Renal ischemia-reperfusion injury (IRI) is histologically characterized by tubular cell death. Diverse pathways of regulated cell death (RCD) have been reported to contribute to renal IRI in recent studies. In this review, we discuss the signaling pathways, regulators and crosstalk of RCD, including necroptosis, ferroptosis and pyroptosis, and their role in renal IRI in order to pave the way for new therapeutic opportunities.
Subject(s)Apoptosis , Ferroptosis , Humans , Kidney/metabolism , Necroptosis , Regulated Cell Death , Reperfusion Injury/drug therapy
Hypertension is one of the strongest risk factors for cardiovascular diseases, cerebral stroke, and kidney failure. Lifestyle and nutrition are important factors that modulate blood pressure. Hypertension can be controlled by increasing physical activity, decreasing alcohol and sodium intake, and stopping tobacco smoking. Chronic kidney disease patients often have increased blood pressure, which indicates that kidney is one of the major organs responsible for blood pressure homeostasis. The decrease of renal sodium reabsorption and increase of diuresis induced by high potassium intake is critical for the blood pressure reduction. The beneficial effect of a high potassium diet on hypertension could be explained by decreased salt reabsorption by sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT). In DCT cells, NCC activity is controlled by with-no-lysine kinases (WNKs) and its down-stream target kinases, Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress-responsive 1 (OSR1). The kinase activity of WNKs is inhibited by intracellular chloride ([Cl-]i) and WNK4 is known to be the major WNK positively regulating NCC. Based on our previous studies, high potassium intake reduces the basolateral potassium conductance, decreases the negativity of DCT basolateral membrane (depolarization), and increases [Cl-]i. High [Cl-]i inhibits WNK4-SPAK/OSR1 pathway, and thereby decreases NCC phosphorylation. In this review, we discuss the role of DCT in the blood pressure regulation by dietary potassium intake, which is the mechanism that has been best dissected so far.
Subject(s)Blood Pressure , Diet , Humans , Kidney/metabolism , Kidney Tubules, Distal/metabolism , Phosphorylation , Potassium/pharmacology , Protein Serine-Threonine Kinases , Solute Carrier Family 12, Member 3/metabolism
Vascular endothelial growth factor-A (VEGF-A) is a critical angiogenic factor which is mainly secreted from podocytes and epithelial cells in kidney and plays an important role in renal pathophysiology. In recent years, functions of different isoforms of VEGF-A and the new secretion approach via extracellular vesicles (EVs) have been identified. Thus, further understanding are needed for the role of VEGF-A and its isoforms in renal injury and repair. In this review, we summarized the expression, secretion and regulation of VEGF-A, its biological function, and the role of different isoforms of VEGF-A in the development of different renal diseases. Meanwhile, the research progress of VEGF-A as diagnostic marker and therapeutic target for renal diseases were discussed.
Subject(s)Humans , Kidney/metabolism , Kidney Diseases , Protein Isoforms/metabolism , Vascular Endothelial Growth Factor A/physiology
The kidney is one of the main target organs involved in hypertension, and it regulates water and salt metabolism, blood volume and vascular resistance. High salt intake induces salt and water retention, persistent endothelial dysfunction and elevation of blood pressure in salt sensitive individuals. Dahl salt sensitive (Dahl-SS) rats, as a classic animal model for salt sensitive hypertension, have many similar stably inherited physiological characteristics to human with salt sensitive hypertension, such as salt sensitivity, hyperlipidemia, insulin resistance, renal failure, increased urinary protein secretion and low plasma renin activity. Based on renal physiology and biochemistry researches and multi-omics analyses in Dahl-SS rats, this review will summarize the relationship between salt sensitive hypertension and renal redox, NO, amino acids, glucose and lipid metabolism.
Subject(s)Animals , Blood Pressure , Hypertension , Kidney/metabolism , Rats , Rats, Inbred Dahl , Sodium Chloride, Dietary
Wnt/β-catenin is an evolutionarily conserved, complex developmental signal pathway that regulates embryogenesis, cell fate, tissue homeostasis, injury repair, and the pathogenesis of human diseases. Mounting evidence demonstrates that Wnt/β-catenin signaling plays a key role in early nephrogenesis. It is relatively silent in normal adult kidneys but reactivated in a wide variety of animal models of nephropathies and in human kidney diseases. Activation of Wnt/β-catenin after acute kidney injury contributes to proper repair and regeneration of damaged renal tubules. However, sustained activation of this signal cascade is closely related to the development and progression of fibrotic chronic kidney disease. In this paper, we systematically review the components and mechanisms of Wnt/β-catenin signaling and its role in kidney repair and fibrosis after injury. A better delineation of the mechanisms of this pathway will provide novel targets and new strategies for designing effective treatment of various kidney diseases.
