Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 11 de 11
Filtrar
Mais filtros











Base de dados
Intervalo de ano de publicação
1.
Front Physiol ; 8: 723, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29018354

RESUMO

Background: Advanced glycation endproducts elicit inflammation. However, their role in adipocyte macrophage infiltration and in the development of insulin resistance, especially in the absence of the deleterious biochemical pathways that coexist in diabetes mellitus, remains unknown. We investigated the effect of chronic administration of advanced glycated albumin (AGE-albumin) in healthy rats, associated or not with N-acetylcysteine (NAC) treatment, on insulin sensitivity, adipose tissue transcriptome and macrophage infiltration and polarization. Methods: Male Wistar rats were intraperitoneally injected with control (C) or AGE-albumin alone, or, together with NAC in the drinking water. Biochemical parameters, lipid peroxidation, gene expression and protein contents were, respectively, determined by enzymatic techniques, reactive thiobarbituric acid substances, RT-qPCR and immunohistochemistry or immunoblot. Carboxymethyllysine (CML) and pyrraline (PYR) were determined by LC/mass spectrometry (LC-MS/MS) and ELISA. Results: CML and PYR were higher in AGE-albumin as compared to C. Food consumption, body weight, systolic blood pressure, plasma lipids, glucose, hepatic and renal function, adipose tissue relative weight and adipocyte number were similar among groups. In AGE-treated animals, insulin resistance, adipose macrophage infiltration and Col12a1 mRNA were increased with no changes in M1 and M2 phenotypes as compared to C-albumin-treated rats. Total GLUT4 content was reduced by AGE-albumin as compared to C-albumin. NAC improved insulin sensitivity, reduced urine TBARS, adipose macrophage number and Itgam and Mrc mRNA and increased Slc2a4 and Ppara. CD11b, CD206, Ager, Ddost, Cd36, Nfkb1, Il6, Tnf, Adipoq, Retn, Arg, and Il12 expressions were similar among groups. Conclusions: AGE-albumin sensitizes adipose tissue to inflammation due to macrophage infiltration and reduces GLUT4, contributing to insulin resistance in healthy rats. NAC antagonizes AGE-albumin and prevents insulin resistance. Therefore, it may be a useful tool in the prevention of AGE action on insulin resistance and long-term complications of DM.

2.
PLoS One ; 12(7): e0179199, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28678861

RESUMO

BACKGROUND: Ecstasy (Ec) use produces hyperthermia, excessive sweating, intense thirst, an inappropriate antidiuretic hormone secretion (SIADH) and a multisystemic toxicity due to oxidative stress (OS). Intense thirst induces high intake of pure water, which associated with SIADH, usually develops into acute hyponatremia (Hn). As Hn is induced rapidly, experiments to check if Ec acted directly on the Inner Medullary Collecting Ducts (IMCD) of rats were conducted. Rhabdomyolysis and OS were also studied because Ec is known to induce Reactive Oxygen Species (ROS) and tissue damage. To decrease OS, the antioxidant inhibitors N-acetylcysteine (NAC) and Allopurinol (Allo) were used. METHODS: Rats were maintained on a lithium (Li) diet to block the Vasopressin action before Ec innoculation. AQP2 (Aquaporin 2), ENaC (Epitheliun Sodium Channel) and NKCC2 (Sodium, Potassium, 2 Chloride) expression were determined by Western Blot in isolated IMCDs. The TBARS (thiobarbituric acid reactive substances) and GSH (reduced form of Glutathione) were determined in the Ec group (6 rats injected with Ec-10mg/kg), in Ec+NAC groups (NAC 100mg/Kg/bw i.p.) and in Allo+Ec groups (Allo 50mg/Kg/i.p.). RESULTS: Enhanced AQP2 expression revealed that Ec increased water transporter expression, decreased by Li diet, but the expression of the tubular transporters did not change. The Ec, Ec+NAC and Allo+Ec results showed that Ec increased TBARS and decreased GSH, showing evidence of ROS occurrence, which was protected by NAC and Allo. Rhabdomyolysis was only protected by Allo. CONCLUSION: Results showed that Ec induced an increase in AQP2 expression, evidencing another mechanism that might contribute to cause rapid hyponatremia. In addition, they showed that NAC and Allo protected against OS, but only Allo decreased rhabdomyolysis and hyperthermia.


