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1.
Rev. bras. neurol ; 57(4): 16-22, out.-dez. 2021. tab, graf
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1359204

ABSTRACT

INTRODUÇÃO: A neuropatia periférica diabética (ND) é comum na nefropatia diabética (NFD) e não há informações se o hiperparatireoidismo secundário (HPS) aumenta seus sintomas. O objetivo foi determinar ND por sinais em pacientes com HPS. MATERIAL E MÉTODOS: É um estudo caso-controle. O Grupo Controle (GC) é composto por doentes com NFD e valores de paratormônio (PTH)<60pg / ml. O Grupo de Hiperparatireoidismo (GH) engloba pacientes com NFD e PTH≥60pg/ml e critérios bioquímicos de HPS. As variáveis foram, entre outras, a presença de sinais de ND e foram comparados com o teste t de Student e o qui-quadrado. RESULTADOS: Foram 60 participantes em cada grupo, sendo 35 (58,3%) homens no GC vs 33 (55,0%) em GH (p = 0,713). A idade do GC foi de 67±11,0 anos, vs 72±11 anos GH (p=0,009). A taxa de filtração glomerular (TFG) no GC foi 53,82±25,13 vs GH 35,34±18,43ml/min/1,73m2 (p <0,001). O PTH no GC foi de 38,02±15,32 pg/ml, em GH 119,07±84,33 pg/ml (p <0,001). A ND, devido aos sintomas no GC, foi de 28,3% e 36,6% no GH (p=0,330). A neuropatia por sinais no GC foi de 38,3% e no GH 83,3% (p<0,001). O odds ratio de GH para neuropatia presente devido a sinais foi de 8,044 (IC 95% 3,42­8,92). CONCLUSÃO: Constatou-se uma maior presença de sinais de NPD em pacientes com HPS em nosso centro


BACKGROUND: Diabetic peripheral neuropathy (DN) is common in diabetic nephropathy (DNP), and there is no information if secondary hyperparathyroidism (SHP) increases its symptoms. The purpose was to determine DN by signs in patients with SHP. METHODS: It is a case-control study. Control patients (CG) with DN and parathyroid hormone (PTH) values<60pg/ml. The Hyperparathyroidism group (HG), patients with DNP and PTH≥60pg/ml and HPS biochemical criteria. The variables were, among others, the presence of DN signs, and were compared with Student's t and chi-square. RESULTS: There were 60 participants in each group, 35(58.3%) men in CG vs.33(55.0%) in GH (p=0.713). The age of the CG was 67±11.0 years, vs 72±11years HG (p=0.009). The glomerular filtration rate (GFR) in the CG was 53.82±25.13 vs in HG 35.34±18.43ml/min/1.73m2(p<0.001). The PTH in the CG were 38.02±15.32pg/ml and in GH 119.07±84.33pg/ml(p<0.001). The DN due to symptoms in CG was 28.3% and in GH 36.6%(p=0.330). Neuropathy due to signs in the CG was 38.3% and in GH 83.3% (p<0.001). The HG odds ratio to present neuropathy due to signs was 8.044 (95% CI 3.42­18.92). CONCLUSION: There was a statistical association between HPS and signs of DN in patients with DNP in our canter.


Subject(s)
Humans , Male , Adult , Middle Aged , Aged , Diabetes Mellitus, Type 2/diagnosis , Diabetic Neuropathies/complications , Diabetic Neuropathies/diagnosis , Diabetic Neuropathies/epidemiology , Hyperparathyroidism, Secondary/etiology , Case-Control Studies , Prevalence , Diabetes Mellitus, Type 2/complications , Diabetic Nephropathies
2.
Bol. latinoam. Caribe plantas med. aromát ; 20(3): 303-314, may. 2021. tab, ilus
Article in English | LILACS | ID: biblio-1343478

ABSTRACT

In this study, against streptozotocin (STZ) induced diapetic nephropathy (DN); it is aimed to investigate the use of thymoquinone (TQ) and ß-aminoisobutyric acid (BAIBA) and to compare the effects of these agents. With random selection of 35 male rats, five groups (seven rats in each group) were constituted as follows: Control, STZ, STZ + TQ, STZ + BAIBA, STZ + TQ + BAIBA. In the STZ group; body weight, glutathione (GSH) and insulin levels decreased, relative kidney weight, malondialdehyde (MDA), glucose, blood urea nitrogen (BUN) and creatinine (Cr) levels were increased. Also, in kidney tissue; histopathological changes (such as thickening of the capsular, glomerular and tubular basement membranes, increased mesangial matrix amount, increased cytoplasmic vacuolization in some of the tubular epithelial cells, increased tumor necrosis factor-alpha (TNF-α) expression, and inflammatory cell infiltrations in interstitial tissue) were detected. It was observed that these changes occurring after diabetes mellitus (DM) reversed significantly in TQ, BAIBA and TQ + BAIBA groups.


