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- ItemSomente MetadadadosAção Do Suco De Uva E Suco De Maçã Em Rins De Ratos Expostos Ao Cloreto De Cádmio(Universidade Federal de São Paulo (UNIFESP), 2018-03-12) Handan, Bianca Andrade [UNIFESP]; Ribeiro, Daniel Araki [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Cadmium Is A Non-Essential Metal That Can Cause Several Diseases, Including Cancer. In This Study, Nutraceutical Potential Of Grape Juice (G8000") And Apple Juice Were Evaluated Against Cadmium-Induced Renal Toxicity. A Total Of 20 Male-Wistar Rats Were Distributed Into Four Groups (N=5): Control Group: Animals Received An Intraperitoneal (Ip) Injection Of 0.9% Saline Solution And After 15 Days, 1 Ml Of Water Was Administered For 15 Days, Via Gavage; Cadmium Group: Animals Received An Ip Injection Of Cadmium Chloride (1.2 Mg/Kg) And After 15 Days, 1 Ml Of Water Was Administered For 15 Days Via Gavage; Cadmium Group + Grape Juice: Animals Received An Ip Injection Of Cadmium Chloride (1.2 Mg/Kg), And After 15 Days, 0.8 Ml Of Grape Juice G8000" Was Administered For 15 Days, Via Gavage; Cadmium Group + Apple Juice: Animals Received An Ip Injection Of Cadmium Chloride (1.2 Mg/Kg) And After 15 Days, 1.0 Ml Of Apple Juice Was Administered For 15 Days, Via Gavage. A Severe Tubular Lesion With Areas Of Necrosis Was Ob
- ItemAcesso aberto (Open Access)Alprostadil attenuates inflammatory aspects and leucocytes adhesion on renal ischemia and reperfusion injury in rats(Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia, 2014-01-01) Soares, Bruno Leonardo de Freitas [UNIFESP]; Freitas, Maria Andréia Lopes de; Montero, Edna Frasson de Souza [UNIFESP]; Pitta, Guilherme Benjamin Brandão; Miranda Júnior, Fausto; Universidade Federal de São Paulo (UNIFESP); Federal University do Vale do São Francisco Faculty of Nursing; University of São Paulo Faculty of Medicine Department of Surgery; University of Health Sciences of Alagoas Faculty of MedicinePURPOSE:To evaluate the effects of alprostadil in an experimental model of ischemia and reperfusion injury (IRI) in rat renal tissue.METHODS: Adult male Wistar rats were randomized into three groups Vehicle-treated group(Veh), Alprostadil-treated(Al), and sham(Sh) group. Veh and Al groups had suprarenal aorta occluded for 30 minutes and reperfused for 60 minutes. Saline or 20 µg/kg of Alprostadil was intravenously infused immediately before declamping. Sh group animals underwent similar procedure without aortic occlusion. Left nephrectomy and blood sampling were performed after 60 minutes of reperfusion. Renal ICAM-1 expression and histological analysis were performed to estimate inflammatory response and tissue disarrangement. Serum biochemical markers for IRI were also measured. Kruskal-Wallis test was used to assess differences between the groups.RESULTS: There was lower expression of ICAM-1 in groups Veh and Sh. On histologically evaluation, inflammation and necrosis in the Veh group was significantly higher (grades III/IV) than Al group (Veh>Al=Sh; p = 0.025), as well as CPK levels (Veh>Al=Sh; p = 0.03).CONCLUSION: Alprostadil attenuates the immunohistochemical and histological repercussions in the renal tissue of rats submitted to a post-ischemic reperfusion with supra-renal aortic clamping.
- ItemAcesso aberto (Open Access)Análise da expressão dos receptores envolvidos no controle vesical em pacientes com bexiga desfuncionalizada e do comportamento miccional após o transplante renal(Universidade Federal de São Paulo (UNIFESP), 2017-11-09) Neves Neto, João Ferreira [UNIFESP]; Mesquita, Roberto Andre Soler [UNIFESP]; http://lattes.cnpq.br/9038872306641159; http://lattes.cnpq.br/0556885434249812; Universidade Federal de São Paulo (UNIFESP)Objective: End-stage renal disease (ESRD) patients undergoing dialysis may develop anuria. Long periods of anuria lead to interruption of the physiological storage and voiding cycle, a condition known as defunctionalized bladder (DB). The objective of this study is to evaluate the expression of bladder receptors in patients with DB and to assess voiding behavior after refunctionalization. Methods: A total of 68 patients with ESRD undergoing dialysis who were candidates to kidney transplant were divided in two groups: DB (diuresis < 300 mL/24 h; n=33) and NDB (non-DB; diuresis 300 mL/24 h; n=35). During kidney transplant a sample of the already dissected mucosa and detrusor at the site of the future ureteral implantation were collected. The expression of the following receptors was evaluated by real-time polymerase chain reaction (RT-PCR) in the mucosa and detrusor: M2, M3, 1D, 3, P2X1, P2X2, P2X3, TRPV1, TRPV4, TRPA1 and TRPM8. At 3, 6 and 12 months after kidney transplant patients answered IPSS and ICIQ-OAB questionnaires. They also filled a 3-day 24 h frequency/volume chart at 6 and 12 months. Results: There was no difference in sex and age between DB and NDB groups. Lower diuresis volume in 24 h and longer pretransplant dialysis duration was observed in DB patients. The expression of all receptors in the mucosa and in the detrusor was similar in both groups, except from 1D, which was overexpressed in the detrusor of DB relatively to NDB group. TRPM8 expression was not demonstrated in any bladder layer of any group. ICIQ-OAB symptom score was similar between the groups at 3, 6 and 12 months. There was a reduction of this score in both groups throughout the follow-up. The same pattern was found for IPSS score. Bother scores were similar between groups. No difference was observed for all parameters extracted from the frequency-volume charts between DB and NDB patients. Conclusion: Gene expression of bladder receptors involved in micturition control was similar in patients with or without DB. Bladder behavior had a similar pattern independently of pretransplant residual diuresis. These findings question the relevance of the term DB in pretransplant patients.
