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1.
Bratisl Lek Listy ; 120(9): 630-635, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31475544

RESUMO

OBJECTIVES: To test the hypothesis if mitochondrial bioenergetic function analyzed in circulating platelets may represent peripheral signature of mitochondrial dysfunction in nephropathy associated to non-communicable human diseases such as cardiovascular diseases, diabetes and with statins treatment. METHODS: High-resolution respirometry was used for analysis of mitochondrial bioenergetics in human platelets isolated from peripheral blood. This method is less-invasively compared to skeletal muscle biopsy. Patients with nephropathies and in combination with non-communicable diseases were included in the study. RESULTS: This pilot study showed platelet mitochondrial bioenergy dysfunction in patients with nephropathies and non-communicable diseases. Positive effect of treatment with 10 mg atorvastatin on platelet mitochondrial respiratory chain Complex I-linked respiration and ATP production in patients with nephropathies, diabetes and 80 mg atorvastatin in patient with nephropathy and dialysis was found. Positive effect of 80 mg fluvastatin treatment, and negative effect of thrombocytopenia and renal transplantation on platelet mitochondrial bioenergy was determined. CONCLUSION: High-resolution respirometry allowed detection of small changes in platelet mitochondrial function. This method could be used as a sensitive bioenergetic test of mitochondrial function for diagnosis and monitoring the therapy in patients with nephropathy (Tab. 1, Fig. 3, Ref. 39).


Assuntos
Plaquetas/metabolismo , Metabolismo Energético , Nefropatias/metabolismo , Mitocôndrias/metabolismo , Doenças não Transmissíveis , Respiração Celular , Humanos , Projetos Piloto
3.
Toxicol Lett ; 314: 63-74, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31306741

RESUMO

This study aimed to verify the toxic effects of prenatal caffeine exposure (PCE) on the podocyte development in male offspring, and to explore the underlying intrauterine programming mechanisms. The pregnant rats were administered with caffeine (30 to 120 mg/kg⋅d) during gestational day (GD) 9 to 20. The male fetus on GD20 and the offspring at postnatal week (PW) 6 and PW28 were sacrificed. The results indicated that PCE caused ultrastructural abnormalities on podocyte, and inhibited the expression of podocyte marker genes such as Nephrin, Wilms tumor 1 (WT1), the histone 3 lysine 9 acetylation (H3K9ac) level in the Kruppel-like factor 4 (KLF4) promoter and its expression in the male offspring from GD20 to PW28. Meanwhile, the expression of glucocorticoid receptor (GR) and histone deacetylase 7 (HDAC7) in the fetus were increased by PCE. In vitro, corticosterone increased GR and HDAC7 whereas reduced the H3K9ac level of KLF4 and KLF4/Nephrin expression. KLF4 over-expression reversed the reduction of Nephrin expression, knockdown of HDAC7 and GR antagonist RU486 partially reversed the inhibitory effects of corticosterone on H3K9ac level and KLF4 expression. In conclusion, PCE caused podocyte developmental toxicity in male offspring, which was associated with corticosterone-induced low-functional programming of KLF4 through GR/HDAC7/H3K9ac pathway.


Assuntos
Cafeína/toxicidade , Estimulantes do Sistema Nervoso Central/toxicidade , Histonas/metabolismo , Nefropatias/induzido quimicamente , Fatores de Transcrição Kruppel-Like/metabolismo , Podócitos/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Acetilação , Animais , Células Cultivadas , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Idade Gestacional , Glucocorticoides/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Nefropatias/embriologia , Nefropatias/genética , Nefropatias/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Lisina , Masculino , Exposição Materna , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Fenótipo , Podócitos/metabolismo , Podócitos/ultraestrutura , Gravidez , Regiões Promotoras Genéticas , Ratos Wistar , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Transdução de Sinais/efeitos dos fármacos
4.
Cell Biochem Funct ; 37(6): 443-451, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31317578