En este estudio, contra la nefropatía diapética (ND) inducida por estreptozotocina (STZ); tiene como objetivo investigar el uso de timoquinona (TQ) y ácido ß-aminoisobutírico (BAIBA) y comparar los efectos de estos agentes. Con la selección aleatoria de 35 ratas macho, se constituyeron cinco grupos (siete ratas en cada grupo) como sigue: Control, STZ, STZ + TQ, STZ + BAIBA, STZ + TQ + BAIBA. En el grupo STZ; el peso corporal, los niveles de glutatión (GSH) y de insulina disminuyeron, el peso relativo de los riñones, el malondialdehído (MDA), la glucosa, el nitrógeno ureico en sangre (BUN) y los niveles de creatinina (Cr) aumentaron. Además, en tejido renal; se detectaron cambios histopatológicos (como engrosamiento de las membranas basales capsular, glomerular y tubular, aumento de la cantidad de matriz mesangial, aumento de la vacuolización citoplasmática en algunas de las células epiteliales tubulares, aumento de la expresión del factor de necrosis tumoral alfa (TNF-α) e infiltraciones de células inflamatorias en tejido intersticial). Se observó que estos cambios que ocurren después de la diabetes mellitus (DM) se revirtieron significativamente en los grupos TQ, BAIBA y TQ + BAIBA.


Subject(s)
Animals , Male , Rats , Benzoquinones/administration & dosage , Diabetic Nephropathies/drug therapy , Aminoisobutyric Acids/administration & dosage , Blood Urea Nitrogen , Body Weight , Immunohistochemistry , Rats, Sprague-Dawley , Streptozocin , Oxidative Stress , Creatinine/analysis , Disease Models, Animal , Glucose/analysis , Glutathione/analysis , Kidney/drug effects
3.
Rev. chil. endocrinol. diabetes ; 14(2): 90-94, 2021.
Article in Spanish | LILACS | ID: biblio-1283560

ABSTRACT

La diabetes mellitus tipo 2 (DM2), habitualmente asociada a adultos en edad media y adulto mayor, ha presentado un aumento en su incidencia en pacientes menores de 40 años, lo que se conoce como DM2 de inicio en paciente joven. Varios estudios sugieren que este tipo de diabetes presenta no sólo un deterioro más rápido de las células beta-pancreáticas en comparación con la DM2 de inicio más tardío, sino que también un mayor riesgo de complicaciones que pacientes con DM Tipo1, lo que sugiere una variable independiente de los años de exposición a la enfermedad y por tanto, un fenotipo más agresivo. Por otra parte, hay evidencia que afirma que existen grupos poblacionales en mayor riesgo de desarrollar esta patología, particularmente ciertas etnias. En el presente trabajo se exponen los principales hallazgos de una reciente revisión del tema y se los compara con los datos nacionales disponibles. Dada la alta prevalencia de DM2 en la población chilena y la escasa cantidad de estudios epidemiológicos de calidad que permitan conocer nuestro panorama con mayor precisión, es que se destaca la importancia de estos últimos para poder tomar medidas de salud pública adecuadas.


Type 2 diabetes mellitus type 2 (T2DM), commonly associated with the middle to old aged adults group, has shown an increase in incidence in patients younger than 40 years old, which is known as young-onset type 2 diabetes mellitus. Several studies suggest that this type of diabetes not only exhibits a faster deterioration of the beta-pancreatic cells in comparison with type 1 diabetes mellitus patients, but also a greater risk of complications not regarding the time of exposure to the disease, therefore a more aggressive phenotype. Otherwise, there is evidence which asserts that some population groups are in mayor risk of developing this disease, especially certain ethnics. In this work it is exposed the main findings of a recent review of the subject and it is contrasted with available national data. Given the high prevalence of T2DM in the chilean population and the little amount of epidemiological high-quality studies that allows us to know our outlook with greater precision, it is highlighted the need for them in order to make adequate public health decisions.


Subject(s)
Humans , Adult , Age Factors , Diabetes Mellitus, Type 2/epidemiology , Chile/epidemiology , Risk Factors , Age of Onset , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/mortality , Diabetic Nephropathies/etiology , Diabetic Nephropathies/epidemiology , Diabetic Neuropathies/etiology , Diabetic Neuropathies/epidemiology
4.
Article in Chinese | WPRIM | ID: wpr-921989

ABSTRACT

OBJECTIVE@#To explore the influence of long non-coding (lnc) RNA Gm15645 on the podocyte injury in mice with diabetic nephropathy.@*METHODS@#Male db/db mice (with Type 2 diabetes) with a genetic background of C57BLKs/J and db/m mice (healthy) born in littermates were randomly divided into three groups. db/db group was injected with lncRNAGm15645 shRNA lentivirus with a podocyte-specific marker NPHS2; db/db blank group was injected with saline, and db/db control group was injected withnon-sense lentivirus. The results of PAS staining, pathological changes of renal tissue, relative expression of GSK-3beta, and podocin expression were compared.@*RESULTS@#lncRNAGm15 645 was overexpressed and podocin was down-regulated in the lentivirus overexpressed group. Mesangial cell proliferation, mesangial matrix hyperplasia, thickened basement membrane, widely fused foot process, and podocyte injury were observed by PAS staining. The expression of Gm15645 in the db/db group was significantly lower than that of the db/db blank group and db/db control group (P< 0.05), while the expression of podocin was higher (P< 0.05). Gm15645 was co-stained with podocin in renal tissue, and the target gene was GSK-3beta.@*CONCLUSION@#lncRNAGm15645 may provide an early biomarker for the occurrence of podocyte injury in diabetic nephropathy. The mechanism may be related to the feedback regulation of GSK-3beta gene.


