scholarly journals Indoxyl sulfate caused behavioral abnormality and neurodegeneration in mice with unilateral nephrectomy

Aging ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 6681-6701
Author(s):  
Chiao-Yin Sun ◽  
Jian-Ri Li ◽  
Ya-Yu Wang ◽  
Shih-Yi Lin ◽  
Yen-Chuan Ou ◽  
...  
Keyword(s):  
Indoxyl Sulfate ◽  
Unilateral Nephrectomy ◽  
Behavioral Abnormality

Inflammatory effects on knee joint tissue by indoxyl sulfate

2013 ◽  
Author(s):  
Ya-Yun Chen ◽  
Herng-Sheng Lee ◽  
Yu-Juei Hsu
Keyword(s):  
Knee Joint ◽  
Indoxyl Sulfate ◽  
Joint Tissue

Pilot Study of Probiotic Supplementation on Uremic Toxicity and Inflammatory Cytokines in Chronic Kidney Patients

2020 ◽  
Vol 16 (4) ◽  
pp. 470-480
Author(s):  
Cristina T. Roth-Stefanski ◽  
Carla Dolenga ◽  
Lia S. Nakao ◽  
Roberto Pecoits-Filho ◽  
Thyago P. de Moraes ◽  
...  
Keyword(s):  
Pilot Study ◽  
Inflammatory Cytokines ◽  
Lactobacillus Acidophilus ◽  
Serum Levels ◽  
Uremic Toxins ◽  
Indoxyl Sulfate ◽  
Bacterial Metabolism ◽  
Probiotic Supplementation ◽  
Primary Endpoints ◽  
Inflammatory Profile

Background: Bacterial metabolism contributes to the generation of uremic toxins in patients with chronic kidney disease (CKD). It has been investigated the use of probiotics in the reduction of uremic toxins intestinal production. Objective: The aim of this pilot study was to evaluate the effect of probiotic supplementation on reducing the production of uremic toxins and the inflammatory profile of CKD patients. Methods: We performed a randomized, blind, placebo-controlled, crossover study on patients with CKD stages 3 and 4. The intervention was a probiotic formulation composed of Lactobacillus acidophilus strains given orally three times a day for 3 months. Changes in uremic toxins (p-Cresylsulfate and Indoxyl Sulfate) and serum inflammatory cytokines were the primary endpoints. Results: Of the 44 patients randomized, 25 completed the study (mean age 51 ± 9.34, 64% female, mean eGFR 36 ± 14.26 mL/min/1.73m², mean BMI 28.5 ± 5.75 kg/m²). At 3 months, there were no significant changes in any of the studied biomarkers including p-cresylsulfate (p = 0.57), Indoxyl sulfate (p = 0.08) and interleukin-6 (p = 0.55). Conclusion: Lactobacillus acidophilus strains given as probiotic were not able to reduce serum levels of uremic toxins and biomarkers of inflammation in CKD patients in stage 3 and 4.

Early increase in pulsatile growth hormone release after unilateral nephrectomy in adult rats

1994 ◽  
Vol 266 (4) ◽  
pp. F628-F632 ◽  
Author(s):  
A. Haramati ◽  
M. D. Lumpkin ◽  
S. E. Mulroney
Keyword(s):  
Growth Hormone ◽  
Early Time ◽  
Peak Level ◽  
Unilateral Nephrectomy ◽  
Sham Operation ◽  
Renal Growth ◽  
Adult Rats ◽  
Compensatory Renal Growth ◽  
Jugular Veins ◽  
Hypertrophic Response

Removal of one kidney results, within days, in accelerated growth of the remaining kidney. However, the mechanisms that underlie this compensatory renal hypertrophic response, particularly in the early time period following nephrectomy, are not understood. In this study we tested the hypothesis that removal of one kidney leads to a change in the pulsatile release of growth hormone (GH), which facilitates compensatory renal growth. Adult Wistar rats were implanted with Silastic cannulas in jugular veins and underwent either unilateral nephrectomy (UNX) or sham operation. Plasma levels of GH were determined 24 and 48 h after sham operation or UNX. Blood samples were taken every 20 min over a 6-h period from conscious, unrestrained animals. Pulsatile GH release was markedly elevated 24 h after UNX in both the amplitude of the surges as well as in the duration of release. Peak GH levels after 24 h were three- to fourfold higher in UNX rats compared with sham controls (417 +/- 75 vs. 119 +/- 23 ng/ml, P < 0.05). However, this enhanced release of GH appeared to be of short duration and began declining by 48 h post-UNX (peak level of 227 +/- 37 ng/ml, P < 0.05 vs. both 24 h UNX and sham controls). To examine whether this rise in GH release post-UNX contributed to the compensatory renal growth, rats underwent UNX and were immediately treated with an antagonist to GH-releasing factor (GRF-AN; i.e., [N-Ac-Tyr1,D-Arg2]GRF-(1-29) amide, 200 micrograms/kg twice daily), and the effects on GH release and renal growth were determined. Administration of GRF-AN significantly suppressed the increase in GH release post-UNX and was associated with a significant attenuation in renal growth 48 h post-UNX in GRF-AN-treated rats (8.7 +/- 2.6% vs. 22.7 +/- 3.0% in UNX controls, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Uremic toxin indoxyl sulfate promotes proinflammatory macrophage activation by regulation of β-catenin and YAP pathways