RESUMO

Renal cells need oxygen for homeostasis; it is known for adjusting cellular functioning and the energy obtainment have a broad relationship with cellular respiration, through the O2 bioavailability. O2 homeostasis regulation in the kidney is mediated by hypoxia-inducible factors (HIFs). HIF is divided into three α isoforms, represented by HIF-1α, HIF-2α, and HIF-3α in addition to three paralogs of HIF-1ß; these are involved in some metabolic processes, as well as in the pathogenesis of several diseases. Renal biopsy analyses of patients and experimental animal models aim to understand the relationship between HIF and protection against developing renal diseases or the induction of their onset, being thus this molecule can be considered a potential biomarker of renal disease. We carried out a systematic review to which we included studies on HIF-1α and renal disease in the last 5 years (2013-2018) in researches with humans and/or animal model through searches in three databases: LILACS, PubMed, and SciELO by two researchers. We obtained 22 articles that discussed the relationship with HIF as inductor or protector against renal disease and no relation between HIF and renal. We observed controversies remain regarding the relation between of HIF with renal diseases; this may be related to the different intracellular pathways mediated by HIF-1α, thereby determining differentiated cellular responses.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Nefropatias/metabolismo , Animais , Biomarcadores/metabolismo , Humanos , Nefropatias/patologia
5.
Nat Commun ; 10(1): 2832, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31249312

RESUMO

Defining cellular and molecular identities within the kidney is necessary to understand its organization and function in health and disease. Here we demonstrate a reproducible method with minimal artifacts for single-nucleus Droplet-based RNA sequencing (snDrop-Seq) that we use to resolve thirty distinct cell populations in human adult kidney. We define molecular transition states along more than ten nephron segments spanning two major kidney regions. We further delineate cell type-specific expression of genes associated with chronic kidney disease, diabetes and hypertension, providing insight into possible targeted therapies. This includes expression of a hypertension-associated mechano-sensory ion channel in mesangial cells, and identification of proximal tubule cell populations defined by pathogenic expression signatures. Our fully optimized, quality-controlled transcriptomic profiling pipeline constitutes a tool for the generation of healthy and diseased molecular atlases applicable to clinical samples.


Assuntos
Núcleo Celular/genética , Nefropatias/genética , Rim/metabolismo , Rim/patologia , Análise de Sequência de RNA/métodos , Idoso , Núcleo Celular/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Nefropatias/diagnóstico , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Células Mesangiais/metabolismo , Pessoa de Meia-Idade , Análise de Célula Única/métodos
6.
Int. j. morphol ; 37(2): 459-465, June 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1002243

RESUMO

Recent evidence has indicated that adipose tissue produces bioactive substances that contribute to obesity-related kidney disease, altering the renal function and structure. Eight of the AQPs are expressed in the kidney, where several of them contribute to water absorption and maintenance of body water balance. In the study, we mainly examined the localization of AQP2, AQP3 and V2R in renal medulla of Normal Diet (ND) and High-fat Diet (HFD) of rats, respectively. In renal medulla of HFD, immunolight microscopy revealed weak expression of AQP2 at the apical plasma membrane and intracellular vesicles of principal cells of the IMCD and OMCD. AQP3 and V2R expression also observed a decrease in immunolabelling in the IMCD and OMCD. It was suggested that excess lipid accumulation may lead to lipotoxicity and may be the major driver of organ dysfunction such as water reabsorption dysfunction, which may be resulted from abnormal response of rphan G-protein-coupled receptors in kidney.


La evidencia reciente ha indicado que el tejido adiposo produce sustancias bioactivas que contribuyen a la enfermedad renal relacionada con la obesidad, alterando la función y la estructura renal. Ocho de los AQP se expresan en el riñón, donde varios de ellos contribuyen a la absorción de agua y al mantenimiento del equilibrio hídrico corporal. En el estudio, examinamos principalmente la localización de AQP2, AQP3 y V2R en la médula renal de ratas con dieta normal (ND) y ratas con dieta alta en grasas (HFD). En la médula renal del grupo HFD, la microscopía electrónica de barrido reveló una expresión débil de AQP2 en la membrana plasmática apical y las vesículas intracelulares de las células principales de IMCD y OMCD. La expresión de AQP3 y V2R también observó una disminución en el inmunomarcador en IMCD y OMCD. Se sugiere que el exceso de acumulación de lípidos puede conducir a lipotoxicidad y ser el principal impulsor de la disfunción orgánica, como la disfunción de reabsorción de agua, que puede ser el resultado de la respuesta anormal de los receptores acoplados a proteína rphan G en el riñón.