Subject(s)
Animals , Diabetes Mellitus, Type 2 , Diabetic Nephropathies/genetics , Glycogen Synthase Kinase 3 beta , Male , Mice , Podocytes , RNA, Long Noncoding/genetics
5.
Article in Chinese | WPRIM | ID: wpr-878991

ABSTRACT

This study aimed to explore the effect of Salviae Miltiorrhizae Radix et Rhizoma, its stems and leaves on the diversity of intestinal microflora in rats with diabetic kidney injury. Diabetic rats model was established by feeding high glucose and high fat diet and 5% glucose solution with intraperitoneal injection of 30 mg·kg~(-1) streptozocin(STZ). The rats were randomly divided into normal group, model group, irbesartan control group, Huangkui Capsules control group, as well as low, middle and high dose groups of Sal-viae Miltiorrhizae Radix et Rhizoma, its stems and leaves. After administration for 2 weeks, 16 S rRNA technique was used to analyze the diversity of intestinal microflora in the feces of each group. The results showed rats in the model group developed renal tubular epithelial vacuole degeneration and a large amount of inflammatory cell infiltration in the renal interstitium. A small amount of inflammatory cell infiltration was seen in each administration group. The kidney structure of rats in irbesartan group, Huangkui Capsules group, high-dose group of Salviae Miltiorrhizae Radix et Rhizoma and its stem water extract, as well as high dose group of Salviae Miltiorrhizae Radix et Rhizoma and its stem ethnol extract group was close to the normal group. The diversity and structure of intestinal flora in the model group were significantly different from those in the normal group. Each administration group improved the fecal flora diversity in rats with diabetic kidney injury to a certain extent, especially the high dose of Salviae Miltiorrhizae Radix et Rhizoma and its stems water extract. Different flora were found in feces of diabetic nephropathy model rats on class, order, family and genus levels. On families and genera levels, the relative abundance of Bifidobacterium, Turicibacter, Peptostreptococcaceae, Desulfovibrio, and SMB53 showed an upward trend in model group, but that of Lactobacillus, Clostridium, Rikenella, Rumen fungi showed a downward trend. The administration groups can improve the relative abundance of the above intestinal flora in the model rats to a normal-like level. The results of this study provide a reference for resource utilization and further development of Salviae Miltiorrhizae Radix et Rhizoma.


Subject(s)
Animals , Diabetes Mellitus, Experimental/drug therapy , Diabetic Nephropathies/drug therapy , Drugs, Chinese Herbal , Gastrointestinal Microbiome , Rats , Salvia miltiorrhiza
6.
Article in Chinese | WPRIM | ID: wpr-888148

ABSTRACT

This study explored the in vivo effects and mechanisms of the modern classical prescription Supplemented Gegen Qinlian Decoction Formula(SGDF) against diabetic kidney disease(DKD). Sixty rats were randomly divided into the normal group, model group, SGDF group, and rosiglitazone(ROS) group. The modified DKD rat model was established by employing the following three methods: exposure to high-fat diet, unilateral nephrectomy, and intraperitoneal injection of streptozotocin(STZ). After modeling, rats in the four groups were treated with double distilled water, SGDF suspension, and ROS suspension, respectively, by gavage every day. At the end of the 6 th week of drug administration, all the rats were sacrificed for collecting urine, blood, and kidney tissue, followed by the examination of rat general conditions, urine and blood biochemical indicators, glomerulosclerosis-related indicators, podocyte pyroptosis markers, insulin resistance(IR)-related indicators, and key molecules in the insulin receptor substrate(IRS) 1/phosphatidylinositol-3-kinase(PI3 K)/serine threonine kinase(Akt) signaling pathway. The results showed that SGDF and ROS improved the general conditions, some renal function indicators and glomerulosclerosis of DKD model rats without affecting the blood glucose(BG). Besides, they ameliorated the expression characteristics and levels of podocyte pyroptosis markers, alleviated IR, and up-regulated the protein expression levels of the key molecules in IRS1/PI3 K/Akt pathway to varying degrees. In conclusion, similar to ROS, SGDF relieves DKD by targeting multiple targets in vivo. Specifically, it exerts the therapeutic effects by alleviating podocyte pyroptosis and IR. This study has preliminarily provided the pharmacological evidence for the research and development of new drugs for the treatment of DKD based on SGDF.


Subject(s)
Animals , Diabetes Mellitus , Diabetic Nephropathies/drug therapy , Drugs, Chinese Herbal , Insulin Resistance , Podocytes , Pyroptosis , Rats
7.
Article in Chinese | WPRIM | ID: wpr-887861

ABSTRACT

Objective To discuss the value of contrast-enhanced ultrasound(CEUS)parameters in evaluating the formation of Kimmelstiel-Wilson(K-W)nodules in diabetic nephropathy(DN).Methods Sixty-two patients pathologically diagnosed with DN and undergoing CEUS in the First Medical Center of Chinese PLA General Hospital from March 2017 to January 2020 were assigned into two groups according to whether K-W nodules were formed.The cortical CEUS parameters and the ratios of cortical to medullary CEUS parameters were compared between the two groups.Results The 62 patients included 19 patients without K-W nodules(group A)and 43 patients with K-W nodules(group B).The median rise time(


Subject(s)
Contrast Media , Diabetes Mellitus , Diabetic Nephropathies/diagnostic imaging , Humans , Ultrasonography
8.
Chinese Medical Journal ; (24): 814-820, 2021.
Article in English | WPRIM | ID: wpr-878055

