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1.
Genet Mol Res ; 13(4): 9202-12, 2014 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-25501142

RESUMO

In 2006, an experiment examining families belonging to the first selection stage of the Sugar Cane Breeding Program of Universidade Federal Rural do Rio de Janeiro/Rede Interuniversitária para o Desenvolvimento do Setor Sucroalcooleiro was conducted. Families and plants within families were evaluated to select superior plants for subsequent stages of the breeding program. The experiment was arranged in a randomized block design, in which progenies were grouped into 4 sets, each with 4 replicates and 100 seedlings per plot. The following traits were evaluated: average stem diameter, total plot weight, number of stems, Brix of the lower stem, and Brix of the upper stem. The study of families used the restricted maximum likelihood/best linear unbiased procedure mixed models. After selection, families were genotyped via inter-simple sequence repeat to assess the genetic distance of genotypes. This approach was found to be efficient for selecting new genotypes.


Assuntos
Repetições de Microssatélites/genética , Modelos Genéticos , Saccharum/genética , Seleção Genética , Marcadores Genéticos , Filogenia
2.
Artigo em Português | LILACS | ID: lil-737703

RESUMO

Asiaticoside is a triterpenoid present in Centella asiatica extract, responsible for the therapeutic activity of this plant in chronic liver disease. The hepatocyte is the cell responsible for the endocrine and exocrine functions of the liver, in addition to the conversion of harmful substances into non-toxic compounds that are excreted in the bile. That is why the liver is sensitive to the action of some drugs, such as paracetamol. Hence, paracetamol was used as an experimental model of liver damage, with the aim of assessing the effectiveness of asiaticoside, in a standard therapeutic dose, as a hepatoprotector in Wistar rats. In this experiment, 40 animals were used and divided into two groups: those treated with asiaticoside and the untreated control group. Animals from the first group were subjected to pretreatment with the active ingredient (1mg/kg/dia P.O.) for eight days and exposed to a toxic dose of paracetamol (3 g/kg P.O.) on the eighth day. After 24 h and 72 h, these rats were sacrificed for the collection of blood samples and liver fragments. To assess hepatoprotective activity, serum enzymes (AST, ALT and alkaline phosphatase) indicative of liver damage were measured and histological and morphological analyses of liver tissue were performed. The results obtained showed that asiaticoside exerted hepatoprotective action, since it promoted a reduction in histological lesions and a decrease in serum levels of AST and ALT. From these results, we conclude that asiaticoside, in the dose most commonly used in herbal medicine, protects the liver against acute hepatitis induced by paracetamol...


O asiaticosídeo é um triterpenóide presente no extrato da Centella asiatica, sendo responsável pela atividade terapêutica desta planta em doenças hepáticas crônicas. O hepatócito é a célula responsável pelas funções endócrinas e exócrinas do fígado, além de converter substâncias nocivas em materiais não tóxicos excretados pela bile. Por esse motivo, o fígado é sensível à ação de alguns fármacos, como, por exemplo, o paracetamol. Assim, utilizando o paracetamol como modelo experimental de lesão hepática, o objetivo deste estudo foi avaliar a ação hepatoprotetora do asiaticosídeo, na dose estabelecida como terapêutica, em ratos Wistar. Dois grupos compostos por vinte animais cada, tratados com asiaticosídeo (1mg/kg/dia v.o.) por oito dias e não tratados foram submetidos à intoxicação com elevada dose de paracetamol (3 g/kg v.o) no oitavo dia. Em seguida, os animais foram eutanasiados após 24 h ou 72 h para coleta de amostras de sangue e fragmentos de fígado. Para avaliação da atividade hepatoprotetora, foi realizada a dosagem sérica de enzimas indicativas de lesão hepática (AST, ALT e Fosfatase Alcalina) e a análise histológica e morfométrica do tecido hepático. Os resultados obtidos permitiram evidenciar que na dose utilizada, o asiaticosídeo apresenta atividade hepatoprotetora, uma vez que o grupo submetido ao tratamento prévio apresentou menos lesões histológicas e menores níveis séricos de AST e ALT quando comparado ao grupo controle. Estes resultados permitem concluir que o asiaticosídeo, na dose mais usualmente empregada na fitoterapia, apresentou atividade hepatoprotetora na hepatite aguda causada por elevada dose de paracetamol...