Assuntos
Animais , Ratos , Receptores de Vasopressinas/metabolismo , Aquaporinas/metabolismo , Dieta Hiperlipídica , Nefropatias/metabolismo , Medula Renal/patologia , Obesidade , Imuno-Histoquímica , Ratos Sprague-Dawley , Aquaporina 1/metabolismo , Aquaporina 2/metabolismo , Medula Renal/metabolismo , Microscopia
7.
J Toxicol Sci ; 44(5): 317-326, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31068537

RESUMO

The purpose of this study was to explore whether renal endothelial cell injury is associated with oxidative stress in trichloroethylene (TCE)-induced immune kidney damage by detecting adhesion molecules and oxidative stress indexes. In this study, a mouse model of skin sensitization with the antioxidant Tempol was used to explore the mechanism. Blood urea nitrogen (BUN), creatinine (Cre), and histological examination were used for kidney function evaluation. Kidney homogenates were used for detecting renal nitric oxide (NO), nitric oxide synthase (NOS), superoxide dismutase (SOD) and malondialdehyde (MDA). Renal endothelial nitric oxide synthase (eNOS), E-selectin, vascular cell adhesion molecule (VCAM-1) and intercellular adhesion molecule (ICAM-1) protein levels were measured by immunohistochemical and Western blot. We found that BUN and Cre levels increased in the TCE sensitization positive group and the TCE+Tempol sensitization positive group. In the TCE sensitization positive group, a partial area of vacuolar degeneration and lysed epithelial cells were observed in renal tubules. In TCE+Tempol sensitization positive group, small areas were also found to be vacuolar degenerated and renal tubules were dissolved. Renal NO, NOS, SOD and eNOS levels decreased and MDA levels increased, renal E-selectin, VCAM-1and ICAM-1 protein levels increased in the TCE sensitization positive group and the TCE+Tempol sensitization positive group. Tempol attenuated TCE induced up-regulation of MDA, E-selectin, VCAM-1and ICAM-1 and down-regulation of NO, NOS, SOD and eNOS. In conclusion, trichloroethylene-sensitized mice renal immune injury is associated with the renal endothelial cells' oxidative stress state.


Assuntos
Células Endoteliais/efeitos dos fármacos , Haptenos/toxicidade , Nefropatias/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Solventes/toxicidade , Tricloroetileno/toxicidade , Animais , Antioxidantes/farmacologia , Óxidos N-Cíclicos/farmacologia , Dermatite Alérgica de Contato/metabolismo , Dermatite Alérgica de Contato/patologia , Selectina E/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Feminino , Molécula 1 de Adesão Intercelular/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Nefropatias/metabolismo , Nefropatias/patologia , Malondialdeído/metabolismo , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Marcadores de Spin , Superóxido Dismutase/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo
8.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(5): 528-532, 2019 May 30.
Artigo em Chinês | MEDLINE | ID: mdl-31140415

RESUMO

OBJECTIVE: To evaluate the changes in renal oxygenation in rats with acute aristolochic acid nephropathy using blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) at 7.0T. METHODS: Wistar rats were randomly divided into AAN group (n=18) and control group (n=6) for intraperitoneal injections of AAI at 40 mg/kg and PEG400, respectively, on a daily basis for 6 consecutive days. All the control rats and 6 rats from AAN group underwent BOLD MRI scan before and at 2, 4, and 6 days after the initial injection for measuring renal cortical and medullary R2* values. At each of the 4 time points, 3 rats in AAN group were sacrificed for histological evaluation; the control rats were examined at 6 days after the initial injection. RESULTS: The cortical and medullary R2* values of the rats in AAN group on days 4 and 6 were significantly higher than those in the control group (P < 0.05). In AAN group, the cortical R2* values showed no obvious changes on day 2 as compared with the baseline values, but increased significantly on day 4 (P < 0.05) and day 6 (P < 0.01); the medullary R2* values increased progressively and were significantly higher than the baseline values on day 4 (P < 0.01) and day 6 (P < 0.01). In the control group, no significant changes were detected in either cortical or medullary R2* values throughout the experiment. CONCLUSIONS: BOLD MRI allows non-invasive measurement of renal oxygenation levels in rats with AAN. The increase of renal cortical and medullary R2* values, and particularly the latter, indicates a lowered renal oxygenation level, which provides potentially useful information for clinical decisions.