Subject(s)Animals , Fibrosis , Humans , Kidney/metabolism , Renal Insufficiency, Chronic , Wnt Signaling Pathway , beta Catenin/metabolism
Acute kidney injury (AKI) refers to a clinical syndrome in which renal function declines rapidly in a short period of time caused by various pathological factors. During the development of AKI, renal tubules with the functions of reabsorption and excretion are prone to cell death due to external pathological stimuli, which is an important cause of impaired renal function. In recent years, a variety of new cell death pathways have been gradually recognized. Researchers have now found that regulated cell death (RCD), such as necroptosis, pyroptosis and ferroptosis, are important regulatory mechanisms of AKI. This article will summarize the research advances of various types of RCD involved in the process of AKI, aiming to deepen the understanding of AKI and provide innovative thoughts for the clinical treatment of AKI.
Subject(s)Acute Kidney Injury/metabolism , Cell Death , Humans , Kidney/metabolism , Necroptosis , Necrosis/pathology , Regulated Cell Death
SUMMARY: Water metabolism in kidney is critical for organisms living in arid environments. In this study, the kidney structure and the expression of AQP1 and AQP2 in Phrynocephalus vlangalii and Camelus bactrianus were studied. It was found that the Phrynocephalus vlangalii has fewer renal corpuscle but developed kidney tubules, and AQP1 and AQP2 were mainly expressed in the kidney tubules. Camelus bactrianus has a large diameter of glomerulus, thick bulbar membrane, and long and dense urinary tract. AQP1 was highly expressed in the proximal convoluted tubule, proximal straight tubule, and Ansa nephroni (Henle´s loop), and AQP2 was also highly expressed in the collecting tubule and distal convoluted tubule. In the long-term evolutionary adaptation, the morphological structure of animal kidney is consistent with its environment. In addition to structural and functional adaptation, aquaporin also participates in the adaptation to water scarcity environment, and may also play a key role.
RESUMEN: El metabolismo del agua en los riñones es fundamental para los organismos que viven en ambientes áridos. En este estudio, se estudió la estructura renal y la expresión de AQP1 y AQP2 en Phrynocephalus vlangalii y Camelus bactrianus. Se encontró que Phrynocephalus vlangalii tiene menos corpúsculos renales. pero desarrolló túbulos renales, y AQP1 y AQP2 se expresaron principalmente en los túbulos renales. Camelus bactrianus tiene un glomérulo de gran diámetro, una membrana bulbar gruesa y un tracto urinario largo y denso. AQP1 se expresó en gran medida en el túbulo contorneado proximal, el túbulo recto proximal y el Ansa nephroni o asa nefrónica (asa de Henle), y AQP2 también se expresó en gran medida en el túbulo colector y el túbulo contorneado distal. A largo plazo, en la adaptación evolutiva la estructura morfológica del riñón animal es coherente con su entorno. Además de la adaptación estructural y funcional, la acuaporina también es parte de la adaptación al entorno de escasez de agua y puede desempeñar un papel clave.
Subject(s)Animals , Camelus , Aquaporins/pharmacokinetics , Kidney/anatomy & histology , Kidney/metabolism , Immunohistochemistry
It is known that the combined use of antibiotics, such as isoniazid and rifampicin, in the treatment of tuberculosis causes oxidative kidney damage. The aim of this study was to biochemically and histopathologically investigate the effect of lycopene on oxidative kidney damage due to the administration of isoniazid and rifampicin in albino Wistar male rats. Lycopene at a dose of 5 mg/kg was orally administered to lycopene+isoniazid+rifampicin (LIR) rats, and normal sunflower oil (0.5 mL) was orally administered to isoniazid+rifampicin (IR) and healthy control (HG) rats as vehicle by gavage. One hour after the administration of lycopene and vehicle, 50 mg/kg isoniazid and rifampicin were given orally to the LIR and IR groups. This procedure was performed once a day for 28 days. Rats were sacrificed by a high dose of anesthesia at the end of this period, and oxidant-antioxidant parameters were measured in the removed kidney tissues. Creatinine and blood urea nitrogen (BUN) levels were measured in blood samples, and kidney tissues were also evaluated histopathologically. The combined administration of isoniazid and rifampicin changed the oxidant-antioxidant balance in favor of oxidants, and it increased blood urea nitrogen and creatinine levels, which are indicators of kidney function. Co-administration of isoniazid and rifampicin also caused oxidative kidney damage. Lycopene biochemically and histopathologically decreased oxidative kidney damage induced by isoniazid and rifampicin administration. These results suggested that lycopene may be beneficial in the treatment of nephrotoxicity due to isoniazid and rifampicin administration.