Assuntos
Animais , Masculino , Ratos , Acetaminofen/toxicidade , Extratos Vegetais/farmacologia , Ratos Wistar
3.
J Dent Res ; 92(12 Suppl): 189S-94S, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24158344

RESUMO

Partially edentulous patients may be rehabilitated by the placement of removable dental prostheses, implant-supported removable dental prostheses, or partial implant fixed dental prostheses. However, it is unclear the impact of each prosthesis type over the masticatory aspects, which represents the objective of this paired clinical trial. Twelve patients sequentially received and used each of these 3 prosthesis types for 2 months, after which maximum bite force was assessed by a strain sensor and food comminution index was determined with the sieving method. Masseter and temporal muscle thicknesses during rest and maximal clenching were also evaluated by ultrasonography. Each maxillary arch received a new complete denture that was used throughout the study. Data were analyzed by analysis of variance for repeated measures, followed by the Tukey test (p < .05). Maximum bite force and food comminution index increased (p < .0001) after implant-supported dental prosthesis and implant fixed dental prosthesis use, with the higher improvement found after the latter's use. Regardless of implant-retained prosthesis type, masseter muscle thickness during maximal clenching also increased (p < .05) after implant insertion. Partial implant-supported prostheses significantly improved masseter muscle thickness and mastication, and the magnitude of this effect was related to prosthesis type.


Assuntos
Prótese Dentária Fixada por Implante , Prótese Parcial , Mastigação/fisiologia , Idoso , Idoso de 80 Anos ou mais , Força de Mordida , Ligas de Cromo/química , Grampos Dentários , Implantação Dentária Endóssea , Implantes Dentários , Oclusão Dentária Balanceada , Planejamento de Dentadura , Retenção de Dentadura , Prótese Total Superior , Prótese Parcial Fixa , Prótese Parcial Removível , Feminino , Alimentos , Humanos , Arcada Parcialmente Edêntula/reabilitação , Masculino , Músculo Masseter/diagnóstico por imagem , Músculo Masseter/patologia , Pessoa de Meia-Idade , Contração Muscular/fisiologia , Osseointegração/fisiologia , Músculo Temporal/diagnóstico por imagem , Músculo Temporal/patologia , Ultrassonografia
4.
Artigo em Inglês | LILACS | ID: lil-621568

RESUMO

A própolis é uma resina natural que apresenta diversas ações biológicas devido a presença de fenólicos, especialmente flavonóides, em sua composição. O fruto do açaí (Euterpe oleracea Mart) é fonte de antocianinas, que também pertencem ao grupo dos flavonóides. O objetivo deste estudo foi avaliar o efeito antioxidante e antimicrobiano dos extratos de açaí e propolis em associação. A atividade antimicrobiana foi avaliada por ensaio em caldo enriquecido e a atividade antioxidante foi avaliada pelo método do sequestro de radicais DPPH. Os resultados mostraram que o extrato de própolis em pequenas concentrações apresentou atividade sobre o crescimento de S. aureus e S. epidermidis, e que ambos os extratos apresentaram atividade antioxidante. Foi possível concluir que ocorreu sinergismo entre os extratos de própolis e de açaí em relação à atividade antioxidante, bem como esta associação poderá apresentar atividade antimicrobiana caso o extrato de própolis seja utilizado em quantidade suficiente na formulação. Assim, esses extratos podem ser usados em formulações para uso tópico para prevenir o envelhecimento da pele e, possivelmente, transtornos causados pelos microrganismos empregados no estudo.


