Indoxyl sulfate in atherosclerosis

Lu, Cong; Wu, Li; Tang, Mu-Yao; Liu, Yifan; Liu, Lei; Liu, Xi-Ya; Zhang, Chun; Huang, Liang

doi:10.1016/j.toxlet.2023.07.001

Cited by 6 publications

(3 citation statements)

References 127 publications

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“…Uremic toxins produce persistent inflammation, oxidative stress, and endothelial dysfunction resulting in accelerated atherosclerosis [ 22 , 23 ]. Recently, the diverse atherogenic effects of IS [ 24 ] have been highlighted, and other authors have reported that the serum levels of PC are positively correlated with the occurrence and severity of atherosclerosis [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Uremic Toxins Induce THP-1 Monocyte Endothelial Adhesion and Migration through Specific miRNA Expression

Carmona,

Guerrero,

Muñoz-Castañeda

et al. 2023

IJMS

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Atherosclerosis is initiated by the activation of endothelial cells that allows monocyte adhesion and transmigration through the vascular wall. The accumulation of uremic toxins such as indoxyl sulphate (IS) and p-cresol (PC) has been associated with atherosclerosis. Currently, miRNAs play a crucial role in the regulation of monocyte activation, adhesion, and trans-endothelial migration. The aim of the present study is to evaluate the effect of IS and PC on monocyte adhesion and migration processes in monocytes co-cultured with endothelial cells as well as to determine the underlying mechanisms. The incubation of HUVECs and THP-1 cells with both IS and PC toxins resulted in an increased migratory capacity of THP-1 cells. Furthermore, the exposure of THP-1 cells to both uremic toxins resulted in the upregulation of BMP-2 and miRNAs-126-3p, -146b-5p, and -223-3p, as well as the activation of nuclear factor kappa B (NF-κB) and a decrease in its inhibitor IĸB. Uremic toxins, such as IS and PC, enhance the migratory and adhesion capacity of THP-1 cells to the vascular endothelium. These toxins, particularly PC, contribute significantly to uremia-associated vascular disease by increasing in THP-1 cells the expression of BMP-2, NF-κB, and key miRNAs associated with the development of atherosclerotic vascular diseases.

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Section: Discussionmentioning

confidence: 99%

Uremic Toxins Induce THP-1 Monocyte Endothelial Adhesion and Migration through Specific miRNA Expression

Carmona,

Guerrero,

Muñoz-Castañeda

et al. 2023

IJMS

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“…Of interest to this review are the two sulfonated PBUTs, indoxyl sulfate (IxS) and p -cresyl sulfate ( p CS), which have gained significant research interest in the last decade due to their toxicological impacts on serum accumulation ( Figure 1 ). We refer the readers to several excellent reviews on the toxicology of IxS and p CS (e.g., [ 6 , 14 , 15 , 16 , 17 , 18 , 19 ]), which are known to be associated with cardiovascular outcomes in CKD patients [ 20 ], colonic cancer [ 15 ], oxidative stress [ 21 ], and the progression of CKD [ 17 , 19 ]. Recently, Vanholder et al [ 6 ] have also ranked both IxS and p CS as uremic compounds of significant toxicological interest.…”

Section: Introductionmentioning

confidence: 99%

“…Both IxS and p CS are excreted into the urine via renal tubular secretion [ 25 ]. In patients with renal dysfunction, the accumulation of IxS and p CS may lead to the manifestation of toxicities in various organ and tissue systems (e.g., [ 6 , 14 , 15 , 16 , 17 , 18 , 19 ]). Further examples include significant correlations observed between urine IxS concentrations and urinary oxidative stress markers such as 15-isoprostane F 2t and pteridine in patients with type 2 diabetes mellitus [ 26 ] and elevated plasma p CS concentrations being associated with ischemic strokes in hemodialysis patients [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Liquid Chromatography-Mass Spectrometry Analytical Methods for the Quantitation of p-Cresol Sulfate and Indoxyl Sulfate in Human Matrices: Biological Applications and Diagnostic Potentials

Al-Dajani,

Hou,

Kiang

2024

Pharmaceutics

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Indoxyl sulfate (IxS) and p-cresyl sulfate (pCS) are toxic uremic compounds with documented pathological outcomes. This review critically and comprehensively analyzes the available liquid chromatography-mass spectrometry methods quantifying IxS and pCS in human matrices and the biological applications of these validated assays. Embase, Medline, PubMed, Scopus, and Web of Science were searched until December 2023 to identify assays with complete analytical and validation data (N = 23). Subsequently, citation analysis with PubMed and Scopus was utilized to identify the biological applications for these assays (N = 45). The extraction methods, mobile phase compositions, chromatography, and ionization methods were evaluated with respect to overall assay performance (e.g., sensitivity, separation, interference). Most of the assays focused on human serum/plasma, utilizing acetonitrile or methanol (with ammonium acetate/formate or formic/acetic acid), liquid–liquid extraction, reverse phase (e.g., C18) chromatography, and gradient elution for analyte separation. Mass spectrometry conditions were also consistent in the identified papers, with negative electrospray ionization, select multiple reaction monitoring transitions and deuterated internal standards being the most common approaches. The validated biological applications indicated IxS and/or pCS were correlated with renal disease progression and cardiovascular outcomes, with limited data on central nervous system disorders. Methods for reducing IxS and/or pCS concentrations were also identified (e.g., drugs, natural products, diet, dialysis, transplantation) where inconsistent findings have been reported. The clinical monitoring of IxS and pCS is gaining significant interest, and this review will serve as a useful compendium for scientists and clinicians.

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Berberine Inhibits Ferroptosis and Stabilizes Atherosclerotic Plaque through NRF2/SLC7A11/GPX4 Pathway

Wang,

Yu,

Zheng

et al. 2024

Chin. J. Integr. Med.

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Indoxyl sulfate in atherosclerosis

Cited by 6 publications

References 127 publications

Uremic Toxins Induce THP-1 Monocyte Endothelial Adhesion and Migration through Specific miRNA Expression

Uremic Toxins Induce THP-1 Monocyte Endothelial Adhesion and Migration through Specific miRNA Expression

Liquid Chromatography-Mass Spectrometry Analytical Methods for the Quantitation of p-Cresol Sulfate and Indoxyl Sulfate in Human Matrices: Biological Applications and Diagnostic Potentials

Berberine Inhibits Ferroptosis and Stabilizes Atherosclerotic Plaque through NRF2/SLC7A11/GPX4 Pathway

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