ABSTRACT

BACKGROUND@#Vitamin D deficiency has been reported to be associated with diabetic microvascular complications, but previous studies have only focused on the relationship between vitamin D and specific complications. Therefore, we aimed to explore the relationship between vitamin D level and diabetic microvascular complications in general, including diabetic retinopathy (DR), diabetic nephropathy (DN), and diabetic peripheral neuropathy (DPN).@*METHODS@#This was a cross-sectional study of 815 patients with type 2 diabetes mellitus (T2DM). Clinical information and laboratory results were collected from the medical records. The relationship between vitamin D and the three diabetic microvascular complications was investigated.@*RESULTS@#The serum 25-hydroxyvitamin D (25 [OH] D) level of patients with DPN and/or DN was significantly lower than that of T2DM patients without any microvascular complications (P < 0.01). Univariate analysis showed that the 25 (OH) D level was related to DPN and DN, but not DR. After adjustment, the 25 (OH) D level was confirmed to be an independent protective factor for DPN (odds ratio [OR]: 0.968, P = 0.004]) and DN (OR: 0.962, P = 0.006). The prevalence of DPN and DN increased significantly as the serum 25 (OH) D levels decreased. Furthermore, patients with both DPN and DN had the lowest concentration of serum 25 (OH) D (P < 0.001), and the prevalence of macroalbuminuria increased more abruptly than that of microalbuminuria across the 25 (OH) D tertiles. Among the patients with vitamin D insufficiency, those with DPN presented more comorbid macroalbuminuria than those without DPN (15.32% vs. 4.91%; P = 0.001).@*CONCLUSIONS@#Vitamin D deficiency is independently associated with higher risk of DPN and DN, but not DR, in T2DM patients. Further, it may be a potential predictor for both the occurrence and severity of DPN and DN.


Subject(s)
Cross-Sectional Studies , Diabetes Mellitus, Type 2/complications , Diabetic Nephropathies , Diabetic Neuropathies , Humans , Risk Factors , Vitamin D
9.
Article in Chinese | WPRIM | ID: wpr-879143

ABSTRACT

Pharmacology network was used to investigate the common key target and signaling pathway of Notoginseng Radix et Rhizoma in the protection against diabetic nephropathy(DN), diabetic encephalopathy(DE) and diabetic cardiomyopathy(DCM). The chemical components of Notoginseng Radix et Rhizoma were obtained through TCMSP database and literature mining, and SwissTargetPrediction database was used to predict potential targets of Notoginseng Radix et Rhizoma. The disease targets of DN, DE and DCM were obtained through OMIM and GeneCards databases. The overlapped targets of component targets and disease targets of DN, DE and DCM were obtained, and the network of "chemical component-target-disease" was established. The enriched GO and KEGG of the overlapped genes were investigated by using ClueGo plug-in with Cytoscape. At the same time, the PPI network was constructed through STRING database, and the common key targets for the treatment of three diseases by Notoginseng Radix et Rhizoma were obtained through topological parametric mathematical analysis by Cytoscape. A total of 166 chemical components and 835 component targets were screened out from Notoginseng Radix et Rhizoma. Briefly, 216, 194 and 230 disease targets of DN, DE and DCM were collected, respectively. And 54, 45 and 57 overlapped targets were identified when overlapping these disease targets with component targets of Notoginseng Radix et Rhizoma, respectively. Enrichment analysis indicated that the AGE-RAGE signaling pathway and FoxO signaling pathway were the common pathways in the protection of Notoginseng Radix et Rhizoma against DN, DE and DCM. Network analysis of the overlapped targets showed that TNF, STAT3, IL6, VEGFA, MAPK8, CASP3 and SIRT1 were identified as key targets of Notoginseng Radix et Rhizoma against DN, DE and DCM, the selected key targets were verified by literature review, and it was found that TNF, IL6, VEGFA, CASP3 and SIRT1 had been reported in the literature. In addition, there were the most compounds corresponding to the commom core target STAT3, indicating that more compounds in Notoginseng Radix et Rhizoma could regulate STAT3. This study indicated that Notoginseng Radix et Rhizoma potentially protected against DN, DE and DCM through regulating AGE-RAGE signaling pathway and FoxO signaling pathway and 7 common targets including TNF, STAT3, IL6, VEGFA, MAPK8, CASP3 and SIRT1. This study provided a reference for the research of "different diseases with same treatment" and also elucidated the potential mechanism of Notoginseng Radix et Rhizoma against DN, DE and DCM.