Assuntos
Ácidos Aristolóquicos , Nefropatias , Oxigênio , Animais , Rim , Nefropatias/metabolismo , Imagem por Ressonância Magnética , Distribuição Aleatória , Ratos , Ratos Wistar
9.
Toxicol Lett ; 311: 27-36, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31039415

RESUMO

Methotrexate (MTX) is a derivate of folic acid, commonly used as an anchor drug for the treatment and management of malignant diseases and autoimmune disorders. However, nephrotoxicity is an important drawback of MTX therapy. Unfortunately, there are not enough studies reporting the nature of the renal failure induced by MTX. Thus, the aim of this study was to evaluate the time course of renal handling of water and electrolytes in male Wistar rats, after the exposure to a unique dose of MTX (80 mg/kg b.w.). Experiments were carried out at day 2, day 4, day 8 and day 14 after MTX administration. Several parameters of kidney function related to water and electrolytes handling were evaluated. Renal expression and urinary excretion of aquaporin-2 (AQP2) and Na-K-2Cl-cotransporter (NKCC2) were determined by Western blotting. MTX produced alterations on water handling on the second day after treatment, showing a significant increase in solute free water reabsorption which might be mediated by the increased expression of AQP2 in apical membranes. On the other hand, MTX produced alterations on electrolytes handling on the fourth day after treatment, showing a significant decrease of sodium chloride excretion, mediated at least in part, by the increase renal expression of NKCC2. These results provide valuable information to clinical practice in order to be able to find therapeutic targets that diminish adverse effects and health deterioration. Moreover, MTX treatment altered AQP2 and NKCC2 urinary excretion allowing postulating these transporters as potential biomarkers of MTX induced nephrotoxicity.


Assuntos
Aquaporina 2/metabolismo , Eletrólitos/metabolismo , Nefropatias/induzido quimicamente , Túbulos Renais/efeitos dos fármacos , Metotrexato/toxicidade , Reabsorção Renal/efeitos dos fármacos , Membro 1 da Família 12 de Carreador de Soluto/metabolismo , Água/metabolismo , Animais , Biomarcadores/metabolismo , Cloretos/metabolismo , Nefropatias/metabolismo , Túbulos Renais/metabolismo , Masculino , Potássio/metabolismo , Ratos Wistar , Sódio/metabolismo , Fatores de Tempo , Urodinâmica/efeitos dos fármacos
10.
Toxicol Lett ; 311: 17-26, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31039417

RESUMO

Prenatal ethanol exposure (PEE) causes intrauterine growth retardation (IUGR), and the occurrence of glomerulosclerosis is closely related to IUGR. This study aimed to confirm the kidney toxic effect of PEE and explore its intrauterine programming mechanism in female offspring. The Wistar female fetuses on gestational day (GD) 20 and the adult offspring at postnatal week 24 were anesthetized and decapitated. The adult offspring kidneys in the PEE group displayed glomerular hyperplasia and glomerulosclerosis. Blood urea nitrogen (BUN) and the BUN / Serum creatinine (Scr) concentration ratio in the PEE group was increased significantly compared to the control group (P<0.01, P<0.05). Meanwhile, the renal glucocorticoid-activation system was inhibited, whereas the insulin-like growth factor 1 (IGF1) signaling pathway was activated in the female adult offspring of the PEE group. In the fetal kidney of the PEE group, pathological observation showed kidney dysplasia, and the gene expression of the glial-cell-line-derived neurotrophic factor/tyrosine kinase receptor (GDNF/c-Ret) signaling pathway was reduced compared to that of the control group. Moreover, the glucocorticoid-activation system was activated, whereas the IGF1 signaling pathway was inhibited in the fetal kidneys of the PEE group. In conclusion, PEE caused fetal kidney dysplasia and adult glomerulosclerosis in the female offspring rats, and the intrauterine programming alteration of glucocorticoid-insulin-like growth factor 1 (GC-IGF1) axis might be involved in fetal-originated glomerulosclerosis.


