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Dr. Andrea Stinghen
Universidade Federal do Paraná, Curitiba, Brazil

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0 Chronic Kidney Disease
0 Fabry disease
0 Endothelial dysfunction
0 uremic toxins
0 Experimental Nephrology

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Chronic Kidney Disease
uremic toxins
Endothelial dysfunction
Fabry disease

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Review
Published: 30 July 2021 in Cells
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Over the development of eukaryotic cells, intrinsic mechanisms have been developed in order to provide the ability to defend against aggressive agents. In this sense, a group of proteins plays a crucial role in controlling the production of several proteins, guaranteeing cell survival. The heat shock proteins (HSPs), are a family of proteins that have been linked to different cellular functions, being activated under conditions of cellular stress, not only imposed by thermal variation but also toxins, radiation, infectious agents, hypoxia, etc. Regarding pathological situations as seen in cardiorenal syndrome (CRS), HSPs have been shown to be important mediators involved in the control of gene transcription and intracellular signaling, in addition to be an important connector with the immune system. CRS is classified as acute or chronic and according to the first organ to suffer the injury, which can be the heart (CRS type 1 and type 2), kidneys (CRS type 3 and 4) or both (CRS type 5). In all types of CRS, the immune system, redox balance, mitochondrial dysfunction, and tissue remodeling have been the subject of numerous studies in the literature in order to elucidate mechanisms and propose new therapeutic strategies. In this sense, HSPs have been targeted by researchers as important connectors between kidney and heart. Thus, the present review has a focus to present the state of the art regarding the role of HSPs in the pathophysiology of cardiac and renal alterations, as well their role in the kidney–heart axis.

ACS Style

Carolina Junho; Carolina Azevedo; Regiane da Cunha; Ainhoa de Yurre; Emiliano Medei; Andréa Stinghen; Marcela Carneiro-Ramos. Heat Shock Proteins: Connectors between Heart and Kidney. Cells 2021, 10, 1939 .

AMA Style

Carolina Junho, Carolina Azevedo, Regiane da Cunha, Ainhoa de Yurre, Emiliano Medei, Andréa Stinghen, Marcela Carneiro-Ramos. Heat Shock Proteins: Connectors between Heart and Kidney. Cells. 2021; 10 (8):1939.

Chicago/Turabian Style

Carolina Junho; Carolina Azevedo; Regiane da Cunha; Ainhoa de Yurre; Emiliano Medei; Andréa Stinghen; Marcela Carneiro-Ramos. 2021. "Heat Shock Proteins: Connectors between Heart and Kidney." Cells 10, no. 8: 1939.

Journal article
Published: 01 May 2021 in Toxicology Letters
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P-Cresyl sulfate (PCS), indoxyl sulfate (IS), and inorganic phosphate (Pi) are uremic toxins found in chronic kidney disease (CKD) that are closely related to endothelial extracellular vesicles (EVs) formation. The present study aimed to understand the role of EVs and their role in cell adhesion and migration, inflammation, and oxidative stress. Human endothelial cells were treated with PCS, IS, and Pi in pre-established uremic and kinetic recommendations. EVs were characterized using scanning electron microscopy, flow cytometry, and NanoSight assays. The concentrations of EVs were established using Alamar Blue and MTT assays. Cell adhesion to extracellular matrix proteins was analyzed using an adhesion assay. Inflammation and oxidative stress were assessed by vascular cell adhesion molecule-1 expression/monocyte migration and reactive oxygen species production, respectively. The capacity of EVs to stimulate endothelial cell migration was evaluated using a wound-healing assay. Our data showed that endothelial cells stimulated with uremic toxins can induce the formation of EVs of different sizes, quantities, and concentrations, depending on the uremic toxin used. Cell adhesion was significantly (P < 0.01) stimulated in cells exposed to PCS-induced extracellular vesicles (PCSEVs) and inorganic phosphate-induced extracellular vesicles (PiEVs). Cell migration was significantly (P < 0.05) stimulated by PCSEVs. VCAM-1 expression was evident in cells treated with PCSEVs and IS-induced extracellular vesicles (ISEVs). EVs are not able to stimulate monocyte migration or oxidative stress. In conclusion, EVs may be a biomarker of endothelial injury and the inflammatory process, playing an important role in cell-to-cell communication and pathophysiological processes, although more studies are needed to better understand the mechanisms of EVs in uremia.

ACS Style

Giane Favretto; Regiane Stafim da Cunha; Andressa Flores Santos; Amanda Leitolis; Elberth Manfron Schiefer; Paulo Cézar Gregório; Célia Regina Cavichiolo Franco; Ziad Massy; Maria Aparecida Dalboni; Andréa Emilia Marques Stinghen. Uremic endothelial-derived extracellular vesicles: Mechanisms of formation and their role in cell adhesion, cell migration, inflammation, and oxidative stress. Toxicology Letters 2021, 347, 12 -22.

AMA Style

Giane Favretto, Regiane Stafim da Cunha, Andressa Flores Santos, Amanda Leitolis, Elberth Manfron Schiefer, Paulo Cézar Gregório, Célia Regina Cavichiolo Franco, Ziad Massy, Maria Aparecida Dalboni, Andréa Emilia Marques Stinghen. Uremic endothelial-derived extracellular vesicles: Mechanisms of formation and their role in cell adhesion, cell migration, inflammation, and oxidative stress. Toxicology Letters. 2021; 347 ():12-22.

Chicago/Turabian Style

Giane Favretto; Regiane Stafim da Cunha; Andressa Flores Santos; Amanda Leitolis; Elberth Manfron Schiefer; Paulo Cézar Gregório; Célia Regina Cavichiolo Franco; Ziad Massy; Maria Aparecida Dalboni; Andréa Emilia Marques Stinghen. 2021. "Uremic endothelial-derived extracellular vesicles: Mechanisms of formation and their role in cell adhesion, cell migration, inflammation, and oxidative stress." Toxicology Letters 347, no. : 12-22.

Journal article
Published: 28 March 2021 in Research, Society and Development
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Piper amalago L. is a medicinal plant traditionally used as a healing agent for wounds, burns, abscesses, boils, and insect bites. The current study aimed to evaluate the possible effects of the aqueous crude extract obtained from P. amalago leaves, in different concentrations and in different incubation times, using the in vitro model of mouse fibroblasts (3T3). The extract was tested in different concentrations at the 24 h incubation time for analysis of cell viability, cytotoxicity, proliferation, cell morphology, immunostaining, adhesion and cell spreading assays, as well as to determine the hydroxyproline concentration and activity of the metalloproteinase MMP2. Morphologically, after exposure to the concentrations of 15 and 150 µg/mL, the cells maintained the morphology, yet a greater number of cells with more expansions of the cell body and larger than the control cells were observed. The treated cell culture also showed a greater number of cells, larger cells, a greater expansion of the cell body, adherent cells spread over the substrate, and a more juxtaposed, central and spherical nucleus. The treatment induced greater cell adhesion to the polymer, fibronectin, and collagen I. Biochemical results showed a significant increase in the hydroxyproline amino acid after exposure for 96 h. The extract did not induce loss of cell viability until the concentration reached 150 µg/mL, positively modulating proliferation, morphology, adhesion, degree of spreading, and organization of microfilaments. The extract also promoted a significant increase in the hydroxyproline amino acid.

