Allantoin as an independent marker associated with carotid intima-media thickness in subclinical atherosclerosis

Santana, Marli Stela; Nascimento, Karolline Pereira; Lotufo, Paulo A; Benseñor, Isabela M.; Meotti, Flávia Carla

doi:10.1590/1414-431x20187543

Cited by 10 publications

(9 citation statements)

References 19 publications

(42 reference statements)

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“…Allantoin has been used as a biomarker of oxidative stress in studies on people with diabetes, , inflammation, , cystic fibrosis, response to exercise, and smoking . Nevertheless, concentrations and inter- and intraindividual variability in urinary allantoin in healthy individuals have not been studied.…”

Section: Introductionmentioning

confidence: 99%

Allantoin as a Marker of Oxidative Stress: Inter- and Intraindividual Variability in Urinary Concentrations in Healthy Individuals

Martinez-Moral

2019

Environ. Sci. Technol. Lett.

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Altered systemic oxidative stress is a consequence of environmental exposures and diseases, among other stress factors. The extent of oxidative stress in humans is assessed through the analysis of oxidative stress biomarkers (OSBs) in biospecimens such as urine. Allantoin is an OSB, a specific product of the oxidation of uric acid, that is measurable in urine. In this study, concentrations and inter-and intraindividual variability in urinary concentrations of allantoin were determined in healthy individuals. The results were compared with those found for other OSBs of lipids, proteins, and DNA in the same set of samples. Allantoin was found in all urine samples (N = 515), at concentrations that ranged from 0.88 to 41.7 mmol mol −1 creatinine (0.90 to 112 μg mL −1 urine). The intraclass correlation coefficient (ICC) of urinary allantoin measured in samples collected longitudinally for over a month from 19 individuals (0.74 for creatinine corrected and 0.80 for volumetric concentrations) showed an excellent reliability and notable interindividual variability. Among eight biomarkers measured in the same set of urine samples, allantoin was the predominant one, and it was positively and significantly correlated with urinary creatinine and other OSBs of lipids, proteins, and DNA. We suggest that urinary allantoin is a suitable biomarker of oxidative stress because of its requirement for simple and rapid analysis and long-term reliability/reproducibility as determined by high ICC values.

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Section: Introductionmentioning

confidence: 99%

Allantoin as a Marker of Oxidative Stress: Inter- and Intraindividual Variability in Urinary Concentrations in Healthy Individuals

Martinez-Moral

2019

Environ. Sci. Technol. Lett.

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“…Additionally, the correlation of uric acid and allantoin with c-IMT was independent of the above-mentioned risk factors, indicating that uric acid oxidation is occurring at the beginning of the atherosclerotic process and may have a causal role in disease progression. Of note, no positive correlation between allantoin and myeloperoxidase was found, indicating that, in this initial condition, the other two electron oxidants and other vascular peroxidases, including PXDN, might be leading to uric acid oxidation [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…Urate levels are positively associated with cardiovascular diseases [ 9 , 10 , 11 , 12 ], and several mechanisms point to a causal role for urate. This metabolite increases oxidative stress, decreases the availability of nitric oxide, causes endothelial dysfunction, promotes inflammation, upregulates the angiotensin system, and induces proliferation and migration of vascular smooth muscle cells [ 13 , 14 , 15 , 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

“…Considering the important role of PXDN in extracellular matrix formation and vascular endothelial homeostasis, we hypothesized that the oxidation of uric acid by PXDN could contribute to vascular disease by two mechanisms: (1) the oxidation of uric acid could divert the production of HOBr and collagen IV crosslink by the enzyme; (2) the production of urate free radical and its electrophilic-derived products could contribute to oxidative stress and alter the function of proteins that are targets for oxidation/uratylation [ 21 , 22 , 36 ]. Because urate has well-known effects on endothelial dysfunction, atherosclerosis, and cardiovascular diseases [ 9 , 11 , 37 , 38 ], we wondered whether the reaction of urate with PXDN could be one of the mechanisms for the harmful effect of uric acid in vascular tissue.…”

