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indoxyl sulfate

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https://www.readbyqxmd.com/read/29222397/indoxyl-sulfate-upregulates-liver-p-glycoprotein-expression-and-activity-through-aryl-hydrocarbon-receptor-signaling
#1
Tacy Santana Machado, Stéphane Poitevin, Pascale Paul, Nathalie McKay, Noémie Jourde-Chiche, Tristan Legris, Annick Mouly-Bandini, Françoise Dignat-George, Philippe Brunet, Rosalinde Masereeuw, Stéphane Burtey, Claire Cerini
In patients with CKD, not only renal but also, nonrenal clearance of drugs is altered. Uremic toxins could modify the expression and/or activity of drug transporters in the liver. We tested whether the uremic toxin indoxyl sulfate (IS), an endogenous ligand of the transcription factor aryl hydrocarbon receptor, could change the expression of the following liver transporters involved in drug clearance: SLC10A1, SLC22A1, SLC22A7, SLC47A1, SLCO1B1, SLCO1B3, SLCO2B1, ABCB1, ABCB11, ABCC2, ABCC3, ABCC4, ABCC6, and ABCG2 We showed that IS increases the expression and activity of the efflux transporter P-glycoprotein (P-gp) encoded by ABCB1 in human hepatoma cells (HepG2) without modifying the expression of the other transporters...
December 8, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29203210/indoxyl-sulfate-upregulates-the-cannabinoid-type-1-receptor-gene-via-an-atf3-c-jun-complex-mediated-signaling-pathway-in-the-model-of-uremic-cardiomyopathy
#2
Yu-Juei Hsu, Shih-Che Hsu, Yung-Lung Chang, Shih-Ming Huang, Chun-Che Shih, Chien-Sung Tsai, Chih-Yuan Lin
BACKGROUND: The risk of cardiovascular disease is notably increased in patients with chronic kidney disease (CKD) and cannabinoid receptor type 1 (CB1R) plays an important role in the development of uremic cardiomyopathy. However, the molecular mechanism underlying the uremic toxin-induced upregulation of CB1R remains elusive. METHODS: The expression of the ATF3/c-Jun complex and CB1R in both in vivo and in vitro models of CKD were measured. We also determined the impact of the ATF3/c-Jun complex on CB1R expression by transfecting H9c2 cells with dominant negative mutants of ATF3 or c-Jun...
December 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/29195902/indoxyl-sulfate-accelerates-vascular-smooth-muscle-cell-calcification-via-microrna-29b-dependent-regulation-of-wnt-%C3%AE-catenin-signaling
#3
Han Zhang, Jing Chen, Ziyan Shen, Yulu Gu, Linghan Xu, Jiachang Hu, Xiaoyan Zhang, Xiaoqiang Ding
Vascular calcification (VC) is a very common phenomenon in patients with chronic kidney disease(CKD) and it increases the incidence of cardiovascular disease and leads to high mortality in CKD patients. It has been reported that some microRNAs (miRs) play roles in vascular calcification as an epigenetic regulator. Indoxyl sulfate (IS) is a protein-bound uremic toxin which has been proven as one of the major risk factors of cardiovascular disease in CKD. Here we investigated whether microRNA-29b (miR-29b) is involved in IS-induced vascular calcification...
November 28, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29169110/disorder-of-gut-amino-acids-metabolism-during-ckd-progression-is-related-with-gut-microbiota-dysbiosis-and-metagenome-change
#4
Yang Liu, Jianping Li, Jingao Yu, Yingyi Wang, Jingbo Lu, Er-Xin Shang, Zhenhua Zhu, Jianming Guo, Jinao Duan
Chronic kidney disease (CKD) is a worldwide public health problem. Uremic retention solutes such as indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are accumulated in CKD patients and are associated with the incidence of CKD progression. Amino acids are the major precursors of uremic retention solutes in gut. The dynamic change of amino acid metabolism in the gut during CKD progression has not been reported previously. In this paper, we studied the dynamic change of gut IS/PCS precursor and amino acid metabolism profile during CKD progression in 5/6 nephrectomized (5/6Nx) rats model...
November 15, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29167170/canagliflozin-reduces-plasma-uremic-toxins-and-alters-the-intestinal-microbiota-composition-in-a-chronic-kidney-disease-mouse-model
#5
Eikan Mishima, Shinji Fukuda, Yoshitomi Kanemitsu, Daisuke Saigusa, Chikahisa Mukawa, Kei Asaji, Yotaro Matsumoto, Hiroki Tsukamoto, Tatsuki Tachikawa, Tomoya Tsukimi, Noriko N Fukuda, Hsin-Jung Ho, Koichi Kikuchi, Chitose Suzuki, Fumika Nanto, Takehiro Suzuki, Sadayoshi Ito, Tomoyoshi Soga, Yoshihisa Tomioka, Takaaki Abe
Accumulation of uremic toxins, which exert deleterious effects in chronic kidney disease, is influenced by the intestinal environment; the microbiota contributes to the production of representative uremic toxins including p-cresyl sulfate and indoxyl sulfate. Canagliflozin is a sodium/glucose co-transporter (SGLT) 2 inhibitor, and it also exerts a modest inhibitory effect on SGLT1. The inhibition of intestinal SGLT1 can influence the gastrointestinal environment. We examined the effect of canagliflozin on the accumulation of uremic toxins in chronic kidney disease using adenine-induced renal failure mice...