- ItemSomente MetadadadosAnálise dos eventos infecciosos ocorridos com receptores de transplante renal com doador falecido com critério expandido(Universidade Federal de São Paulo (UNIFESP), 2020-07-30) Sousa, Sirlei Regina De [UNIFESP]; Barbosa, Dulce Aparecida [UNIFESP]; Universidade Federal de São PauloIntroduction: despite advances in dialysis methods and kidney transplantation, mortality from chronic kidney disease remains high. There are few epidemiological studies on risk factors for infection / colonization by multi-resistant bacteria in kidney recipients with Deceased Donor with Expanded Criteria. Objectives: to analyze risk factors for infection / colonization by multi-resistant bacteria in kidney transplant recipients with Deceased Donor with Expanded Criteria. Method: a retrospective, epidemiological, cohort study that analyzed the presence of infection in 466 kidney transplant recipients with an expanded deceased donor. A descriptive analysis of the data presented was performed using absolute and percentage frequencies, means, standard deviations, minimum and maximum values, when appropriate, univariate and multivariate analysis for risk factors for infection. The level of significance adopted was 0.05. The statistical program used to perform the calculations was RStudio, version 1.2.1335 and R, version 3.4.4. Results: A total of 466 kidney transplant recipients with Deceased Donor with Expanded Criterion were included in the study. 63% were male, mean age 47 years, mixed race (44.2%) prevailed, 89% were positive for cytomegalovirus, 49% received even a bag of hemacene concentrate before transplantation. The mean cold ischemia time was 1503 minutes, 53.4% underwent urethral anastomosis using the Gregoir technique, requiring hemodialysis after transplantation 3 to 4 times, the use of thymoglobulin was observed in 39.9% for one dose and in 15.9% for 4 doses. The main cause of death of the donor was stroke (31.5%) followed by traumatic brain injury (32%). The presence of acute tubular necrosis was observed in 64.2% of the donor kidney before transplantation. A total of 551 episodes of infection were recorded, 162 by cytomegalovirus, 80 by urinary tract infection and others. Episodes of infections were 70.2% in kidney transplant recipients with Deceased Donor with Expanded Criterion. The risk factors for infection for the 327 (70.20%) recipients were using the immunosuppressive protocol Tacrolimus, Prednisone and Azathioprine, Tacrolimus, Prednisone and Mycophenolate Sodium, induction with thymoglobulin and presence of CMV infection. The incidence of infection with multidrug-resistant bacteria was 6.1%. The most common infection was Urinary Tract Infection (70%), and the carbapenemase-producing etiologic agent Klebsiella pneumoniae was diagnosed in eleven urine cultures (78.50%). Klebsiella pneumoniae carbapenemase-producing pneumonia was present in four patients and in one due to surgical site infection. One patient had multidrug-resistant Eschichia Coli urinary tract infection, a vancomycin-resistant Enterococcus blood-correcting infection, and two had carbapenemase-producing Klebsiella pneumoniae and Eschichia Coli. Survival was 96% among patients with infection. Patients without infection survived at a rate of 100% two years after the transplant. Survival was shorter for recipients who had CMV infection in the first month after transplantation. Conclusions: the most frequent infectious episodes were due to cytomegalovirus and urinary tract infection. The etiologic agent most present in the result of urine culture was the carbapenemase-producing Klebsiella pneumoniae. The risk factors for infection were length of stay, having infection with Cytomegalovirus, use of Tacrolimus, Prednisone and Azathioprine, Tacrolimus, Prednisone and Mycophenolate Sodium, induction with Timoglobulin and diabetes. Death occurred in 3.3% of the studied population and the main cause of death was infectious. Survival was 96% among patients with infection.
