Adhesion of
calcium oxalate (CaOx) crystals to kidney cells may be a key event in the pathogenesis of
kidney stones associated with marked
hyperoxaluria. Previously, we found that 1,2,3,4,6-penta-O-galloyl-β-D-glucose (
PGG), isolated from a traditional medicinal herb, reduced CaOx crystal adhesion to renal epithelial cells by acting on the cells as well as on the crystal surface. Here we used the
ethylene glycol (EG)-mediated hyperoxaluric rat model and found evidence of
oxidant stress as indicated by decreases in the activities of the renal
antioxidant enzymes,
superoxide dismutase,
catalase, and
glutathione peroxidase, with increased kidney cell apoptosis and serum
malondialdehyde levels, all evident by 21 days of EG treatment. These effects of
hyperoxaluria were reversed by concurrent
PGG treatment along with decreased urinary
oxalate levels and CaOx supersaturation. Renal epithelial cell expression of the crystal binding molecule
hyaluronan increased diffusely within 7 days of EG initiation, suggesting it is not a result of but precedes crystal deposition. Renal cell
osteopontin (OPN) was also upregulated in EG-treated animals, and
PGG significantly attenuated overexpression of both OPN and
hyaluronan. Thus, our findings demonstrate that
PGG reduces renal crystallization and oxidative renal cell injury, and may be a candidate chemopreventive agent for
nephrolithiasis.