Propolis is a natural resin, collected mainly by the honey bee, Apis mellifera, which has been shown to have many biological roles, including antioxidant and antimicrobial effects, both conferred by phenolic compounds, especially flavonoids. The fruit of the açai palm is an important source of anthocyanins, which are also phenolics of the flavonoid group. The aim of this study was to assess the antioxidant and antimicrobial effects of a mixture of propolis and açai extracts. Antimicrobial activity was assessed by BHI broth culture with diluted extract, followed by agar subculture, while antioxidant activity was assessed by the DPPH radical scavenging assay. The results showed that around 2% of the propolis extract showed antimicrobial activity against Staphylococcus aureus and S. epidermidis, while low concentrations of both the ethanolic propolis and aqueous açai extracts, alone and combined, exhibited antioxidant activity. In conclusion, this study showed that the antioxidant effects of propolis and açai were summed in the mixed extracts. Furthermore, this combination would show antimicrobial activity if the minimum inhibitory concentration of propolis extract established in this study were used in the formulation. Hence, these extracts could be mixed into formulations used topically to prevent skin aging and, possibly, disorders caused by microbes, such as acne.


Assuntos
Anti-Infecciosos , Antioxidantes , Flavonoides/farmacologia , Própole/farmacologia
5.
Artigo em Inglês | LILACS | ID: lil-621572

RESUMO

The traditional Mediterranean herb thyme (Thymus vulgaris) is a source of an essential oil that has been shown to possess antimicrobial activity against many microorganisms. A considerable part of the general population has dental caries and Streptococcus mutans is one of the microorganisms responsible. The aim of this study was to assess the effect of the essential oil extracted from thyme on the growth of S. mutans, the main bacterium involved in the etiology of dental caries, as well as to incorporate this oil into a toothpaste formulation for preliminary assessment. The broth dilution technique was used in threefold tests for antibacterial activity. The concentrations tested were 1%, 5% and 10% essential oil diluted in ethanol or mineral oil. The controls were triclosan at 0.25% and 0.5%, chlorhexidine digluconate at 0.06% and 0.12%, and ethanol. The 1% solution of thyme essential oil in ethanol proved to be the most efficient against Streptococcus mutans and may be considered viable as an ingredient of toothpaste, both with regard to cost and to the sensory profile of the product. Also, analyses of the characteristics of the formulation indicated that the product is stable.


Thymus vulgaris (tomilho) é uma fonte de óleo essencial que tem demonstrado atividade antimicrobiana. Uma parcela considerável da população tem apresentado problemas dentários, tais como a cárie, na qual o Streptococcus mutans é um microrganismo de fundamental importância. O objetivo deste trabalho foi avaliar o efeito do óleo essencial de tomilho sobre o crescimento do Streptococcus mutans, a principal bactéria relacionada com a etiologia da cárie dentária, bem como veicular este óleo essencial em uma formulação de creme dental para estudo preliminar. O método empregado foi diluição em caldo. As concentrações utilizadas de óleo essencial foram 1%, 5% e 10% de óleo essencial diluído em etanol ou óleo mineral. Os controles foram triclosan a 0,25% e 0,5%, bem como digluconato de clorexidina a 0,06% e 0,12%. A amostra contendo 1% de óleo essencial de tomilho diluída em etanol foi a mais eficaz, sendo efetiva contra Streptococcus mutans e, portanto considerada viável em relação ao custo e ao sensorial conferido ao produto, sendo que a formulação avaliada foi considerada estável.


Assuntos
Antibacterianos , Cárie Dentária/prevenção & controle , Óleos Voláteis/uso terapêutico , Streptococcus mutans , Thymus serpyllum , Testes de Sensibilidade Microbiana/métodos , Plantas Medicinais
6.
Scand J Immunol ; 73(5): 428-35, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21272051