Assuntos
Sequestradores de Radicais Livres/farmacologia , Rim/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos , N-Metil-3,4-Metilenodioxianfetamina/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Rabdomiólise/induzido quimicamente , Acetilcisteína/farmacologia , Alopurinol/farmacologia , Animais , Aquaporina 2/metabolismo , Western Blotting , Canais Epiteliais de Sódio/metabolismo , Glutationa/metabolismo , Alucinógenos/toxicidade , Rim/metabolismo , Túbulos Renais Coletores/efeitos dos fármacos , Túbulos Renais Coletores/metabolismo , Masculino , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Ratos Wistar , Rabdomiólise/prevenção & controle , Membro 1 da Família 12 de Carreador de Soluto/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Água/metabolismo
3.
Stem Cells Transl Med ; 5(8): 1048-57, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27280799

RESUMO

UNLABELLED: : The pathophysiology of sepsis involves complex cytokine and inflammatory mediator networks. Downregulation of endothelial nitric oxide synthase contributes to sepsis-induced endothelial dysfunction. Human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are known to reduce expression of proinflammatory cytokines and markers of apoptosis. We hypothesized that treatment with WJ-MSCs would protect renal, hepatic, and endothelial function in a cecal ligation and puncture (CLP) model of sepsis in rats. Rats were randomly divided into three groups: sham-operated rats; rats submitted to CLP and left untreated; and rats submitted to CLP and intraperitoneally injected, 6 hours later, with 1 × 10(6) WJ-MSCs. The glomerular filtration rate (GFR) was measured at 6 and 24 hours after CLP or sham surgery. All other studies were conducted at 24 hours after CLP or sham surgery. By 6 hours, GFR had decreased in the CLP rats. At 24 hours, Klotho renal expression significantly decreased. Treatment with WJ-MSCs improved the GFR; improved tubular function; decreased the CD68-positive cell count; decreased the fractional interstitial area; decreased expression of nuclear factor κB and of cytokines; increased expression of eNOS, vascular endothelial growth factor, and Klotho; attenuated renal apoptosis; ameliorated hepatic function; increased glycogen deposition in the liver; and improved survival. Sepsis-induced acute kidney injury is a state of Klotho deficiency, which WJ-MSCs can attenuate. Klotho protein expression was higher in WJ-MSCs than in human adipose-derived MSCs. Because WJ-MSCs preserve renal and hepatic function, they might play a protective role in sepsis. SIGNIFICANCE: Sepsis is the leading cause of death in intensive care units. Although many different treatments for sepsis have been tested, sepsis-related mortality rates remain high. It was hypothesized in this study that treatment with human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) would protect renal, hepatic, and endothelial function in a model of sepsis in rats. Treatment with WJ-MSCs improved the glomerular filtration rate, improved tubular function, decreased expression of nuclear factor κB and of cytokines, increased expression of eNOS and of Klotho, attenuated renal apoptosis, and improved survival. Sepsis-induced acute kidney injury is a state of Klotho deficiency, which WJ-MSCs can attenuate.


Assuntos
Injúria Renal Aguda/prevenção & controle , Endotélio Vascular/fisiopatologia , Hepatopatias/prevenção & controle , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Sepse/cirurgia , Geleia de Wharton/citologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/fisiopatologia , Animais , Apoptose , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Endotélio Vascular/metabolismo , Taxa de Filtração Glomerular , Glucuronidase/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Proteínas Klotho , Fígado/metabolismo , Fígado/patologia , Fígado/fisiopatologia , Hepatopatias/etiologia , Hepatopatias/metabolismo , Hepatopatias/fisiopatologia , Masculino , Células-Tronco Mesenquimais/metabolismo , NF-kappa B/metabolismo , Fenótipo , Ratos Wistar , Sepse/metabolismo , Sepse/microbiologia , Sepse/fisiopatologia , Fatores de Tempo
4.
Atherosclerosis ; 237(1): 343-52, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25305669