2021 ◽  
Author(s):  
Ying Li ◽  
Jing Yan ◽  
Minjia Wang ◽  
Jing Lv ◽  
Fei Yan ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Inflammatory Response ◽  
Macrophage Polarization ◽  
Indoxyl Sulfate ◽  
Uremic Toxin ◽  
Lps Challenge ◽  
Hla Dr ◽  
M1 Macrophage

AbstractEvidence has been shown that indoxyl sulfate (IS) could impair kidney and cardiac functions. Moreover, macrophage polarization played important roles in chronic kidney disease and cardiovascular disease. IS acts as a nephron-vascular toxin, whereas its effect on macrophage polarization during inflammation is still not fully elucidated. In this study, we aimed to investigate the effect of IS on macrophage polarization during lipopolysaccharide (LPS) challenge. THP-1 monocytes were incubated with phorbol 12-myristate-13-acetate (PMA) to differentiate into macrophages, and then incubated with LPS and IS for 24 h. ELISA was used to detect the levels of TNFα, IL-6, IL-1β in THP-1-derived macrophages. Western blot assay was used to detect the levels of arginase1 and iNOS in THP-1-derived macrophages. Percentages of HLA-DR-positive cells (M1 macrophages) and CD206-positive cells (M2 macrophages) were detected by flow cytometry. IS markedly increased the production of the pro-inflammatory factors TNFα, IL-6, IL-1β in LPS-stimulated THP-1-derived macrophages. In addition, IS induced M1 macrophage polarization in response to LPS, as evidenced by the increased expression of iNOS and the increased proportion of HLA-DR+ macrophages. Moreover, IS downregulated the level of β-catenin, and upregulated the level of YAP in LPS-stimulated macrophages. Activating β-catenin signaling or inhibiting YAP signaling suppressed the IS-induced inflammatory response in LPS-stimulated macrophages by inhibiting M1 polarization. IS induced M1 macrophage polarization in LPS-stimulated macrophages via inhibiting β-catenin and activating YAP signaling. In addition, this study provided evidences that activation of β-catenin or inhibition of YAP could alleviate IS-induced inflammatory response in LPS-stimulated macrophages. This finding may contribute to the understanding of immune dysfunction observed in chronic kidney disease and cardiovascular disease.

Inhibitory effects of indoxyl sulfate and creatinine on the renal transport of meropenem and biapenem in rats

2021 ◽  
pp. 100406
Author(s):  
Yuichi Ichimura ◽  
Natsumi Kudoh ◽  
Takashi Murabe ◽  
Takumi Akao ◽  
Sho Watanuki ◽  
...  
Keyword(s):  
Indoxyl Sulfate ◽  
Renal Transport ◽  
Inhibitory Effects

scholarly journals Indoxyl-Sulfate-Induced Redox Imbalance in Chronic Kidney Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 936
Author(s):  
Chien-Lin Lu ◽  
Cai-Mei Zheng ◽  
Kuo-Cheng Lu ◽  
Min-Tser Liao ◽  
Kun-Lin Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Muscle Wasting ◽  
Mesangial Cells ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Indoxyl Sulfate ◽  
Uremic Toxin ◽  
Tubulointerstitial Injury

The accumulation of the uremic toxin indoxyl sulfate (IS) induces target organ damage in chronic kidney disease (CKD) patients, and causes complications including cardiovascular diseases, renal osteodystrophy, muscle wasting, and anemia. IS stimulates reactive oxygen species (ROS) production in CKD, which impairs glomerular filtration by a direct cytotoxic effect on the mesangial cells. IS further reduces antioxidant capacity in renal proximal tubular cells and contributes to tubulointerstitial injury. IS-induced ROS formation triggers the switching of vascular smooth muscular cells to the osteoblastic phenotype, which induces cardiovascular risk. Low-turnover bone disease seen in early CKD relies on the inhibitory effects of IS on osteoblast viability and differentiation, and osteoblastic signaling via the parathyroid hormone. Excessive ROS and inflammatory cytokine releases caused by IS directly inhibit myocyte growth in muscle wasting via myokines’ effects. Moreover, IS triggers eryptosis via ROS-mediated oxidative stress, and elevates hepcidin levels in order to prevent iron flux in circulation in renal anemia. Thus, IS-induced oxidative stress underlies the mechanisms in CKD-related complications. This review summarizes the underlying mechanisms of how IS mediates oxidative stress in the pathogenesis of CKD’s complications. Furthermore, we also discuss the potential role of oral AST-120 in attenuating IS-mediated oxidative stress after gastrointestinal adsorption of the IS precursor indole.