RESUMO

The innate immune system plays an important role as a first response to tissue injury. This first response is carried out via germline-encoded receptors. They can recognize exogenous Pathogen-Associated Molecular Patterns and endogenous Dangers-Associated Molecular Patterns. The Toll-Like Receptor (TLR) family is well-studied, but more recently another family in the cytoplasmic compartment, called nod-like receptor (NLR), was discovered. In addition to being present in inflammatory cells, these receptors are widely distributed in various cell types, including renal tissue, where these receptors have an important role in triggering the inflammatory response during renal diseases. This review summarizes the present data regarding the role of TLRs and NLRs in the course and development of various kidney pathologies.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/imunologia , Nefropatias/imunologia , Receptores Toll-Like/imunologia , Animais , Humanos , Imunidade Inata/imunologia
7.
Inflamm Res ; 59(10): 861-9, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20396927

RESUMO

INTRODUCTION: Ischemia and reperfusion injury (IRI) are mainly caused by leukocyte activation, endothelial dysfunction and production of reactive oxygen species. Moreover, IRI can lead to a systemic response affecting distant organs, such as the lungs. AIM: The objective was to study the pulmonary inflammatory systemic response after renal IRI. METHODS: Male C57Bl/6 mice were subjected to 45 min of bilateral renal ischemia, followed by 4, 6, 12, 24 and 48 h of reperfusion. Blood was collected to measure serum creatinine and cytokine concentrations. Bronchoalveolar lavage fluid (BALF) was collected to determine the number of cells and PGE(2) concentration. Expressions of iNOS and COX-2 in lung were determined by Western blot. Gene analyses were quantified by real time PCR. RESULTS: Serum creatinine increased in the IRI group compared to sham mainly at 24 h after IRI (2.57 +/- 0.16 vs. 0.43 +/- 0.07, p < 0.01). The total number of cells in BAL fluid was higher in the IRI group in comparison with sham, 12 h (100 x 10(4) +/- 15.63 vs. 18.1 x 10(4) +/- 10.5, p < 0.05) 24 h (124 x 10(4) +/- 8.94 vs. 23.2 x 10(4) +/- 3.5, p < 0.05) and 48 h (79 x 10(4) +/- 15.72 vs. 22.2 x 10(4) +/- 4.2, p < 0.05), mainly by mononuclear cells and neutrophils. Pulmonary COX-2 and iNOS were up-regulated in the IRI group. TNF-alpha, IL-1beta, MCP-1, KC and IL-6 mRNA expression were up-regulated in kidney and lungs 24 h after renal IRI. ICAM-1 mRNA was up-regulated in lungs 24 h after renal IRI. Serum TNF-alpha, IL-1beta and MCP-1 and BALF PGE(2) concentrations were increased 24 h after renal IRI. CONCLUSION: Renal IRI induces an increase of cellular infiltration, up-regulation of COX-2, iNOS and ICAM-1, enhanced chemokine expression and a Th1 cytokine profile in lung demonstrating that the inflammatory response is indeed systemic, possibly leading to an amplification of renal injury.


Assuntos
Rim/fisiopatologia , Pneumonia , Traumatismo por Reperfusão , Síndrome de Resposta Inflamatória Sistêmica , Animais , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Quimiocinas/sangue , Quimiocinas/imunologia , Ciclo-Oxigenase 2/imunologia , Citocinas/sangue , Citocinas/imunologia , Molécula 1 de Adesão Intercelular/imunologia , Rim/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/imunologia , Pneumonia/etiologia , Pneumonia/imunologia , Pneumonia/fisiopatologia , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/fisiopatologia , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia
8.
Artigo em Português | LILACS | ID: lil-535426

RESUMO

Ascorbic acid (AA), or vitamin C, is widely used in the pharmaceutical, cosmetic and food industries as an antioxidant and cosmetics containing AA have been gaining popularity in the last few years for the treatment of photoageing. To solve the problem of its low stability, some esters have been synthesised, such as magnesium ascorbyl phosphate (MAP), also available encapsulated in collagen-based microspheres (EMAP). The aim of this research was to study the physical and chemical stability of O/W emulsions containing AA, MAP or EMAP, by rheological and HPLC analysis, respectively. These emulsions were stored at 25, 37 and 45ºC for 28days and samples tested weekly during storage. It was concluded that all the formulations showed pseudoplastic behaviour. The presence of MAP provoked an initial rise in thixotropy. The formulation containing AA did not show any marked change in rheological behaviour. In the chemical analysis, the formulation with EMAP was more stable than those with MAP and AA. Hence, replacement of AA with EMAP in this cosmetic formulation may be a viable way to enhance the stability of the active principle.


