Mp63-14 Impact of Obesity and Aging on Turnover of Ascorbic Acid to Urinary Oxalate in the Gulo Deficient Mouse

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology (MP63)1 May 2024MP63-14 IMPACT OF OBESITY AND AGING ON TURNOVER OF ASCORBIC ACID TO URINARY OXALATE IN THE GULO DEFICIENT MOUSE Brody Rhodes, Xingsheng Li, Joseph J. Crivelli, and John Knight Brody RhodesBrody Rhodes , Xingsheng LiXingsheng Li , Joseph J. CrivelliJoseph J. Crivelli , and John KnightJohn Knight View All Author Informationhttps://doi.org/10.1097/01.JU.0001009436.52988.91.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Increased urinary oxalate excretion is a risk factor for calcium oxalate kidney stone formation. Ascorbic acid (AsA) is an antioxidant that is non-enzymatically degraded to oxalate, and increased AsA intake is associated with increased risk of forming calcium oxalate stones. Most animals, unlike humans, can synthesize AsA which has made studying the conversion of AsA to oxalate in an animal model difficult. The Gulo-/- mouse, like humans, lacks gulonolactone oxidase and therefore cannot synthesize AsA. A better understanding of factors influencing the conversion of AsA to urinary oxalate may lead to improved dietary recommendations or novel pharmaceutical targets for calcium oxalate stone formers. Thus, we examined the influence of obesity and aging on the turnover of AsA to urinary oxalate. METHODS: Prior to beginning infusion studies, baseline, diet-induced obese, and aged cohorts of Gulo-/-mice were provided ad-libitum water containing 330 mg/L AsA followed by a 5-day AsA depletion period to eliminate tissue stores of AsA. Mice were then intravenously infused with the stable isotope of AsA, 13C6-AsA, via a surgically implanted osmotic pump at a rate of 10 µmoles/kg/h. After allowing 8 days for recovery and equilibration, 24-hour urines were collected for 3 consecutive days in metabolic cages. Urinary oxalate isotopomers, 12C2-oxalate, and 13C2-oxalate, were measured using ion chromatography/mass spectrometry to calculate the percent contribution of AsA to urinary oxalate. Statistical analysis was performed using one-way ANOVA with adjustment for multiple comparisons. RESULTS: We compared 3 groups of Gulo-/- mice (n=4-5 per group): a baseline cohort (age 14-24 weeks), a diet-induced obese cohort (60% high fat diet, age 23-31 weeks), and an aged cohort (age 79-101 weeks). We found that AsA contributes to a mean±standard deviation of 23.5±1.6% of urinary oxalate under baseline conditions, 27.4±1.7% under obese conditions, and 33.1±2.7% under aged conditions (p=0.06 for obese vs. baseline; p<0.001 for aged vs. baseline). CONCLUSIONS: Non-enzymatic conversion of ascorbic acid to oxalate accounted for almost one quarter of urinary oxalate under baseline conditions in the Gulo-/- mouse and increased significantly with aging. Download PPT Source of Funding: This work was supported in part by the Urology Care Foundation Summer Medical Student Fellowship Program and the Herbert Brendler, MD, Research Fund; the Urology Care Foundation Research Scholar Endourological Society/Raju Thomas, MD Award; and NIH 1R01DK126774 © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1036 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Brody Rhodes More articles by this author Xingsheng Li More articles by this author Joseph J. Crivelli More articles by this author John Knight More articles by this author Expand All Advertisement PDF downloadLoading ...