Assuntos
Etanol/toxicidade , Glucocorticoides/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Nefropatias/induzido quimicamente , Glomérulos Renais/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Idade Gestacional , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Fator de Crescimento Insulin-Like I/genética , Nefropatias/genética , Nefropatias/metabolismo , Nefropatias/patologia , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Gravidez , Proteínas Proto-Oncogênicas c-ret/genética , Proteínas Proto-Oncogênicas c-ret/metabolismo , Ratos Wistar , Fatores Sexuais , Transdução de Sinais/efeitos dos fármacos
11.
Int J Mol Sci ; 20(8)2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31022990

RESUMO

The present investigation was executed to reveal the protective mechanism of rosmarinic acid (RA) against cadmium (Cd)-induced nephrotoxicity. RA exhibited a concentration-dependent anti-apoptotic effect against CdCl2 in isolated mouse proximal tubular epithelial cells. Cd treatment significantly (p < 0.01) imparted oxidative stress to the renal cells via excessive ROS production, triggering NO level, NADPH oxidase activation, and impairment of cellular redox defense system. Cd-mediated oxidative stress significantly (p < 0.01) endorsed apoptosis to the murine kidney cells by triggering NF-κB/PKC-δ/TNFR2 activation. In addition, CdCl2 induced renal fibrosis by triggering TGF-ß1/SMAD3/α-SMA/collagen signaling within renal cells. On the other hand, RA significantly (p < 0.05-0.01) attenuated Cd-provoked oxidative stress and associated pathological signal transduction in murine renal cells. RA treatment also could significantly (p < 0.05-0.01) reciprocate Cd-mediated pathological changes in blood and urine parameters in mice. In addition, histological data supported the pharmacological findings. In silico chemometric analyses predicted the possible interactions between RA and different signal proteins and anticipated drug-likeness characteristics of RA. Hence, RA can potentially be applied as a therapeutic agent to treat Cd-mediated nephrotoxicity in future.


Assuntos
Antioxidantes/uso terapêutico , Cádmio/toxicidade , Cinamatos/uso terapêutico , Depsídeos/uso terapêutico , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Fibrose , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Rim/metabolismo , Rim/patologia , Nefropatias/metabolismo , Nefropatias/patologia , Camundongos
12.
Mediators Inflamm ; 2019: 3496836, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31015795

RESUMO

Objective: Ischemia-reperfusion injury (IRI) produces systemic inflammation with the potential for causing organ failure in tissues peripheral to the initial site of injury. We speculate that treatment strategies that dampen inflammation may be therapeutically beneficial to either the initial site of injury or peripheral organs. To test this, we evaluated the impact of FTY720-induced sequestration of circulating mature lymphocytes on renal IRI and secondary organ injury. Methods: A microvascular clamp was surgically placed around the left renal pedicle of anesthetized male Sprague-Dawley rats with either vehicle or FTY720 treatment (0.3 mg/kg) intravenously injected after 15 min of ischemia. Blood flow was restored after 60 min. Cohorts of anesthetized rats were euthanized at 6, 24, or 72 hrs with tissue samples collected for analysis. Results: FTY720 treatment resulted in profound T lymphocyte reduction in peripheral blood. Histopathologic examination, clinical chemistries, and gene transcript expression measurements revealed that FTY720 treatment reduced hepatocellular degeneration, reduced serum markers of liver injury (ALT/AST), and reduced the expression of gene targets associated with IRI. Conclusion: These findings support an anti-inflammatory effect of FTY720 in the liver where the expression of genes associated with apoptosis, chemotaxis, and the AP-1 transcription factor was reduced. Findings presented here provide the basis for future studies evaluating FTY720 as a potential therapeutic agent to treat complications resulting from renal IRI.