Subject(s)
Brain Diseases , Diabetes Mellitus , Diabetic Cardiomyopathies/genetics , Diabetic Nephropathies/genetics , Humans , Research Design , Signal Transduction
10.
Int. j. morphol ; 38(4): 1003-1009, Aug. 2020. tab, graf
Article in English | LILACS | ID: biblio-1124889

ABSTRACT

This study was set to investigate the effect of gum Arabic (G.A.) on diabetic kidney disease. We divided sixty male Sprague rats randomly into six groups. Normal control, normal rats treated with G.A., untreated diabetic rats, diabetic rats treated with insulin, diabetic rats treated with G.A., and diabetic rats treated with both insulin and G.A. Diabetes was induced by a single intraperitoneal injection of STZ. Forty eight hr post injections. Insulin was injected subcutaneously (1.6/IU/100g/day). We provided G.A. in drinking water (10 %w/ v).). At the end of the twelve weeks, blood was drawn for measurement of blood glucose, glycosylated hemoglobin (HbA1C), serum lipids, serum creatinine, and blood urea. Renal tissue oxidative stress (O.S.) was assessed by measuring the activities of superoxide dismutase (SOD) and catalase (CAT), and the concentrations of reduced glutathione (GSH) and malondialdehyde (MDA). For histological assessments, sections from segments of kidneys were processed and stained with hematoxylin and eosin (H&E) for assessment under the light microscope. STZinduced diabetes caused an elevation of blood glucose, HbA1c, urea and creatinine, triglycerides LDL and cholesterol, MDA with reduction of HDL, GSH level, and CAT and SOD activities. Histologically, kidneys from diabetic rats showed marked glomerular and tubular changes. Administration of G.A. alone to diabetic rats had a significant hypoglycemic, hypolipidemic, and antioxidant effect, although the levels achieved remained significantly abnormal compared with the untreated group with no effect on urea and creatinine levels. Co-administration of G.A. with insulin reversed the impact of D.M. on all parameters evaluated including the histological changes and led to normal urea and creatinine levels. We concluded that G.A., in combination with insulin, improves chemically-induced diabetes and its renal complications, possibly by modulation of oxidative stress.


En este estudio se evaluó el efecto de la goma arábiga (GA) en la enfermedad renal diabética. Dividimos sesenta ratas macho Sprague Dawley al azar en seis grupos. Control normal, ratas normales tratadas con GA, ratas diabéticas no tratadas, ratas diabéticas tratadas con insulina, ratas diabéticas tratadas con GA y ratas diabéticas tratadas con insulina y GA. La diabetes fue inducida por una sola inyección intraperitoneal de STZ. Cuarenta y ocho horas después se inyectó insulina por vía subcutánea (1,6 / UI / 100 g / día). A los animales se les dió GA en agua potable (10 % p / v)). Al final de las doce semanas, se extrajo sangre para medir la glucosa, la hemoglobina glicosilada (HbA1C), los lípidos en suero, la creatinina en suero y la urea en sangre. El estrés oxidativo del tejido renal (SO) se evaluó midiendo las actividades de la enzima superóxido dismutasa (SOD) y la catalasa (CAT), y las concentraciones de glutatión reducido (GSH) y malondialdehído (MDA). Para las evaluaciones histológicas, se procesaron secciones de segmentos de riñones y se tiñeron con hematoxilina y eosina (H & E) para análisis bajo microscopio óptico. La diabetes inducida por STZ causó una elevación de la glucosa en sangre, HbA1c, urea y creatinina, triglicéridos LDL y colesterol, MDA con reducción de las actividades de HDL, GSH y CAT y SOD. Histológicamente, los riñones de ratas diabéticas mostraron marcados cambios glomerulares y tubulares. La administración de GA solo en las ratas diabéticas tuvo un efecto hipoglucémico, hipolipidémico y antioxidante significativo, aunque los niveles alcanzados permanecieron significativamente anormales en comparación con el grupo no tratado, sin ningún efecto sobre los niveles de urea y creatinina. La dministración conjunta de GA con insulina revirtió el impacto de DM en todos los parámetros evaluados, incluidos los cambios histológicos y condujeron a niveles normales de urea y creatinina. Concluimos que GA en combinación con insulina, mejora la diabetes inducida químicamente y sus complicaciones renales, posiblemente mediante la modulación del estrés oxidativo.


Subject(s)
Animals , Male , Rats , Diabetic Nephropathies/prevention & control , Gum Arabic/administration & dosage , Antioxidants/administration & dosage , Rats, Sprague-Dawley , Oxidative Stress/drug effects , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Experimental/drug therapy , Diabetic Nephropathies/pathology , Gum Arabic/pharmacology , Injections, Intraperitoneal , Kidney/drug effects , Antioxidants/pharmacology
11.
Braz. j. med. biol. res ; 53(4): e9288, 2020. graf
Article in English | LILACS | ID: biblio-1089349

ABSTRACT

Diabetic nephropathy (DN) is one of the leading causes of mortality in diabetic patients. Long non-coding RNA zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) plays a crucial role in the development of various diseases, including DN. However, the molecular mechanism of ZEB1-AS1 in DN pathogenesis remains elusive. An in vitro DN model was established by treating HK-2 cells with high glucose (HG). Quantitative polymerase chain reaction (qRT-PCR) was utilized to detect the expression levels of ZEB1-AS1, microRNA-216a-5p (miR-216a-5p), and bone morphogenetic protein 7 (BMP7). Western blot assay was used to evaluate the protein levels of BMP7, epithelial-to-mesenchymal transition (EMT)-related proteins, and fibrosis markers. Additionally, the interaction among ZEB1-AS1, miR-216a-5p, and BMP7 was predicted by MiRcode (http://www.mircode.org) and starBase 2.0 (omics_06102, omicX), and confirmed by luciferase reporter assay. ZEB1-AS1 and BMP7 were down-regulated, while miR-216a-5p was highly expressed in kidney tissues of DN patients. Consistently, HG treatment decreased the levels of ZEB1-AS1 and BMP7, whereas HG increased miR-216a-5p expression in HK-2 cells in a time-dependent manner. ZEB1-AS1 upregulation inhibited HG-induced EMT and fibrogenesis. Furthermore, ZEB1-AS1 directly targeted miR-216a-5p, and overexpression of miR-216a-5p restored the inhibitory effects of ZEB1-AS1 overexpression on EMT and fibrogenesis. BMP7 was negatively targeted by miR-216a-5p. In addition, ZEB1-AS1 suppressed HG-induced EMT and fibrogenesis by regulating miR-216a-5p and BMP-7. lncRNA ZEB1-AS1 inhibited high glucose-induced EMT and fibrogenesis via regulating miR-216a-5p/BMP7 axis in diabetic nephropathy, providing a potential target for DN therapy.