ACS Style

Vera Lucia Pereira dos Santos; Célia Regina Cavichiolo Franco; Ricardo Wagner; Caroline Dadalt Silva; Giane Favretto dos Santos; Regiane Stafim da Cunha; Andréa Emilia Marques Stinghen; Luciane Mendes Monteiro; Julia Emília Bussade; Jane Manfron Budel; Iara José de Messias-Reason. In vitro study after exposure to the aqueous extract of Piper amalago L. shows changes of morphology, proliferation, cytoskeleton and molecules of the extracellular matrix. Research, Society and Development 2021, 10, 1 .

AMA Style

Vera Lucia Pereira dos Santos, Célia Regina Cavichiolo Franco, Ricardo Wagner, Caroline Dadalt Silva, Giane Favretto dos Santos, Regiane Stafim da Cunha, Andréa Emilia Marques Stinghen, Luciane Mendes Monteiro, Julia Emília Bussade, Jane Manfron Budel, Iara José de Messias-Reason. In vitro study after exposure to the aqueous extract of Piper amalago L. shows changes of morphology, proliferation, cytoskeleton and molecules of the extracellular matrix. Research, Society and Development. 2021; 10 (4):1.

Chicago/Turabian Style

Vera Lucia Pereira dos Santos; Célia Regina Cavichiolo Franco; Ricardo Wagner; Caroline Dadalt Silva; Giane Favretto dos Santos; Regiane Stafim da Cunha; Andréa Emilia Marques Stinghen; Luciane Mendes Monteiro; Julia Emília Bussade; Jane Manfron Budel; Iara José de Messias-Reason. 2021. "In vitro study after exposure to the aqueous extract of Piper amalago L. shows changes of morphology, proliferation, cytoskeleton and molecules of the extracellular matrix." Research, Society and Development 10, no. 4: 1.

Journal article
Published: 22 February 2021
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This study aimed to evaluate the potential anti-inflammatory effects of vitamin D supplementation under uremic conditions, both in vivo and in vitro, and its effects on the parameters of mineral metabolism. Thirty-two hemodialysis patients were randomly assigned to receive placebo (N=14) or cholecalciferol (N=18) for six months. Serum levels of calcium, phosphate, total alkaline phosphatase, intact parathyroid hormone (iPTH), and vitamin D were measured at baseline and after three and six months. The levels of fibroblast growth factor-23 (FGF-23), interleukin-1β (IL-1β), and high-sensitivity C-reactive protein (hs-CRP) were also measured at baseline and at six months. Human monocytes were used for in vitro experiments and treated with cholecalciferol (150 nM) and uremic serum. Cell viability, reactive oxygen species (ROS) production, and cathelicidin (CAMP) expression were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, dichloro-dihydro-fluorescein diacetate assay, and real time-quantitative polymerase chain reaction, respectively. Both patient groups were clinically and biochemically similar at baseline. After six months, the levels of vitamin D and iPTH were higher and lower, respectively, in the cholecalciferol group than in the placebo group (p<0.05). There was no significant difference between the parameters of mineral metabolism, such as IL-1β and hs-CRP levels, in both groups. Treatment with uremic serum lowered the monocyte viability (p<0.0001) and increased ROS production (p<0.01) and CAMP expression (p<0.05); these effects were counterbalanced by cholecalciferol treatment (p<0.05). Thus, cholecalciferol supplementation is an efficient strategy to ameliorate hypovitaminosis D in hemodialysis patients, but its beneficial effects on the control of secondary hyperparathyroidism are relatively unclear. Even though cholecalciferol exhibited anti-inflammatory effects in vitro, its short-term supplementation was not effective in improving the inflammatory profile of patients on hemodialysis, as indicated by the IL-1β and hs-CRP levels.

ACS Style

Paulo C Gregório; Sergio Bucharles; Regiane S da Cunha; Tárcio Braga; Ana Clara Almeida; Railson Henneberg; Andréa E M Stinghen; Fellype C Barreto. In vitro anti-inflammatory effects of vitamin D supplementation may be blurred in hemodialysis patients. 2021, 76, e1821 .

AMA Style

Paulo C Gregório, Sergio Bucharles, Regiane S da Cunha, Tárcio Braga, Ana Clara Almeida, Railson Henneberg, Andréa E M Stinghen, Fellype C Barreto. In vitro anti-inflammatory effects of vitamin D supplementation may be blurred in hemodialysis patients. . 2021; 76 ():e1821.

Chicago/Turabian Style

Paulo C Gregório; Sergio Bucharles; Regiane S da Cunha; Tárcio Braga; Ana Clara Almeida; Railson Henneberg; Andréa E M Stinghen; Fellype C Barreto. 2021. "In vitro anti-inflammatory effects of vitamin D supplementation may be blurred in hemodialysis patients." 76, no. : e1821.

Journal article
Published: 21 January 2021 in Toxicology and Applied Pharmacology
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COVID-19 is a pandemic with no end in sight. There is only one approved antiviral agent but global stocks are deemed insufficient. Despite in vitro antiviral activity, clinical trials of chloroquine and hydroxychloroquine were disappointing, and they may even impair outcomes. Chloroquine causes zebroid deposits reminiscent of Fabry disease (α-galactosidase A deficiency) and endothelial cells are key targets of COVID-19. We have explored the effect of chloroquine on cultured endothelial cells and its modulation by recombinant α-galactosidase A (agalsidase). Following dose-response studies, 0.5 μg/mL chloroquine was added to cultured human endothelial cells. Neutral red and Lysotracker were used to assess lysosomes. Cytotoxicity was evaluated by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) - MTT assay and cell stress by assessing reactive oxygen species (ROS) and nitric oxide (NO). In endothelial cells, chloroquine induced dose-dependent cytotoxicity at in vitro test concentrations for COVID-19 therapy. At a sublethal concentration, chloroquine significantly induced the accumulation of acid organelles (P < 0.05), increased ROS levels, and decreased NO production (P < 0.05). These adverse effects of chloroquine on endothelial cell biology were decreased by agalsidase-β (P < 0.05). Chloroquine-induced endothelial cell cytotoxicity and stress is attenuated by agalsidase-β treatment. This suggests that endothelial cell injury may contribute to the failure of chloroquine as therapy for COVID-19 and may be at least in part related to causing dysfunction of the lysosomal enzyme α-galactosidase A.