Assuntos
Cloridrato de Fingolimode/uso terapêutico , Inflamação/tratamento farmacológico , Nefropatias/tratamento farmacológico , Animais , Modelos Animais de Doenças , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Nefropatias/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão , Fator de Transcrição AP-1/metabolismo
13.
Biomed Res Int ; 2019: 3851718, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30993112

RESUMO

We examined whether and how uric acid induces epithelial to mesenchymal transition (EMT) in renal tubular cells, along with the mechanism by which telmisartan acts on uric acid-induced renal injury. Rat renal proximal tubular epithelial cells (NRK-52E) were exposed to various concentrations of uric acid in the presence or absence of telmisartan. Treatment with uric acid increased the expression of α-SMA, decreased the expression of E-cadherin, and promoted EMT in NRK-52E cells. Uric acid treatment also led to increased endothelin-1 (ET-1) production, activation of extracellular-regulated protein kinase 1/2 (ERK1/2), and the upregulation of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4). Use of ET-1 receptor inhibitor (BQ123 or BQ788) could inhibit uric acid-induced EMT in NRK-52E cells. Pretreatment with the ERK inhibitor (U0126 or PD98059) suppressed the release of ET-1 and EMT induced by uric acid. Additionally, pretreatment with a traditional antioxidant (diphenylene iodonium or apocynin) inhibited the activation of ERK1/2, release of ET-1, and uric acid-induced EMT in NRK-52E cells. These findings suggested that uric acid-induced EMT in renal tubular epithelial cells occurs through NADPH oxidase-mediated ERK1/2 activation and the subsequent release of ET-1. Furthermore, telmisartan (102 nmol/L to 104 nmol/L) inhibited the expression of NOX4, intracellular reactive oxygen species (ROS), activation of ERK1/2, and the release of ET-1 in a dose-dependent manner, thereby preventing uric acid-induced EMT in NRK-52E. In conclusion, telmisartan could ameliorate uric acid-induced EMT in NRK-52E cells likely through inhibition of the NADPH oxidase/ERK1/2/ET-1 pathway.


Assuntos
Antioxidantes/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Nefropatias/metabolismo , Túbulos Renais Proximais/metabolismo , Telmisartan/farmacologia , Animais , Caderinas/metabolismo , Linhagem Celular , Nefropatias/induzido quimicamente , Nefropatias/patologia , Túbulos Renais Proximais/patologia , NADPH Oxidase 4/metabolismo , Ratos , Ácido Úrico/toxicidade
14.
Int J Mol Sci ; 20(7)2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30939806

RESUMO

Lipid disorders have been associated with glomerulopathies, a distinct type of renal pathologies, such as nephrotic syndrome. Global analyses targeting kidney lipids in this pathophysiologic context have been extensively performed, but most often regardless of the architectural and functional complexity of the kidney. The new developments in mass spectrometry imaging technologies have opened a promising field in localized lipidomic studies focused on this organ. In this article, we revisit the main works having employed the Matrix Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) technology, and the few reports on the use of TOF-Secondary Ion Mass Spectrometry (TOF-SIMS). We also present a first analysis of mouse kidney cortex sections by cluster TOF-SIMS. The latter represents a good option for high resolution lipid imaging when frozen unfixed histological samples are available. The advantages and drawbacks of this developing field are discussed.


Assuntos
Nefropatias/metabolismo , Glomérulos Renais/metabolismo , Metabolismo dos Lipídeos , Espectrometria de Massas/métodos , Animais , Humanos , Nefropatias/diagnóstico por imagem , Glomérulos Renais/diagnóstico por imagem
15.
Biochem Cell Biol ; 97(2): 176-186, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30933551

RESUMO

This study was designed to evaluate the possible mechanisms through which Echinops spinosus (ES) extract demonstrates nephroprotective effect on the paracetamol acetominophen (N-acetyl-p-aminophenol (APAP)) induced nephrotoxicity in rats. Twenty-four Swiss albino rats were divided into four groups (six rats each). The placebo group was orally administered sterile saline, the APAP group received APAP (200 mg·kg-1·day-1 i.p.) daily, the ES group was given ES extract orally (250 mg/kg), and the APAP + ES group received APAP as for the APAP group and administrated the ES extract as for the ES group. Pretreatment of methyl alcohol extract of ES reduced the protein expression of inflammatory parameters including cyclooxygenase-2 and nuclear factor κB in the kidney. It also reduced the mRNA gene expression of tumor necrosis factor-α and interleukin-1ß. The ES extract compensated for deficits in the total antioxidant activity, suppressed lipid peroxidation, and amended the APAP-induced histopathological kidney alterations. Moreover, ES treatment restored the elevated levels of urea nitrogen in the blood and creatinine in the serum by APAP. The ES extract attenuated the APAP-induced elevations in renal nitric oxide levels. We clarified that the ES extract has the potential to defend the kidney from APAP-induced inflammation, and the protection mechanism might be through decreasing oxidative stress and regulating the inflammatory signaling pathway through modulating key signaling inflammatory biomarkers.