Cosméticos contendo ácido ascórbico (AA) têm sido muito empregados nos últimos anos na prevenção e tratamento do fotoenvelhecimento cutâneo. Para solucionar o problema de sua baixa estabilidade, alguns derivados têm sido utilizados como substitutos dessa vitamina e dentre eles o Magnesium Ascorbyl Phosphate (MAP), disponível também em microesferas à base de colágeno (EMAP). O objetivo desta pesquisa foi estudar a reologia e a estabilidade química de emulsões contendo AA, MAP ou EMAP. Assim, formulações contendo AA, MAP ou EMAP foram armazenadas a 25, 37 e 45ºC durante 28 dias e avaliadas. Concluiu-se que todas as formulações apresentaram comportamento pseudoplástico. A presença de MAP provocou um aumento inicial da tixotropia e a formulação contendo AA não apresentou grande alteração no comportamento reológico. Nos estudos químicos a formulação contendo EMAP foi mais estável que o MAP e AA, com o maior prazo de validade. Desta forma, a substituição de AA pela EMAP em cosméticos pode ser uma alternativa viável do ponto de vista da estabilidade da formulação.


Assuntos
Ácido Ascórbico , Estabilidade de Cosméticos , Estabilidade de Medicamentos , Reologia/métodos
9.
Transplant Proc ; 39(2): 409-11, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17362743

RESUMO

BACKGROUND: Toll-like receptors recognize pattern-associated molecules found in pathogens as well as in endogen cells and in matrix degradation products. Despite the effectiveness of cisplatin against various solid tumors the administered dose is limited by its nephrotoxicity, namely, induction of tubular cell apoptosis. Herein, we investigated whether the cell toxicity of cisplatin was mediated by toll-like receptor 4 signaling. METHODS: C3H/He J (Toll-like receptor 4 deficient) and C3H/HePas (control) were treated with cisplatin (20 mg/kg). We evaluated renal function as well as expression of (HO-1) heme oxygenase 1 and MCP-1 mRNAs. RESULTS: Animals deficient in Toll-like receptor 4 showed less renal dysfunction after cisplatin therapy, which was more evident at later time points. Moreover, MCP-1 mRNA expression in kidneys from these animals were lower than controls, mainly at 96 hours after treatment. No differences were seen in HO-1 mRNA expression. CONCLUSIONS: These results suggested that cisplatin-induced renal toxicity is mediated in part though toll-like receptor 4.


Assuntos
Cisplatino/toxicidade , Nefropatias/induzido quimicamente , Nefropatias/fisiopatologia , Receptor 4 Toll-Like/deficiência , Receptor 4 Toll-Like/fisiologia , Animais , Quimiocina CCL2/genética , Heme Oxigenase-1/genética , Testes de Função Renal , Camundongos , Camundongos Endogâmicos C3H , Camundongos Knockout , RNA Mensageiro/genética
10.
Transplant Proc ; 39(2): 417-20, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17362745

