Ethylene Glycol Induced Hyperoxaluria Increases Plasma and Renal Tissue Asymmetrical Dimethylarginine in Rats: A New Pathogenetic Link in Hyperoxaluria Induced Disorders

Aydın, Hasan; Yencilek, Faruk; Mutlu, Nilgün; Çomunoglu, Nil Üstündag; Koyuncu, Hakan; Sarıca, Kemal

doi:10.1016/j.juro.2009.09.076

Cited by 11 publications

(9 citation statements)

References 28 publications

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“…Some recent studies reported a local relationship of endothelial nitric oxide synthase in experimentally induced hyperoxaluric animals [10]. But, in one of our recent studies, we demonstrated that hyperoxaluria induces both local and systemic endothelial dysfunction as shown by increased plasma Asymmetrical Di Methyl Arginine (ADMA) levels which is a measure of endothelial dysfunction [11].…”

Section: Introductionmentioning

confidence: 75%

“…Since urolithiasis is a systemic metabolic disorder, the idea of dysfunction in endothelium merits consideration. First study on this relationship was carried out by Aydin et al [11] they have shown that asymmetrical dimethyl arginine increased early in the hyperoxaluric mileu both in local renal tissue and systemic circulation. Linas and Repine had shown that renal proximal epithelial cell transport was controlled by nearby endothelial tissue [9].…”

Section: Discussionmentioning

confidence: 99%

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Ethylene Glycol Induced Hyperoxaluria Increases Circulating Endothelial Cells in Peripheral Blood: A Possible Link of Urolithiasis to Cardiovascular Diseases

Sari

Yencilek

Demirel

et al. 2018

ETUN

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The aim of this study was to establish the role of hyperoxaluria on endothelial dysfunction by using Circulating Endothelial Cells (CECs). A total of 24 Sprague Dowley rats have been included into study. Group IA, B and C (n=6 in each): Hyperoxaluria-induced group; Group II (n=6): Control group. Rats were euthanized after collection of 24-hour urine samples for the analysis of oxalate excretion either at 24 th hour (group A), 14 th day (group B) or 28 th day (group C) and blood samples were collected for the analysis of CECs. Rats in control group were euthanized after collecting 24-hour urine samples. CECs were determined via multicolor flow cytometric method with the help of rat anti-CD 146-PE antibodies together with CD31, CD45 and CD34 monoclonal antibodies. Compared to controls, the amount of CECs was found to be higher in hyperoxaluric group. Highest levels were achieved at day 14 (1.60±0.27, 1.93±0.42, and 1.20±0.20, 24-hour, 14-day and 28-day samples, respectively). The amount of CECs correlated positively with urinary oxalate excretion (p=0.002, r=0.679). Ethylene glycol-induced hyperoxaluria causes systemic endothelial dysfunction. This may contribute to the pathogenesis of increased risk of cardiovascular diseases in urolithiasis.

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Section: Introductionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Ethylene Glycol Induced Hyperoxaluria Increases Circulating Endothelial Cells in Peripheral Blood: A Possible Link of Urolithiasis to Cardiovascular Diseases

Sari

Yencilek

Demirel

et al. 2018

ETUN

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“…A possible role of vascular endothelium on stone formation through NOS on epithelium ion transport has been suggested previously [ 15 ]. Aydin [ 5 ] firstly showed the effect of endothelium on calcium oxalate (CaOx) stone formation and outlined an increased local and systemic ADMA in an ethylene glycol-induced hyperoxaluria rat model. ADMA, as an endogenous competitive inhibitor of NOS, has been linked to ED, atherosclerosis, and mortality in patients with peripheral arterial disease [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is considered a key element in the development of atherosclerosis cardiovascular disease and has been associated with systemic inflammatory disorders such as diabetes, obesity, or metabolic syndrome. Hyperoxaluria has also been reported to cause systemic ED both in animal models and cell culture studies [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Urolithiasis Develops Endothelial Dysfunction as a Clinical Feature

