Size-Dependent Cytotoxicity of Hydroxyapatite Crystals on Renal Epithelial Cells

Int J Nanomedicine. 2020 Jul 15:15:5043-5060. doi: 10.2147/IJN.S232926. eCollection 2020.

Abstract

Background: Hydroxyapatite (HAP) is a common component of most idiopathic calcium oxalate (CaOx) stones and is often used as a nidus to induce the formation of CaOx kidney stones.

Methods: This work comparatively studies the cytotoxicity of four kinds of HAP crystals with different sizes (40 nm to 2 μm), namely, HAP-40 nm, HAP-70 nm, HAP-1 μm, and HAP-2 μm, on human renal proximal tubular epithelial cells (HK-2).

Results: HAP crystals reduce the viability and membrane integrity of HK-2 cells in a concentration-dependent manner and consequently cause cytoskeleton damage, cell swelling, increased intracellular reactive oxygen species level, decreased mitochondrial membrane potential, increased intracellular calcium concentration, blocked cell cycle and stagnation in G0/G1 phase, and increased cell necrosis rate. HAP toxicity to HK-2 cells increases with a decrease in crystal size.

Conclusion: Cell damage caused by HAP crystals increases the risk of kidney stone formation.

Keywords: cell injury; crystal size; cytotoxicity; hydroxyapatite; nanocrystal.

MeSH terms

  • Calcium Oxalate / chemistry
  • Cell Cycle / drug effects
  • Cell Line
  • Cytotoxins / chemistry*
  • Cytotoxins / toxicity*
  • Durapatite / chemistry*
  • Durapatite / toxicity*
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Humans
  • Kidney / cytology*
  • Membrane Potential, Mitochondrial / drug effects
  • Reactive Oxygen Species / metabolism

Substances

  • Cytotoxins
  • Reactive Oxygen Species
  • Calcium Oxalate
  • Durapatite