ACS Style

PauloC. Gregório; Regiane S. da Cunha; Gilson Biagini; Bruna Bosquetti; Júlia Budag; Alberto Ortiz; Maria Dolores Sánchez-Niño; Fellype C. Barreto; Andréa E.M. Stinghen. Chloroquine may induce endothelial injury through lysosomal dysfunction and oxidative stress. Toxicology and Applied Pharmacology 2021, 414, 115412 -115412.

AMA Style

PauloC. Gregório, Regiane S. da Cunha, Gilson Biagini, Bruna Bosquetti, Júlia Budag, Alberto Ortiz, Maria Dolores Sánchez-Niño, Fellype C. Barreto, Andréa E.M. Stinghen. Chloroquine may induce endothelial injury through lysosomal dysfunction and oxidative stress. Toxicology and Applied Pharmacology. 2021; 414 ():115412-115412.

Chicago/Turabian Style

PauloC. Gregório; Regiane S. da Cunha; Gilson Biagini; Bruna Bosquetti; Júlia Budag; Alberto Ortiz; Maria Dolores Sánchez-Niño; Fellype C. Barreto; Andréa E.M. Stinghen. 2021. "Chloroquine may induce endothelial injury through lysosomal dysfunction and oxidative stress." Toxicology and Applied Pharmacology 414, no. : 115412-115412.

Articles
Published: 01 December 2020 in Brazilian Journal of Nephrology
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In the study published in this issue of the BJN, Matsumoto et al. investigated the association between deficiency of 25-hydroxyvitamin D and inflammatory and oxidative stress in a cohort of pre-dialysis CKD patients5. The study included 206 pre-dialysis CKD patients who were not using vitamin D supplementation. A large number of inflammatory and oxidative stress biomarkers, such as interleukin (IL)-6, adiponectin, F2-isoprostane, advanced oxidation protein products (AOPP), hs-C reactive protein (hs-CRP), were measured. The prevalence of vitamin D deficiency, defined as serum levels of 25(OH)-vitamin D below 20 ng/mL, in the study population was 27% (55/204) and it was inversely correlated with renal function. The multivariate analyses could not demonstrate any significant effect of vitamin D on the levels of inflammatory and oxidative stress biomarkers5. Contrarily, CKD stages were correlated with oxidative stress. The authors concluded that vitamin D deficiency might not play a role in the increased oxidative stress state commonly seen in pre-dialysis CKD patients5.

ACS Style

Fellype Carvalho Barreto; Andréa Emilia Marques Stinghen. Vitamin D and chronic kidney disease: an uneasy relationship. Brazilian Journal of Nephrology 2020, 42, 386 -387.

AMA Style

Fellype Carvalho Barreto, Andréa Emilia Marques Stinghen. Vitamin D and chronic kidney disease: an uneasy relationship. Brazilian Journal of Nephrology. 2020; 42 (4):386-387.

Chicago/Turabian Style

Fellype Carvalho Barreto; Andréa Emilia Marques Stinghen. 2020. "Vitamin D and chronic kidney disease: an uneasy relationship." Brazilian Journal of Nephrology 42, no. 4: 386-387.

Review
Published: 20 June 2020 in Toxins
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Uremic toxins can induce endothelial dysfunction in patients with chronic kidney disease (CKD). Indeed, the structure of the endothelial monolayer is damaged in CKD, and studies have shown that the uremic toxins contribute to the loss of cell–cell junctions, increasing permeability. Membrane proteins, such as transporters and receptors, can mediate the interaction between uremic toxins and endothelial cells. In these cells, uremic toxins induce oxidative stress and activation of signaling pathways, including the aryl hydrocarbon receptor (AhR), nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) pathways. The activation of these pathways leads to overexpression of proinflammatory (e.g., monocyte chemoattractant protein-1, E-selectin) and prothrombotic (e.g., tissue factor) proteins. Uremic toxins also induce the formation of endothelial microparticles (EMPs), which can lead to the activation and dysfunction of other cells, and modulate the expression of microRNAs that have an important role in the regulation of cellular processes. The resulting endothelial dysfunction contributes to the pathogenesis of cardiovascular diseases, such as atherosclerosis and thrombotic events. Therefore, uremic toxins as well as the pathways they modulated may be potential targets for therapies in order to improve treatment for patients with CKD.

ACS Style

Regiane Stafim Da Cunha; Andressa Flores Santos; Fellype Carvalho Barreto; Andréa Emilia Marques Stinghen. How do Uremic Toxins Affect the Endothelium? Toxins 2020, 12, 412 .

AMA Style

Regiane Stafim Da Cunha, Andressa Flores Santos, Fellype Carvalho Barreto, Andréa Emilia Marques Stinghen. How do Uremic Toxins Affect the Endothelium? Toxins. 2020; 12 (6):412.

Chicago/Turabian Style

Regiane Stafim Da Cunha; Andressa Flores Santos; Fellype Carvalho Barreto; Andréa Emilia Marques Stinghen. 2020. "How do Uremic Toxins Affect the Endothelium?" Toxins 12, no. 6: 412.

Journal article
Published: 01 June 2020 in Nephrology Dialysis Transplantation
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Background and Aims Intradialytic hypoxemia is associated with oxidative stress, endothelial dysfunction, inflammation, higher erythropoietin requirements, and higher all-cause hospitalization and mortality in hemodialysis (HD) patients (Meyring-Wosten, et al., 2016). The aim of the present study was to further expand our insights into the hypoxia-uremia axis by investigating the oxidative balance in endothelial cells (EC) under hypoxic and uremic conditions. Method Human umbilical EC were incubated with DMEM medium supplemented with 10% of fetal bovine serum (FBS; control) or with sera obtained from healthy subjects (S-CON) or HD patients (S-HD, 1:10), respectively, for 40 minutes, 4 hours, and 24 hours under normoxic (21% O2) or hypoxic (5% O2) conditions (Culture Chamber ProOx, Biospherix). EC were analyzed by flow cytometer (BD Accuri™ C6 Plus) to assess a) intracellular production of reactive oxygen species (ROS, DCFH-DA probe, Abcam); b) reduced glutathione (GSH) content (ThiolTracker Violet probe, Thermo Fisher Scientific). Results S-HD increased intracellular ROS production at all time points compared to S-CON. Moreover, ROS production was higher under hypoxic conditions. ROS production declined after 24 hours. S-HD induced slightly higher GSH content when compared to S-CON in normoxia (Table 1). Conclusion In our in vitro experiments, hypoxia and uremia jointly favor EC oxidative imbalance. This effect is particularly pronounced after 4 hours. Translational studies are warranted to explore the clinical relevance of our findings.

ACS Style

Andrea N Moreno-Amaral; Caroline Carvalho Silva; Gabriela Bohnen Andrade; Julia Monteiro; Nadja Grobe; Roberto Flavio Silva Pecoits Filho; Andréa Stinghen; Peter Kotanko. P0942HYPOXEMIA AND UREMIA INDUCE OXIDATIVE IMBALANCE IN ENDOTHELIAL CELLS. Nephrology Dialysis Transplantation 2020, 35, 1 .