RESUMO

In chronic kidney disease (CKD) nontraditional risk factors, such as oxidative stress and advanced glycation end products (AGE) contribute to cardiovascular disease. Particularly, disturbances in reverse cholesterol transport favor the development of atherosclerosis. We analyzed the influence of N-acetylcysteine (NAC) in CKD rats on plasma concentration of lipid peroxides (TBARS) and AGE and on the impact of serum albumin in the development of macrophage endoplasmic reticulum stress (ERS) and cholesterol efflux, namely apo A-I and HDL2-mediated cholesterol removal and ABCA-1 and ABCG-1 protein level. CKD was induced by 5/6 nephrectomy in 2-month old male Wistar rats. Controls (Sham) were false operated. Animals were treated or not with NAC (600 mg/L of water). After 60 days serum albumin was isolated by FPLC and purified by alcoholic extraction. J774 macrophages were incubated with serum albumin (1 mg/mL; 18 h) from all groups, and the expression of ERS markers (protein disulfide isomerase - PDI, Grp78 and Grp94), ABCA-1 and ABCG-1 determined by immunoblot. HDL2 or apo A-I were used for cholesterol efflux assays. Protein and lipid composition of total HDL from Sham and CKD was determined and these particles tested on their abilities to accept cell cholesterol. Comparisons were done by one-way ANOVA and Newman Keuls post test. After 60 days of CKD, body weight was 10% lower in CKD compared to Sham (p < 0.01). This was prevented by NAC. Urea, creatinine, total cholesterol (TC), triglycerides (TG) (mg/dL), proteinuria (mg/24 h) (Sham, n = 31; Sham + NAC, n = 20; CKD, n = 74; CKD + NAC, n = 32), total AGE and pentosidine (n = 8; fluorescence arbitrary unit) and TBARS (n = 7; nmoL/mL) were higher in CKD (122 ± 8; 0.9 ± 0.07; 151 ± 6; 83 ± 4; 46 ± 2.5; 32,620 ± 673; 16,700 ± 1,370; 6.6 ± 0.5, respectively) and in CKD + NAC (91.4 ± 5; 0.6 ± 0.02; 126 ± 7.5; 73 ± 6; 51 ± 3.5; 24,720 ± 1,114; 10,080 ± 748; 4.5 ± 0.5, respectively) in comparison to Sham (41 ± 0.9; 0.4 ± 0.03; 76 ± 2.7; 51.5 ± 3; 14 ± 0.9; 21,750 ± 960; 5,314 ± 129; 2.0 ± 0.2, respectively; p < 0.001) and Sham + NAC (40 ± 0.9; 0.3 ± 0.02; 76 ± 2.6; 68 ± 4; 18.4 ± 1.5; 20,040 ± 700; 5,050 ± 267; 1.8 ± 0.2, respectively; p < 0.001). TC, urea, creatinine, total AGE, pentosidine and TBARS were respectively, 17%, 25%, 33%, 24%, 40% and 28% (p < 0.01) lower in CKD + NAC, than in CKD. Glycemia was higher in Sham + NAC (107 ± 4.6) and CKD + NAC (107 ± 2.6) than in Sham (96 ± 1.8; p < 0.05) and CKD (98 ± 1.6; p < 0.01), respectively. In macrophages (n = 6), CKD albumin increased PDI (3 and 6 times, p < 0.01) and Grp94 (66% and 80%, p < 0.01) in comparison to Sham and CKD + NAC-albumin treated cells, respectively. ABCA-1 expression was lower (87% and 70%, p < 0.001) in macrophage treated with Sham + NAC and CKD albumin respectively in comparison to Sham albumin; ABCG-1 was higher (4 and 7 times, p < 0.001) in macrophages treated with Sham + NAC and CKD + NAC albumin, respectively in comparison to Sham and CKD albumin. Apo A-I mediated cholesterol efflux was lower (59% and 70%, p < 0.0001) in macrophage treated with Sham + NAC and CKD albumin respectively in comparison to Sham albumin, however, the HDL2 mediated cholesterol efflux was higher (54% and 25%, p < 0.0001) in macrophage treated with Sham + NAC albumin, in comparison to Sham and CKD + NAC albumin, respectively. CKD-HDL was enriched in total protein and lipids compared to Sham-HDL but preserved its capacity to remove cholesterol from macrophages. NAC reduces plasma lipid peroxidation and AGE and abrogates ERS induced by CKD-albumin. Despite diminishing ABCA-1, NAC increases ABCG-1 that counteracts the reduction in apo A-I-mediated cholesterol efflux. NAC may contribute to attenuate the deleterious effects of CKD-albumin on lipid accumulation in macrophages helping to prevent atherogenesis in CKD.