Subject(s)
Humans , Diabetic Nephropathies/metabolism , Bone Morphogenetic Protein 7/metabolism , Epithelial-Mesenchymal Transition/physiology , RNA, Long Noncoding/physiology , Zinc Finger E-box-Binding Homeobox 1/metabolism , Down-Regulation , Up-Regulation , Cells, Cultured , MicroRNAs/metabolism , Diabetic Nephropathies/genetics , Real-Time Polymerase Chain Reaction
12.
Rev. Assoc. Med. Bras. (1992) ; 66(supl.1): s17-s24, 2020. tab, graf
Article in English | LILACS | ID: biblio-1057108

ABSTRACT

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
13.
Cienc. tecnol. salud ; 7(1)2020. ^c27 cmilus
Article in Spanish | LILACS | ID: biblio-1121008

ABSTRACT

La prevalencia de enfermedad renal ha aumentado considerablemente en la última década y está previsto que crezca en los próximos años. Recientemente, diversos modelos se han utilizado para entender los procesos fisiopatológicos de daño renal y para la búsqueda de futuros candidatos farmacológicos. El objetivo de esta revisión es proporcionar una descripción de la evidencia actual de modelos in vitro e in vivo de nefrotoxicidad, nefropatía diabética y deshidratación, y los fundamentos de las principales vías de señalización fisiopatológicas, con el fin de proponer biomarcadores candidatos para futura investigación farmacológica. Actualmente, los roedores constituyen un pilar importante en estudios de daño renal, existiendo diferencias específicas según el estímulo nocivo, lo que sugiere considerar para un modelo relevante aspectos como especie, cepa, género y estructuras renales objetivo. Diversas estructuras renales se han complementado in vitro, principalmente a partir de líneas celulares, como del epitelio tubular, podocitos, células mesangiales glomerulares y conducto colector medular interno. Este enfoque se ha utilizado como complementario en modelos de nefrotoxicidad por exposición a aminoglucósidos (principalmente), deshidratación por cloruro de sodio hiperosmolar, y nefropatía diabética por medio de glucosa alta y productos derivados de glucólisis y glicación. Recientemente, estos modelos han mostrado similitud en diversas rutas de señalización celular, con algunos biomarcadores en común, entre múltiples causas de daño renal como el daño oxidativo, disfunción mitocondrial, procesos inflamatorios, desregulación de sistemas de defensa y sobrevivencia celular, y apoptosis. El enfoque en seleccionar biomarcadores relevantes contribuirá al diseño de estrategias terapéuticas de nefroprotectores sobre múltiples factores etiológicos.


The prevalence of kidney disease has increased considerably in the last decade and is expected to growth in the coming years. Recently, various models have been used to understand the pathophysiological processes of kidney damage and to search for future pharmacological candidates. The aim of this review is to provide a description of the current evidence of in vitro and in vivo models of nephrotoxicity, diabetic nephropathy and dehydration, and the foundations of the main pathophysiological signaling pathways, in order to propose candidate biomarkers for future drug discovery. Currently, rodents are an important pillar in studies of kidney damage, with specific differences depending on the noxious stimulus, which suggests considering aspects such as species, strain, gender and target structures for a relevant model. Several renal structures have been complemented through in vitro approaches, mainly using cell lines, such as the tubular epithelium, podocytes, glomerular mesangial cells and inner medullary collecting duct. These cells have been used as models of nephrotoxicity by exposure to aminoglycosides (mainly), dehydration by exposure to hyperosmolar sodium chloride, and diabetic nephropathy by exposure to high glucose and products derived from glycolysis and glycation. Recently, these models have shown common cell signaling pathways on multiple etiologies of kidney injury, sharing several biomarkers such as oxidative damage, mitochondrial dysfunction, inflammatory processes, dysregulation of defense systems and cell survival, and apoptosis. Approaching kidney injury based on the selection of relevant biomarkers will contribute to the design of therapeutic strategies for nephroprotection on multiple etiological factors.


Subject(s)
Humans , Animals , Male , Adolescent , Adult , Rats , In Vitro Techniques/methods , Biomarkers , Diabetic Nephropathies , Rodentia , Rats, Wistar , Apoptosis , Epithelium , Mesangial Cells , Glucose/analysis
14.
Braz. j. med. biol. res ; 53(7): e9628, 2020. tab, graf
Article in English | ColecionaSUS, LILACS, ColecionaSUS | ID: biblio-1132530

ABSTRACT

Ophiopogonin D (OP-D) is the principal pharmacologically active ingredient from Ophiopogon japonicas, which has been demonstrated to have numerous pharmacological activities. However, its protective effect against renal damage in streptozotocin (STZ)-induced diabetic nephropathy (DN) rats remains unclear. The present study was performed to investigate the protective effect of OP-D in the STZ-induced DN rat model. DN rats showed renal dysfunction, as evidenced by decreased serum albumin and creatinine clearance, along with increases in serum creatinine, blood urea nitrogen, TGF-β1, and kidney hypertrophy, and these were reversed by OP-D. In addition, STZ induced oxidative damage and inflammatory response in diabetic kidney tissue. These abnormalities were reversed by OP-D treatment. The findings obtained in the present study indicated that OP-D might possess the potential to be a therapeutic agent against DN via inhibiting renal inflammation and oxidative stress.