AMA Style

Andrea N Moreno-Amaral, Caroline Carvalho Silva, Gabriela Bohnen Andrade, Julia Monteiro, Nadja Grobe, Roberto Flavio Silva Pecoits Filho, Andréa Stinghen, Peter Kotanko. P0942HYPOXEMIA AND UREMIA INDUCE OXIDATIVE IMBALANCE IN ENDOTHELIAL CELLS. Nephrology Dialysis Transplantation. 2020; 35 (Supplement):1.

Chicago/Turabian Style

Andrea N Moreno-Amaral; Caroline Carvalho Silva; Gabriela Bohnen Andrade; Julia Monteiro; Nadja Grobe; Roberto Flavio Silva Pecoits Filho; Andréa Stinghen; Peter Kotanko. 2020. "P0942HYPOXEMIA AND UREMIA INDUCE OXIDATIVE IMBALANCE IN ENDOTHELIAL CELLS." Nephrology Dialysis Transplantation 35, no. Supplement: 1.

Journal article
Published: 01 June 2020 in Nephrology Dialysis Transplantation
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Background and Aims Uremic toxins (UTs) accumulate in the circulation of patients with chronic kidney disease (CKD), contributing to poor outcomes. One of the main objectives of renal replacement therapies is the removal of UTs, and while HD is restricted to the clearance of low molecular weight UTs, hemodiafiltration (HDF) adds efficiency to the removal of medium molecular weight UTs through the association of diffusion and convection methods. Metabolomic analysis from nuclear magnetic resonance (NMR) spectra offers efficient data about metabolites profile, indicating the main features of HDF, and possibly highlighting the positive effects of this modality. Thus, the aim of the present study is to evaluate the profile of metabolites in the circulation of a cohort of patients undergoing HDF. Method From 97 individuals participating in the HDF arm of a randomized control trial (ClinicalTrials.gov Identifier: NCT02787161), we randomly (using Python language; NumPy library) selected 6 patients (mean age 49, 6 males, 44% diabetics, average duration of 245 minutes, blood flow of 400 mL/min, target convective volume of 22 L per treatment). Patient’s serum samples were collected in the beginning of the study (baseline) and 6 months. The samples were prepared with deuterium oxide, sodium trimethylsilylpropanesulfonate as internal standard (ð=0.0 ppm), and further submitted to 1H NMR spectra recorded with Bruker 600 MHz AVANCE III spectrometer in order to identify the patient’s metabolomic profile. Data was evaluated with t-test and results were then compared with the Human Metabolome Database (HMDB) for descending order of the Jaccard similarity score. Results A total of 50 metabolites were investigated. Interestingly, 2 metabolites were significantly (P<0.05) reduced in the serum after 6 months compared to baseline, acetate (3.3 ± 0.1) % and dimethylglyoxal (7.6 ± 0.1) % (Figure 1). In order to confirm the presence of these metabolites in human serum, further studies will be conducted with 2D 1H-13C-HSQCed NMR. Conclusion We observed a reduction of acetate and dimethylglyoxal levels after six months of HDF treatment, in comparison to baseline, most likely as a consequence of the increase in clearance of these molecules. Hypothetically these changes in solute removal could explain the positive effects of HDF on clinical outcomes, and further studies should address this potential benefit of the modality.

ACS Style

Andressa Flores; Elberth Manfron Schiefer; Guilherme Sassaki; Leociley Menezes; Renato Fonseca; Regiane Cunha; Maria Eugenia Canziani; Murilo Guedes; Andrea N Moreno-Amaral; Wesley Souza; Roberto Flavio Silva Pecoits Filho; Andréa Stinghen. P1057UNTARGETED 1H NMR-BASED SERUM METABOLIC PROFILE ANALYSIS OF PATIENTS TREATED WITH HIGH VOLUME HEMODIAFILTRATION (HDF). Nephrology Dialysis Transplantation 2020, 35, 1 .

AMA Style

Andressa Flores, Elberth Manfron Schiefer, Guilherme Sassaki, Leociley Menezes, Renato Fonseca, Regiane Cunha, Maria Eugenia Canziani, Murilo Guedes, Andrea N Moreno-Amaral, Wesley Souza, Roberto Flavio Silva Pecoits Filho, Andréa Stinghen. P1057UNTARGETED 1H NMR-BASED SERUM METABOLIC PROFILE ANALYSIS OF PATIENTS TREATED WITH HIGH VOLUME HEMODIAFILTRATION (HDF). Nephrology Dialysis Transplantation. 2020; 35 (Supplement):1.

Chicago/Turabian Style

Andressa Flores; Elberth Manfron Schiefer; Guilherme Sassaki; Leociley Menezes; Renato Fonseca; Regiane Cunha; Maria Eugenia Canziani; Murilo Guedes; Andrea N Moreno-Amaral; Wesley Souza; Roberto Flavio Silva Pecoits Filho; Andréa Stinghen. 2020. "P1057UNTARGETED 1H NMR-BASED SERUM METABOLIC PROFILE ANALYSIS OF PATIENTS TREATED WITH HIGH VOLUME HEMODIAFILTRATION (HDF)." Nephrology Dialysis Transplantation 35, no. Supplement: 1.

Journal article
Published: 01 January 2020 in Archives of Medical Research
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Uremic sarcopenia is a complication of chronic kidney disease, particularly in its later stages, which leads to musculoskeletal disability. Uremic toxins have been linked to the pathogenesis of several manifestations of uremic syndrome. We sought to investigate whether indoxyl sulphate (IS), a protein-bound uremic toxin, is implicated in the development of uremic sarcopenia. Myoblasts were exposed to IS at normal (0.6 mg/L, IS0.6), uremic (53 mg/L, IS53) or maximum uremic (236 mg/L, IS236) concentrations for 24, 48 and 72 h. Cell viability was evaluated by MTT assay and by 7-aminoactinomycin D staining. ROS generation and apoptosis were evaluated by flow cytometry. MyoD and myogenin mRNA expression was evaluated by qRT-PCR and myosin heavy chain expression by immunocytochemistry. Myoblast viability was reduced by IS236 in a time-dependent pattern (p <0.05; 84.4, 68.0, and 63.6%). ROS production was significantly higher (p <0.05) in cells exposed to IS53 and IS236 compared to control (untreated cells). The apoptosis rate was significantly higher in cells treated with IS53 and IS236 than in control after 48h (p <0.05; 4.7 ± 0.1% and 4.6 ± 0.3% vs. 3.1 ± 0.1%, respectively) and 72h (p <0.05; 9.6 ± 1.1% and 10.4 ± 0.3% vs. 3.1 ± 0.7%, respectively). No effect was observed on MyoD, myogenin, myosin heavy chain expression, and markers of myoblast differentiation at any IS concentration tested or time-point experiment. These data indicate that IS has direct toxic effects on myoblast by decreasing its viability and increasing cell apoptosis. IS may be a potential target for treating uremic sarcopenia.

