Shape-dependent cellular toxicity on renal epithelial cells and stone risk of calcium oxalate dihydrate crystals

Abstract Renal epithelial cell injury causes crystal retention and leads to renal stone formation. However, the effects of crystal shape on cell injury and stone risk remain unclear. This study compared the cytotoxicity degrees of calcium oxalate dihydrate (COD) crystals having different shapes towa...

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Main Authors: Xin-Yuan Sun, Jian-Ming Ouyang, Kai Yu
Format: Article
Language:English
Published: Nature Portfolio 2017-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-07598-7
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author Xin-Yuan Sun
Jian-Ming Ouyang
Kai Yu
author_facet Xin-Yuan Sun
Jian-Ming Ouyang
Kai Yu
author_sort Xin-Yuan Sun
collection DOAJ
description Abstract Renal epithelial cell injury causes crystal retention and leads to renal stone formation. However, the effects of crystal shape on cell injury and stone risk remain unclear. This study compared the cytotoxicity degrees of calcium oxalate dihydrate (COD) crystals having different shapes toward human kidney proximal tubular epithelial (HK-2) cells to reveal the effect of crystal shape on cell injury and to elucidate the pathological mechanism of calcium oxalate kidney stones. The effects of exposure to cross-shaped (COD-CS), flower-like (COD-FL), bipyramid (COD-BD), and elongated–bipyramid (COD-EBD) COD crystals on HK-2 cells were investigated by examining the cell viability, cell membrane integrity, cell morphology change, intracellular reactive oxygen species, mitochondrial membrane potential (Δψm), and apoptotic and/or necrotic rate. Crystals with large (100) faces (COD-EBD) and sharp edges (COD-CS) showed higher toxicity than COD-BD and COD-FL, respectively. COD crystal exposure caused cell membrane rupture, upregulated intracellular reactive oxygen, and decreased Δψm. This series of phenomena ultimately led to a high apoptotic rate and a low necrotic rate. Crystals with large active faces have a large contact area with epithelial cell surface, and crystals with sharp edges can easily scratch epithelial cells; these factors could promote crystal adhesion and aggregation, thus increasing stone risk.
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spelling doaj.art-b225a3ffb6c44a0bb3ef59ca179dbc442022-12-21T20:31:23ZengNature PortfolioScientific Reports2045-23222017-08-017111310.1038/s41598-017-07598-7Shape-dependent cellular toxicity on renal epithelial cells and stone risk of calcium oxalate dihydrate crystalsXin-Yuan Sun0Jian-Ming Ouyang1Kai Yu2Department of Chemistry, Jinan UniversityDepartment of Chemistry, Jinan UniversityDepartment of Chemistry, Jinan UniversityAbstract Renal epithelial cell injury causes crystal retention and leads to renal stone formation. However, the effects of crystal shape on cell injury and stone risk remain unclear. This study compared the cytotoxicity degrees of calcium oxalate dihydrate (COD) crystals having different shapes toward human kidney proximal tubular epithelial (HK-2) cells to reveal the effect of crystal shape on cell injury and to elucidate the pathological mechanism of calcium oxalate kidney stones. The effects of exposure to cross-shaped (COD-CS), flower-like (COD-FL), bipyramid (COD-BD), and elongated–bipyramid (COD-EBD) COD crystals on HK-2 cells were investigated by examining the cell viability, cell membrane integrity, cell morphology change, intracellular reactive oxygen species, mitochondrial membrane potential (Δψm), and apoptotic and/or necrotic rate. Crystals with large (100) faces (COD-EBD) and sharp edges (COD-CS) showed higher toxicity than COD-BD and COD-FL, respectively. COD crystal exposure caused cell membrane rupture, upregulated intracellular reactive oxygen, and decreased Δψm. This series of phenomena ultimately led to a high apoptotic rate and a low necrotic rate. Crystals with large active faces have a large contact area with epithelial cell surface, and crystals with sharp edges can easily scratch epithelial cells; these factors could promote crystal adhesion and aggregation, thus increasing stone risk.https://doi.org/10.1038/s41598-017-07598-7
spellingShingle Xin-Yuan Sun
Jian-Ming Ouyang
Kai Yu
Shape-dependent cellular toxicity on renal epithelial cells and stone risk of calcium oxalate dihydrate crystals
Scientific Reports
title Shape-dependent cellular toxicity on renal epithelial cells and stone risk of calcium oxalate dihydrate crystals
title_full Shape-dependent cellular toxicity on renal epithelial cells and stone risk of calcium oxalate dihydrate crystals
title_fullStr Shape-dependent cellular toxicity on renal epithelial cells and stone risk of calcium oxalate dihydrate crystals
title_full_unstemmed Shape-dependent cellular toxicity on renal epithelial cells and stone risk of calcium oxalate dihydrate crystals
title_short Shape-dependent cellular toxicity on renal epithelial cells and stone risk of calcium oxalate dihydrate crystals
title_sort shape dependent cellular toxicity on renal epithelial cells and stone risk of calcium oxalate dihydrate crystals
url https://doi.org/10.1038/s41598-017-07598-7
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AT kaiyu shapedependentcellulartoxicityonrenalepithelialcellsandstoneriskofcalciumoxalatedihydratecrystals