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Article ; Online: p-Cresyl Sulfate.

Gryp, Tessa / Vanholder, Raymond / Vaneechoutte, Mario / Glorieux, Griet

2017 Volume 9, Issue 2

Abstract: If chronic kidney disease (CKD) is associated with an impairment of kidney function, several uremic solutes are retained. Some of these exert toxic effects, which are called uremic toxins. ...

Abstract	If chronic kidney disease (CKD) is associated with an impairment of kidney function, several uremic solutes are retained. Some of these exert toxic effects, which are called uremic toxins.
MeSH term(s)	Animals ; Bacteria/metabolism ; Colon/microbiology ; Cresols/adverse effects ; Cresols/metabolism ; Dietary Proteins/metabolism ; Dysbiosis ; Fermentation ; Gastrointestinal Microbiome ; Humans ; Kidney/drug effects ; Kidney/metabolism ; Kidney/physiopathology ; Prognosis ; Protein Binding ; Renal Insufficiency, Chronic/chemically induced ; Renal Insufficiency, Chronic/metabolism ; Renal Insufficiency, Chronic/physiopathology ; Renal Insufficiency, Chronic/therapy ; Renal Replacement Therapy ; Risk Factors ; Sulfuric Acid Esters/adverse effects ; Sulfuric Acid Esters/metabolism
Chemical Substances	Cresols ; Dietary Proteins ; Sulfuric Acid Esters ; 4-cresol sulfate (56M34ZQY1S)
Language	English
Publishing date	2017-01-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2518395-3
ISSN	2072-6651 ; 2072-6651
ISSN (online)	2072-6651
ISSN	2072-6651
DOI	10.3390/toxins9020052
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Article ; Online: Associations of Indoxyl Sulfate and p-cresyl Sulfate with Serum Uncarboxylated Matrix γ-carboxyglutamate Protein in Chronic Kidney Disease Patients.

Tang, Xiaofang / Liu, Di / Xia, Ming / Liu, Yu / Liu, Hong

Current medicinal chemistry

2024

Abstract: Background: Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are two important protein-bound uremic ... The serum level of ucMPG was associated with total IS (r = 0.456, p < 0.001) and total PCS (r =0.413, p < 0 ... of IS (β = 0.442, p <0.001), but not the level of PCS concentrations after adjusting ...

Abstract	Background: Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are two important protein-bound uremic retention solutes. Increased serum levels of IS and PCS are associated with cardiovascular calcification. Matrix γ-carboxyglutamate protein (MGP) is a potent inhibitor of vascular calcification and inactivated uncarboxylated MGP (ucMGP) is related to vascular calcification. Nevertheless, whether serum levels of IS and PCS are associated with the serum ucMGP level in chronic kidney disease (CKD) patients with different stages is unknown. Method: This cross-sectional study enrolled 90 patients in different stages of chronic kidney disease. Serum levels of IS and PCS were determined. The serum concentration of ucMGP was measured with an enzyme-linked immunosorbent assay. Independent associations between serum total IS and PCS with ucMGP were evaluated. Results: The mean serum level of ucMGP in participants of this study is 10.78±5.22 μg/mL. Serum levels of the two above-mentioned uremic toxins and ucMGP were elevated commensurately with deteriorating renal function. The serum level of ucMPG was associated with total IS (r = 0.456, p < 0.001) and total PCS (r =0.413, p < 0.001) levels. Multiple linear regression analysis showed that ucMGP was significantly related to levels of IS (β = 0.442, p <0.001), but not the level of PCS concentrations after adjusting for other confounding variables. Conclusion: Our study showed that a higher serum IS level was independently associated with ucMGP in deteriorating CKD. Therefore, it would be worthwhile to investigate the effect of IS on ucMGP in the pathogenesis of vascular calcification in future studies.
Language	English
Publishing date	2024-01-12
Publishing country	United Arab Emirates
Document type	Journal Article
ZDB-ID	1319315-6
ISSN	1875-533X ; 0929-8673
ISSN (online)	1875-533X
ISSN	0929-8673
DOI	10.2174/0109298673272856231225173757
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Article ; Online: P-cresyl sulfate causes mitochondrial hyperfusion in H9C2 cardiomyoblasts.

Huang, Tien-Hung / Yip, Hon-Kan / Sun, Cheuk-Kwan / Chen, Yi-Ling / Yang, Chih-Chao / Lee, Fan-Yen

Journal of cellular and molecular medicine

2020 Volume 24, Issue 15, Page(s) 8379–8390

Abstract: Increased circulating level of uraemic solute p-cresyl sulphate (PCS) in patients ...