Assuntos
Acetilcisteína/metabolismo , Apolipoproteína A-I/metabolismo , Retículo Endoplasmático/metabolismo , Falência Renal Crônica/metabolismo , Lipídeos/química , Macrófagos/efeitos dos fármacos , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/metabolismo , Albuminas/metabolismo , Animais , Transporte Biológico , Peso Corporal , Colesterol/metabolismo , Relação Dose-Resposta a Droga , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Peroxidação de Lipídeos , Lipoproteínas/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos , Nefrectomia , Oxigênio/química , Ratos , Ratos Wistar , Albumina Sérica/metabolismo
5.
PLoS One ; 9(2): e86828, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24551041

RESUMO

BACKGROUND: Venom-induced acute kidney injury (AKI) is a frequent complication of Bothrops snakebite with relevant morbidity and mortality. The aim of this study was to assess the effects of Schizolobium parahyba (SP) extract, a natural medicine with presumed anti-Bothrops venom effects, in an experimental model of Bothrops jararaca venom (BV)-induced AKI. METHODOLOGY: Groups of 8 to 10 rats received infusions of 0.9% saline (control, C), SP 2 mg/kg, BV 0.25 mg/kg and BV immediately followed by SP (treatment, T) in the doses already described. After the respective infusions, animals were assessed for their glomerular filtration rate (GFR, inulin clearance), renal blood flow (RBF, Doppler), blood pressure (BP, intra-arterial transducer), renal vascular resistance (RVR), urinary osmolality (UO, freezing point), urinary neutrophil gelatinase-associated lipocalin (NGAL, enzyme-linked immunosorbent assay [ELISA]), lactate dehydrogenase (LDH, kinetic method), hematocrit (Hct, microhematocrit), fibrinogen (Fi, Klauss modified) and blinded renal histology (acute tubular necrosis score). PRINCIPAL FINDINGS: BV caused significant decreases in GFR, RBF, UO, HcT and Fi; significant increases in RVR, NGAL and LDH; and acute tubular necrosis. SP did not prevent these changes; instead, it caused a significant decrease in GFR when used alone. CONCLUSION: SP administered simultaneously with BV, in an approximate 10∶1 concentration, did not prevent BV-induced AKI, hemolysis and fibrinogen consumption. SP used alone caused a decrease in GFR.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Bothrops/metabolismo , Fabaceae/química , Extratos Vegetais/uso terapêutico , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/fisiopatologia , Injúria Renal Aguda/urina , Proteínas de Fase Aguda/urina , Animais , Biomarcadores/urina , Moléculas de Adesão Celular/urina , Venenos de Crotalídeos , Hematócrito , Hemodinâmica/efeitos dos fármacos , Testes de Função Renal , Necrose Tubular Aguda/complicações , Necrose Tubular Aguda/patologia , Necrose Tubular Aguda/fisiopatologia , Necrose Tubular Aguda/urina , Lipocalina-2 , Lipocalinas/urina , Masculino , Fitoterapia , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas/urina , Ratos , Ratos Wistar
6.
PLoS One ; 7(1): e29893, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22235348

RESUMO

BACKGROUND: Despite advances in supportive care, sepsis-related mortality remains high, especially in patients with acute kidney injury (AKI). Erythropoietin can protect organs against ischemia and sepsis. This effect has been linked to activation of intracellular survival pathways, although the mechanism remains unclear. Continuous erythropoietin receptor activator (CERA) is an erythropoietin with a unique pharmacologic profile and long half-life. We hypothesized that pretreatment with CERA would be renoprotective in the cecal ligation and puncture (CLP) model of sepsis-induced AKI. METHODS: RATS WERE RANDOMIZED INTO THREE GROUPS: control; CLP; and CLP+CERA (5 µg/kg body weight, i.p. administered 24 h before CLP). At 24 hours after CLP, we measured creatinine clearance, biochemical variables, and hemodynamic parameters. In kidney tissue, we performed immunoblotting--to quantify expression of the Na-K-2Cl cotransporter (NKCC2), aquaporin 2 (AQP2), Toll-like receptor 4 (TLR4), erythropoietin receptor (EpoR), and nuclear factor kappa B (NF-κB)--and immunohistochemical staining for CD68 (macrophage infiltration). Plasma interleukin (IL)-2, IL-1ß, IL-6, IL-10, interferon gamma, and tumor necrosis factor alpha were measured by multiplex detection. RESULTS: Pretreatment with CERA preserved creatinine clearance and tubular function, as well as the expression of NKCC2 and AQP2. In addition, CERA maintained plasma lactate at normal levels, as well as preserving plasma levels of transaminases and lactate dehydrogenase. Renal expression of TLR4 and NF-κB was lower in CLP+CERA rats than in CLP rats (p<0.05 and p<0.01, respectively), as were CD68-positive cell counts (p<0.01), whereas renal EpoR expression was higher (p<0.05). Plasma levels of all measured cytokines were lower in CLP+CERA rats than in CLP rats. CONCLUSION: CERA protects against sepsis-induced AKI. This protective effect is, in part, attributable to suppression of the inflammatory response.