- ItemAcesso aberto (Open Access)Análise morfológica e fisiológica dos fígados e rins de ratas prenhes e seus fetos tratados pela associação zidovudina, lamivudina e ritonavir durante toda a prenhez(Federação Brasileira das Sociedades de Ginecologia e Obstetrícia, 2010-11-01) Wagner, Adriana; Carvalho, Adelino Moreira de; Nakamura, Mary Uchiyama [UNIFESP]; Simões, Ricardo Santos; Fontes, Tereza Maria Pereira [UNIFESP]; Espiridião, Silvia [UNIFESP]; Kulay Júnior, Luiz [UNIFESP]; Universidade José do Rosário Vellano Departamento de Obstetrícia e Ginecologia; Universidade José do Rosário Vellano Serviço de Clínica Médica; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); Universidade Gama Filho Departamento de Ginecologia e Obstetrícia; ABC Faculdade de Medicina Departamento de Obstetrícia e PediatriaPURPOSE: to evaluate the effect of administration of three different doses of the zidovudine/lamivudine/ritonavir combination on the liver and kidneys of pregnant rats and their concepts from a morphological and physiological standpoint. METHODS: 40 pregnant EPM-1 Wistar rats were randomly divided into 4 groups: 1 control (Ctrl: drug vehicle control, n=10) and 3 experimental groups: Exp1x, Exp3x and Exp9x. An oral solution of the zidovudine/lamivudine/ritonavir combination was administered to the experimental groups from the day 0 to day 20 of pregnancy: Exp1x=10/5/20 mg/kg; Exp3x=30/15/60 mg/kg; Exp9x=90/45/180 mg/kg. On the 20th pregnancy day the rats were anesthetized and blood was taken directly from the ventricular chambers for further biochemical determinations: aspartate-(AST) and alanine-(ALT) aminotransferases (Calorimetric method), urea nitrogen (BUN) by an enzymatic-kinetic method, and creatinine by a kinetic-calorimetric method. Maternal and fetal liver and kidney samples were taken, fixed in 10% formaldehyde and processed histologically for paraffin embedding. Five µm-thick fragments of maternal and fetal livers and kidneys were stained with hematoxilyn-eosin, being analyzed by light microscopy. To interpret the results, the well-known pattern of normality for livers and kidneys was considered on the basis of the following structures: hepatocytes, portal structure, hepatic veins, renal corpuscles, renal tubules and loop of Henle. Regarding the fetal livers, we also considered the erythrocytes in their different stages of development as well as the megacariocytes. If there was a change in the established staining pattern for liver and kidney structures, changes in nuclear morphology, rupture of some cytoplasmic organelles, and presence of vascular congestion, this was considered to be due to the drug doses. Results were submitted to analysis of variance (ANOVA) and to the Tukey-Kramer multiple comparisons test (p<0.05). RESULTS: no morphological changes were observed in the maternal livers of the Ctrl, Exp1x and Exp3x groups. In the maternal liver of the Exp9x group, hepatocytes showed signs of atrophy and apoptosis (eosinophilic cytoplasm and pycnotic nuclei) and marked sinusoid capillary vasodilation (congestion) was observed. The maternal kidneys of the Ctrl and Exp1x groups were normal, with renal corpuscles, convoluted tubules and typical loops of Henle. In contrast, the Exp3x and Exp9x groups showed vascular congestion and small glomeruli rich in cells containing hyperchromatic nuclei which were more intense in Exp9x. Regarding the fetal organs, no morphological or physiological changes were observed. A significant increase of AST (305.70±55.80, p<0.05) and creatinine (0.50±0.09, p<0.05) was observed in group Exp9x. CONCLUSIONS: our results show that the administration of the zidovudine, lamivudine and ritonavir combination to pregnant rats at high doses caused morphological and physiological changes in the maternal liver and kidneys. On the other hand, there were no changes in fetal organs.
- ItemAcesso aberto (Open Access)Análise renal de ultramaratonista em prova de 75 km(Escola Paulista de Enfermagem, Universidade Federal de São Paulo (UNIFESP), 2009-01-01) Lopes, Thiago Ribeiro [UNIFESP]; Mastroianni Kirsztajn, Gianna [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)OBJECTIVE: To identify urinary abnormalities, indicative of renal involvement, in 75 km ultra-marathon racer and pacer (cyclist that gives support to the racer). METHODS: Renal analysis consisted of urine dipstick tests in four different times and anthropometric measures. RESULTS: Both the racer and the pacer were in eutrophic conditions. There was an association between the capacity for maximum physical effort and detection of urinary abnormalities determined by the presence of hematuria and/or proteinuria. CONCLUSION: Renal analysis allowed the identification of transitory renal involvement in both healthy individuals during intense exercise.
- ItemEmbargoAngiotensina II e angiotensina (1-7) modulam a aquaporina 2 em células do ducto coletor medular interno (IMCD)(Universidade Federal de São Paulo, 2024-03-12) Braga, Tamires da Silva [UNIFESP]; Casarini, Dulce Elena [UNIFESP]; Oliveira, Lilian Caroline Gonçalves de [UNIFESP]; http://lattes.cnpq.br/7497259224229778; http://lattes.cnpq.br/0534906942293338; http://lattes.cnpq.br/7997207253291872As aquaporinas (AQPs) são proteínas que funcionam como canais de água e estão presentes nos túbulos coletores renais, ajudam na reabsorção de água e manutenção da homeostase eletrolítica. No presente trabalho, foram utilizadas células imortalizadas do ducto coletor medular murino (IMCD) a fim de avaliar a hipótese de que os componentes do Sistema Renina-Angiotensina-Aldosterona (SRAA), Angiotensina II (Ang II) e Angiotensina (1-7) (Ang (1-7)), poderiam induzir a translocação da aquaporina 2 (AQP2) para a membrana apical destas células, de forma a aumentar a reabsorção de água. Como controle positivo de tratamento, as células IMCD foram também estimuladas com o hormônio vasopressina (AVP), que sabidamente desempenha tal função, e assim proporcionar embasamento teórico para o possível desenvolvimento de novos fármacos que visem o tratamento de disfunções no balanço hídrico corporal. Objetivo: Avaliar os efeitos dos componentes do SRAA, Ang II e Ang (1-7), na expressão e translocação da AQP2 em células IMCD, de forma a