Subject(s)
Animals , Male , Rats , Saponins/therapeutic use , Oxidative Stress/drug effects , Ophiopogon/chemistry , Diabetes Mellitus, Experimental/drug therapy , Diabetic Nephropathies/drug therapy , Inflammation/prevention & control , Spirostans/therapeutic use , Rats, Sprague-Dawley , Streptozocin
15.
Braz. j. med. biol. res ; 53(9): e9360, 2020. graf
Article in English | ColecionaSUS, LILACS, ColecionaSUS | ID: biblio-1132557

ABSTRACT

Diabetic nephropathy (DN) has been identified as the major cause of end-stage renal disease (ESRD) in most developed countries. MicroRNA-770-5p depletion could repress high glucose (HG)-triggered apoptosis in podocytes, and downregulation of E2F transcription factor 3 (E2F3) could facilitate podocyte injury. Nevertheless, whether E2F3 is involved in miR-770-5p knockdown-mediated improvement of DN is still unclear. The expression levels of miR-770-5p and E2F3 were detected in HG-treated podocytes by RT-qPCR. The expression levels of E2F3, apoptosis-related proteins Bcl-2 related X protein (Bax), B-cell lymphoma-2 (Bcl-2), Bad, apoptotic peptidase activating factor 1 (APAF1), C-caspase3, C-caspase7, and C-caspase9 were detected by western blot assay. The effects of miR-770-5p and E2F3 on HG-treated podocytes proliferation and apoptosis were detected by CCK-8 and flow cytometry assays. The interaction between miR-770-5p and E2F3 was predicted by Targetscan, and then verified by the dual-luciferase reporter assay. MiR-770-5p was upregulated and E2F3 was downregulated in HG-treated podocytes. MiR-770-5p inhibited proliferation and promoted apoptosis and E2F3 promoted proliferation and suppressed apoptosis in HG-treated podocytes. E2F3 is a target gene of miR-770-5p and it partially abolished the effect of miR-770-5p in HG-triggered proliferation and apoptosis of podocytes. MiR-770-5p deficiency blocked HG-induced APAF1/caspase9 pathway via targeting E2F3 in podocytes. We firstly confirmed that E2F3 was a target of miR-770-5p in podocytes. These findings suggested that miR-770-5p expedited podocyte injury by targeting E2F3, and the miR-770-5p/E2F3 axis might represent a pathological mechanism of DN progression.


Subject(s)
Humans , MicroRNAs , Diabetes Mellitus , Diabetic Nephropathies , Podocytes , Apoptosis , E2F3 Transcription Factor , Glucose
17.
Article in Korean | WPRIM | ID: wpr-811256

ABSTRACT

PURPOSE: Diabetic nephropathy is one of the most important diabetic complications prompted by chronic hyperglycemia, characterized by glomerulosclerosis, tubular fibrosis, and it eventually causes kidney failure. Nobiletin is a polymethoxyflavone present in tangerine and other citrus peels, and has anti-cancer and anti-inflammatory effects. This study investigated the effects of nobiletin on glomerular fibrosis through inhibition of the transforming growth factor (TGF)-β1-Src-caveolin-1 pathway.METHODS: Human renal mesangial cells (HRMC) were incubated in media containing 33 mM glucose with or without 1–20 uM nobiletin for 3 day. The cellular expression levels of fibrogenic collagen IV, fibronectin, connective tissue growth factor (CTGF), TGF-β1, Src and caveolin-1 were all examined. In addition, TGF-β1, Src and caveolin-1 proteins were screened to reveal the relationship among TGF-β1-Src-caveolin-1 signaling in glomerular fibrosis.RESULTS: High glucose promoted the production of collagen IV, fibronectin and CTGF in HRMC, which was inhibited in a dose dependent manner by 1–20 uM nobiletin. The Western blot data showed that high glucose elevated the expression of TGF-β1, Src, caveolin-1 and Rho GTPase. When nobiletin was treated to the HRMC exposed to high glucose, the expression of TGF-β1-Src-caveolin-1 was dampened. Finally, TGF-β1-Src-caveolin-1 signaling pathway was activated in high glucose-exposed HRMC, and such activation was encumbered by nobiletin.CONCLUSION: These result demonstrated that nobiletin blunted high glucose-induced extracellular matrix accumulation via inhibition of the TGF-β1-Src-caveolin-1 related intracellular signaling pathway. Nobiletin may be a potent renoprotective agent to counteract diabetes-associated glomerular fibrosis that leads to kidney failure.