Subject(s)Animals , Male , Rats , Rifampin/toxicity , Isoniazid/toxicity , Carotenoids/metabolism , Oxidative Stress , Lycopene/metabolism , Kidney/metabolism , Antioxidants/metabolism
OBJECTIVES To determine the role of the RBP4/PiC/SIRT3 signaling pathway in the opening of the mitochondria permeability transition pore (mPTP) in offspring rats with hypothyroidism during pregnancy. METHODS Sixty Sprague-Dawley (SD) rats were employed in this study. Pregnancy was deemed successful when a sperm was found in the uterus. After one week of pregnancy, offspring rats were divided into the following groups: overall hypothyroidism group (OH group), subclinical hypothyroidism group (SCH group), and normal control group (CON group). The establishment of the hypothyroidism model was confirmed when the serum thyroid stimulating hormone (TSH) levels were higher than normal value and TT4 level was within the normal range. The renal mitochondria of offspring rats were extracted on the 14th postnatal day (P14) and 35th postnatal day (P35). RESULTS At P14, no significant differences in the degree of mPTP opening and expression of phosphoric acid carrier vector (PiC) were detected between the rats in the OH group and the SCH group. However, the expression level of silent mating-type information regulation 3 homolog (SIRT3) was markedly reduced. Retinol-binding protein 4 (RBP4) expression increased in the rats from the OH group, relative to that in those from the SCH group. At P35, the degree of mPTP opening and the expression levels of PiC and RBP4 in the OH group were higher than those in the SCH group. However, SIRT3 expression in the OH group was lower than that observed in the SCH group. CONCLUSION RBP4 plays an important role in early renal mitochondrial damage and renal impairment in rats suffering from hypothyroidism during pregnancy. The RBP4/PiC/SIRT3 pathway is thus involved in the opening of the renal mPTP in offspring rats with hyperthyroidism.
Subject(s)Animals , Female , Pregnancy , Rats , Pregnancy Complications , Hypothyroidism/complications , Hypothyroidism/chemically induced , Kidney/metabolism , Kidney/pathology , Mitochondria , Permeability , Rats, Sprague-Dawley , Retinol-Binding Proteins, Plasma
OBJECTIVES: To investigate the efficacy and potential molecular mechanism of Huangkui capsule in combination with leflunomide (HKL) for the treatment of immunoglobulin A nephropathy (IgAN) METHODS: IgAN rat models were constructed by treating rats with bovine serum albumin, lipopolysaccharide, and tetrachloromethane. Th22 cells were isolated from the blood samples of patients with IgAN using a CD4+ T cell isolation kit. The expression levels of the components of the TGF-β1/Smad3 signaling pathway, namely, TGF-β1, Smad2, Smad3, Smad4, and Smad7, were detected using quantitative reverse transcription polymerase chain reaction. Cell proliferation was determined using the MTT assay, cell viability was determined using the WST 1 method, and the chemotaxis of Th22 cells was observed using the wound healing assay. Changes in the histology of the kidney tissues were analyzed using hematoxylin and eosin staining. RESULTS: Compared with IgAN rats, the rats subjected to HKL treatment showed good improvement in kidney injuries, and the combined drug treatment performed much better than the single-drug treatment. In addition, following HKL treatment, the viability, proliferation, and chemotaxis of Th22 cells dramatically decreased (*p<0.05, **p<0.01, and ***p<0.001). In addition, CCL20, CCL22, and CCL27 levels decreased and the expression of the key components of the TGF-β1/Smad3 signaling pathway was downregulated in IgAN rats and Th22 cells (*p<0.05, ***p<0.001). CONCLUSIONS: By targeting the TGF-β1/Smad3 signaling pathway, HKL treatment can improve kidney injury in IgAN rats as well as the excessive proliferation and metastasis of Th22 cells.