participar do controle hídrico renal. Materiais e Métodos: Foram utilizadas células imortalizadas IMCD. Como agonistas, foram utilizadas o AVP (controle positivo), a Ang II e Ang (1-7). A técnica de Western Blotting (WB) foi utilizada para avaliar a expressão proteica em cada tratamento, comparados aos controles negativo e positivo de cada grupo. Também foram utilizadas as técnicas de reação em cadeia da polimerase com transcriptase reversa para análise da expressão gênica de AQP2 e receptores do SRAA, e imunofluorescência para análise da localização das proteínas nas células. Para análise estatística, foram utilizados os testes de análise de variância ANOVA, seguido de Tukey como pós-teste. Resultados: Foi observado aumento da expressão gênica e proteica de AQP2 após os tratamentos com Ang II e AVP. O tratamento com Ang (1-7) induziu aumento da expressão gênica dos receptores AT1, AT2 e MAS, e a diminuição da expressão gênica e proteica de AQP2. Os resultados corroboram com dados da literatura, e apresentam evidências da importância da atuação dos peptídeos estudados na função renal exercida por células do ducto coletor medular e mediada pela ação de AQP2. Conclusão: Os resultados apresentados neste estudo corroboram dados da literatura e vão ao encontro da hipótese inicial do estudo. Foi possível demonstrar o papel da Ang II e da Ang (1-7) nas células IMCD na mediação da translocação dos canais sanguíneos. água do citoplasma para a membrana plasmática. Sugere-se que Ang II e Ang (1-7) possam modular tanto a migração de AQP2 quanto a resposta do gene do receptor RAAS, o que leva a sugerir que os receptores AT1, AT2 e MAS também podem estar envolvidos na translocação de AQP2. A ativação do receptor V2 pode permitir a interação com os receptores do SRAA, formando dímeros ou trímeros que permitem a translocação do AQP2, fenômeno que requer mais estudos para comprovar esta teoria. Por fim, pode-se afirmar que os peptídeos do SRAA estudados, Ang II e Ang (1-7), além do AVP, são capazes de alterar os níveis de expressão de AQP2 em células IMCD e sua atividade através dos receptores MAS, AT1 e AT2.
- ItemSomente MetadadadosAssessment of fructose overload in the metabolic profile and oxidative/nitrosative stress in the kidney of senescent female rats(Pergamon-Elsevier Science Ltd, 2017) Costalonga Seraphim, Deborah Chianelli [UNIFESP]; Punaro, Giovana Rita [UNIFESP]; Fernandes, Thamires de Oliveira [UNIFESP]; Ginoza, Milton [UNIFESP]; Lopes, Guiomar Silva [UNIFESP]; Suemitsu Higa, Elisa Mieko [UNIFESP]The aging process is a complex phenomenon that leads the body to several changes, affecting its integrity and resulting in chronic pathologies, which compromises health and quality of life of elderly people. Animals supplemented with fructose have been used as an experimental model for induction of insulin resistance. The objective of this study was to evaluate the metabolic effects and the levels of oxidative/nitrosative stress in the kidney of senescent rats with a high fructose intake. The animals were allocated into 4 groups: young control (Y), aged control (A), young fructose (YF) and aged fructose (AF). Groups Y and A received water and groups YF and AF received fructose (100 g/L) in the water, both ad libitum. After 12 weeks of high fructose intake, the animals were sacrificed to collect their kidneys, blood and the thoracic aorta. The results are presented as mean +/- SE, analyzed by the One-Way ANOVA test with Newman-Keuls post-test; significant at p < 0.05. The fructose overload caused metabolic dysfunctions and insulin resistance, confirming the efficacy of the chosen model. In this study, we observed a body weight gain in the studied groups (except in the elderly fructose group), and an increase in general caloric intake, diuresis and adipose tissue; insulin resistance, increased fasting glucose, triglycerides and cholesterol in the fructose groups. We also found a loss of renal function, increased oxidative/nitrosative stress and inflammation, and a reduction of antioxidants and a lower vasodepressor response in the studied groups, especially those who consumed fructose. In summary, our data showed that aging or high fructose intake contributed to the increase of oxidative/nitrosative stress in animals, demonstrating that at the dose and the period of fructose treatment utilized in this study, fructose was not able to aggravate several aspects which were already altered by aging. We believe that the high fructose intake simulates most of the effects of aging, and this understanding would be useful to prevent or minimize many of the alterations caused by this condition.
- ItemAcesso aberto (Open Access)Atividade inflamatória, oxidante e proliferativa em fígado e rim de ratos expostos ao crack(Universidade Federal de São Paulo, 2021-09-29) Souza, Daniel Vitor de [UNIFESP]; Ribeiro, Daniel Araki [UNIFESP]; Peres, Rogerio Correa [UNIFESP]; http://lattes.cnpq.br/9555994793258800; http://lattes.cnpq.br/9969803499258672; http://lattes.cnpq.br/7955161915979529; Universidade Federal de São Paulo (UNIFESP)O crack é uma das drogas ilícitas mais utilizadas ao redor do mundo, sendo o consumo e a disseminação desenfreada representam grande problema de saúde pública. O objetivo do presente estudo foi investigar os efeitos da exposição subaguda de crack no contexto inflamatório, oxidativo e proliferativo em fígado e rim de ratos Wistar. Para tanto, o trabalho foi dividido em 4 capítulos a citar: o Capítulo I foi dedicado a estabelecer uma revisão de literatura acerca do assunto; o Capítulo II apresentamos uma revisão de literatura intitulada “Genotoxicity, oxidative stress and inflammatory response induced by crack cocaine: relevance to carcingoenesis” publicada na Revista Environmental Science and Pollution Research; o Capítulo III apresentamos o artigo intitulado “Histopathological and inflammatory response in multiple organs of rats exposed to crack“, que foi aceito para a publicação na Revista International Journal of Environmental Health Research e finalmente o Capítulo IV apresentamos o artigo intitulado “Genomic instability suppresses toll like signaling pathway in rat liver exposed to crack cocaine, que foi aceito para publicação na revista In Vivo.
