Abstract
Calcium oxalate (CaOx) kidney stones accumulate within the renal tubule due to high concentrations of insoluble deposits in the urine. Pb[2+]-induced Ca[2+] mobilization along with Pb[2+]-induced nephrotoxic effects within the proximal tubule have been well established; however, Pb[2+] mediated effects within the collecting duct remains insufficiently studied. Thus in vitro and ex vivo model systems were treated with increasing concentrations of lead (II) acetate (PbAc) ± sodium oxalate (Na2C2O4) for 1 h, both individually and in combination. Pb[2+]-mediated solution turbidity increased 2 to 5 times greater post-exposure to 75, 100 and 200 μM Pb[2+] with the additional co-treatment of 10 mM oxalate in mouse inner medullary collecting duct (mIMCD-3) cells. Additionally, 100 μM and 200 μM Pb[2+] alone induced significant levels of intracellular Ca[2+] release. To validate Pb[2+]-mediated effects on the formation of CaOx crystals, alizarin red staining confirmed the presence of CaOx crystallization. Pb[2+]-induced intracellular Ca[2+] was also observed ex vivo in fly Malpighian tubules with significant increases in CaOx crystal formation via Pb[2+]-induced intracellular Ca[2+] release significantly increasing the average crystal number, size, and total area of crystal formation, which was ameliorated by tissue-specific SPoCk C transporter and Capa receptor knockdown. These studies demonstrate Pb[2+]-induced Ca[2+] release likely increases the formation of CaOx crystals, which is modulated by a Gq-linked mechanism with concurrent Ca[2+] extracellular mobilization.