Subject(s)Humans , Animals , Rats , Drugs, Chinese Herbal/pharmacology , Smad3 Protein/metabolism , Transforming Growth Factor beta1/metabolism , Leflunomide/pharmacology , Glomerulonephritis, IGA/metabolism , Glomerulonephritis, IGA/drug therapy , Signal Transduction , Kidney/metabolism
OBJECTIVES: Contrast-induced acute kidney injury (CI-AKI) is an important clinical problem that can be aggravated by diabetes mellitus, a major risk factor. However, heme oxygenase-1 (HO-1), a promising therapeutic target, can exert antioxidant effects against CI-AKI. Thus, we investigated the role of HO-1 in CI-AKI in the presence of diabetes mellitus. METHODS: Twenty-eight male Wistar rats weighing 250-300g were subjected to left uninephrectomy, and concomitantly, diabetes induced by streptozotocin (65 mg/kg). After 12 weeks, iodinated contrast (meglumine ioxithalamate, 6 mL/kg) and hemin (HO-1 inducer-10 mg/k) were administered 60 min before iodinated contrast treatment. The rats were randomly divided into four groups: control, diabetes mellitus (DM), DM iodinated contrast (DMIC), and DMIC hemin (DMICH). Kidney function, albuminuria, oxidative profile, and histology were assessed. All experimental data were subjected to statistical analyses. RESULTS: CI-AKI in preclinical diabetic models decreased creatinine clearance and increased urinary neutrophil gelatinase-associated lipocalin (NGAL) levels and the degree of albuminuria. Additionally, the levels of oxidative and nitrosative stress metabolites (urinary peroxides, thiobarbituric acid-reactive substances, and NO) were elevated, while thiol levels in kidney tissue were reduced. Kidney histology showed tubular cell vacuolization and edema. HO-1 inducer treatment improved kidney function and reduced urinary the NGAL levels. The oxidative profile showed an increase in the endogenous thiol-based antioxidant levels. Additionally, the tubular injury score was reduced following HO-1 treatment. CONCLUSIONS: Our findings highlight the renoprotective effects of HO-1 in CI-AKI and preclinical diabetic models. Therefore, HO-1 ameliorates kidney dysfunction, reduces oxidative stress, and prevents cell necrosis.
Subject(s)Animals , Male , Rats , Diabetes Mellitus , Acute Kidney Injury/chemically induced , Acute Kidney Injury/prevention & control , Rats, Wistar , Streptozocin/metabolism , Oxidative Stress , Heme Oxygenase-1/metabolism , Heme Oxygenase (Decyclizing)/metabolism , Kidney/metabolism
BACKGROUND@#Since 2019, a novel coronavirus named 2019 novel coronavirus (2019-nCoV) has emerged worldwide. Apart from fever and respiratory complications, acute kidney injury has been observed in a few patients with coronavirus disease 2019. Furthermore, according to recent findings, the virus has been detected in urine. Angiotensin-converting enzyme II (ACE2) has been proposed to serve as the receptor for the entry of 2019-nCoV, which is the same as that for the severe acute respiratory syndrome. This study aimed to investigate the possible cause of kidney damage and the potential route of 2019-nCoV infection in the urinary system.@*METHODS@#We used both published kidney and bladder cell atlas data and new independent kidney single-cell RNA sequencing data generated in-house to evaluate ACE2 gene expression in all cell types in healthy kidneys and bladders. The Pearson correlation coefficients between ACE2 and all other genes were first generated. Then, genes with r values larger than 0.1 and P values smaller than 0.01 were deemed significant co-expression genes with ACE2.@*RESULTS@#Our results showed the enriched expression of ACE2 in all subtypes of proximal tubule (PT) cells of the kidney. ACE2 expression was found in 5.12%, 5.80%, and 14.38% of the proximal convoluted tubule cells, PT cells, and proximal straight tubule cells, respectively, in three published kidney cell atlas datasets. In addition, ACE2 expression was also confirmed in 12.05%, 6.80%, and 10.20% of cells of the proximal convoluted tubule, PT, and proximal straight tubule, respectively, in our own two healthy kidney samples. For the analysis of public data from three bladder samples, ACE2 expression was low but detectable in bladder epithelial cells. Only 0.25% and 1.28% of intermediate cells and umbrella cells, respectively, had ACE2 expression.@*CONCLUSION@#This study has provided bioinformatics evidence of the potential route of 2019-nCoV infection in the urinary system.