- ItemSomente MetadadadosAvaliação da expressão genica do estresse oxidativo e da defesa antioxidante em rim de camundongos, submetidos a isquemia e repercussão intestinal, sob oxigenação hiperbólica(Universidade Federal de São Paulo (UNIFESP), 2012) Teruya, Roberto [UNIFESP]; Fagundes, Djalma José [UNIFESP]Objetivo: determinar o perfil da expressao genica relacionado ao estresse oxidativo e a resposta antioxidante em rim de camundongos submetidos a isquemia e reperfusao de intestino delgado e submetidos a oxigenacao hiperbarica. Metodos: Trinta camundongos (C57-BL/6) foram submetidos a anestesia, laparotomia, sendo vinte e quatro animais submetidos a isquemia intestinal de 60 minutos seguido de 60 minutos de reperfusao. Tres desses grupos com seis animais foram submetidos a oxigenacao hiperbarica em periodos distintos: durante a isquemia (GOHB-I), durante o periodo de reperfusao (GOHB-R), nos periodos de isquemia e reperfusao (GOHB-IR) e um grupo nao recebeu a OHB (GIR). Um grupo foi somente anestesiado, operado, sem realizar clampeamento vascular do intestino (GC). Foram coletados especimes de intestino e rim para estudo histologico (coloracao HE) e avaliacao do grau de lesao morfologica. A expressao de 84 genes foi determinada pelo sistema, da Reacao de Polimerase em Cadeia em Tempo Real (RT-qPCR - SA BiosciencesTM - Quiagen Co). Para dados da expressao genica foi considerada a variacao do ciclo limiar (Ct) do grupo estudo comparado com o ciclo limiar (Ct) grupo controle expressos na base logaritmica (2) pela formula [2-ΔΔCt], admitido um p≤0,05 para rejeicao da hipotese de nulidade. Resultados: nos animais do grupo GIR, houve expressao genica acima do limiar de normalidade, mostrando relacao da isquemia intestinal com o estresse oxidativo no tecido renal. Nos grupos GOHB-R (36.9%) e no GOHB-IR (47.6%), tambem ocorreu expressao acima do limiar de normalidade. No GOHB-I (8,3%), houve reducao do numero de genes com expressao acima da normalidade, evidenciando uma acao favoravel da OHB nessa situacao sobre o estresse oxidativo e da defesa antioxidante. Conclusoes. A IR intestinal promoveu um perfil de hiperexpressao dos genes relacionados ao estresse oxidativo e defesa antioxidante a distancia sobre o tecido renal. A aplicacao da OHB durante a isquemia promoveu uma significante reducao no numero de genes expressos acima do limiar da normalidade. A OHB aplicada durante a reperfusao ou na isquemia/reperfusao manteve um perfil similar ao do grupo controle
- ItemEmbargoAvaliação histopatológica hepática e renal de ratos expostos a drogas antineoplásicas em concentração ambientalmente relevantes(Universidade Federal de São Paulo, 2023-07-04) Aranha, Maria Luiza Garcia [UNIFESP]; Perobelli, Juliana Elaine [UNIFESP]; http://lattes.cnpq.br/2047233951021632; http://lattes.cnpq.br/3171774667404416; Universidade Federal de São Paulo (UNIFESP)O câncer é uma das doenças que mais afeta pessoas no mundo, sendo estimados cerca de 18,1 milhões novos casos no ano de 2020. Consequentemente, o consumo de medicamentos destinados ao tratamento dessa doença tem aumentado a cada ano. Uma vez consumidos, esses medicamentos são metabolizados e excretados, atingindo efluentes hospitalares e urbanos, sendo por isso considerados contaminantes de preocupação emergente. Concentrações na faixa de ng/L a μg/L desses medicamentos já foram detectadas em efluentes hospitalares, águas residuais e águas superficiais ao redor do mundo. Entre as drogas antineoplásicas mais utilizadas e encontradas no ambiente estão os antimetabólitos 5-Fluorouracil e Metotrexato. Embora a toxicidade hepática e renal dessas duas drogas seja conhecida quando testadas em concentrações terapêuticas, os efeitos em concentrações ambientalmente relevantes ainda são desconhecidos. Assim o presente estudo, objetivou investigar se a exposição prolongada à concentração de 10 ng/L de 5-fluorouracil e/ou metotrexato, isolados ou em mistura binária, causa repercussões sobre parâmetros histopatológicos de fígado e rins de ratos machos adultos da linhagem Wistar. Os animais foram, expostos à essas drogas via água de beber do dia pós-natal 70 ao 160, quando foram eutanasiados e coletados o rim esquerdo e uma porção do lóbulo esquerdo do fígado para posterior processamento e avaliação de parâmetros histológicos. Embora não tenham sido observados resultados estatisticamente significativos quanto aos achados histopatológicos, não se descarta a possibilidade de toxicidade hepática e renal dessas drogas nessa concentração. Estudos futuros se fazem necessários a fim de melhor se investigar parâmetros bioquímicos e fisiológicos nesses órgãos.
