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.
Highlights
Kidney stone formation is a complex biological regulation process that usually includes crystal nucleation, growth, aggregation, and retention[1]
This study suggests that the configuration of nanoparticles affects their toxicity more than size, and defects due to nanoparticle exposure occur through different biological mechanisms[10]
calcium oxalate dihydrate (COD) crystals with different shapes were prepared by altering reactant concentration, reaction temperature, stirring speed, and additive
Summary
Kidney stone formation is a complex biological regulation process that usually includes crystal nucleation, growth, aggregation, and retention[1]. In recurrent stone formers, CaOx crystallites mainly comprise aggregated octahedral COD crystals 10–12 μm in size with sharp edges. Recent studies have demonstrated that the cytotoxicity of CaOx crystals toward renal epithelial cells is closely related to crystal phase and size[6, 7]. The cytotoxic effect of COD crystals on renal epithelial cells is size dependent and exacerbates in the following order: 50 nm > 100 nm > 600 nm > 3 μm > 10 μm[7]. Huang et al reported that mesoporous silica nanoparticles with high aspect ratios are taken up in large amounts and demonstrate fast internalization rates[12] They found that particles with high aspect ratios exert significant effects on cellular processes, including proliferation, apoptosis, cytoskeleton formation, adhesion, and migration
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