and MDCK Cells

Thamilselvan, Sivagnanam; Byer, Karen J.; Hackett, Raymond L.; Khan, Saeed R.

doi:10.1097/00005392-200007000-00065

Cited by 50 publications

(71 citation statements)

References 29 publications

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“…Our previous studies [19], as well as those of others [24], demonstrated that oxalate exposure increases free radical production in renal epithelial cells. When we expose cells to oxalate concurrent with calcium oxalate monohydrate (COM) crystals, the production of ROS is greater than in cells exposed to oxalate alone [19]. Similarly, oxalate exposure results in increased MDA content and this effect is further enhanced by the addition of COM crystals to renal tubular cells [19].…”

Section: Discussionmentioning

confidence: 88%

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Molecular Mechanism of Oxalate-Induced Free Radical Production and Glutathione Redox Imbalance in Renal Epithelial Cells: Effect of Antioxidants

Rashed¹,

Menon²,

Thamilselvan³

2004

Am J Nephrol

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Background: Peroxidation of renal cells is a critical event in the nucleation and formation of calcium oxalate crystals under hyperoxaluric conditions. We previously demonstrated that oxalate-induced peroxidative injury is one of the major mechanisms in promoting crystal attachment to renal epithelial cells. Methods: In this study we have demonstrated that the mechanism of oxalate-induced peroxidative injury is through the induction of TGF-β₁ and glutathione (GSH) redox imbalance in LLC-PK₁ cells. Results: LLC-PK₁, renal epithelial cells exposed to oxalate had significantly higher reactive oxygen species (ROS) production; higher TGF-β₁ levels, as measured by ELISA (1.89 ± 0.035 fold increase) or Western blot (1.65 ± 0.01 fold increase); increased malondialdehyde formation; increased LDH release, and loss of cell viability. In addition, oxalate exposure significantly decreased GSH content, glutathione reductase, glucose-6-phosphate dehydrogenase activities, and increased oxidized GSH content. Treatment with vitamin E, neutralizing anti-TGF-β antibody, or diphenylene iodium, an inhibitor of NAD(P)H oxidase, significantly inhibited oxalate-induced ROS production and prevented peroxidative injury and cytolysis. Vitamin E, catalase, or desferoxamine treatment also significantly restored the oxalate-induced cellular GSH redox status toward the control level, and vitamin E treatment significantly attenuated the oxalate-mediated increase in TGF-β₁ protein in cultured LLC-PK₁ cells. Conclusions: This is the first study to demonstrate that the mechanism of oxalate-induced free radical production in renal tubular epithelial cells is through the activation of NAD(P)H oxidase via cytokine TGF-β₁ induction. These results also provide direct evidence that antioxidant therapy might prevent calcium oxalate nucleation and kidney stone formation by preventing oxalate-mediated peroxidative injury and GSH redox imbalance.

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Section: Discussionmentioning

confidence: 88%

“…Lipid peroxidation was measured as MDA content, a product of lipid peroxidation, using a thiobarbituric acid method as previously described [19]. …”

Section: Methodsmentioning

confidence: 99%

Molecular Mechanism of Oxalate-Induced Free Radical Production and Glutathione Redox Imbalance in Renal Epithelial Cells: Effect of Antioxidants

Rashed¹,

Menon²,

Thamilselvan³

2004

Am J Nephrol

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“…Further experiments on MDCK and LLC-PK1 (pig kidney epithelial cells with properties of proximal tubule epithelial cells) monolayers showed that crystal-related cell damage is associated with an increased production of free radicals and cell death. These phenomena were related to oxalate concentration, whereas free radical scavenging and degrading enzymes such as catalase (CAT) and superoxide dismutase (SOD) provided strong protection from the injury (52,53). In experiments with fresh rat urothelium, crystals formed at the site of the damaged superfi cial cells in a free radical-rich environment, whereas administration of antioxidants (mannitol or ascorbic acid) abolished crystal formation (54).…”