Abstract	Increased circulating level of uraemic solute p-cresyl sulphate (PCS) in patients with chronic kidney disease (CKD) is known to increase myocardial burden relevant to mitochondrial abnormalities. This study aimed at investigating mitochondrial response to PCS in H9C2 cardiomyoblasts. H9C2 cardiomyoblasts were treated with four different concentrations of PCS (3.125, 6.25, 12.5 and 25.0 µg/mL) to study the changes in cell proliferation, cell size and mitochondrial parameters including morphology, respiration, biogenesis and membrane potential. The lowest effective dose of PCS (6.25 µg/mL) induced mitochondrial hyperfusion with enhanced mitochondrial connectivity, mitochondrial oxygen consumption rates, mitochondrial mass, mitochondrial DNA copy number and increased volume of cardiomyoblasts. After PCS treatment, phosphorylation of energy-sensing adenosine monophosphate-activated protein kinase (AMPK) was increased without induction of apoptosis. In contrast, mitochondrial mass was recovered after AMPK silencing. Additionally, mitochondrial hyperfusion and cell volume were reversed after cessation of PCS treatment. The results of the present study showed that low-level PCS not only caused AMPK-dependent mitochondrial hyperfusion but also induced cell enlargement in H9C2 cardiomyoblasts in vitro.
MeSH term(s)	AMP-Activated Protein Kinases/metabolism ; Animals ; Apoptosis/drug effects ; Cell Line ; Cell Proliferation/drug effects ; Cresols/pharmacology ; Membrane Potential, Mitochondrial/drug effects ; Mitochondria/drug effects ; Mitochondria/metabolism ; Myocytes, Cardiac/drug effects ; Myocytes, Cardiac/metabolism ; Oxygen Consumption/drug effects ; Rats ; Sulfuric Acid Esters/pharmacology
Chemical Substances	Cresols ; Sulfuric Acid Esters ; 4-cresol sulfate (56M34ZQY1S) ; AMP-Activated Protein Kinases (EC 2.7.11.31)
Language	English
Publishing date	2020-07-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2074559-X
ISSN	1582-4934 ; 1582-4934 ; 1582-1838
ISSN (online)	1582-4934
ISSN	1582-4934 ; 1582-1838
DOI	10.1111/jcmm.15303
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Zs.A 5752: Show issues

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Article ; Online: Renocardiac Effects of p-Cresyl Sulfate Administration in Acute Kidney Injury Induced by Unilateral Ischemia and Reperfusion Injury

Falconi, Carlos Alexandre / Fogaça-Ruiz, Fernanda / da Silva, Jéssica Verônica / Neres-Santos, Raquel Silva / Sanz, Carmen Lucía / Nakao, Lia Sumie / Stinghen, Andréa Emília Marques / Junho, Carolina Victoria Cruz / Carneiro-Ramos, Marcela Sorelli

Toxins

2023 Volume 15, Issue 11

Abstract: ... and the retention of uremic toxins like p-cresyl sulfate (PCS) remain incompletely understood ...

Abstract	The precise mechanisms underlying the cardiovascular complications due to acute kidney injury (AKI) and the retention of uremic toxins like p-cresyl sulfate (PCS) remain incompletely understood. The objective of this study was to evaluate the renocardiac effects of PCS administration in animals subjected to AKI induced by ischemia and reperfusion (IR) injury. C57BL6 mice were subjected to distinct protocols: (i) administration with PCS (20, 40, or 60 mg/L/day) for 15 days and (ii) AKI due to unilateral IR injury associated with PCS administration for 15 days. The 20 mg/L dose of PCS led to a decrease in renal mass, an increase in the gene expression of Cystatin C and kidney injury molecule 1 (KIM-1), and a decrease in the α-actin in the heart. During AKI, PCS increased the renal injury biomarkers compared to control; however, it did not exacerbate these markers. Furthermore, PCS did not enhance the cardiac hypertrophy observed after 15 days of IR. An increase, but not potentialized, in the cardiac levels of interleukin (IL)-1β and IL-6 in the IR group treated with PCS, as well as in the injured kidney, was also noticed. In short, PCS administration did not intensify kidney injury, inflammation, and cardiac outcomes after AKI.
MeSH term(s)	Animals ; Mice ; Sulfates ; Mice, Inbred C57BL ; Kidney ; Acute Kidney Injury ; Ischemia/complications ; Reperfusion Injury/complications
Chemical Substances	Sulfates
Language	English
Publishing date	2023-11-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518395-3
ISSN	2072-6651 ; 2072-6651
ISSN (online)	2072-6651
ISSN	2072-6651
DOI	10.3390/toxins15110649
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Article ; Online: p-Cresyl Sulfate

Tessa Gryp / Raymond Vanholder / Mario Vaneechoutte / Griet Glorieux

Toxins, Vol 9, Iss 2, p

2017 Volume 52

Abstract: ... solutes are retained. Some of these exert toxic effects, which are called uremic toxins. p-Cresyl sulfate ...

