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Oxalate formation from ascorbic acid

抗坏血酸形成草酸盐

基本信息

批准号：
10374713
负责人：
John Knight
金额：
$ 62.31万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10374713
关键词：
Adult Affect Animal Model Animals Antioxidants Ascorbic Acid Attenuated Biological Models Calcium Calcium Oxalate Carbon Cell Line Cell model Chromatography Consumption Coupled Cultured Cells Detection Diet Dietary intake Disease Dose Excretory function Female Food Generations Glutathione Gulo Health Care Costs Human Human Volunteers Ingestion Intake Intravenous Investigation Ions Kidney Kidney Calculi Knockout Mice Label Measurement Measures Metabolic Metabolism Mitochondria Modeling Mus Non obese Nutrient Nutritional Study Obesity Oral Organelles Oxalates Oxidants Oxidative Stress Plasma Population Process Procysteine Production Quality of life Reactive Oxygen Species Recommended Daily Allowances Research Risk Risk Factors Role Sampling Small Interfering RNA Source Techniques Testing Thinness Urine defined contribution dietary dietary control epidemiology study experimental study human subject male mouse model neutrophil obese person screening stable isotope uptake urinary

项目摘要

Project Summary Calcium oxalate stone disease occurs in nearly 10% of the U.S. population and contributes significantly to health care costs and negatively impacts quality of life. The amount of oxalate excreted in urine is a known risk factor for calcium oxalate stone disease. Approximately 50% of urinary oxalate is derived from the diet and the remaining from endogenous synthesis. The metabolism of ascorbic acid (AA), an important antioxidant, is a source of urinary oxalate derived from endogenous synthesis. However, the contribution of this source to urinary oxalate excretion is not well defined. Prior experiments have been hampered by 1) a lack of control of dietary oxalate to urinary oxalate excretion and 2) the confounding generation of oxalate from AA in non- acidified urine samples. The turnover of AA each day is approximately 80 mg and could feasibly result in the formation of up to 40 mg of oxalate per day. We have measured the contribution of AA turnover to urinary oxalate excretion with carbon-13 labelled AA oral dosing in a small number of normal adults and have confirmed that AA contributes 40 -50 % of the endogenous oxalate excreted in urine. These preliminary findings suggest AA turnover is a major source of urinary oxalate derived from endogenous synthesis. In this proposal we will assess the conversion of AA to oxalate in non-stone forming adults and CaOx stone forming adults using the stable isotope of AA, carbon-13 AA. We will further examine the effects of obesity, which is known to be associated with systemic oxidative stress and a decreased plasma AA concentration, on this conversion as well as increased oxalate excretion. Subjects in nutritional studies will ingest known amounts of food-derived AA in diets also controlled in their contents of oxalate, calcium and other nutrients. Experiments will be conducted in cultured cells and mouse models to systematically examine the relationships between AA and oxalate, the role of pro-oxidants in this process, the role of mitochondria and AA transport into this organelle, and to determine whether antioxidants can blunt oxalate formation from AA. If these studies are successful they will open new avenues of research for decreasing urinary oxalate excretion and kidney stone formation.

项目总结