Porphyra yezoensis polysaccharide and potassium citrate synergistically inhibit calcium oxalate crystallization induced by renal epithelial cells and cytotoxicity of the formed crystals.

Mineralization crystallization is considered to be the initial stage of stone formation. However, the formation of crystals and subsequent cell damage have rarely been investigated. An oxidatively damaged cell model was established using oxalic acid to injure human proximal tubular epithelial cells (HK-2). Subsequently, CaOx crystallization was induced by adding 2.0 mmol/L sodium oxalate solution. We compared the synergistic effects of PYPs with molecular weights of 49.54 kDa (PYP1) and 4.02 kDa (PYP2) and KCit on the inhibition of CaOx crystallization and studied the nucleation, growth, and retention process of CaOx crystals on the cell surface and the subsequent damage of the formed crystals to the cells. Normal HK-2 cells mainly induced the formation of CaOx dihydrate (COD), whereas the damaged cells mainly induced the formation of CaOx monohydrate (COM) crystals. Under the protection of PYPs, the state of cells was improved, and the proportion of COD crystals in the formed crystals increased. Small-molecular-weight PYP2 exhibited better abilities of inhibiting CaOx crystallization and improving cell state compared with PYP1. Under the synergistic effects of PYPs and KCit, the number of formed crystals was obviously reduced, and the size was obviously decreased. PYPs can repair damaged cells and inhibit the conversion of COD phase to COM phase. KCit can obviously inhibit the nucleation of CaOx crystal and reduce the amount of crystal formation. The repair of damaged cells by PYPs and the synergistic inhibition of CaOx crystallization by PYPs and KCit reduce cell damage and crystal formation on the cell surface. By simultaneously repairing damaged cells and inhibiting crystallization, this strategy is expected to exert a desirable effect in preventing the formation and recurrence of stones.