RESUMO

UNLABELLED: Renal ischemia followed by reperfusion leads to acute renal failure in both native kidneys and renal allografts. Cyclosporine has known nephrotoxic effects. Thus, cyclosporine therapy subsequent to ischemia/reperfusion (I/R) injury may further exacerbate graft dysfunction. Rapamycin is a newer agent that suppresses the immune system by a different mechanism. In the present study, the effects of Cyclosporine and rapamycin at low and higher concentrations were investigated in an I/R-induced injury model. METHODS: Cyclosporine (100 mg/kg or 50 mg/kg), rapamycin (3 mg/kg per day or 1.5 mg/kg), or both were administered to mice before being subjected to 45 minutes of ischemia. Blood and kidney samples were collected at 24, 48, and 120 hours after surgery. We quantified acute tubular necrosis and tubular regeneration. RESULTS: Animals subjected to I/R showed impaired renal function that peaked at 24 hours (2.05 +/- 0.23 mg/dL), decreasing thereafter. Treatment with higher concentrations of cyclosporine or rapamycin caused even more renal dysfunction at 48 hours, which was sustained up to 120 hours after reperfusion (1.53 +/- 0.6 mg/dL), when compared to the low concentrations of cyclosporine or rapamycin (1.08 +/- 0.19 mg/dL; 0.99 +/- 0.14 mg/dL, P < .05, respectively). Cyclosporine delayed tubular regeneration, which was higher in controls at day 5 (67.0% vs 37.6%, P < .05). CONCLUSIONS: These results demonstrated that cyclosporine or rapamycin might further aggravate ischemically injured organs, negatively affecting posttransplantation recovery in a concentration-dependent fashion.


Assuntos
Ciclosporina/efeitos adversos , Imunossupressores/efeitos adversos , Transplante de Rim/imunologia , Traumatismo por Reperfusão/induzido quimicamente , Sirolimo/efeitos adversos , Animais , Testes de Função Renal , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Complicações Pós-Operatórias/induzido quimicamente , Transplante Isogênico , Resultado do Tratamento
11.
Transplant Proc ; 39(2): 424-6, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17362747

RESUMO

INTRODUCTION: Ischemia/reperfusion injury (IRI) represents the single major antigen-independent factor implicated in pathogenesis of chronic graft dysfunction. Tacrolimus is a calcineurin inhibitor, which has been suggested to be helpful in cyclosporine-related chronic toxicity. Rapamycin has antiproliferative properties that may impair renal regeneration after IRI. Therefore, immunosuppressive drugs might impair renal graft outcome in those organs suffering IRI. MATERIAL AND METHODS: C57B1/6 male mice subjected to 45 minutes of renal pedicle ligation were reperfused for 24 hours. Mice were treated with rapamycin, cyclosporine, or tacrolimus. Blood and renal tissue samples were collected at 24 hours after IRI. Urea levels were measured. Heme Oxygenase 1 (HO-1) gene transcript was amplified by a real-time polymerase chain reaction technique. RESULTS: Animals treated with cyclosporine and subjected to IRI showed impaired renal function that peaked at 24 hours. Additional pretreatment with rapamycin produced even more impairment of renal function, when compared with controls. However, tacrolimus pretreatment was associated with a better renal outcome. HO-1 expression was upregulated after IRI by 2.6 arbitrary units at 24 hours. Rapamycin showed worse impairment of renal function. CONCLUSION: Tacrolimus was not associated with worsening renal function when compared with animals just subjected to IRI. Upregulation of HO-1 may be an attractive approach to limit graft injury.


Assuntos
Heme Oxigenase-1/genética , Imunossupressores/toxicidade , Nefropatias/imunologia , Traumatismo por Reperfusão/imunologia , Transcrição Gênica , Animais , Ciclosporina/efeitos adversos , Nefropatias/enzimologia , Nefropatias/fisiopatologia , Testes de Função Renal , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/fisiopatologia , Sirolimo/efeitos adversos , Tacrolimo/efeitos adversos
12.
Transplant Proc ; 39(2): 457-9, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17362758