ACS Style

Gabriela Gomes Cardoso Rodrigues; Humberto Dellê; Rodrigo Barbosa Oliveira Brito; Vinícius Oliveira Cardoso; Kristianne Fernandes; Raquel Agnelli Mesquita-Ferrari; Regiane Stafim Cunha; Andréa Stinghen; Maria Aparecida Dalboni; Fellype Carvalho Barreto. Indoxyl Sulfate Contributes to Uremic Sarcopenia by Inducing Apoptosis in Myoblasts. Archives of Medical Research 2020, 51, 21 -29.

AMA Style

Gabriela Gomes Cardoso Rodrigues, Humberto Dellê, Rodrigo Barbosa Oliveira Brito, Vinícius Oliveira Cardoso, Kristianne Fernandes, Raquel Agnelli Mesquita-Ferrari, Regiane Stafim Cunha, Andréa Stinghen, Maria Aparecida Dalboni, Fellype Carvalho Barreto. Indoxyl Sulfate Contributes to Uremic Sarcopenia by Inducing Apoptosis in Myoblasts. Archives of Medical Research. 2020; 51 (1):21-29.

Chicago/Turabian Style

Gabriela Gomes Cardoso Rodrigues; Humberto Dellê; Rodrigo Barbosa Oliveira Brito; Vinícius Oliveira Cardoso; Kristianne Fernandes; Raquel Agnelli Mesquita-Ferrari; Regiane Stafim Cunha; Andréa Stinghen; Maria Aparecida Dalboni; Fellype Carvalho Barreto. 2020. "Indoxyl Sulfate Contributes to Uremic Sarcopenia by Inducing Apoptosis in Myoblasts." Archives of Medical Research 51, no. 1: 21-29.

Journal article
Published: 11 December 2019 in Clinica Chimica Acta
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Vitamin K is a key cofactor for the activation of proteins involved in blood coagulation, apoptosis, bone mineralization regulation, and vessel health. Scientific evidence shows an important role of activated osteocalcin and matrix-Gla protein in bone and vessels, markedly affected along the course of chronic kidney disease (CKD). In fact, CKD corresponds to an unique condition of vitamin K deficiency caused by dietary restriction, intestinal dysfunction, and impaired vitamin K recycling. Clinical data suggest that vitamin K status can be modulated and this prompts us to speculate whether patients with CKD might benefit from vitamin K supplementation. However, as important as whether the improvement in vitamin K status would be able to result in better bone quality, less vascular calcification, and lower mortality rates, several issues need to be clarified. These include better standardized methods for measuring vitamin K levels, and definition of the optimal concentration range for supplementation in different subgroups. Here, we review the literature data concerning the impact of vitamin K deficiency and supplementation on CKD-associated mineral and bone disorders (CKD-MBD). We present and discuss the available evidence from basic science and clinical studies, and highlight perspectives for further research.

ACS Style

Rodrigo Bueno de Oliveira; Andréa Emilia Marques Stinghen; Ziad A. Massy. Vitamin K role in mineral and bone disorder of chronic kidney disease. Clinica Chimica Acta 2019, 502, 66 -72.

AMA Style

Rodrigo Bueno de Oliveira, Andréa Emilia Marques Stinghen, Ziad A. Massy. Vitamin K role in mineral and bone disorder of chronic kidney disease. Clinica Chimica Acta. 2019; 502 ():66-72.

Chicago/Turabian Style

Rodrigo Bueno de Oliveira; Andréa Emilia Marques Stinghen; Ziad A. Massy. 2019. "Vitamin K role in mineral and bone disorder of chronic kidney disease." Clinica Chimica Acta 502, no. : 66-72.

Review
Published: 13 May 2019 in Toxins
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Endothelial microparticles (EMPs) are vesicles derived from cell membranes, which contain outsourced phosphatidylserine and express adhesion molecules, such as cadherin, intercellular cell adhesion molecule-1 (ICAM-1), E-selectin, and integrins. EMPs are expressed under physiological conditions and continue circulating in the plasma. However, in pathologic conditions their levels increase, and they assume a pro-inflammatory and pro-coagulant role via interactions with monocytes; these effects are related to the development of atherosclerosis. Chronic kidney dysfunction (CKD) characterizes this dysfunctional scenario through the accumulation of uremic solutes in the circulating plasma, whose toxicity is related to the development of cardiovascular diseases. Therefore, this review aims to discuss the formation of EMPs and their biological effects in the uremic environment. Data from previous research demonstrate that uremic toxins are closely associated with the activation of inflammatory biomarkers, cardiovascular dysfunction processes, and the release of EMPs. The impact of a decrease in circulating EMPs in clinical studies has not yet been evaluated. Thus, whether MPs are biochemical markers and/or therapeutic targets has yet to be established.

ACS Style

Giane Favretto; Regiane Stafim Da Cunha; Maria Aparecida Dalboni; Rodrigo Bueno De Oliveira; Fellype De Carvalho Barreto; Ziad A. Massy; Andréa Emilia Marques Stinghen. Endothelial Microparticles in Uremia: Biomarkers and Potential Therapeutic Targets. Toxins 2019, 11, 267 .

AMA Style

Giane Favretto, Regiane Stafim Da Cunha, Maria Aparecida Dalboni, Rodrigo Bueno De Oliveira, Fellype De Carvalho Barreto, Ziad A. Massy, Andréa Emilia Marques Stinghen. Endothelial Microparticles in Uremia: Biomarkers and Potential Therapeutic Targets. Toxins. 2019; 11 (5):267.

Chicago/Turabian Style

Giane Favretto; Regiane Stafim Da Cunha; Maria Aparecida Dalboni; Rodrigo Bueno De Oliveira; Fellype De Carvalho Barreto; Ziad A. Massy; Andréa Emilia Marques Stinghen. 2019. "Endothelial Microparticles in Uremia: Biomarkers and Potential Therapeutic Targets." Toxins 11, no. 5: 267.

Journal article
Published: 07 October 2018 in Toxins
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Endothelial dysfunction in uremia can result in cell-to-cell junction loss and increased permeability, contributing to cardiovascular diseases (CVD) development. This study evaluated the impact of the uremic milieu on endothelial morphology and cell junction’s proteins. We evaluated (i) serum levels of inflammatory biomarkers in a cohort of chronic kidney disease (CKD) patients and the expression of VE-cadherin and Zonula Occludens-1 (ZO-1) junction proteins on endothelial cells (ECs) of arteries removed from CKD patients during renal transplant; (ii) ECs morphology in vitro under different uremic conditions, and (iii) the impact of uremic toxins p-cresyl sulfate (PCS), indoxyl sulfate (IS), and inorganic phosphate (Pi) as well as of total uremic serum on VE-cadherin and ZO-1 gene and protein expression in cultured ECs. We found that the uremic arteries had lost their intact and continuous endothelial morphology, with a reduction in VE-cadherin and ZO-1 expression. In cultured ECs, both VE-cadherin and ZO-1 protein expression decreased, mainly after exposure to Pi and uremic serum groups. VE-cadherin mRNA expression was reduced while ZO-1 was increased after exposure to PCS, IS, Pi, and uremic serum. Our findings show that uremia alters cell-to-cell junctions leading to an increased endothelial damage. This gives a new perspective regarding the pathophysiological role of uremia in intercellular junctions and opens new avenues to improve cardiovascular outcomes in CKD patients.