November 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29153138/p-cresol-sulfate-and-indoxyl-sulfate-some-clouds-are-gathering-in-the-uremic-toxin%C3%A2-sky
#6
Pieter Evenepoel, Griet Glorieux, Bjorn Meijers
An increasing body of experimental and clinical evidence suggests that p-cresol sulfate and indoxyl sulfate contribute to the high cardiovascular burden in patients with chronic kidney disease. In a post hoc analysis on the HEMO trial, Shafi et al. failed to confirm an association between total p-cresol sulfate and indoxyl sulfate and cardiovascular outcomes in dialysis patients. Analytical issues and case-mix may explain the discrepant findings.
December 2017: Kidney International
https://www.readbyqxmd.com/read/29151180/from-bench-to-the-hemodialysis-clinic-protein-bound-uremic-toxins-modulate-nf-%C3%AE%C2%BAb-nrf2-expression
#7
Milena B Stockler-Pinto, Christophe O Soulage, Natália A Borges, Ludmila F M F Cardozo, Carla J Dolenga, Lia S Nakao, Roberto Pecoits-Filho, Denis Fouque, Denise Mafra
PURPOSE: Uremic toxins produced by gut microbiota (indoxyl sulfate-IS, p-cresyl sulfate-p-CS, and indole-3-acetic acid-IAA) accumulate in hemodialysis (HD) patients and exhibit potent inflammatory effects. However, the impact of these toxins on nuclear E2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB) expression in HD patients remains poorly defined. The aim of this study was to evaluate the association between uremic toxins and Nrf2/NF-κB expression in vitro (RAW 264.7 macrophage-like cells) and in peripheral blood mononuclear cells from HD patients...
November 18, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/29151105/eryptosis-the-neglected-cause-of-anemia-in-end-stage-renal-disease
#8
Florian Lang, Rosi Bissinger, Majed Abed, Ferruh Artunc
End stage renal disease (ESRD) invariably leads to anemia which has been mainly attributed to compromised release of erythropoietin from the defective kidneys with subsequent impairment of erythropoiesis. However, erythropoietin replacement only partially reverses anemia pointing to the involvement of additional mechanisms. As shown more recently, anemia of ESRD is indeed in large part a result of accelerated erythrocyte loss due to suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the cell surface...
October 23, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29137321/the-role-of-indoxyl-sulfate-in-renal-anemia-in-patients-with-chronic-kidney-disease
#9
Chih-Jen Wu, Cheng-Yi Chen, Thung-S Lai, Pei-Chen Wu, Chih-Kuang Chuang, Fang-Ju Sun, Hsuan-Liang Liu, Han-Hsiang Chen, Hung-I Yeh, Chih-Sheng Lin, Cheng-Jui Lin
Renal anemia is a common complication in patients with advanced chronic kidney disease. In vitro studies have shown that indoxyl sulfate decreases erythropoietin production. Whether this effect is seen in vivo remains unclear. Our goal was to explore the role of indoxyl sulfate in renal anemia. We found serum indoxyl sulfate levels are significantly and negatively associated with erythropoietin levels in human. A multiple stepwise linear regression analyses after adjustment for other independent parameters revealed that free indoxyl sulfate, and total indoxyl sulfate were significantly associated with erythropoietin levels...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29107962/apoptosis-signal-regulating-kinase-1-inhibition-attenuates-cardiac-hypertrophy-and-cardiorenal-fibrosis-induced-by-uremic-toxins-implications-for-cardiorenal-syndrome
#10
Feby Savira, Longxing Cao, Ian Wang, Wendi Yang, Kevin Huang, Yue Hua, Beat M Jucker, Robert N Willette, Li Huang, Henry Krum, Zhiliang Li, Qiang Fu, Bing Hui Wang
Intracellular accumulation of protein-bound uremic toxins in the setting of cardiorenal syndrome leads to adverse effects on cardiorenal cellular functions, where cardiac hypertrophy and cardiorenal fibrosis are the hallmarks. In this study, we sought to determine if Apoptosis Signal-Regulated Kinase 1 (ASK1), an upstream regulator of cellular stress response, mediates cardiac hypertrophy and cardiorenal fibrosis induced by indoxyl sulfate (IS) and p-cresol sulfate (PCS) in vitro, and whether ASK1 inhibition is beneficial to ameliorate these cellular effects...