Subject(s)Angiotensin-Converting Enzyme 2/metabolism , COVID-19 , Gene Expression , Humans , Kidney/metabolism , SARS-CoV-2 , Sequence Analysis, RNA , Single-Cell Analysis , Urinary Bladder/metabolism
Un tercio de la población mundial tiene niveles anormalmente altos de presión arterial, hipertensión, responsable de casi el 50% de las muertes por accidente cerebrovascular y enfermedad coronaria. La sensibilidad a la sal es un factor de riesgo para la morbilidad y mortalidad cardiovascular y también para otras enfermedades. En estudios previos describimos un modelo de hipertensión sal sensible (HSS) en ratas Wistar ovariectomizadas (oVx) adultas. Las ratas oVx son normotensas con ingesta normal de sal (NS, 0.24% de NaCl), pero desarrollan un perfil de HSS con una ingesta elevada de sal (HS, 1% de NaCl). En los estudios en riñón encontramos que el circuito receptor D1 de dopamina, citocromo P450 4A y Na+, K+-ATPasa está alterado por la ausencia de hormonas ováricas, lo que se asocia a menor excreción de sodio e hipertensión arterial. La ingesta HS en ratas oVx también promueve cambios en la expresión de proteínas relacionadas con el transporte de sodio en células mononucleares de sangre periférica, principalmente linfocitos periféricos. Por lo tanto, el transporte de sodio se modifica en varios niveles de la fisiología normal. En estudios recientes observamos que el estradiol aumenta la proliferación y diferenciación de células epiteliales en cultivos de corteza renal humana. Sensibilidad a la sal, inmunidad adaptativa, presión arterial y proliferación de células epiteliales en riñón son fenómenos de gran importancia biológica regulados por estradiol.
Female sex hormones participate in the regulation of blood pressure and renal epithelial proliferation, effects not related to their reproductive function. About one-third of the world's population has abnormally high levels of blood pressure, hypertension, which is responsible for almost 50% of deaths from stroke and coronary heart disease. Salt sensitivity is a risk factor for cardiovascular morbidity and mortality and other diseases as well. We reported a model of salt sensitive hypertension in adult ovariectomized (oVx) Wistar rats. oVx rats are normotensive under normal salt intake (NS, 0.24% NaCl), but upon a high salt intake (HS, 1% NaCl) oVx rats developed a blood pressure profile of salt-sensitive hypertension. Our studies on kidney molecules related to sodium balance found that the circuit dopamine D1-like receptor, cytochrome P450 4A and Na+, K+-ATPase is altered by the absence of ovary hormones which is accompanied by a reduced ability to excrete sodium. In oVx rats HS intake also promotes changes in the expression of proteins related to sodium transport in peripheral blood mononuclear cells, mainly peripheral lymphocytes. Therefore, sodium transport is modified at several levels of normal physiology. Lately, we described that estradiol increases the rate of renal epithelial cell proliferation in primary cultures developed from human renal cortex. Thus, salt sensitivity, adaptive immunity, blood pressure and renal cell proliferation are complex biological responses regulated by female sex hormones.
Subject(s)Humans , Animals , Female , Rats , Sodium Chloride/metabolism , Estradiol/metabolism , Hypertension/metabolism , Kidney/metabolism , Blood Pressure , Sodium Chloride/adverse effects , Rats, Wistar , Sodium-Potassium-Exchanging ATPase , Cell Proliferation , Hypertension/physiopathology
Subject(s)Humans , Biomarkers/blood , Cystatin C/blood , Kidney/metabolism , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/mortality , Cathepsins/metabolism , Cross-Sectional Studies , Peritoneal Dialysis/methods , Risk Assessment , Creatinine/blood , Cystatin C/genetics , Cystatin C/metabolism , Acute Kidney Injury/metabolism , Glomerular Filtration Rate/genetics , Graft Rejection/metabolism , Kidney/physiopathology , Kidney Function Tests/methods
SUMMARY Type 2 diabetes mellitus is an important public health problem, with a significant impact on cardiovascular morbidity and mortality and an important risk factor for chronic kidney disease. Various hypoglycemic therapies have proved to be beneficial to clinical outcomes, while others have failed to provide an improvement in cardiovascular and renal failure, only reducing blood glucose levels. Recently, sodium-glucose cotransporter-2 (SGLT2) inhibitors, represented by the empagliflozin, dapagliflozin, and canagliflozin, have been showing satisfactory and strong results in several clinical trials, especially regarding the reduction of cardiovascular mortality, reduction of hospitalization due to heart failure, reduction of albuminuria, and long-term maintenance of the glomerular filtration rate. The benefit from SGLT2 inhibitors stems from its main mechanism of action, which occurs in the proximal tubule of the nephron, causing glycosuria, and a consequent increase in natriuresis. This leads to increased sodium intake by the juxtaglomerular apparatus, activating the tubule glomerular-feedback and, finally, reducing intraglomerular hypertension, a frequent physiopathological condition in kidney disease caused by diabetes. In addition, this class of medication presents an appropriate safety profile, and its most frequently reported complication is an increase in the incidence of genital infections. Thus, these hypoglycemic agents gained space in practical recommendations for the management of type 2 diabetes mellitus and should be part of the initial therapeutic approach to provide, in addition to glycemic control, cardiovascular outcomes, and the renoprotection in the long term.
