Oxalate formation from ascorbic acid
抗坏血酸形成草酸盐
基本信息
- 批准号:10583560
- 负责人:
- 金额:$ 62.31万
- 依托单位:
- 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:
- 关键词:AccelerationAdultAffectAnimal ExperimentsAnimal ModelAntioxidantsAscorbic AcidAttenuatedBiological ModelsCalciumCalcium OxalateCarbonCell LineCell modelChromatographyConsumptionCoupledCultured CellsCysteineDetectionDietDietary intakeDiseaseDoseExcretory functionFemaleFoodGenerationsGlutathioneGuloHealth Care CostsHumanHuman VolunteersIngestionIntakeIntravenousInvestigationIonsKidneyKidney CalculiKnockout MiceLabelMeasurementMeasuresMetabolicMetabolismMitochondriaModelingMusNutrientNutritional StudyObesityOralOrganellesOxalatesOxidantsOxidative StressPlasmaPopulationProcessProductionQuality of lifeReactive Oxygen SpeciesRecommended Daily AllowancesResearchRiskRisk FactorsRoleSamplingSmall Interfering RNASourceTechniquesTestingThinnessUrineabsorptiondefined contributiondietarydietary controlepidemiology studyexperimental studyhuman subjectmalemouse modelneutrophilobese personscreeningstable isotopeuptakeurinary
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.
项目摘要
草酸钙结石病发生在近10%的美国人口中,
卫生保健费用和负面影响的生活质量。草酸排泄量在尿液中是一个已知的风险
草酸钙结石病的因素。大约50%的尿草酸盐来自饮食,
抗坏血酸(AA)是一种重要的抗氧化剂,它的代谢是一个复杂的过程。
尿草酸来源于内源性合成。然而,这种来源的贡献,
尿草酸盐排泄没有很好的定义。先前的实验受到以下因素的阻碍:1)缺乏对尿草酸盐排泄的控制,
饮食中草酸与尿中草酸排泄的比值; 2)非肥胖者AA中草酸的混杂生成
每天AA的周转量约为80 mg,并可能导致
每天形成高达40毫克的草酸盐。我们已经测量了AA周转对尿的贡献,
在少数正常成年人中,用13 C标记的AA口服给药的草酸排泄,
证实AA贡献了尿中排泄的内源性草酸的40 - 50%。
研究结果表明AA周转是内源性合成的尿草酸的主要来源。
我们将评估非结石形成成人和CaOx结石形成成人中AA向草酸盐的转化
成年人使用AA的稳定同位素,碳-13 AA。我们将进一步研究肥胖的影响,这是
已知与全身氧化应激和血浆AA浓度降低有关,
转化以及草酸排泄增加。营养研究中的受试者将摄入已知量的
膳食中的食物来源AA还控制其草酸盐、钙和其他营养素的含量。
将在培养的细胞和小鼠模型中进行,以系统地研究AA之间的关系
和草酸的作用,促氧化剂在这一过程中的作用,线粒体和AA运输到这一作用,
细胞器,并确定是否抗氧化剂可以钝草酸形成AA。如果这些研究是
他们的成功将为减少尿草酸排泄和肾结石的研究开辟新的途径
阵
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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John Knight其他文献
Analytic Theology and the academic study of Religion, by William Wood. Oxford University Press, 2021. 299 pages, $100.00 (hb)
- DOI:
10.1007/s11153-022-09847-w - 发表时间:
2022-09-22 - 期刊:
- 影响因子:0.700
- 作者:
John Knight - 通讯作者:
John Knight
John Knight的其他文献
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{{ truncateString('John Knight', 18)}}的其他基金
Oxalobacter formigenes colonization and oxalate excretion in calcium oxalate kidney stone disease
草酸钙肾结石病中产草酸杆菌的定植和草酸盐排泄
- 批准号:
9896806 - 财政年份:2017
- 资助金额:
$ 62.31万 - 项目类别:
Oxalobacter formigenes colonization and oxalate excretion in calcium oxalate kidney stone disease
草酸钙肾结石病中产草酸杆菌的定植和草酸盐排泄
- 批准号:
9240267 - 财政年份:2017
- 资助金额:
$ 62.31万 - 项目类别:
Oxalate handling and Oxalobacter formigenes colonization in a mouse model
小鼠模型中的草酸盐处理和产草酸杆菌定植
- 批准号:
8212289 - 财政年份:2011
- 资助金额:
$ 62.31万 - 项目类别:
Oxalate handling and Oxalobacter formigenes colonization in a mouse model
小鼠模型中的草酸盐处理和产草酸杆菌定植
- 批准号:
8802873 - 财政年份:2011
- 资助金额:
$ 62.31万 - 项目类别:
Oxalate handling and Oxalobacter formigenes colonization in a mouse model
小鼠模型中的草酸盐处理和产草酸杆菌定植
- 批准号:
8585762 - 财政年份:2011
- 资助金额:
$ 62.31万 - 项目类别:
Oxalate handling and Oxalobacter formigenes colonization in a mouse model
小鼠模型中的草酸盐处理和产草酸杆菌定植
- 批准号:
8042403 - 财政年份:2011
- 资助金额:
$ 62.31万 - 项目类别:
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