Section: Introductionmentioning

confidence: 99%

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Uric Acid Reacts with Peroxidasin, Decreases Collagen IV Crosslink, Impairs Human Endothelial Cell Migration and Adhesion

et al. 2022

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Uric acid is considered the main substrate for peroxidases in plasma. The oxidation of uric acid by human peroxidases generates urate free radical and urate hydroperoxide, which might affect endothelial function and explain, at least in part, the harmful effects of uric acid on the vascular system. Peroxidasin (PXDN), the most recent heme-peroxidase described in humans, catalyzes the formation of hypobromous acid, which mediates collagen IV crosslinks in the extracellular matrix. This enzyme has gained increasing scientific interest since it is associated with cardiovascular disease, cancer, and renal fibrosis. The main objective here was to investigate whether uric acid would react with PXDN and compromise the function of the enzyme in human endothelial cells. Urate decreased Amplex Red oxidation and brominating activity in the extracellular matrix (ECM) from HEK293/PXDN overexpressing cells and in the secretome of HUVECs. Parallelly, urate was oxidized to 5-hydroxyisourate. It also decreased collagen IV crosslink in isolated ECM from PFHR9 cells. Urate, the PXDN inhibitor phloroglucinol, and the PXDN knockdown impaired migration and adhesion of HUVECs. These results demonstrated that uric acid can affect extracellular matrix formation by competing for PXDN. The oxidation of uric acid by PXDN is likely a relevant mechanism in the endothelial dysfunction related to this metabolite.

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“…Uric acid is also abundant in other extracellular fluids and acts as a substrate for the neutrophil enzyme myeloperoxidase to produce the oxidants urate free radical and urate hydroperoxide. As a consequence, oxidation of uric acid favors a pro-oxidant environment and might have a causal role in vascular diseases [ [30] , [31] , [32] ] [ [30] , [31] , [32] ] [ [30] , [31] , [32] ]. In infection, the oxidation of uric acid by myeloperoxidase and prevention of HOCl formation is a putative cause of the lower ability of neutrophils to kill P. aeruginosa [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

Peroxiredoxin AhpC1 protects Pseudomonas aeruginosa against the inflammatory oxidative burst and confers virulence

et al. 2021

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Pseudomonas aeruginosa is an opportunistic bacterium in patients with cystic fibrosis and hospital acquired infections. It presents a plethora of virulence factors and antioxidant enzymes that help to subvert the immune system. In this study, we identified the 2-Cys peroxiredoxin, alkyl-hydroperoxide reductase C1 (AhpC1), as a relevant scavenger of oxidants generated during inflammatory oxidative burst and a mechanism of P. aeruginosa (PA14) escaping from killing. Deletion of AhpC1 led to a higher sensitivity to hypochlorous acid (HOCl, IC 50 3.2 ± 0.3 versus 19.1 ± 0.2 μM), hydrogen peroxide (IC 50 91.2 ± 0.3 versus 496.5 ± 6.4 μM) and the organic peroxide urate hydroperoxide. ΔahpC1 strain was more sensitive to the killing by isolated neutrophils and less virulent in a mice model of infection. All mice intranasally instilled with ΔahpC1 survived as long as they were monitored (15 days), whereas 100% wild-type and ΔahpC1 complemented with ahpC1 gene (Δ ahpC 1 attB : ahpC1 ) died within 3 days. A significantly lower number of colonies was detected in the lung and spleen of ΔahpC1 -infected mice. Total leucocytes, neutrophils, myeloperoxidase activity, pro-inflammatory cytokines, nitrite production and lipid peroxidation were much lower in lungs or bronchoalveolar liquid of mice infected with ΔahpC1 . Purified AhpC neutralized the inflammatory organic peroxide, urate hydroperoxide, at a rate constant of 2.3 ± 0.1 × 10 6 M −1 s −1 , and only the ΔahpC1 strain was sensitive to this oxidant. Incubation of neutrophils with uric acid, the urate hydroperoxide precursor, impaired neutrophil killing of wild-type but improved the killing of ΔahpC1 . Hyperuricemic mice presented higher levels of serum cytokines and succumbed much faster to PA14 infection when compared to normouricemic mice. In summary, ΔahpC1 PA14 presented a lower virulence, which was attributed to a poorer ability to neutralize the oxidants generated by inflammatory oxidative burst, leading to a more efficient killing by the host. The enzyme is particularly relevant in detoxifying the newly reported inflammatory organic peroxide, urate hydroperoxide.

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Allantoin as an independent marker associated with carotid intima-media thickness in subclinical atherosclerosis

Cited by 10 publications

References 19 publications

Allantoin as a Marker of Oxidative Stress: Inter- and Intraindividual Variability in Urinary Concentrations in Healthy Individuals

Allantoin as a Marker of Oxidative Stress: Inter- and Intraindividual Variability in Urinary Concentrations in Healthy Individuals

Uric Acid Reacts with Peroxidasin, Decreases Collagen IV Crosslink, Impairs Human Endothelial Cell Migration and Adhesion

Peroxiredoxin AhpC1 protects Pseudomonas aeruginosa against the inflammatory oxidative burst and confers virulence

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