Subject(s)Humans , Cardiovascular Diseases/prevention & control , Diabetes Mellitus, Type 2/drug therapy , Sodium-Glucose Transporter 2/pharmacology , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Hypoglycemic Agents/pharmacology , Kidney Diseases/prevention & control , Benzhydryl Compounds/therapeutic use , Cardiovascular Diseases/etiology , Cardiovascular Diseases/mortality , Diabetes Mellitus, Type 2/complications , Diabetic Nephropathies/etiology , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/prevention & control , Sodium-Glucose Transporter 2/therapeutic use , Canagliflozin/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Glomerular Filtration Rate , Glucose/metabolism , Glucosides/therapeutic use , Hypoglycemic Agents/therapeutic use , Kidney/drug effects , Kidney/physiopathology , Kidney/metabolism , Kidney Diseases/etiology , Kidney Diseases/metabolism
Abstract Purpose To evaluate renal histological changes by stereology and morphometry and analyze the main markers of oxidative stress in rats undergoing natural aging. Methods Seventy two Wistar rats were divided into six groups of 12 rats each, which were euthanized at 3, 6, 9, 12, 18, and 24 months of age. Right kidney was stereologically and morphometrically analyzed to calculate the volumetric density (Vv[glom]), numerical density (Nv[glom]) and glomerular volume (Vol[glom]). Left kidney was used to determine the levels of nonprotein thiols, lipid peroxidation, and protein carbonylation, as well as the activities of superoxide-dismutase and catalase enzymes. Results Both Vv[glom] and Nv[glom] values showed gradual decreases between groups. Activity of superoxide-dismutase was elevated at 24 months of age, and the levels of nonprotein thiols were higher in older animals. Greater catalase activity and protein carbonylation were observed in animals between 6 and 12 months of age but lessened in older rats. Lipid peroxidation decreased in the older groups. Conclusions Morphometric and stereological analyses revealed a gradual decrease in the volume and density of renal glomeruli during aging, as well as kidney atrophy. These findings related to oxidative stress clarify many changes occurring in kidney tissues during senescence in rats.
Subject(s)Animals , Rats , Catalase/metabolism , Superoxide Dismutase/metabolism , Aging , Lipid Peroxidation , Rats, Wistar , Oxidative Stress , Kidney/metabolism , Kidney Diseases
RESUMEN Con el objetivo de determinar el efecto del consumo de harina de cáscara o harina de pulpa de dos variedades de Solanum tuberosum (papa Yungay y papa Canchán) sobre la acumulación de tejido adiposo, peso de órganos y estrés oxidativo en hígado de ratas realizamos un estudio experimental en 24 ratas Holtzman obesas, divididos en cuatro grupos y, sometidas a dietas que contenían 10% de harina de las dos variedades de papa. Los grupos fueron T1: cáscara Yungay, T2: pulpa Yungay; T3: cáscara Canchán; y T4: pulpa Canchán. Al finalizar, se sacrificaron todos los animales para registrar los pesos de órganos y tejido adiposo, y extraer muestras para determinar la actividad enzimática de superóxido dismutasa y catalasa en el hígado. El grupo de ratas obesas que consumió pulpa de variedad Yungay tuvo menor estrés oxidativo en el hígado; además, independientemente de la parte de tubérculo consumido, esta variedad redujo el peso de los riñones.
ABSTRACT This study aimed to determine the effect of the consumption of peel flour or pulp flour from two varieties of Solanum tuberosum (Yungay potato and Canchán potato) on the accumulation of adipose tissue, organ weight, and oxidative stress in the liver of rats. We carried out an experimental study in 24 obese Holtzman rats, divided into four groups and subjected to diets containing 10% flour from both varieties of potato. The groups were T1: Yungay peel; T2: Yungay pulp; T3: Canchán peel; and T4: Canchán pulp. When the study was completed, all the animals were slaughtered to record the weights of organs and adipose tissue and to extract samples to determine the enzyme activity of superoxide dismutase and catalase in the liver. The group of obese rats that consumed the pulp of the Yungay variety had less oxidative stress in the liver. Also, regardless of the tuber part consumed, this variety reduced the weight of the kidneys.
