MP34-13 PPAR-α/γ AGONISTS HAVE DIFFERENT EFFECTS ON RENAL CRYSTAL FORMATION IN HYPEROXALURIC ANIMAL MODELS

Abstract

You have accessJournal of UrologyStone Disease: Basic Research II1 Apr 2015MP34-13 PPAR-α/γ AGONISTS HAVE DIFFERENT EFFECTS ON RENAL CRYSTAL FORMATION IN HYPEROXALURIC ANIMAL MODELS Kazumi Taguchi, Rei Unno, Yasuhiro Hirose, Shuzo Hamamoto, Takahiro Kobayashi, Ryosuke Ando, Atsushi Okada, Yasunori Itoh, Takahiro Yasui, Keiichi Tozawa, Yutaro Hayashi, and Kenjiro Kohri Kazumi TaguchiKazumi Taguchi More articles by this author , Rei UnnoRei Unno More articles by this author , Yasuhiro HiroseYasuhiro Hirose More articles by this author , Shuzo HamamotoShuzo Hamamoto More articles by this author , Takahiro KobayashiTakahiro Kobayashi More articles by this author , Ryosuke AndoRyosuke Ando More articles by this author , Atsushi OkadaAtsushi Okada More articles by this author , Yasunori ItohYasunori Itoh More articles by this author , Takahiro YasuiTakahiro Yasui More articles by this author , Keiichi TozawaKeiichi Tozawa More articles by this author , Yutaro HayashiYutaro Hayashi More articles by this author , and Kenjiro KohriKenjiro Kohri More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1309AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Urolithiasis has inflammatory and oxidative stress-related characteristics resembling metabolic syndrome (Mets). No therapy targeting the molecular biology of crystal formation has been developed, although statins and peroxisome proliferator-activated receptor (PPAR) agonists are used to treat Mets. Hence, we evaluated the in vivo efficacy of PPAR agonists for preventing renal crystal formation and investigated changes in gene expression of PPARs and related inflammatory and oxidative molecules in a hyperoxaluric animal model. METHODS We first examined PPAR gene expression by microarray analysis of a mouse kidney stone model in which hyperoxaluria was induced by daily intra-abdominal glyoxylate injection. Affymetrix GeneSpring GX11.0 was used with unbiased gene expression profiling to investigate global renal gene expression. Then, we investigated the effects of 3 different PPAR agonists, the PPARα agonists bezafibrate (BZF) and fenofibrate (FF), and the PPARγ agonist pioglitazone (PGZ). SD rats were untreated (Ctl) or treated with 1% ethylene glycol (EG), 1% EG and 30 mg/kg BZF (EG + B), 1% EG and 30 mg/kg FF (EG + F), or 1% EG and 10 mg/kg PGZ (EG + P). Blood and 24-h urine samples and kidney sections were collected after 14 days□f treatment. We examined crystal formation using Pizzolato staining and polarized light optical microscopy and evaluated inflammation, cell injury, apoptosis, and oxidative stress with immunohistochemistry and quantitative polymerase chain reaction. RESULTS Microarray analysis showed increased PPARγ expression after crystal formation but no change in PPARα expression during crystal formation. Renal crystal formation was significantly lower in the EG + P and higher in the EG + B and EG + F groups than in the EG group (Figure). The serum and urinary levels of Ca, P, and Mg and urinary level of oxalate did not differ among the EG + B, EG + F, and EG + P groups. PGZ administration markedly decreased cell injury, apoptosis, and oxidative stress. Administration of both BZF and FF increased serum levels of creatinine that caused glomerulotubular injury. CONCLUSIONS PPAR-α agonists suppresses renal crystal formation via its renal tubular cytoprotective effects whereas PPAR-α agonists accelerate crystal formation via its renal toxicity. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e415 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kazumi Taguchi More articles by this author Rei Unno More articles by this author Yasuhiro Hirose More articles by this author Shuzo Hamamoto More articles by this author Takahiro Kobayashi More articles by this author Ryosuke Ando More articles by this author Atsushi Okada More articles by this author Yasunori Itoh More articles by this author Takahiro Yasui More articles by this author Keiichi Tozawa More articles by this author Yutaro Hayashi More articles by this author Kenjiro Kohri More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...