2017: PloS One
https://www.readbyqxmd.com/read/29100619/indoxyl-3-sulfate-inhibits-maturation-and-activation-of-human-monocyte-derived-dendritic-cells
#11
Sakhila Ghimire, Carina Matos, Massimiliano Caioni, Daniela Weber, Katrin Peter, Ernst Holler, Marina Kreutz, Kathrin Renner
Indole is produced from l-tryptophan by commensal bacteria and further metabolized to indoxyl 3-sulfate (I3S) in the liver. Physiologic concentrations of I3S are related to a lower risk to develop graft versus host disease in allogeneic stem cell transplanted patients pointing towards an immunoregulatory function of I3S. Here we investigated the impact of I3S on the maturation of human monocyte-derived dendritic cells (DCs). Even pathophysiologic concentrations of I3S did not affect viability of mature DCs, but I3S decreased the expression of co-stimulatory molecules such as CD80 and CD86 on mature DCs...
October 6, 2017: Immunobiology
https://www.readbyqxmd.com/read/29100420/protein-bound-uremic-toxins-impaired-mitochondrial-dynamics-and-functions
#12
Chiao-Yin Sun, Mei-Ling Cheng, Heng-Chih Pan, Jia-Hung Lee, Chin-Chan Lee
Protein-bound uremic toxins, indoxyl sulfate and p-cresol sulfate, increase oxidative stress and adversely affect chronic kidney disease progression and cardiovascular complications. In this study, we examined whether mitochondria are the target of indoxyl sulfate and p-cresol sulfate intoxication in vivo and in vitro. The kidneys of 10-week-old male B-6 mice with ½-nephrectomy treated with indoxyl sulfate and p-cresol sulfate were used for the animal study. Cultured human renal tubular cells were used for the in vitro study...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29097715/carbon-adsorbents-with-dual-porosity-for-efficient-removal-of-uremic-toxins-and-cytokines-from-human-plasma
#13
D Pavlenko, D Giasafaki, G Charalambopoulou, E van Geffen, K G F Gerritsen, T Steriotis, D Stamatialis
The number of patients with chronic kidney disease increases while the number of available donor organs stays at approximately the same level. Unavoidable accumulation of the uremic toxins and cytokines for these patients comes as the result of malfunctioning kidneys and their high levels in the blood result in high morbidity and mortality. Unfortunately, the existing methods, like hemodialysis and hemofiltration, provide only partial removal of uremic toxins and/or cytokines from patients' blood. Consequently, there is an increasing need for the development of the extracorporeal treatments which will enable removal of broad spectrum of uremic toxins that are usually removed by healthy kidneys...
November 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29094331/pterostilbene-protects-against-uraemia-serum-induced-endothelial-cell-damage-via-activation-of-keap1-nrf2-ho-1-signaling
#14
Zhi-Wei Chen, Hai-Feng Miu, Hui-Ping Wang, Zhi-Niu Wu, Wen-Juan Wang, Yu-Jing Ling, Xiao-Hui Xu, Hai-Jian Sun, Xia Jiang
Chronic kidney disease causes uremia-related endothelial cell dysfunction associated with high risk for cardiovascular diseases. The vascular endothelium is permanently exposed to uraemic toxins including indoxyl sulfate, which provokes endothelial damage in subjects with end-stage renal disease. Pterostilbene (PT) is identified to be homologous derivative of resveratrol and exerts antioxidant and anti-inflammatory actions. However, the effects of PT on uraemic serum-induced endothelial cell damage have not been elucidated...
November 1, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/29058056/gut-microbiota-contribute-to-age-related-changes-in-skeletal-muscle-size-composition-and-function-biological-basis-for-a-gut-muscle-axis
#15
REVIEW
Gregory J Grosicki, Roger A Fielding, Michael S Lustgarten
Skeletal muscle is a highly plastic tissue that plays a central role in human health and disease. Aging is associated with a decrease in muscle mass and function (sarcopenia) that is associated with a loss of independence and reduced quality of life. Gut microbiota, the bacteria, archaea, viruses, and eukaryotic microbes residing in the gastrointestinal tract are emerging as a potential contributor to age-associated muscle decline. Specifically, advancing age is characterized by a dysbiosis of gut microbiota that is associated with increased intestinal permeability, facilitating the passage of endotoxin and other microbial products (e...
