Effects of physical properties of nano-sized hydroxyapatite crystals on cellular toxicity in renal epithelial cells

Abstract

Hydroxyapatite (HAP) is not only a common component of most idiopathic CaOx stones, but also the core of Randall's plaque. HAP is a nest that can induce the formation of Randall's plaques and even kidney stones. We studied the toxic effects and mechanisms of four different types of nano-HAP crystals (H-Sphere, 72.5 nm × 72.5 nm; H-Needle, 37.2 nm × 162.7 nm; H-Rod, 42.3 nm × 115.3 nm; and H-Plate, 145.5 nm × 272.9 nm) on human renal proximal tubular epithelial cells (HK-2). HAP crystals could cause oxidative stress that triggered a series of cell dysfunction problems, resulting in decreased cell viability, loss of cell membrane integrity, cell swelling, and cell necrosis. The toxic effect of HAP was mainly attributed to its entry into cell by endocytosis and its accumulation in the lysosomes, causing the level of intracellular reactive oxygen species (ROS) to rise, the mitochondrial membrane potential (Δψm) to decrease, the lysosomal integrity to be destroyed, and the cell cycle blocked during the G0/G1 phase. The cytotoxicity of the four kinds of HAP crystals was ranked as follows: H-Sphere > H-Needle > H-Rod > H-Plate. The cytotoxicity of each crystal was positively correlated with low absolute zeta potential, conduciveness to internalized morphology, large specific surface area and aspect ratio, and small particle size. These results indicated that nano-HAP could damage HK-2 cells, and the physical properties of HAP crystals play a vital effect in their cytotoxicity.