Assuntos
Acetaminofen/efeitos adversos , Echinops (Planta)/química , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Rim/metabolismo , Extratos Vegetais/farmacologia , Acetaminofen/farmacologia , Animais , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Rim/patologia , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Extratos Vegetais/química , Ratos
16.
Int J Mol Sci ; 20(7)2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30934817

RESUMO

Patients with chronic kidney disease (CKD) have an increased risk of developing vascular calcifications, as well as bone dynamics impairment, leading to a poor quality of life and increased mortality. Certain vitamin K dependent proteins (VKDPs) act mainly as calcification inhibitors, but their involvement in the onset and progression of CKD are not completely elucidated. This review is an update of the current state of knowledge about the relationship between CKD and four extrahepatic VKDPs: matrix Gla protein, osteocalcin, growth-arrest specific protein 6 and Gla-rich protein. Based on published literature in the last ten years, the purpose of this review is to address fundamental aspects about the link between CKD and circulating VKDPs levels as well as to raise new topics about how the interplay between molecular weight and charge could influence the modifications of circulating VKDPs at the glomerular level, or whether distinct renal etiologies have effect on VKDPs. This review is the output of a systematic literature search and may open future research avenues in this niche domain.


Assuntos
Nefropatias/metabolismo , Proteínas/metabolismo , Vitamina K/metabolismo , Animais , Humanos , Diálise Renal
17.
Hematology ; 24(1): 426-438, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30947625

RESUMO

OBJECTIVES: Beta-thalassemias are a group of recessively autosomal inherited disorders of hemoglobin synthesis, which, due to mutations of the beta-globin gene, lead to various degrees of defective beta-chain production, an imbalance in alpha/beta-globin chain synthesis, ineffective erythropoiesis, and anemia. Improved survival in thalassemic patients has led to the emergence of previously unrecognized complications, such as renal disease. METHODS: A comprehensive literature review through PubMed was undertaken to summarize the published evidence on the epidemiology and pathophysiology of renal disease in thalassemia. Literature sources published in English since 1990 were searched, using the terms beta-thalassemia, renal disease. RESULTS: Renal disease is considered to be the 4th cause of morbidity among patients with transfusion dependent thalassemia. Chronic anemia, hypoxia and iron overload are the main mechanisms implicated in development of renal injury, whereas several studies also suggested a contributive role of iron chelators. DISCUSSION AND CONCLUSION: Kidney disease may develop through progressive renal tubular and glomerular damage; thus, its early recognition is important in order to prevent and/or reverse deterioration. This review will provide an insight on the involved mechanisms implicated in kidney disease in thalassemic patients and will discuss the updates on diagnosis and prevention of renal complications in thalassemia.


Assuntos
Hipóxia , Sobrecarga de Ferro , Nefropatias , Talassemia beta , Feminino , Humanos , Hipóxia/complicações , Hipóxia/metabolismo , Hipóxia/mortalidade , Hipóxia/terapia , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/mortalidade , Sobrecarga de Ferro/terapia , Nefropatias/etiologia , Nefropatias/metabolismo , Nefropatias/mortalidade , Nefropatias/terapia , Masculino , Talassemia beta/complicações , Talassemia beta/metabolismo , Talassemia beta/mortalidade , Talassemia beta/terapia
18.
Ren Fail ; 41(1): 211-219, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30943799

RESUMO

AIM: Stearoyl-CoA desaturase (SCD)-1 and elongase-6 (Elovl-6) are associated with fatty acid (FA) synthesis. We evaluated the effect of omega-3 FA on erythrocyte membrane FA contents through SCD-1 and Elovl-6 expression in the liver and kidney of a cyclosporine (CsA)-induced rat model. METHODS: Male Sprague Dawley rats were divided into control, CsA, and CsA treated with omega-3 FA groups. We measured SCD-1 and Elovl-6 expression levels via western blot and immunohistochemistry analysis. RESULTS: Erythrocyte membrane oleic acid content was lower in the CsA with omega-3 FA group compared to the CsA group. Compared to the control group, CsA-induced rats showed elevated SCD-1 expression in the kidney and liver, which omega-3 FA treatment reversed. Elovl-6 expression was increased in the liver, but decreased in the kidney in CsA group compared to control, which omega-3 FA treatment also reversed. CONCLUSIONS: Omega-3 FA supplementation decreased erythrocyte membrane oleic acid content by modulating SCD-1 and Elovl-6 expression in the kidney and liver of CsA-induced rats.