RESUMO

UNLABELLED: Renal fibrosis is a hallmark of end-stage renal diseases and of chronic allograft nephropathy (CAN). Rapamycin, besides its action through blockade of lymphocyte proliferation, also has antiproliferative, antiviral, and antitumor actions. Its use in clinical in patients with CAN has recently been advocated. OBJECTIVES: Our goal was to evaluate the effect of rapamycin in an established model of renal fibrosis, unilateral ureteral obstruction. MATERIALS AND METHODS: C57BL/6 mice were divided into two groups, treated or not with daily doses of rapamycin (0.2 mg/kg) beginning on day-1. The obstruction was performed as day 0. Blood and kidney tissues were collected at 1, 4, 7, and 14 days after the surgery to quantify bone morphogenic protein (BMP)-7 and transforming growth factor (TGF)-beta mRNA by real time PCR. RESULTS: Daily treatment with rapamycin caused a significant reduction in serum creatinine at day 1 (0.57 +/- 0.03 vs 0.95 +/- 0.15 mg/dL, P = .002) and at day 14 (0.56 +/- 0.04 vs 0.73 +/- 0.07 mg/dL, P = .040). This profile was corroborated by histological morphometric analyses showing less fibrosis at day 14. However, rapamycin surprisingly induced an upregulation of TGF-beta at day 4 (3.05 +/- 0.46 vs 1.85 +/- 0.41, P = .006) and at day 7 (6.33 +/- 0.55 vs 4.97 +/- 0.38, P = .024) with a reduced expression by day 14 (4.03 +/- 1.07 vs 7.89 +/- 0.83, P < .001). Surprisingly, rapamycin also promoted an increment in BMP-7, completely reversing the ratio of TGF-beta to BMP-7, allowing a more protective phenotype. CONCLUSION: Rapamycin slightly ameliorated the renal dysfunction and, at later time points, induced less fibrosis and less decrease in the TGF-beta to BMP-7 ratio.


Assuntos
Fibrose/induzido quimicamente , Rim/patologia , Sirolimo/efeitos adversos , Animais , Proteína Morfogenética Óssea 7 , Proteínas Morfogenéticas Ósseas/genética , Creatinina/sangue , Modelos Animais de Doenças , Progressão da Doença , Imunossupressores/efeitos adversos , Rim/efeitos dos fármacos , Falência Renal Crônica/patologia , Testes de Função Renal , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , Fator de Crescimento Transformador beta/genética
13.
Kidney Int ; 70(10): 1742-9, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17003813

RESUMO

Ischemia and reperfusion injury (IRI) is the main etiology of acute renal failure in native and transplanted kidneys. In the transplantation field, immunosuppressive drugs may play an additional role in acute graft dysfunction. Rapamycin may impair renal regeneration post IRI. Heme oxygenase 1 (HO-1) is a protective gene with anti-inflammatory and anti-apoptotic actions. We investigated whether HO-1 played a role in rapamycin-induced renal dysfunction in an established model of IRI. Rapamycin (3 mg/kg) was administered to mice before being subjected to 45 min of ischemia. Animals subjected to IRI presented with impaired renal function that peaked at 24 h (2.05+/-0.23 mg/dl), decreasing thereafter. Treatment with rapamycin caused even more renal dysfunctions (2.30+/-0.33 mg/dl), sustained up to 120 h after reperfusion (1.54+/-0.4 mg/dl), when compared to the control (0.63+/-0.09 mg/dl, P<0.05). Rapamycin delayed tubular regeneration that was normally higher in the control group at day 5 (68.53+/-2.30 vs 43.63+/-3.11%, P<0.05). HO-1 was markedly upregulated after IRI and its expression was even enhanced by rapamycin (1.32-fold). However, prior induction of HO-1 by cobalt protoporphyrin improved the renal dysfunction imposed by rapamycin, mostly at later time points. These results demonstrated that rapamycin used in ischemic-injured organs could also negatively affect post-transplantation recovery. Modulation of HO-1 expression may represent a feasible approach to limit rapamycin acute toxicity.


Assuntos
Heme Oxigenase-1/metabolismo , Imunossupressores/efeitos adversos , Rim/efeitos dos fármacos , Traumatismo por Reperfusão/fisiopatologia , Sirolimo/efeitos adversos , Injúria Renal Aguda/enzimologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/fisiopatologia , Animais , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/genética , Heme Oxigenase-1/genética , Imunossupressores/farmacologia , Rim/patologia , Rim/fisiopatologia , Transplante de Rim/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Protoporfirinas/farmacologia , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/enzimologia , Sirolimo/farmacologia
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