- ItemAcesso aberto (Open Access)Avaliação morfofuncional renal na síndrome metabólica induzida por dieta hiperlipídica associada à sobrecarga salina aguda em ratos hipertensos(Universidade Federal de São Paulo (UNIFESP), 2017-10-26) Pereira, Renata Oliveira [UNIFESP]; Farah, Vera de Moura Azevedo [UNIFESP]; http://lattes.cnpq.br/0437040349763990; http://lattes.cnpq.br/2813967766375998; Universidade Federal de São Paulo (UNIFESP)The metabolic syndrome is characterized by the combination of at least 3 risk factors, for example diabetes, dyslipidemia, hypertension and obesity in the same person. The incidence of this syndrome has increased associated with an increase in the number of patients with nephropathies. Studies show that genetic and environmental factors are involved in the genesis of the components of the metabolic syndrome. Among the environmental factors, there is the consumption of food with high levels of salt and fat. The aim of this study was to investigate the effect of the association of high-fat diet (30% lipids) and saline overload (1% salt during 10 days) on the renal function of spontaneously hypertensive rats (SHR). Weaned male SHR rats (40-50g) were separated into 4 groups: Control (SC), Salt (SS), High-fat (SHL), High-fat Salt (SHLS) and the animals were followed during 8 weeks. The main results obtained were that the animals treated with the high-fat diet (SHL and SHLS) presented: 1) Decreased glomerular filtration rate; 2) Increased renal lipids deposition; 3) Increased collagen deposition in the kidney; 4) Decreased diameter of the glomerular tuft. In addition, we observed an increase in the expression of inflammatory cytokines IL-1β and TNF-α in the kidneys of the animals that received only saline overload (SS group), while we observed an increase of collagen IV in the kidney of all treated animals. In conclusion, our results show that the hypertensive animals fed a high-fat diet presented an important impairment in renal function, evidenced by the decrease of the glomerular filtration rate. It seems to be associated with a renal fibrogenesis process. However, the administration of an acute saline overload was not able to modify the glomerular filtration rate of the spontaneously hypertensive animals, although it has caused renal histological alterations and has changed the inflammatory cytokines.
- ItemAcesso aberto (Open Access)Caracterização da disfunção mitocondrial no rim de ratos Zucker(Universidade Federal de São Paulo (UNIFESP), 2016-04-05) Trindade, André Soares [UNIFESP]; Higa, Elisa Mieko Suemitsu [UNIFESP]; http://lattes.cnpq.br/8578252701813423; http://lattes.cnpq.br/963336381205462; Universidade Federal de São Paulo (UNIFESP)Introduction: Obesity is characterized as an inflammatory condition associated to several chronic diseases. Besides promoting cardiovascular, hepatic and renal alterations, adipose tissue accumulation can generate an increased reninangiotensin-aldosterone system activity, increased oxidative stress and mitochondrial dysfunction. Aim: The aim of this study was to evaluate the kidney mitochondrial function of Zucker rats through cellular respiration, membrane potential, osmotic swelling, oxidative stress and antioxidant defense. Methods: Ten adult male rats were distributed into obese (Zucker rat strain with a mutation in the gene fa-/fa- and obese phenotype, N=5) and lean (lean Zucker rat strain, heterozygous fa+/fa- with eutrophic phenotype, N=5). In the kidney mitochondria we evaluated: the osmotic swelling with 3 different calcium concentrations (10, 25 or 50 µM Ca+2); the lipid peroxidation was measured by malondialdehyde (MDA) generation, oxidation of thiol groups, levels of reduced glutathione (GSH) and generation of reactive oxygen species by dichlorofluorescein diacetate (DCFDA). Results: In the analysis of kidney mitochondrial swelling, the obese rats showed lower values only at 10µM Ca+2 concentration vs lean (P<0.05). The kidney mitochondrial MDA (µM/mg protein) was also reduced in obese when compared to lean (P<0.05), even in the presence of the pro - oxidant tert-butylhydroperoxide (t-BOOH). Obese kidney mitochondrial sulphydryl (SH, nmol/mg protein) levels did not show statistical differences when compared to lean DCFDA (nmol/mg protein) levels increased only in the presence of t-BOOH , with no difference between the obese vs lean. Obese rats presented decreased levels of mitochondrial GSH (nmol/mg protein) vs lean rats (81±8 vs 133±18; P<0.05). Conclusion: In summary, our data showed that obese rats had a reduced kidney osmotic mitochondrial swelling if compared to lean rats, suggesting that the mitochondrial permeability could be altered in the obesity. The renal mitochondrial oxidative stress between obese and lean was different only in the evaluation of the MDA, being the antioxidant system reduced in the obese, comparatively to lean. So, in this study we observed that there are differences between the redox system of the obese and lean kidney mitochondria, which can be relevant when the mitochondria would be the target in the treatment of this pathology.