Section: Formation Of Oxalate Crystals and Onset Of Ksdmentioning

confidence: 99%

Oxalate: From the Environment to Kidney Stones

Brzica

Breljak

Burckhardt

et al. 2013

Archives of Industrial Hygiene and Toxicology

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Oxalate urolithiasis (nephrolithiasis) is the most frequent type of kidney stone disease. Epidemiological research has shown that urolithiasis is approximately twice as common in men as in women, but the underlying mechanism of this sex-related prevalence is unclear. Oxalate in the organism partially originate from food (exogenous oxalate) and largely as a metabolic end-product from numerous precursors generated mainly in the liver (endogenous oxalate). Oxalate concentrations in plasma and urine can be modifi ed by various foodstuffs, which can interact in positively or negatively by affecting oxalate absorption, excretion, and/or its metabolic pathways. Oxalate is mostly removed from blood by kidneys and partially via bile and intestinal excretion. In the kidneys, after reaching certain conditions, such as high tubular concentration and damaged integrity of the tubule epithelium, oxalate can precipitate and initiate the formation of stones. Recent studies have indicated the importance of the SoLute Carrier 26 (SLC26) family of membrane transporters for handling oxalate. Two members of this family [Sulfate Anion Transporter 1 (SAT-1; SLC26A1) and Chloride/Formate EXchanger (CFEX; SLC26A6)] may contribute to oxalate transport in the intestine, liver, and kidneys. Malfunction or absence of SAT-1 or CFEX has been associated with hyperoxaluria and urolithiasis. However, numerous questions regarding their roles in oxalate transport in the respective organs and male-prevalent urolithiasis, as well as the role of sex hormones in the expression of these transporters at the level of mRNA and protein, still remain to be answered.

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“…SOD catalyzes the conversion of superoxides (O2 · ) into H2O2; the H2O2 is further reduced to H2O by CAT. Treatment with CAT and SOD helps prevent ROS-induced damage in LLC-PK1 cells [36,44] and reduced the oxidative stress-induced lipid peroxidation in vivo [45]. GSH-px catalyzed the intercellular reduced GSH which as a hydrogen donor to generate oxidized glutahthine(GSSG), and eliminated H2O2 and catalyzed the reduction of peroxides in living organ [46,47].…”

Section: Discussionmentioning

confidence: 99%

Antioxidative effects of fermented sesame sauce against hydrogen peroxide-induced oxidative damage in LLC-PK1 porcine renal tubule cells

Song

Choi²,

Seo³

et al. 2014

Nutr Res Pract

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BACKGROUND/OBJECTIVES:This study was performed to investigate the in vitro antioxidant and cytoprotective effects of fermented sesame sauce (FSeS) against hydrogen peroxide (H2O2)-induced oxidative damage in renal proximal tubule LLC-PK1 cells. MATERIALS/METHODS: 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical (• OH), and H2O2 scavenging assay was used to evaluate the in vitro antioxidant activity of FSeS. To investigate the cytoprotective effect of FSeS against H2O2-induced oxidative damage in LLC-PK1 cells, the cellular levels of reactive oxygen species (ROS), lipid peroxidation, and endogenous antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) were measured. RESULTS: The ability of FSeS to scavenge DPPH,• OH and H2O2 was greater than that of FSS and AHSS. FSeS also significantly inhibited H2O2-induced (500 μM) oxidative damage in the LLC-PK1 cells compared to FSS and AHSS (P < 0.05). Following treatment with 100 μg/mL of FSeS and FSS to prevent H2O2-induced oxidation, cell viability increased from 56.7% (control) to 83.7% and 75.6%, respectively. However, AHSS was not able to reduce H2O2-induced cell damage (viability of the AHSS-treated cells was 54.6%). FSeS more effectively suppressed H2O2-induced ROS generation and lipid peroxidation compared to FSS and AHSS (P < 0.05). Compared to the other sauces, FSeS also significantly increased cellular CAT, SOD, and GSH-px activities and mRNA expression (P < 0.05). CONCULUSIONS: These results from the present study suggest that FSeS is an effective radical scavenger and protects against H2O2-induced oxidative damage in LLC-PK1 cells by reducing ROS levels, inhibiting lipid peroxidation, and stimulating antioxidant enzyme activity.

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Free Radical Scavengers, Catalase and Superoxide Dismutase Provide Protection From Oxalate-Associated Injury to LLC-Pk1 and MDCK Cells

Cited by 50 publications

References 29 publications

Molecular Mechanism of Oxalate-Induced Free Radical Production and Glutathione Redox Imbalance in Renal Epithelial Cells: Effect of Antioxidants

Molecular Mechanism of Oxalate-Induced Free Radical Production and Glutathione Redox Imbalance in Renal Epithelial Cells: Effect of Antioxidants

Oxalate: From the Environment to Kidney Stones

Antioxidative effects of fermented sesame sauce against hydrogen peroxide-induced oxidative damage in LLC-PK1 porcine renal tubule cells

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