Assuntos
Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Eritropoetina/farmacologia , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/prevenção & controle , Polietilenoglicóis/farmacologia , Sepse/complicações , Animais , Ceco/cirurgia , Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/metabolismo , Ligadura/efeitos adversos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , NF-kappa B/metabolismo , Punções/efeitos adversos , Ratos , Ratos Wistar , Receptores da Eritropoetina/metabolismo , Sepse/etiologia , Sepse/imunologia , Sepse/metabolismo , Receptor 4 Toll-Like/metabolismo
7.
Am J Physiol Renal Physiol ; 302(1): F216-25, 2012 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-22031848

RESUMO

Lithium (Li)-treated patients often develop urinary concentrating defect and polyuria, a condition known as nephrogenic diabetes insipidus (NDI). In a rat model of Li-induced NDI, we studied the effect that sildenafil (Sil), a phosphodiesterase 5 (PDE5) inhibitor, has on renal expression of aquaporin-2 (AQP2), urea transporter UT-A1, Na(+)/H(+) exchanger 3 (NHE3), Na(+)-K(+)-2Cl(-) cotransporter (NKCC2), epithelial Na channel (ENaC; α-, ß-, and γ-subunits), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase. We also evaluated cGMP levels in medullary collecting duct cells in suspension. For 4 wk, Wistar rats received Li (40 mmol/kg food) or no treatment (control), some receiving, in weeks 2-4, Sil (200 mg/kg food) or Li and Sil (Li+Sil). In Li+Sil rats, urine output and free water clearance were markedly lower, whereas urinary osmolality was higher, than in Li rats. The cGMP levels in the suspensions of medullary collecting duct cells were markedly higher in the Li+Sil and Sil groups than in the control and Li groups. Semiquantitative immunoblotting revealed the following: in Li+Sil rats, AQP2 expression was partially normalized, whereas that of UT-A1, γ-ENaC, and eNOS was completely normalized; and expression of NKCC2 and NHE3 was significantly higher in Li rats than in controls. Inulin clearance was normal in all groups. Mean arterial pressure and plasma arginine vasopressin did not differ among the groups. Sil completely reversed the Li-induced increase in renal vascular resistance. We conclude that, in experimental Li-induced NDI, Sil reduces polyuria, increases urinary osmolality, and decreases free water clearance via upregulation of renal AQP2 and UT-A1.


Assuntos
Diabetes Insípido Nefrogênico/fisiopatologia , Compostos de Lítio/efeitos adversos , Piperazinas/uso terapêutico , Poliúria/tratamento farmacológico , Sulfonas/uso terapêutico , Animais , Aquaporina 2/biossíntese , GMP Cíclico/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/biossíntese , Diabetes Insípido Nefrogênico/induzido quimicamente , Ingestão de Líquidos/efeitos dos fármacos , Canais Epiteliais de Sódio/biossíntese , Taxa de Filtração Glomerular/efeitos dos fármacos , Rim/metabolismo , Medula Renal/enzimologia , Masculino , Proteínas de Membrana Transportadoras/biossíntese , Óxido Nítrico Sintase Tipo II/biossíntese , Óxido Nítrico Sintase Tipo III/biossíntese , Purinas/uso terapêutico , Ratos , Citrato de Sildenafila , Trocador 3 de Sódio-Hidrogênio , Trocadores de Sódio-Hidrogênio/biossíntese , Simportadores de Cloreto de Sódio-Potássio/biossíntese , Membro 1 da Família 12 de Carreador de Soluto , Transportadores de Ureia
8.
PLoS One ; 5(12): e14298, 2010 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-21179206