Abstract	If chronic kidney disease (CKD) is associated with an impairment of kidney function, several uremic solutes are retained. Some of these exert toxic effects, which are called uremic toxins. p-Cresyl sulfate (pCS) is a prototype protein-bound uremic toxin to which many biological and biochemical (toxic) effects have been attributed. In addition, increased levels of pCS have been associated with worsening outcomes in CKD patients. pCS finds its origin in the intestine where gut bacteria metabolize aromatic amino acids, such as tyrosine and phenylalanine, leading to phenolic end products, of which pCS is one of the components. In this review we summarize the biological effects of pCS and its metabolic origin in the intestine. It appears that, according to in vitro studies, the intestinal bacteria generating phenolic compounds mainly belong to the families Bacteroidaceae, Bifidobacteriaceae, Clostridiaceae, Enterobacteriaceae, Enterococcaceae, Eubacteriaceae, Fusobacteriaceae, Lachnospiraceae, Lactobacillaceae, Porphyromonadaceae, Staphylococcaceae, Ruminococcaceae, and Veillonellaceae. Since pCS remains difficult to remove by dialysis, the gut microbiota could be a future target to decrease pCS levels and its toxicity, even at earlier stages of CKD, aiming at slowing down the progression of the disease and decreasing the cardiovascular burden.
Keywords	p-cresyl sulfate ; intestinal microbiota ; chronic kidney disease ; Medicine ; R
Subject code	610
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Possible Effects of Uremic Toxins p-Cresol, Indoxyl Sulfate, p-Cresyl Sulfate on the Development and Progression of Colon Cancer in Patients with Chronic Renal Failure.

Di Paola, Rossella / De, Ananya / Izhar, Raafiah / Abate, Marianna / Zappavigna, Silvia / Capasso, Anna / Perna, Alessandra F / La Russa, Antonella / Capasso, Giovambattista / Caraglia, Michele / Simeoni, Mariadelina

Genes

2023 Volume 14, Issue 6

Abstract: ... and p-Cresyl Sulfate (p-CS). Since these metabolites are normally eliminated in the urine, they tend ... accumulation in the gut and in the blood of several substances, such as p-Cresol (p-C), Indoxyl Sulfate (IS ... to accumulate in the blood of CKD patients proportionally to renal impairment. P-CS, IS and p-C play ...

Abstract	Chronic kidney disease (CKD) induces several systemic effects, including the accumulation and production of uremic toxins responsible for the activation of various harmful processes. Gut dysbiosis has been widely described in CKD patients, even in the early stages of the disease. The abundant discharge of urea and other waste substances into the gut favors the selection of an altered intestinal microbiota in CKD patients. The prevalence of bacteria with fermentative activity leads to the release and accumulation in the gut and in the blood of several substances, such as p-Cresol (p-C), Indoxyl Sulfate (IS) and p-Cresyl Sulfate (p-CS). Since these metabolites are normally eliminated in the urine, they tend to accumulate in the blood of CKD patients proportionally to renal impairment. P-CS, IS and p-C play a fundamental role in the activation of various pro-tumorigenic processes, such as chronic systemic inflammation, the increase in the production of free radicals and immune dysfunction. An up to two-fold increase in the incidence of colon cancer development in CKD has been reported in several studies, although the pathogenic mechanisms explaining this compelling association have not yet been described. Based on our literature review, it appears likely the hypothesis of a role of p-C, IS and p-CS in colon cancer development and progression in CKD patients.
MeSH term(s)	Humans ; Indican ; Uremic Toxins ; Sulfates ; Kidney Failure, Chronic ; Renal Insufficiency, Chronic/metabolism ; Colonic Neoplasms ; Inflammation
Chemical Substances	Indican (N187WK1Y1J) ; Uremic Toxins ; 4-cresol (1MXY2UM8NV) ; Sulfates ; cresol (GF3CGH8D7Z)
Language	English
Publishing date	2023-06-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14061257
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Article ; Online: p-Cresyl Sulfate Predicts Ischemic Stroke among Patients on Hemodialysis