Subject(s)
Blotting, Western , Caveolin 1 , Citrus , Collagen , Connective Tissue Growth Factor , Diabetes Complications , Diabetic Nephropathies , Extracellular Matrix , Fibronectins , Fibrosis , Glucose , GTP Phosphohydrolases , Humans , Hyperglycemia , Mesangial Cells , Renal Insufficiency , Transforming Growth Factors
18.
Article in English | WPRIM | ID: wpr-811139

ABSTRACT

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is required for renal fibrosis, which is a characteristic of diabetic nephropathy (DN). Our previous study demonstrated that fibroblast growth factor 21 (FGF21) prevented DN associated with the suppressing renal connective tissue growth factor expression, a key marker of renal fibrosis. Therefore, the effects of FGF21 on renal fibrosis in a DN mouse model and the underlying mechanisms were investigated in this study.METHODS: Type 1 diabetes mellitus was induced in C57BL/6J mice by intraperitoneal injections of multiple low doses of streptozotocin. Then, diabetic and non-diabetic mice were treated with or without FGF21 in the presence of pifithrin-α (p53 inhibitor) or 10-[4′-(N,N-Diethylamino)butyl]-2-chlorophenoxazine hydrochloride (10-DEBC) hydrochloride (Akt inhibitor) for 4 months.RESULTS: DN was diagnosed by renal dysfunction, hypertrophy, tubulointerstitial lesions, and glomerulosclerosis associated with severe fibrosis, all of which were prevented by FGF21. FGF21 also suppressed the diabetes-induced renal EMT in DN mice by negatively regulating transforming growth factor beta (TGF-β)-induced nuclear translocation of Smad2/3, which is required for the transcription of multiple fibrotic genes. The mechanistic studies showed that FGF21 attenuated nuclear translocation of Smad2/3 by inhibiting renal activity of its conjugated protein p53, which carries Smad2/3 into the nucleus. Moreover pifithrin-α inhibited the FGF21-induced preventive effects on the renal EMT and subsequent renal fibrosis in DN mice. In addition, 10-DEBC also blocked FGF21-induced inhibition of renal p53 activity by phosphorylation of mouse double minute-2 homolog (MDM2).CONCLUSION: FGF21 prevents renal fibrosis via negative regulation of the TGF-β/Smad2/3-mediated EMT process by activation of the Akt/MDM2/p53 signaling pathway.


Subject(s)
Animals , Connective Tissue Growth Factor , Diabetes Mellitus, Type 1 , Diabetic Nephropathies , Epithelial-Mesenchymal Transition , Fibroblast Growth Factors , Fibroblasts , Fibrosis , Hypertrophy , Injections, Intraperitoneal , Kidney , Mice , Phosphorylation , Streptozocin , Transforming Growth Factor beta , Tumor Suppressor Protein p53
19.
Article in English | WPRIM | ID: wpr-811137

ABSTRACT

Renal fibrosis is considered to be the final common outcome of chronic kidney disease. Dipeptidyl peptidase-4 (DPP-4) inhibitors have demonstrated protective effects against diabetic kidney disease. However, the anti-fibrotic effect of evogliptin, a DPP-4 inhibitor, has not been studied. Here, we report the beneficial effects of evogliptin on unilateral ureteral obstruction (UUO)-induced renal fibrosis in mice. Evogliptin attenuated UUO-induced renal atrophy and tubulointerstitial fibrosis. Immunohistochemistry and Western blotting demonstrated that evogliptin treatment inhibits pro-fibrotic gene expressions and extracellular matrix production. In vitro findings showed that the beneficial effects of evogliptin on renal fibrosis are mediated by inhibition of the transforming growth factor-β/Smad3 signaling pathway. The present study demonstrates that evogliptin is protective against UUO-induced renal fibrosis, suggesting that its clinical applications could extend to the treatment of kidney disease of non-diabetic origin.


Subject(s)
Animals , Atrophy , Blotting, Western , Diabetic Nephropathies , Dipeptidyl-Peptidase IV Inhibitors , Extracellular Matrix , Fibrosis , Gene Expression , Immunohistochemistry , In Vitro Techniques , Kidney Diseases , Kidney Failure, Chronic , Mice , Renal Insufficiency, Chronic , Transforming Growth Factor beta , Ureter , Ureteral Obstruction
20.
Article in Korean | WPRIM | ID: wpr-786183

ABSTRACT

Diabetic kidney disease is a microvascular complication of diabetes mellitus and the leading cause of end-stage renal disease resulting in renal replacement therapy. Approximately 30% to 40% of diabetic patients have diabetic kidney disease, which contributes to a significant increase in morbidity and mortality. Microalbuminuria is considered the gold standard for diabetic kidney disease diagnosis; however, its predictive value is restricted. Although blood glucose control, blood pressure control, and angiotensin converting enzyme inhibitors have been the primary treatment strategies, there are no definitive treatment modalities capable of inhibiting the progression of kidney dysfunction in these patients. This study was undertaken to answer seven questions regarding the various aspects of diabetic kidney disease. Why does it develop? what kind of factors affect its development? How is it diagnosed? What are its possible biomarkers? When is a kidney biopsy necessary? What are the preventive and therapeutic options? And what are the novel treatments?


Subject(s)
Angiotensin-Converting Enzyme Inhibitors , Biomarkers , Biopsy , Blood Glucose , Blood Pressure , Diabetes Mellitus , Diabetic Nephropathies , Diagnosis , Humans , Kidney , Kidney Failure, Chronic , Mortality , Renal Replacement Therapy
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