- ItemAcesso aberto (Open Access)Characterization of renin mRNA expression and enzyme activity in rat and mouse mesangial cells(Associação Brasileira de Divulgação Científica, 2002-01-01) Andrade, A.q. [UNIFESP]; Casarini, Dulce Elena [UNIFESP]; Schor, Nestor [UNIFESP]; Boim, Mirian Aparecida [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Renin is an enzyme involved in the stepwise generation of angiotensin II. Juxtaglomerular cells are the main source of plasma renin, but renin activity has been detected in other cell types. In the present study we evaluated the presence of renin mRNA in adult male Wistar rat and mouse (C-57 Black/6) mesangial cells (MC) and their ability to process, store and release both the active and inactive forms of the enzyme. Active renin and total renin content obtained after trypsin treatment were estimated by angiotensinogen consumption analyzed by SDS-PAGE electrophoresis and quantified by angiotensin I generation by HPLC. Renin mRNA, detected by RT-PCR, was present in both rat and mouse MC under basal conditions. Active renin was significantly higher (P<0.05) in the cell lysate (43.5 ± 5.7 ng h-1 10(6) cells) than in the culture medium (12.5 ± 2.5 ng h-1 10(6) cells). Inactive prorenin content was similar for the intra- and extracellular compartments (9.7 ± 3.1 and 3.9 ± 0.9 ng h-1 10(6) cells). Free active renin was the predominant form found in both cell compartments. These results indicate that MC in culture are able to synthesize and translate renin mRNA probably as inactive prorenin which is mostly processed to active renin inside the cell. MC secrete both forms of the enzyme but at a lower level compared with intracellular content, suggesting that the main role of renin synthesized by MC may be the intracellular generation of angiotensin II.
- ItemSomente MetadadadosCininases hepáticas de rato: preparação e caracterização de uma serino-peptidade(Universidade Federal de São Paulo (UNIFESP), 1978) Naffah-Mazzacoratti, Maria da Graca [UNIFESP]; Sampaio, Claudio Augusto Machado [UNIFESP]
- ItemSomente MetadadadosDetermination of elements in kidney, serum and urine of Wistar rats with Acute Renal Insufficiency using NAA(Springer, 2012-02-01) Oliveira, Laura C.; Zamboni, Cibele B.; Pessoa, Edson A. [UNIFESP]; Borges, Fernanda T. [UNIFESP]; IPEN CNEN SP; Universidade Federal de São Paulo (UNIFESP)In this investigation ions in serum, urine and kidney of Wistar rats (control group) and Wistar with Acute Renal Insufficiency (ARI) were quantified using instrumental neutron activation analysis. the measurements in serum and urine were performed before, during and after ischemia-induced ARI. the measurements in kidney were performed for the control and ARI groups. Also, a comparative analysis between the concentration ratios before, during and after ARI was performed in urine and serum samples for both groups. the variations results for Cu in serum and I in urine, before and after ischemia-induced ARI, suggest that these elements must be also investigated in renal dysfunction.
- ItemSomente MetadadadosDNA damage in multiple organs after exposure to chlorhexidine in Wistar rats(Elsevier B.V., 2007-03-01) Grassi, Tony Fernando; Camargo, Elaine Aparecida de; Salvadori, Daisy Maria Favero; Marques, Mariangela Esther Alencar; Ribeiro, Daniel Araki [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)Since chlorhexidine is effective against microorganisms, it is widely recommended in dentistry. However, studies have provided evidence that chlorhexidine is toxic for a variety of cell types. in order to identify potential genotoxins in different cell types, the purpose of this study was to investigate whether chlorhexidine digluconate is able to cause, in terms of DNA damage, alterations in leukocytes, liver, kidney and urinary bladder by the single cell gel (comet) assay. Ten male Wistar rats were divided into two groups: a negative control and the experimental group treated with 3 ml of 0.12% chlorhexidine digluconate by gavage once a day for 8 days. Statistically significant increases of DNA damage was observed in leukocytes and kidney cells of the chlorhexidine digluconate treated group as depicted by the mean tail moment. Taken together, the data indicate that leukocytes and kidney cells are potential targets for primary DNA damage following oral exposure to chlorhexidine digluconate as detected by single cell gel (comet) assay. (c) 2006 Elsevier GmbH. All rights reserved.
- ItemSomente MetadadadosDownregulation of the Vascular Renin-Angiotensin System by Aerobic Training - Focus on the Balance Between Vasoconstrictor and Vasodilator Axes(Japanese Circulation Soc, 2015-06-01) Silva, Sebastiao D.; Zampieri, Thais T.; Ruggeri, Adriana; Ceroni, Alexandre; Aragão, Danielle S. [UNIFESP]; Fernandes, Fernanda B. [UNIFESP]; Casarini, Dulce E. [UNIFESP]; Michelini, Lisete C.; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)Background: Hyperactivity of the renin-angiotensin system (RAS) and functional deficits in hypertension are reduced after exercise training. We evaluate in arteries, kidney and plasma of hypertensive rats the sequential effects of training on vascular angiotensinogen, Ang II and Ang (1-7) content.Methods and Results: Spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were trained or kept sedentary (S) for 3 months. After hemodynamic measurements (weeks 0, 1, 2, 4, 8 and 12), blood, arteries and kidneys were obtained to quantify the angiotensin content (HPLC) and angiotensinogen expression (Western Blotting). SHR-S vs. WKY-S exhibited elevated pressure, increased angiotensinogen and angiotensins' content in the renal artery with a high Ang II/Ang (1-7) ratio (similar to 5-fold higher than in the femoral artery, kidney and plasma, and 14-fold higher than in the aorta). Training promptly reduced angiotensinogen expression and downregulated the RAS in the renal SHR artery (1st-12th week), with a specific reduction of the vasoconstrictor axis; significant reduction of the AngII/Ang (1-7) ratio (36%, T4-T8) occurred simultaneously with significant pressure fall (5%). in other SHR arteries, plasma and kidneys and in all WKY tissues, T-induced AngII and Ang (1-7) reductions were proportional, maintaining the AngII/Ang (1-7) ratio.Conclusions: Vascular RAS is not equally expressed in vessels, having crucial importance in the renal artery. in the renal SHR artery, training downregulates the vasoconstrictor and preserves the vasodilator axis while in other tissues and plasma training reduces both RAS axes, thus maintaining the vasoconstriction/vasodilatation balance in a lower level.