Assuntos
Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Nefropatias/tratamento farmacológico , Ácido Oleico/metabolismo , Estearoil-CoA Dessaturase/metabolismo , Acetiltransferases/metabolismo , Animais , Membrana Celular/metabolismo , Ciclosporina/toxicidade , Modelos Animais de Doenças , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Nefropatias/sangue , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Ratos , Ratos Sprague-Dawley
19.
Ecotoxicol Environ Saf ; 176: 234-241, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-30939403

RESUMO

The present study aimed to explore the repair effect and mechanism of bone marrow mesenchymal stem cells (BMSCs) transplantation on injured kidneys caused by hexavalent chromium (Cr (VI)). Wistar rats were intraperitoneally injected with 0.4 mg/kg•bw Cr (VI) ion solution. After 30 days, 1 × 107 BMSCs were transplanted into rats. After cell transplantation for 2 weeks, there was no significant difference in the chromium content between the model and BMSCs-therapy group by atomic absorption spectrometry. In BMSCs-therapy group, the renal organ index, the serum levels of blood urea nitrogen (BUN) and creatinine (CRE), malonaldehyde (MDA) content were significantly decreased, superoxide dismutase (SOD) activity was significantly elevated, and the pathological changes were improved compared with the model group. The results of immunohistochemical and western blot assays showed that the expressions of apoptosis-related proteins Bax, Cytochrome c, and Caspase-3, as well as autophagy-associated proteins Beclin 1, PINK1, Parkin, p-Parkin, LC3B, and the MAPK signaling pathway, including the ratio of p-p38 to p38 and p-JNK to JNK were all significantly decreased, Bcl-2 and p62 expressions, and the ratio of p-ERK to ERK were significantly elevated in BMSCs-therapy group compared with the model group. These results suggested that BMSCs repaired Cr (VI)-injured kidney through decreasing mitochondria-mediated apoptosis and mitophagy mediated by downregulating phosphorylation of p38 and JNK, upregulating phosphorylation of ERK.


Assuntos
Apoptose/efeitos dos fármacos , Cromo/toxicidade , Nefropatias/terapia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Transplante de Células-Tronco Mesenquimais , Degradação Mitocondrial/efeitos dos fármacos , Animais , Autofagia/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Nefropatias/metabolismo , Nefropatias/patologia , Testes de Função Renal , Masculino , Fosforilação , Ratos , Ratos Wistar
20.
Medicine (Baltimore) ; 98(17): e15350, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31027115

RESUMO

Glomerulocystic kidney (GCK) is often associated with genetic disorders and identified in children or adolescents. However, there are some case reports describing sporadic adult GCK identified by magnetic resonance imaging (MRI). The purpose of this study was to evaluate relationship of GCK identified by MRI in older patients to renal function and renal corticomedullary differentiation (CMD) assessed by MRI.GCK was identified in 16 older patients (mean age, 79.2 years) by T2-weighted imaging. The cysts of GCK were numerous, homogeneously small, and located in the renal cortex on T2-weighted images. Ten of the 16 patients with GCK had renal impairment (estimated glomerular filtration rate <60 ml/min/1.73 m). Six patients who had GCK, chronic liver disease, and renal impairment showed moderate or good CMD.GCK identified by MRI may be related to renal impairment in some older patients, including those with preserved CMD as a result of chronic liver diseases.


Assuntos
Nefropatias/diagnóstico por imagem , Rim/diagnóstico por imagem , Imagem por Ressonância Magnética , Idoso , Idoso de 80 Anos ou mais , Doença Hepática Terminal/complicações , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/metabolismo , Nefropatias/complicações , Nefropatias/metabolismo , Masculino
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