title: 1,2,3,4,6-Penta-O-galloyl-beta-D-glucose reduces renal crystallization and oxidative stress in a hyperoxaluric rat model.
abstract: 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.
authors.affiliation: College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Hyo-Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Jeong
authors.forename: Hyo-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Eun-Ok
authors.initials: EO
authors.lastname: Lee
authors.forename: Hyunsu
authors.initials: H
authors.lastname: Bae
authors.forename: John C
authors.initials: JC
authors.lastname: Lieske
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003460:Crystallization; D019855:Ethylene Glycol; D006820:Hyaluronic Acid / Q000032:analysis; D047348:Hydrolyzable Tannins / Q000494:pharmacology / Q000627:therapeutic use*; D006959:Hyperoxaluria / Q000188:drug therapy*; D007668:Kidney / Q000378:metabolism; D007669:Kidney Calculi / Q000517:prevention & control*; D008297:Male; D053495:Osteopontin / Q000032:analysis; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D047348:Hydrolyzable Tannins; D017382:Reactive Oxygen Species; D053495:Osteopontin; C435084:pentagalloylglucose; D006820:Hyaluronic Acid; D013482:Superoxide Dismutase; D019855:Ethylene Glycol