ACS Style

Rayana A. P. Maciel; Regiane S. Cunha; Valentina Busato; Célia R. C. Franco; Paulo C. Gregório; Carla J. R. Dolenga; Lia S. Nakao; Ziad A. Massy; Agnès Boullier; Roberto Pecoits-Filho; Andréa E. M. Stinghen. Uremia Impacts VE-Cadherin and ZO-1 Expression in Human Endothelial Cell-to-Cell Junctions. Toxins 2018, 10, 404 .

AMA Style

Rayana A. P. Maciel, Regiane S. Cunha, Valentina Busato, Célia R. C. Franco, Paulo C. Gregório, Carla J. R. Dolenga, Lia S. Nakao, Ziad A. Massy, Agnès Boullier, Roberto Pecoits-Filho, Andréa E. M. Stinghen. Uremia Impacts VE-Cadherin and ZO-1 Expression in Human Endothelial Cell-to-Cell Junctions. Toxins. 2018; 10 (10):404.

Chicago/Turabian Style

Rayana A. P. Maciel; Regiane S. Cunha; Valentina Busato; Célia R. C. Franco; Paulo C. Gregório; Carla J. R. Dolenga; Lia S. Nakao; Ziad A. Massy; Agnès Boullier; Roberto Pecoits-Filho; Andréa E. M. Stinghen. 2018. "Uremia Impacts VE-Cadherin and ZO-1 Expression in Human Endothelial Cell-to-Cell Junctions." Toxins 10, no. 10: 404.

Journal article
Published: 23 September 2018 in Toxins
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Uremic toxin (UT) retention in chronic kidney disease (CKD) affects biological systems. We aimed to identify the associations between UT, inflammatory biomarkers and biomarkers of the uremic cardiovascular response (BUCVR) and their impact on cardiovascular status as well as their roles as predictors of outcome in CKD patients. CKD patients stages 3, 4 and 5 (n = 67) were recruited and UT (indoxyl sulfate/IS, p-cresil sulfate/pCS and indole-3-acetic acid/IAA); inflammatory biomarkers [Interleukin-6 (IL-6), high sensitivity C reactive protein (hsCRP), monocyte chemoattractant protein-1 (MCP-1), soluble vascular adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble Fas (sFas)] and BUCVRs [soluble CD36 (sCD36), soluble receptor for advanced glycation end products (sRAGE), fractalkine] was measured. Patients were followed for 5.2 years and all causes of death was used as the primary outcome. Artery segments collected at the moment of transplantation were used for the immunohistochemistry analysis in a separate cohort. Estimated glomerular filtration rate (eGFR), circulating UT, plasma biomarkers of systemic and vascular inflammation and BUCVR were strongly interrelated. Patients with plaque presented higher signs of UT-induced inflammation and arteries from CKD patients presented higher fractalkine receptor (CX3CR1) tissue expression. Circulating IS (p = 0.03), pCS (p = 0.007), IL-6 (p = 0.026), sFas (p = 0.001), sCD36 (p = 0.01) and fractalkine (p = 0.02) were independent predictors of total mortality risk in CKD patients. Our results reinforce the important role of uremic toxicity in the pathogenesis of cardiovascular disease (CVD) in CKD patients through an inflammatory pathway.

ACS Style

Ligia Maria Claro; Andrea N. Moreno-Amaral; Ana Carolina Gadotti; Carla J. Dolenga; Lia S. Nakao; Marina L.V. Azevedo; Lucia De Noronha; Marcia Olandoski; Thyago P. De Moraes; Andréa E. M. Stinghen; Roberto Pécoits-Filho. The Impact of Uremic Toxicity Induced Inflammatory Response on the Cardiovascular Burden in Chronic Kidney Disease. Toxins 2018, 10, 384 .

AMA Style

Ligia Maria Claro, Andrea N. Moreno-Amaral, Ana Carolina Gadotti, Carla J. Dolenga, Lia S. Nakao, Marina L.V. Azevedo, Lucia De Noronha, Marcia Olandoski, Thyago P. De Moraes, Andréa E. M. Stinghen, Roberto Pécoits-Filho. The Impact of Uremic Toxicity Induced Inflammatory Response on the Cardiovascular Burden in Chronic Kidney Disease. Toxins. 2018; 10 (10):384.

Chicago/Turabian Style

Ligia Maria Claro; Andrea N. Moreno-Amaral; Ana Carolina Gadotti; Carla J. Dolenga; Lia S. Nakao; Marina L.V. Azevedo; Lucia De Noronha; Marcia Olandoski; Thyago P. De Moraes; Andréa E. M. Stinghen; Roberto Pécoits-Filho. 2018. "The Impact of Uremic Toxicity Induced Inflammatory Response on the Cardiovascular Burden in Chronic Kidney Disease." Toxins 10, no. 10: 384.

Articles
Published: 21 June 2018 in Brazilian Journal of Nephrology
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Considering the crucial role of the intestinal epithelium barrier as well as its intrinsic relationship with the immune system, Andrade et al. evaluated the effects of uremic serum on colonocytes in vitro, a study published in the present issue of the Brazilian Journal of Nephrology. For this purpose, the authors incubated colonocytes with the serum of healthy individuals, patients on conservative treatment, and patients on hemodialysis (HD), pre- and post-HD. One of the main findings of this study is the significant increase of proinflammatory cytokine interleukin-6 (IL-6) expression by the colonocytes that were incubated with the serum of both pre- and post-HD patients. Corroborating these findings, Lau et al. found an increase in the expression of inflammatory molecules, such as the monocyte chemoattractant protein-1 (MCP-1) and cyclooxygenase-2 (COX-2) proteins, and a greater infiltration of leukocytes in the colon of nephrectomized rats1. These data, therefore, demonstrate that the uremic environment is able to modulate the inflammatory response in the gut barrier. In addition, Andrade et al. did not observe a significant difference in the production of reactive oxygen species (ROS) and expression of toll-like receptors (TLR), proteins that recognize bacterial components and are important for gut homeostasis7.

ACS Style

Regiane S. Cunha; Andréa E. M. Stinghen. The intricate relationship between gut and kidney. Brazilian Journal of Nephrology 2018, 40, 215 -216.

AMA Style

Regiane S. Cunha, Andréa E. M. Stinghen. The intricate relationship between gut and kidney. Brazilian Journal of Nephrology. 2018; 40 (3):215-216.