Subject(s)Animals , Male , Rats , Solanum tuberosum/chemistry , Plant Extracts/pharmacology , Oxidative Stress/drug effects , Obesity/drug therapy , Organ Size/drug effects , Adipose Tissue/drug effects , Rats, Sprague-Dawley , Kidney/drug effects , Kidney/metabolism , Liver/drug effects , Liver/metabolism
Abstract Introduction: It is unclear whether residual renal function (RRF) in dialysis patients can attenuate the metabolic impact of the long 68-hour interdialytic interval, in which water, acid, and electrolyte accumulation occurs. Objective: to evaluate serum electrolyte levels, water balance, and acid-base status in dialytic patients with and without RRF over the long interdialytic interval (LII). Methodology: this was a single-center, cross-sectional, and analytical study that compared patients with and without RRF, defined by diuresis above 200 mL in 24 hours. Patients were weighed and serum samples were collected for biochemical and gasometric analysis at the beginning and at the end of the LII. Results: 27 and 24 patients with and without RRF were evaluated, respectively. Patients without RRF had a higher increase in serum potassium during the LII (2.67 x 1.14 mEq/L, p < 0.001), reaching higher values at the end of the study (6.8 x 5.72 mEq/L, p < 0.001) and lower pH value at the beginning of the interval (7.40 x 7.43, p = 0.018). More patients with serum bicarbonate < 18 mEq/L (50 x 14.8%, p = 0.007) and mixed acid-base disorder (57.7 x 29.2%, p = 0.042), as well as greater interdialytic weight gain (14.67 x 8.87 mL/kg/h, p < 0.001) and lower natremia (137 x 139 mEq/L, p = 0.02) at the end of the interval. Calcemia and phosphatemia were not different between the groups. Conclusion: Patients with RRF had better control of serum potassium, sodium, acid-base status, and volemia throughout the LII.
Resumo Introdução: Não se sabe ao certo se a função renal residual (FRR) de pacientes dialíticos pode atenuar o impacto metabólico do maior intervalo interdialítico (MII) de 68 horas, no qual ocorre acúmulo de volume, ácidos e eletrólitos. Objetivo: Avaliar os níveis séricos de eletrólitos, balanço hídrico e status ácido-básico de pacientes dialíticos com e sem FRR ao longo do MII. Metodologia: Tratou-se de estudo unicêntrico, transversal e analítico, que comparou pacientes com e sem FRR, definida como diurese acima de 200 mL em 24 horas. Para tal, os pacientes foram pesados e submetidos à coleta de amostras séricas para análise bioquímica e gasométrica no início e fim do MII. Resultados: Foram avaliados 27 e 24 pacientes com e sem FRR, respectivamente. Pacientes sem FRR apresentaram maior aumento de potássio sérico durante o MII (2,67 x 1,14 mEq/L, p < 0,001) atingindo valores mais elevados no fim (6,8 x 5,72 mEq/L, p < 0,001); menor valor de pH no início do intervalo (7,40 x 7,43, p = 0,018), maior proporção de pacientes com bicarbonato sérico < 18 mEq/L (50 x 14,8 %, p = 0,007) e distúrbio ácido-básico misto (70,8 x 42,3 %, p = 0,042), além de maior ganho de peso interdialítico (14,67 x 8,87 mL/kg/h, p < 0,001) e menor natremia (137 x 139 mEq/L, p = 0,02) no fim do intervalo. A calcemia e fosfatemia não foram diferentes entre os grupos. Conclusão: Pacientes com FRR apresentaram melhor controle dos níveis séricos de potássio, sódio, status ácido-básico e da volemia ao longo do MII.