Xiao Tan / Jianzhou Zou / Fangfang Xiang / Pan Zhang / Bo Shen / Yaqiong Wang / Xiaoqiang Ding / Xuesen Cao

Disease Markers, Vol

A Prospective Cohort Study

2022 Volume 2022

Abstract: ... at elucidating the association between p-cresyl sulfate and the risk of ischemic stroke in hemodialysis patients ... divided into 2 groups based on plasma p-cresyl sulfate level. The primary end point was the first episode ... of ischemic stroke during follow-up. The association between p-cresyl sulfate and ischemic stroke incidence ...

Abstract	Background and Purpose. Hemodialysis patients face a higher risk of ischemic stroke. p-Cresyl sulfate is a typical protein-bound uremic toxin that contributes to chronic kidney disease and cardiovascular disease progression, as well as mortality in hemodialysis patients. The present study was aimed at elucidating the association between p-cresyl sulfate and the risk of ischemic stroke in hemodialysis patients. Method. Patients on hemodialysis over 6 months were enrolled in this prospective cohort study and were divided into 2 groups based on plasma p-cresyl sulfate level. The primary end point was the first episode of ischemic stroke during follow-up. The association between p-cresyl sulfate and ischemic stroke incidence was analyzed by Kaplan-Meier method and Cox proportional hazard model. Results. 220 patients were enrolled in this study. 44 patients experienced episodes of first ischemic stroke during follow-up for 87.8 (47.6-119.5) months. Kaplan-Meier analysis demonstrated that the incidence of ischemic stroke in the high p-cresyl sulfate group was significantly higher than that in the low p-cresyl sulfate group (Log-Rank P=0.007). Cox regression analysis as well proved that p-cresyl sulfate level was significantly associated with the first incidence of ischemic stroke (HR (hazard ratio) 2.332, 95% CI (95% confidence interval) 1.236-4.399, P=0.009). After being adjusted for other confounding risk factors, the results persisted significant (model 11: HR 2.061, 95% CI 1.030-4.125, P=0.041). Conclusion. Plasma p-cresyl sulfate predicts the first incidence of ischemic stroke in hemodialysis patients.
Keywords	Medicine (General) ; R5-920
Subject code	616
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Contribution of Hypoalbuminemia and Anemia to the Prognostic Value of Plasma p-Cresyl Sulfate and p-Cresyl Glucuronide for Cardiovascular Outcome in Chronic Kidney Disease.

Verbeke, Francis / Vanholder, Raymond / Van Biesen, Wim / Glorieux, Griet

Journal of personalized medicine

2022 Volume 12, Issue 8

Abstract: ... cresyl sulfate (pCS) and p-cresyl glucuronide (pCG) and their predictive value for cardiovascular ... by serum albumin and hemoglobin. The potential association of serum albumin and hemoglobin with free levels of p ...

Abstract	Free plasma concentrations of protein-bound uremic toxins (PBUTs) may be influenced by serum albumin and hemoglobin. The potential association of serum albumin and hemoglobin with free levels of p-cresyl sulfate (pCS) and p-cresyl glucuronide (pCG) and their predictive value for cardiovascular morbidity and mortality were explored. A total of 523 non-dialysis chronic kidney disease (CKD) stages G1-G5 patients were prospectively followed for the occurrence of fatal or non-fatal cardiovascular events over a 5.5-year period. A negative correlation was found between albumin and between hemoglobin, and both total and free pCS and pCG. In multiple linear regression, PBUTs were negatively associated with eGFR (estimated glomerular filtration rate) and hemoglobin but not albumin. In multivariate Cox regression analysis, albumin was a predictor of outcome, independent of pCS and pCG, without interactions between albumin and pCS or pCG. The relation of low hemoglobin with adverse outcome was lost when albumin was entered into the model. Lower concentrations of pCS and pCG are associated with higher serum albumin and hemoglobin. This may indicate that there are two pathways in the blood that potentially contribute to attenuating the vasculotoxic effects of these PBUTs. The association of PBUTs with cardiovascular risk is not explained by albumin levels, which remains a strong and independent predictor for adverse outcome.
Language	English
Publishing date	2022-07-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm12081239
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Article ; Online: p-Cresyl Sulfate Predicts Ischemic Stroke among Patients on Hemodialysis: A Prospective Cohort Study.

