Metabolomics analysis for hydroxy-L-proline-induced calcium oxalate nephrolithiasis in rats based on ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry

Gao, Songyan; Yang, Rui; Peng, Zhongjiang; Lu, Hongtao; Li, Na; Ding, Jiarong; Cui, Xingang; Chen, Wei; Dong, Xin

doi:10.1038/srep30142

Cited by 22 publications

(18 citation statements)

References 51 publications

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“…In this context, altered urinary levels in stone formers may be suggestive of altered glycine metabolism that could lead to increased oxalate production and stone formation [ 35 ]. Our findings are in agreement with literature data [ 35 – 39 ], in which a decrease in the concentration of amino acids, including alanine, tryptophan, and threonine, was suggested to exert a possible inhibitory activity of crystalline aggregation [ 38 , 39 ]. Moreover, renal oxidative vulnerability due to changes in mitochondrial-glutathione and energy homeostasis was described in a rat model of calcium oxalate urolithiasis [ 40 ].…”

Section: Resultssupporting

confidence: 93%

A Specific Urinary Amino Acid Profile Characterizes People with Kidney Stones

et al. 2020

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Background. Urolithiasis is the process of stone formation in the urinary tract. Its etiology is only partly known, and efficient therapeutic approaches are currently lacking. Metabolomics is increasingly used in biomarkers discovery for its ability to identify mediators of relevant (patho)physiological processes. Amino acids may be involved in kidney stone formation. The aim of the present study was to investigate the presence of an amino acid signature in stone former urine through a targeted metabolomic approach. Methods. A panel of 35 amino acids and derivatives was assessed in urines from 15 stone former patients and 12 healthy subjects by UPLC-MS. Partial Least Squares Discriminant Analysis (PLS-DA) was used to define amino acid profiles of cases and controls. Results and Discussion. Our approach led to the definition of a specific amino acid fingerprint in people with kidney stones. A urinary amino acid profile of stone formers was characterized by lower levels of α-aminobutyric acid, asparagine, ethanolamine, isoleucine, methionine, phenylalanine, serine, tryptophan, and valine. Metabolomic analysis may lend insights into the pathophysiology of urolithiasis and allow tracking this prevalent condition over time.

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Section: Resultssupporting

confidence: 93%

A Specific Urinary Amino Acid Profile Characterizes People with Kidney Stones

et al. 2020

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“…To overcome the potential glyoxalate side effects to damage the kidney in the mouse [32], we also applied the 4th animal model using rats fed with hydroxy-L-proline (HLP) for 8 weeks to induce CaOx crystal deposition, since early studies indicated that this rat model has little acute renal injury and more closely mimicks the renal CaOx crystal deposition occurring in human kidney stone formers [33, 34].…”

Section: Resultsmentioning

confidence: 99%

The Protective Roles of Estrogen Receptor β in Renal Calcium Oxalate Crystal Formation via Reducing the Liver Oxalate Biosynthesis and Renal Oxidative Stress-Mediated Cell Injury

Zhu

Zhao

Chou

et al. 2019

Oxidative Medicine and Cellular Longevity

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Females develop kidney stones less frequently than males do. However, it is unclear if this gender difference is related to altered estrogen/estrogen receptor (ER) signaling. Here, we found that ER beta (ERβ) signals could suppress hepatic oxalate biosynthesis via transcriptional upregulation of the glyoxylate aminotransferase (AGT1) expression. Results from multiple in vitro renal cell lines also found that ERβ could function via suppressing the oxalate-induced injury through increasing the reactive oxygen species (ROS) production that led to a decrease of the renal calcium oxalate (CaOx) crystal deposition. Mechanism study results showed that ERβ suppressed oxalate-induced oxidative stress via transcriptional suppression of the NADPH oxidase subunit 2 (NOX2) through direct binding to the estrogen response elements (EREs) on the NOX2 5′ promoter. We further applied two in vivo mouse models with glyoxylate-induced renal CaOx crystal deposition and one rat model with 5% hydroxyl-L-proline-induced renal CaOx crystal deposition. Our data demonstrated that mice lacking ERβ (ERβKO) as well as mice or rats treated with ERβ antagonist PHTPP had increased renal CaOx crystal deposition with increased urinary oxalate excretion and renal ROS production. Importantly, targeting ERβ-regulated NOX2 with the NADPH oxidase inhibitor, apocynin, can suppress the renal CaOx crystal deposition in the in vivo mouse model. Together, results from multiple in vitro cell lines and in vivo mouse/rat models all demonstrate that ERβ may protect against renal CaOx crystal deposition via inhibiting the hepatic oxalate biosynthesis and oxidative stress-induced renal injury.

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“… 4 It has previously been performed to analyze the serum and urine of animal models with CaOx stones, by which potential biomarkers and disturbed metabolic pathways in rats with stones were identified. 15 Recently, metabolomics studies using the urine of patients with kidney stones have also been published, 5 , 6 which are of great significance for the prevention and treatment of kidney stones. However, the previous researches only focused on adults, ignoring children and adolescents.…”

Section: Discussionmentioning

confidence: 99%