Subject(s)Humans , Male , Female , Adult , Middle Aged , Aged , Water-Electrolyte Balance/physiology , Renal Dialysis/adverse effects , Renal Insufficiency/blood , Kidney/physiopathology , Phosphates/blood , Potassium/blood , Sodium/blood , Acid-Base Imbalance/physiopathology , Bicarbonates/blood , Weight Gain , Calcium/blood , Cross-Sectional Studies , Disease Progression , Renal Insufficiency/physiopathology , Renal Insufficiency/urine , Renal Insufficiency/therapy , Kidney/metabolism , Kidney/chemistry , Kidney Function Tests/methods
AQP1 plays an essential role in maintaining body water balance. In the kidney, AQP1 is localized to the apical and basolateral membrane of epithelial cells in the proximal tubule and descending thin limb of Ansa nephroni (Henle's loop) where it reabsorbs the vast majority of filtered water. The growing epidemic of obesity and metabolic diseases particularly obesity-related kidney disease is getting more and more attention in this century. However, a full understanding of mechanisms involved to the progressive renal disease is still unclear, in particular AQPs in the kidney of obesity. In this paper, we examined the localization of AQP1 in renal cortex and medulla of ND (normal diet) and HFD (high-fat diet) at rats. In the renal cortex and medulla, immunolight microscopy revealed weak expression of AQP1 in the apical and basolateral membrane of epithelial cells at the proximal straight/convoluted tubule of HFD compared with ND, respectively. The same result was confirmed in the thick descending limb and descending thin limb of Henle's loop. In the high-fat nutritional obesity of rats, decreased AQP1 levels may not directly cause serious obesity-related kidney disease, e.g. chronic kidney disease, even end-stage renal disease. But at least, AQPs (AQP1 in this study) was one of initially conditions to the incentive of obesity-related kidney disease.
Las acuoporinas tipo 1 (AQP1) constituyen una parte esencial en el mantenimiento del equilibrio del agua en el cuerpo. En el riñón, la AQP1 se localiza en la membrana apical y basolateral de las células epiteliales, en el túbulo proximal y en el segmento descendente del Ansa nephroni o asa nefrónica (asa de Henle), donde reabsorbe la gran mayoría de agua filtrada. La creciente epidemia de obesidad y enfermedades metabólicas en el siglo actual, hacen que la enfermedad renal relacionada con la obesidad esté recibiendo cada vez más atención. Sin embargo, aún no existe un conocimiento definitivo de los mecanismos implicados en la enfermedad renal progresiva, en particular los relacionados a las acuoporinas renales en la obesidad. En este trabajo, examinamos la localización de AQP1 en la corteza y la médula renales de la dieta normal (DN) y dieta alta en grasa (DAG) en ratas. En la corteza y médula renales, la microscopía de luz reveló una expresión débil de AQP1 en la membrana apical y basolateral de las células epiteliales en el túbulo contorneado proximal del grupo DAG en comparación con el grupo DN, respectivamente. El mismo resultado se confirmó en la porción descendente gruesa y en la porción descendente delgada del asa nefrónica. En ratas del grupo DAG, la disminución de los niveles de AQP1 pudo no ser la causa directa de una enfermedad renal grave relacionada con obesidad, como por ejemplo, enfermedad renal crónica, o una enfermedad renal terminal. No obstante, en este estudio, la expresión renal de AQP1 constituyó una de las condiciones iniciales para inducir la enfermedad renal relacionada con obesidad.
Subject(s)Animals , Rats , Aquaporin 1/metabolism , Diet, High-Fat , Kidney/pathology , Immunohistochemistry , Rats, Sprague-Dawley , Kidney/metabolism , Kidney Medulla/pathology
Abstract INTRODUCTION: The levels of the full-length form of the (pro)renin receptor (PRR), a component of the renin-angiotensin system (RAS), may be reduced in the membranes of kidneys in renal diseases. This study aimed to investigate the RAS components in the kidneys of mice submitted to a combination of a high-fat diet and Schistosoma mansoni infection. METHODS: Female BALB/c mice were maintained on a control or high-fat diet from 3 weeks of age. After 10 weeks on the designated diets, half the mice in each group were infected with S. mansoni cercariae. The blood and kidneys were harvested 8 weeks after infection. RESULTS: The high-fat diet increased the number of eggs in the feces and the number of adult worms in the mesenteric bed. Schistosoma mansoni infection reduced the plasma levels of glucose, triglycerides, and HDL cholesterol in the control and high-fat diet groups. In mice on the control diet, S. mansoni infection resulted in increased expression of IL-6 in the kidneys; however, in mice on the high-fat diet, the levels of IL-6 were reduced and those of superoxide anions were increased. The RAS components evaluated were ACE2, renin, PRR, AT1R, and AT2R, and the levels of PRR were found to be reduced in the kidneys of infected mice on the high-fat diet. CONCLUSIONS: The finding regarding PRR is not yet clear. However, combining a high-fat diet and S. mansoni infection resulted in increased oxidative stress in the kidney that can aggravate hypertension as well as its associated complications.