Chicago/Turabian Style

Regiane S. Cunha; Andréa E. M. Stinghen. 2018. "The intricate relationship between gut and kidney." Brazilian Journal of Nephrology 40, no. 3: 215-216.

Journal article
Published: 05 September 2017 in Clinical Kidney Journal
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Advanced glycation end products (AGEs) have been related to the pathogenesis of cardiovascular diseases (CVD), chronic kidney disease (CKD) and diabetes mellitus. We sought to investigate the binding capacity of sevelamer to both AGEs and uremic serum in vitro and then test this pharmaceutical effect as a potential vascular anti-inflammatory strategy. AGEs were prepared by albumin glycation and characterized by absorbance and electrophoresis. Human endothelial cells were incubated in culture media containing AGEs and uremic serum with or without sevelamer. Receptor for advanced glycation end product (RAGE) expression was evaluated through immunocytochemistry and western blot to explore the interactions between AGEs and the endothelium. Inflammatory and endothelial dysfunction biomarkers, such as interleukin 6 (IL-6) and IL-8, monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1) and serum amyloid A (SAA) were also measured in cell supernatant. The chemotactic property of the supernatant was evaluated. AGEs significantly induced the expression of RAGE, inflammatory and endothelial activation biomarkers [IL-6, (P < 0.005); IL-8, MCP-1, PAI-1 and SAA (P < 0.001)] and monocyte chemotaxis as compared with controls. In addition, AGEs increased the levels of inflammatory biomarkers, which were observed after 6 h of endothelial cell incubation with uremic serum [IL-6 (P < 0.001) IL-8, MCP-1 and PAI-1 (P < 0.05)]. On the other hand, after 6 h of endothelial cell treatment with sevelamer, RAGE expression (P < 0.05) and levels of inflammatory biomarkers [IL-6 and IL-8 (P < 0.001), MCP-1 (P < 0.01), PAI-1 and SAA (P < 0.005)] significantly decreased compared with the AGEs/uremic serum treatment alone. Sevelamer decreased both endothelial expression of RAGE and endothelial dysfunction biomarkers, induced by AGEs, and uremic serum. Further studies are necessary for a better understanding of the potential protective role of sevelamer on uremic serum and AGEs-mediated endothelial dysfunction.

ACS Style

Paulo C. Gregório; Giane Favretto; Guilherme Sassaki; Regiane S. Cunha; Alessandra Becker-Finco; Roberto Pecoits-Filho; Wesley M. Souza; Fellype C. Barreto; Andréa E. M. Stinghen. Sevelamer reduces endothelial inflammatory response to advanced glycation end products. Clinical Kidney Journal 2017, 11, 89 -98.

AMA Style

Paulo C. Gregório, Giane Favretto, Guilherme Sassaki, Regiane S. Cunha, Alessandra Becker-Finco, Roberto Pecoits-Filho, Wesley M. Souza, Fellype C. Barreto, Andréa E. M. Stinghen. Sevelamer reduces endothelial inflammatory response to advanced glycation end products. Clinical Kidney Journal. 2017; 11 (1):89-98.

Chicago/Turabian Style

Paulo C. Gregório; Giane Favretto; Guilherme Sassaki; Regiane S. Cunha; Alessandra Becker-Finco; Roberto Pecoits-Filho; Wesley M. Souza; Fellype C. Barreto; Andréa E. M. Stinghen. 2017. "Sevelamer reduces endothelial inflammatory response to advanced glycation end products." Clinical Kidney Journal 11, no. 1: 89-98.

Withdrawal
Published: 01 June 2017 in Revista Brasileira de Farmacognosia
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ACS Style

Luciana C. Nowacki; José Stechman-Neto; Killian E. Cristoff; Andressa F. Santos; Karina B. Felipe; Guilherme L. Sassaki; Lauro M. de Souza; Andréa E.M. Stinghen; Wesley M. de Souza. WITHDRAWN: Ilex paraguariensis extract as a potential alternative to conventional drugs for orofacial pain. Revista Brasileira de Farmacognosia 2017, 1 .

AMA Style

Luciana C. Nowacki, José Stechman-Neto, Killian E. Cristoff, Andressa F. Santos, Karina B. Felipe, Guilherme L. Sassaki, Lauro M. de Souza, Andréa E.M. Stinghen, Wesley M. de Souza. WITHDRAWN: Ilex paraguariensis extract as a potential alternative to conventional drugs for orofacial pain. Revista Brasileira de Farmacognosia. 2017; ():1.

Chicago/Turabian Style

Luciana C. Nowacki; José Stechman-Neto; Killian E. Cristoff; Andressa F. Santos; Karina B. Felipe; Guilherme L. Sassaki; Lauro M. de Souza; Andréa E.M. Stinghen; Wesley M. de Souza. 2017. "WITHDRAWN: Ilex paraguariensis extract as a potential alternative to conventional drugs for orofacial pain." Revista Brasileira de Farmacognosia , no. : 1.

Journal article
Published: 30 May 2017 in Journal of Vascular Research
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ACS Style

Manuela Martins-Green; Yan Liu; Xue Lian Chen; Lei Wang; Alkistis Kapelouzou; Alkiviadis Kostakis; Michalis Peroulis; Michalis Katsimpoulas; Petros Moustardas; Chrysostomos V. Aravanis; Panagiotis E. Karayannakos; Dennis V. Cokkinos; Ivan Ivic; Balazs D. Fulop; Tamás Juhász; Dora Reglődi; Gábor Tóth; Hitoshi Hashimoto; Andrea Tamas; Ákos Koller; Nadine Haase; Constantin Rüder; Hannelore Haase; Stefanie Kamann; Michiyoshi Kouno; Ingo Morano; Ralf Dechend; Dietlind Zohlnhöfer; Tobias Haase; Futian Tang; Meihui Yin; Qianqian Liu; Lan Yu; Yueyan Yang; Meili Lu; Hongxin Wang; Duosheng Luo; Xianglu Rong; Jiao Guo; Roberto Pecoits-Filho; Giane Favretto; Lauro M. Souza; Paulo C. Gregório; Regiane S. Cunha; Rayana A.P. Maciel; Guilherme L. Sassaki; Maria G. Toledo; Wesley M. Souza; Andréa E.M. Stinghen; Stavros Giaglis; Satz Mengensatzproduktion; Druckerei Stückle. Membership of the ESM. Journal of Vascular Research 2017, 54, 194 -194.