- ItemAcesso aberto (Open Access)Efeitos da sobrecarga de frutose no perfil metabólico e no estresse oxidativo/nitrosativo no rim de ratas senescentes(Universidade Federal de São Paulo (UNIFESP), 2017-02-22) Seraphim, Deborah Chianelli Costalonga [UNIFESP]; Higa, Elisa Mieko Suemitsu [UNIFESP]; http://lattes.cnpq.br/8578252701813423; http://lattes.cnpq.br/7394050593605002; Universidade Federal de São Paulo (UNIFESP)The aging process is a complex phenomenon that leads the body to several changes, affecting its integrity and resulting in chronic pathologies, which compromises health and quality of life of elderly people. Animals supplemented with fructose have been used as an experimental model for induction of insulin resistance. The objective of this study was to evaluate the metabolic effects and the levels of oxidative/nitrosative stress in the kidney of senescent rats with a high fructose intake. The animals were alocated into 4 groups, respectively, young control (J), elderly control (I), young fructose (JF) and elderly fructose (IF). Groups J and I received water and JF and IF received fructose (100g/L), both ad libitum. After 12 weeks of supplementation with high fructose, the animals were sacrificed to collect their kidneys, blood and the thoracic aorta. Blood was centrifuged and serum obtained for lipid profile, renal function, thiobarbituric acid reactive species (TBARS) and nitric oxide (NO). Renal tissue was homogenized and prepared for analysis of TBARS, NO, NO synthase enzymes (eNOS and iNOS), nitrotyrosine, superoxide dismutase-1, catalase and NF kB p65. Vascular reactivity was evaluated in the thoracic aorta of the animals. Results are presented as mean±SE, analyzed by statistical test one-way ANOVA with Newman-Keuls post-test or Student T-Test, when appropriate; significant at p <0.05. The fructose overload caused metabolic dysfunction and insulin resistance, confirming the efficacy of the chosen model. In this study we observed a body weight gain in the studied groups (except in the elderly fructose group), and an increase in general caloric intake, diuresis and adipose tissue; insulin resistance, increased fasting glucose, triglycerides and cholesterol were observed in the fructose groups. We also found a loss of renal function, increased oxidative/nitrosative stress and inflammation, with reduction of antioxidants and a lower vasodepressor response in the studied groups, especially those which consumed fructose. In summary, our data show that aging or high fructose intake contributed to the increase of oxidative/nitrosative stress in animals, demonstrating that at the dose and the period of fructose treatment utilized in this study, fructose was not able to aggravate several aspects which were already altered by aging. We believe that the high fructose intake simulates most of the effects of aging, and this understanding would be useful to prevent or minimize many of the alterations observed in the elderly.
- ItemAcesso aberto (Open Access)Effect of antibodies to intercellular adhesion molecule type 1 on the protection of distant organs during reperfusion syndrome in rats(Associação Brasileira de Divulgação Científica, 2003-05-01) Souza-Moraes, M.r. [UNIFESP]; David-Filho, R. [UNIFESP]; Baptista-Silva, José Carlos Costa [UNIFESP]; Ullian, M. [UNIFESP]; Franco, Marcello Fabiano de [UNIFESP]; Gabriel Jr., A. [UNIFESP]; Smith, B. [UNIFESP]; Burihan, E. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)We investigated kidney and lung alterations caused by intercellular adhesion molecule type 1 (ICAM-1) blockade after ischemia and reperfusion of hind limb skeletal muscles. Rats were submitted to ligature of the infrarenal aorta for 6 h. The animals were randomized into three groups of 6 rats each: group I, sacrificed after ischemia; group II, reperfusion for 24 h, and group III, reperfusion for 24 h after receiving monoclonal anti-ICAM-1 antibodies. At the end of the experiment, blood samples were collected for creatinine, lactate dehydrogenase, creatine phosphokinase, potassium, pH and leukocyte counts. Samples were taken from the muscles of the hind limbs and from the kidneys and lungs for histological analysis and measurement of the neutrophil infiltrate by myeloperoxidase staining. The groups did not differ significantly with regard to the laboratory tests. There were no major histological alterations in the kidneys. An intense neutrophil infiltrate in the lungs, similar in all groups, was detected. Myeloperoxidase determination showed that after reperfusion there was significantly less retention of polymorphonuclear neutrophils in the muscles (352 ± 70 vs 1451 ± 235 × 10² neutrophils/mg; P<0.01) and in the kidneys (526 ± 89 vs 852 ± 73 × 10² neutrophils/mg; P<0.01) of the animals that received anti-ICAM-1 before perfusion compared to the group that did not. The use of anti-ICAM-1 antibodies in this experimental model minimized neutrophil influx, thus reducing the inflammatory process, in the muscles and kidneys after ischemia and reperfusion of the hind limbs.
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