Medina

Martínez

Rosado³

et al. 2021

Antioxidants

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An increased risk of cardiovascular morbidity has been reported in lithiasic patients. In this context, endothelial dysfunction (ED), an earlier status of atherogenesis, has been identified in hyperoxaluria rat models of urolithiasis. Objective: The purpose of this study was to determine the endothelial vascular function in patients with urolithiasis in relation to systemic inflammatory, oxidative stress, and vascular function serum markers. Methods: A cross-sectional study was performed between 27 urolithiasic patients, matched for age and sex, with 27 healthy patients. Endothelial function was assessed by measuring flow-mediated dilation (Celermajer method). Fasting blood was collected to determine metabolic parameters (glucose and lipid profile), along with serum CRP, IL-6, MDA, ADMA, and VCAM-1. Results: Both the control and urolithiasis groups were homogenous in anthropometric, exploration, and general laboratory measures. Flow-mediated dilation (%FMD) was 11.85% (SE: 2.78) lower in the lithiasis group (p < 0.001). No significant differences were achieved between groups when CRP, IL-6, MDA, ADMA, and VCAM-1 were compared, although slightly higher values of CRP, ADMA, and VCAM-1 were detected in the lithiasic group. A correlation was not reached in any of the serum markers when they were related to flow-mediated values, although a slight negative correlation trend was observed in MDA, VCAM-1, and IL-6 values. Conclusions: Endothelial dysfunction constitutes an important disorder related to urolithiasis patients. It must be considered as an early feature responsible for future cardiovascular events. Our study did not find a significant association between inflammatory, oxidative stress, endothelial serum markers, and flow-mediated dilation.

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“…Recently, ED has been linked to urolithiasis through clinical and experimental studies [6][7][8][9]. The aim of this review is to summarize the current knowledge and the latest findings on the pathogenic mechanisms underlying endothelial dysfunction in urolithiasis, paying special attention to the role of the reactive oxygen species (ROS) as an underlying mechanism.…”

Section: Introductionmentioning

confidence: 99%

Endothelial Dysfunction: An Intermediate Clinical Feature between Urolithiasis and Cardiovascular Diseases

Medina

Muñoz

Rodríguez

et al. 2022

IJMS

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An epidemiological relationship between urolithiasis and cardiovascular diseases has extensively been reported. Endothelial dysfunction is an early pathogenic event in cardiovascular diseases and has been associated with oxidative stress and low chronic inflammation in hypertension, coronary heart disease, stroke or the vascular complications of diabetes and obesity. The aim of this study is to summarize the current knowledge about the pathogenic mechanisms of urolithiasis in relation to the development of endothelial dysfunction and cardiovascular morbidities. Methods: A non-systematic review has been performed mixing the terms “urolithiasis”, “kidney stone” or “nephrolithiasis” with “cardiovascular disease”, “myocardial infarction”, “stroke”, or “endothelial dysfunction”. Results: Patients with nephrolithiasis develop a higher incidence of cardiovascular disease with a relative risk estimated between 1.20 and 1.24 and also develop a higher vascular disease risk scores. Analyses of subgroups have rendered inconclusive results regarding gender or age. Endothelial dysfunction has also been strongly associated with urolithiasis in clinical studies, although no systemic serum markers of endothelial dysfunction, inflammation or oxidative stress could be clearly related. Analysis of urine composition of lithiasic patients also detected a higher expression of proteins related to cardiovascular disease. Experimental models of hyperoxaluria have also found elevation of serum endothelial dysfunction markers. Conclusions: Endothelial dysfunction has been strongly associated with urolithiasis and based on the experimental evidence, should be considered as an intermediate and changeable feature between urolithiasis and cardiovascular diseases. Oxidative stress, a key pathogenic factor in the development of endothelial dysfunction has been also pointed out as an important factor of lithogenesis. Special attention must be paid to cardiovascular morbidities associated with urolithiasis in order to take advantage of pleiotropic effects of statins, angiotensin receptor blockers and allopurinol.

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Ethylene Glycol Induced Hyperoxaluria Increases Plasma and Renal Tissue Asymmetrical Dimethylarginine in Rats: A New Pathogenetic Link in Hyperoxaluria Induced Disorders

Abstract: Increased systemic and local tissue asymmetrical dimethylarginine may help explain the pathogenetic mechanisms of hyperoxaluria induced disorders such as nephrolithiasis and atherosclerosis.

Cited by 11 publications

References 28 publications

Ethylene Glycol Induced Hyperoxaluria Increases Circulating Endothelial Cells in Peripheral Blood: A Possible Link of Urolithiasis to Cardiovascular Diseases

Ethylene Glycol Induced Hyperoxaluria Increases Circulating Endothelial Cells in Peripheral Blood: A Possible Link of Urolithiasis to Cardiovascular Diseases

Urolithiasis Develops Endothelial Dysfunction as a Clinical Feature

Endothelial Dysfunction: An Intermediate Clinical Feature between Urolithiasis and Cardiovascular Diseases

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