October 20, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/29032117/protective-effects-of-salvia-miltiorrhiza-on-adenine-induced-chronic-renal-failure-by-regulating-the-metabolic-profiling-and-modulating-the-nadph-oxidase-ros-erk-and-tgf-%C3%AE-smad-signaling-pathways
#16
Hongdie Cai, Shulan Su, Yonghui Li, Huiting Zeng, Zhenhua Zhu, Jianming Guo, Yue Zhu, Sheng Guo, Li Yu, Dawei Qian, Yuping Tang, Jinao Duan
ETHNOPHARMACOLOGICAL RELEVANCE: Chronic renal failure (CRF) is defined as a progressive and irreversible loss of renal function and associated with inflammation and oxidative stress. Salvia miltiorrhiza (SM) is an important Chinese herb used in traditional Chinese medicine for treating cardiovascular diseases. The previous studies showed the SM exhibited significant protective effects on CRF. In this present study, the metabolic profiling changes and action mechanism of SM on CRF were explored...
October 12, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29024911/simultaneous-quantitative-analysis-of-uremic-toxins-by-lc-ms-ms-with-a-reversed-phase-cation-exchange-anion-exchange-tri-modal-mixed-mode-column
#17
Yoshitomi Kanemitsu, Kei Asaji, Yotaro Matsumoto, Hiroki Tsukamoto, Daisuke Saigusa, Chikahisa Mukawa, Tatsuki Tachikawa, Takaaki Abe, Yoshihisa Tomioka
Column choice is crucial to the development of liquid chromatography/tandem mass spectrometry (LC-MS/MS) methods because analyte selectivity is dependent on the nature of the stationary phase. Recently, mixed-mode chromatography, which employs a combination of two or more stationary phases and solvent systems, has emerged as an alternative to multiple, complementary, single-column systems. This report describes the development and validation of a novel analytical method based on LC-MS/MS employing a reversed-phase/cation-exchange/anion-exchange tri-modal column (Scherzo SS-C18; Imtakt) for the simultaneous quantification of various uremic toxins (UTx), including creatinine, 1-methyladenosine, trimethylamine-N-oxide, indoxyl sulfate, p-cresyl sulfate, phenyl sulfate and 4-ethylphenyl sulfate...
October 5, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29016645/spontaneous-variability-of-pre-dialysis-concentrations-of-uremic-toxins-over-time-in-stable-hemodialysis-patients
#18
Sunny Eloot, Wim Van Biesen, Sanne Roels, Willem Delrue, Eva Schepers, Annemieke Dhondt, Raymond Vanholder, Griet Glorieux
BACKGROUND AND AIM: Numerous outcome studies and interventional trials in hemodialysis (HD) patients are based on uremic toxin concentrations determined at one single or a limited number of time points. The reliability of these studies however entirely depends on how representative these cross-sectional concentrations are. We therefore investigated the variability of predialysis concentrations of uremic toxins over time. METHODS: Prospectively collected predialysis serum samples of the midweek session of week 0, 1, 2, 3, 4, 8, 12, and 16 were analyzed for a panel of uremic toxins in stable chronic HD patients (N = 18) while maintaining dialyzer type and dialysis mode during the study period...
2017: PloS One
https://www.readbyqxmd.com/read/28992684/paricalcitol-attenuates-indoxyl-sulfate-induced-apoptosis-through-the-inhibition-of-mapk-akt-and-nf-kb-activation-in-hk-2-cells
#19
Jung Sun Park, Hoon In Choi, Eun Hui Bae, Seong Kwon Ma, Soo Wan Kim
Background/Aims: Indoxyl sulfate (IS) is a uremic toxin and an important causative factor in the progression of chronic kidney disease. Recently, paricalcitol (19-nor-1,25-dihydroxyvitamin D2) was shown to exhibit protective effects in kidney injury. Here, we investigated the effects of paricalcitol treatment on IS-induced renal tubular injury. Methods: The fluorescent dye 2',7'-dichlorofluorescein diacetate was used to measure intracellular reactive oxygen species (ROS) following IS administration in human renal proximal tubular epithelial (HK-2) cells...
October 10, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28992067/the-uremic-toxin-indoxyl-sulfate-interferes-with-iron-metabolism-by-regulating-hepcidin-in-chronic-kidney-disease
#20
Hirofumi Hamano, Yasumasa Ikeda, Hiroaki Watanabe, Yuya Horinouchi, Yuki Izawa-Ishizawa, Masaki Imanishi, Yoshito Zamami, Kenshi Takechi, Licht Miyamoto, Keisuke Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki
Background: Hepcidin secreted by hepatocytes is a key regulator of iron metabolism throughout the body. Hepcidin concentrations are increased in chronic kidney disease (CKD), contributing to abnormalities in iron metabolism. Levels of indoxyl sulfate (IS), a uremic toxin, are also elevated in CKD. However, the effect of IS accumulation on iron metabolism remains unclear. Methods: We used HepG2 cells to determine the mechanism by which IS regulates hepcidin concentrations...
August 23, 2017: Nephrology, Dialysis, Transplantation
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