scholarly journals Synbiotics Alleviate the Gut Indole Load and Dysbiosis in Chronic Kidney Disease

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 114
Author(s):  
Chih-Yu Yang ◽  
Ting-Wen Chen ◽  
Wan-Lun Lu ◽  
Shih-Shin Liang ◽  
Hsien-Da Huang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Statistical Significance ◽  
Additional Treatment ◽  
Indoxyl Sulfate ◽  
Uremic Toxin ◽  
Healthy Controls ◽  
Gut Dysbiosis ◽  
Novel Concept

Chronic kidney disease (CKD) has long been known to cause significant digestive tract pathology. Of note, indoxyl sulfate is a gut microbe-derived uremic toxin that accumulates in CKD patients. Nevertheless, the relationship between gut microbiota, fecal indole content, and blood indoxyl sulfate level remains unknown. In our study, we established an adenine-induced CKD rat model, which recapitulates human CKD-related gut dysbiosis. Synbiotic treatment in CKD rats showed a significant reduction in both the indole-producing bacterium Clostridium and fecal indole amount. Furthermore, gut microbiota diversity was reduced in CKD rats but was restored after synbiotic treatment. Intriguingly, in our end-stage kidney disease (ESKD) patients, the abundance of indole-producing bacteria, Bacteroides, Prevotella, and Clostridium, is similar to that of healthy controls. Consistently, the fecal indole tends to be higher in the ESKD patients, but the difference did not achieve statistical significance. However, the blood level of indoxyl sulfate was significantly higher than that of healthy controls, implicating that under an equivalent indole production rate, the impaired renal excretion contributes to the accumulation of this notorious uremic toxin. On the other hand, we did identify two short-chain fatty acid-producing bacteria, Faecalibacterium and Roseburia, were reduced in ESKD patients as compared to the healthy controls. This may contribute to gut dysbiosis. We also identified that three genera Fusobacterium, Shewanella, and Erwinia, in the ESKD patients but not in the healthy controls. Building up gut symbiosis to treat CKD is a novel concept, but once proved effective, it will provide an additional treatment strategy for CKD patients.

scholarly journals The relationship of indoxyl sulfate and p-cresyl sulfate with target cardiovascular proteins in hemodialysis patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ping-Hsun Wu ◽  
Yi-Ting Lin ◽  
Yi-Wen Chiu ◽  
Gabriel Baldanzi ◽  
Jiun-Chi Huang ◽  
...  
Keyword(s):  
Hemodialysis Patients ◽  
Complement Component ◽  
Uremic Toxins ◽  
Indoxyl Sulfate ◽  
Free Form ◽  
Negatively Associated ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
Related Proteins ◽  
The Relationship

AbstractProtein-bound uremic toxins (Indoxyl sulfate [IS] and p-cresyl sulfate [PCS]) are both associated with cardiovascular (CV) and all-cause mortality in subjects with chronic kidney disease (CKD). Possible mechanisms have not been elucidated. In hemodialysis patients, we investigated the relationship between the free form of IS and PCS and 181 CV-related proteins. First, IS or PCS concentrations were checked, and high levels were associated with an increased risk of acute coronary syndrome (ACS) in 333 stable HD patients. CV proteins were further quantified by a proximity extension assay. We examined associations between the free form protein-bound uremic toxins and the quantified proteins with correction for multiple testing in the discovery process. In the second step, the independent association was evaluated by multivariable-adjusted models. We rank the CV proteins related to protein-bound uremic toxins by bootstrapped confidence intervals and ascending p-value. Six proteins (signaling lymphocytic activation molecule family member 5, complement component C1q receptor, C–C motif chemokine 15 [CCL15], bleomycin hydrolase, perlecan, and cluster of differentiation 166 antigen) were negatively associated with IS. Fibroblast growth factor 23 [FGF23] was the only CV protein positively associated with IS. Three proteins (complement component C1q receptor, CCL15, and interleukin-1 receptor-like 2) were negatively associated with PCS. Similar findings were obtained after adjusting for classical CV risk factors. However, only higher levels of FGF23 was related to increased risk of ACS. In conclusion, IS and PCS were associated with several CV-related proteins involved in endothelial barrier function, complement system, cell adhesion, phosphate homeostasis, and inflammation. Multiplex proteomics seems to be a promising way to discover novel pathophysiology of the uremic toxin.

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