Tan, Xiao / Zou, Jianzhou / Xiang, Fangfang / Zhang, Pan / Shen, Bo / Wang, Yaqiong / Ding, Xiaoqiang / Cao, Xuesen

Disease markers

2022 Volume 2022, Page(s) 1358419

Abstract: ... were divided into 2 groups based on plasma p-cresyl sulfate level. The primary end point was the first ... episode of ischemic stroke during follow-up. The association between p-cresyl sulfate and ischemic stroke ... in the high p-cresyl sulfate group was significantly higher than that in the low p-cresyl sulfate group (Log ...

Abstract	Method: Patients on hemodialysis over 6 months were enrolled in this prospective cohort study and were divided into 2 groups based on plasma p-cresyl sulfate level. The primary end point was the first episode of ischemic stroke during follow-up. The association between p-cresyl sulfate and ischemic stroke incidence was analyzed by Kaplan-Meier method and Cox proportional hazard model. Results: 220 patients were enrolled in this study. 44 patients experienced episodes of first ischemic stroke during follow-up for 87.8 (47.6-119.5) months. Kaplan-Meier analysis demonstrated that the incidence of ischemic stroke in the high p-cresyl sulfate group was significantly higher than that in the low p-cresyl sulfate group (Log-Rank Conclusion: Plasma p-cresyl sulfate predicts the first incidence of ischemic stroke in hemodialysis patients.
MeSH term(s)	Adult ; Aged ; Cohort Studies ; Cresols/blood ; Female ; Humans ; Incidence ; Ischemic Stroke/epidemiology ; Male ; Middle Aged ; Predictive Value of Tests ; Prospective Studies ; Renal Dialysis ; Sulfuric Acid Esters/blood
Chemical Substances	Cresols ; Sulfuric Acid Esters ; 4-cresol sulfate (56M34ZQY1S)
Language	English
Publishing date	2022-01-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	604951-5
ISSN	1875-8630 ; 0278-0240
ISSN (online)	1875-8630
ISSN	0278-0240
DOI	10.1155/2022/1358419
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Zs.A 1856: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Curcumin enhances p-cresyl sulfate-induced cytotoxic effects on renal tubular cells.

Wei, Chyou-Wei / Wu, Tsai-Kun / Wu, Shu-Cing / Chen, Yi-Lin / Pan, Ying-Ru / Chien, Yi-Chung / Wu, Jia-Yan / Yu, Yung-Lung / Yiang, Giou-Teng

International journal of medical sciences

2022 Volume 19, Issue 7, Page(s) 1138–1146

Abstract: Indoxyl sulfate (IS) and p-cresyl sulfate (PCS), protein-bound uremic toxins, can induce ...

Abstract	Indoxyl sulfate (IS) and p-cresyl sulfate (PCS), protein-bound uremic toxins, can induce oxidative stress and cause renal disease progression. However, the different cytotoxic effects on renal cells between IS and PCS are not stated. Due to uremic toxins are generally found in CKD patients, the mechanisms of uremic toxins-induced renal injury are required to study. Curcumin has anti-oxidant, anti-inflammatory and anti-apoptotic effects which may be potential used to protect against renal damage. In contrast, curcumin also exert cytotoxic effects on various cells. In addition, curcumin may reduce or enhance cytotoxicity combined with different chemicals treatments. However, whether curcumin may influence uremic toxins-induced renal injury is unclear. The goal of this study is to compare the different cytotoxic effects on renal cells between IS and PCS treatment, as well as the synergistic or antagonistic effects by combination treatments with curcumin and PCS. Our experimental result shows the PCS exerts a stronger antiproliferative effect on renal tubular cells than IS treatment. In addition, our study firstly demonstrates that curcumin enhances PCS-induced cell cytotoxicity through caspase-dependent apoptotic pathway and cell cycle alteration.
MeSH term(s)	Cresols/metabolism ; Curcumin/pharmacology ; Curcumin/therapeutic use ; Humans ; Indican/metabolism ; Indican/toxicity ; Kidney/metabolism ; Renal Insufficiency, Chronic/metabolism ; Sulfates ; Sulfuric Acid Esters/metabolism ; Sulfuric Acid Esters/toxicity
Chemical Substances	Cresols ; Sulfates ; Sulfuric Acid Esters ; Curcumin (IT942ZTH98) ; Indican (N187WK1Y1J)
Language	English
Publishing date	2022-06-27
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2151424-0
ISSN	1449-1907 ; 1449-1907
ISSN (online)	1449-1907
ISSN	1449-1907
DOI	10.7150/ijms.72646
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