AMA Style

Manuela Martins-Green, Yan Liu, Xue Lian Chen, Lei Wang, Alkistis Kapelouzou, Alkiviadis Kostakis, Michalis Peroulis, Michalis Katsimpoulas, Petros Moustardas, Chrysostomos V. Aravanis, Panagiotis E. Karayannakos, Dennis V. Cokkinos, Ivan Ivic, Balazs D. Fulop, Tamás Juhász, Dora Reglődi, Gábor Tóth, Hitoshi Hashimoto, Andrea Tamas, Ákos Koller, Nadine Haase, Constantin Rüder, Hannelore Haase, Stefanie Kamann, Michiyoshi Kouno, Ingo Morano, Ralf Dechend, Dietlind Zohlnhöfer, Tobias Haase, Futian Tang, Meihui Yin, Qianqian Liu, Lan Yu, Yueyan Yang, Meili Lu, Hongxin Wang, Duosheng Luo, Xianglu Rong, Jiao Guo, Roberto Pecoits-Filho, Giane Favretto, Lauro M. Souza, Paulo C. Gregório, Regiane S. Cunha, Rayana A.P. Maciel, Guilherme L. Sassaki, Maria G. Toledo, Wesley M. Souza, Andréa E.M. Stinghen, Stavros Giaglis, Satz Mengensatzproduktion, Druckerei Stückle. Membership of the ESM. Journal of Vascular Research. 2017; 54 (3):194-194.

Chicago/Turabian Style

Manuela Martins-Green; Yan Liu; Xue Lian Chen; Lei Wang; Alkistis Kapelouzou; Alkiviadis Kostakis; Michalis Peroulis; Michalis Katsimpoulas; Petros Moustardas; Chrysostomos V. Aravanis; Panagiotis E. Karayannakos; Dennis V. Cokkinos; Ivan Ivic; Balazs D. Fulop; Tamás Juhász; Dora Reglődi; Gábor Tóth; Hitoshi Hashimoto; Andrea Tamas; Ákos Koller; Nadine Haase; Constantin Rüder; Hannelore Haase; Stefanie Kamann; Michiyoshi Kouno; Ingo Morano; Ralf Dechend; Dietlind Zohlnhöfer; Tobias Haase; Futian Tang; Meihui Yin; Qianqian Liu; Lan Yu; Yueyan Yang; Meili Lu; Hongxin Wang; Duosheng Luo; Xianglu Rong; Jiao Guo; Roberto Pecoits-Filho; Giane Favretto; Lauro M. Souza; Paulo C. Gregório; Regiane S. Cunha; Rayana A.P. Maciel; Guilherme L. Sassaki; Maria G. Toledo; Wesley M. Souza; Andréa E.M. Stinghen; Stavros Giaglis; Satz Mengensatzproduktion; Druckerei Stückle. 2017. "Membership of the ESM." Journal of Vascular Research 54, no. 3: 194-194.

Journal article
Published: 05 May 2017 in Journal of Vascular Research
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Organic anion transporters (OATs) are involved in the uptake of uremic toxins such as p-cresyl sulfate (PCS) and indoxyl sulfate (IS), which play a role in endothelial dysfunction in patients with chronic kidney diseases (CKD). In this study, we investigated the role of OAT1 and OAT3 in the uptake of PCS and IS into human endothelial cells. PCS was synthesized via p-cresol sulfation and characterized using analytical methods. The cells were treated with PCS and IS in the absence and presence of probenecid (Pb), an OAT inhibitor. Cell viability was assessed using the MTT assay. The absorbed toxins were analyzed using chromatography, OAT expression using immunocytochemistry and western blot, and monocyte chemoattractant protein-1 (MCP-1) expression using enzyme-linked immunosorbent assay. Cell viability decreased after toxin treatment in a dose-dependent manner. PCS and IS showed significant internalization after 60 min treatment, while no internalization was observed in the presence of Pb, suggesting that OATs are involved in the transport of both toxins. Immunocytochemistry and western blot demonstrated OAT1 and OAT3 expression in endothelial cells. MCP-1 expression increased after toxins treatment but decreased after Pb treatment. PCS and IS uptake were mediated by OATs, and OAT blockage could serve as a therapeutic strategy to inhibit MCP-1 expression.

ACS Style

Giane Favretto; Lauro Souza; Paulo C. Gregório; Regiane S. Cunha; Rayana A.P. Maciel; Guilherme L. Sassaki; Maria G. Toledo; Roberto Pecoits-Filho; Wesley M. Souza; Andréa E.M. Stinghen. Role of Organic Anion Transporters in the Uptake of Protein-Bound Uremic Toxins by Human Endothelial Cells and Monocyte Chemoattractant Protein-1 Expression. Journal of Vascular Research 2017, 54, 170 -179.

AMA Style

Giane Favretto, Lauro Souza, Paulo C. Gregório, Regiane S. Cunha, Rayana A.P. Maciel, Guilherme L. Sassaki, Maria G. Toledo, Roberto Pecoits-Filho, Wesley M. Souza, Andréa E.M. Stinghen. Role of Organic Anion Transporters in the Uptake of Protein-Bound Uremic Toxins by Human Endothelial Cells and Monocyte Chemoattractant Protein-1 Expression. Journal of Vascular Research. 2017; 54 (3):170-179.

Chicago/Turabian Style

Giane Favretto; Lauro Souza; Paulo C. Gregório; Regiane S. Cunha; Rayana A.P. Maciel; Guilherme L. Sassaki; Maria G. Toledo; Roberto Pecoits-Filho; Wesley M. Souza; Andréa E.M. Stinghen. 2017. "Role of Organic Anion Transporters in the Uptake of Protein-Bound Uremic Toxins by Human Endothelial Cells and Monocyte Chemoattractant Protein-1 Expression." Journal of Vascular Research 54, no. 3: 170-179.

Review
Published: 17 April 2017 in Toxins
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Recently, the clinical and experimental evidences that support the toxic effects of indoxyl sulfate, a protein-bound uremic toxin in chronic kidney disease (CKD) patients, has been discussed. In this panorama, the authors described several in vitro and in vivo studies, suggesting that indoxyl sulfate may play a part in the pathogenesis of low turnover bone disease. However, the discussion claims the need for relevant clinical studies in CKD patients whose bone turnover biomarkers and bone histomorphometry were assessed in order to demonstrate the association between serum levels of indoxyl sulfate and bone turnover. We would like to underline the availability of this clinical data to support the concept that indoxyl sulfate may play a part in the pathogenesis of low turnover bone disease in CKD patients.

ACS Style

Fellype C. Barreto; Daniela V. Barreto; Andrea E. M. Stinghen; Ziad A. Massy. Comment on Indoxyl Sulfate-Review of Toxicity and Therapeutic Strategies. Toxins 2016, 8, 358. Toxins 2017, 9, 142 .

AMA Style

Fellype C. Barreto, Daniela V. Barreto, Andrea E. M. Stinghen, Ziad A. Massy. Comment on Indoxyl Sulfate-Review of Toxicity and Therapeutic Strategies. Toxins 2016, 8, 358. Toxins. 2017; 9 (4):142.

Chicago/Turabian Style

Fellype C. Barreto; Daniela V. Barreto; Andrea E. M. Stinghen; Ziad A. Massy. 2017. "Comment on Indoxyl Sulfate-Review of Toxicity and Therapeutic Strategies. Toxins 2016, 8, 358." Toxins 9, no. 4: 142.