RESUMO

BACKGROUND: The tubule-interstitial fibrosis is the hallmark of progressive renal disease and is strongly associated with inflammation of this compartment. Heme-oxygenase-1 (HO-1) is a cytoprotective molecule that has been shown to be beneficial in various models of renal injury. However, the role of HO-1 in reversing an established renal scar has not yet been addressed. AIM: We explored the ability of HO-1 to halt and reverse the establishment of fibrosis in an experimental model of chronic renal disease. METHODS: Sprague-Dawley male rats were subjected to unilateral ureteral obstruction (UUO) and divided into two groups: non-treated and Hemin-treated. To study the prevention of fibrosis, animals were pre-treated with Hemin at days -2 and -1 prior to UUO. To investigate whether HO-1 could reverse established fibrosis, Hemin therapy was given at days 6 and 7 post-surgery. After 7 and/or 14 days, animals were sacrificed and blood, urine and kidney tissue samples were collected for analyses. Renal function was determined by assessing the serum creatinine, inulin clearance, proteinuria/creatininuria ratio and extent of albuminuria. Arterial blood pressure was measured and fibrosis was quantified by Picrosirius staining. Gene and protein expression of pro-inflammatory and pro-fibrotic molecules, as well as HO-1 were performed. RESULTS: Pre-treatment with Hemin upregulated HO-1 expression and significantly reduced proteinuria, albuminuria, inflammation and pro-fibrotic protein and gene expressions in animals subjected to UUO. Interestingly, the delayed treatment with Hemin was also able to reduce renal dysfunction and to decrease the expression of pro-inflammatory molecules, all in association with significantly reduced levels of fibrosis-related molecules and collagen deposition. Finally, TGF-ß protein production was significantly lower in Hemin-treated animals. CONCLUSION: Treatment with Hemin was able both to prevent the progression of fibrosis and to reverse an established renal scar. Modulation of inflammation appears to be the major mechanism behind HO-1 cytoprotection.


Assuntos
Fibrose/metabolismo , Heme Oxigenase-1/biossíntese , Hemina/farmacologia , Túbulos Renais/metabolismo , Animais , Modelos Animais de Doenças , Progressão da Doença , Ensaio de Imunoadsorção Enzimática/métodos , Perfilação da Expressão Gênica , Imuno-Histoquímica/métodos , Inflamação , Nefropatias/patologia , Masculino , Modelos Biológicos , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta/metabolismo
9.
Transpl Int ; 22(3): 323-31, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19055616

RESUMO

Plasma clearance of (51)Cr-EDTA ((51)Cr-EDTA-Cl) is an alternative method to evaluate glomerular filtration rate (GFR). This study aimed to investigate the concordance between (51)Cr-EDTA-Cl and renal inulin clearance (In-Cl) in renal transplant recipients as well to determine the repeatability of (51)Cr-EDTA-Cl in kidney donors. Forty four kidney recipients and 22 kidney donors were enrolled. Simultaneous measurements of (51)Cr-EDTA-Cl and In-Cl were performed. A single dose of 3.7MBq of (51)Cr-EDTA was injected and the plasma disappearance curve was created by taking blood samples at 2, 4, 6 and 8 h after injection. Bland and Altman statistical approach was used to quantify the agreement between In-Cl and (51)Cr-EDTA-Cl and to determine the better concordance between all possibilities of measure for the (51)Cr-EDTA-Cl. The mean of In-Cl was 44.5 +/- 17.9 ml/min/1.73 m(2). There was a positive correlation between In-Cl and all possible measurements of (51)Cr-EDTA-Cl. (51)Cr-EDTA-Cl with two samples taken at 4 and 8 h or at 4 and 6 h presenting the narrow limits of agreement and a difference (bias) of 2.8 and 2.7 ml/min, respectively. Two plasma sampling for (51)Cr-EDTA-Cl was a reliable method to measure GFR compared with In-Cl and comprises a suitable method to be used in kidney transplanted patients.


Assuntos
Anticoagulantes , Ácido Edético , Testes de Função Renal/métodos , Testes de Função Renal/normas , Transplante de Rim , Adulto , Anticoagulantes/farmacocinética , Radioisótopos de Cromo , Ácido Edético/farmacocinética , Feminino , Taxa de Filtração Glomerular , Humanos , Hipoglicemiantes/farmacocinética , Insulina/farmacocinética , Masculino , Pessoa de Meia-Idade , Modelos Biológicos
10.
Kidney Int ; 74(7): 910-8, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18563054

RESUMO

Tenofovir disoproxil fumarate (TDF) is a first-line drug used in patients with highly active retroviral disease; however, it can cause renal failure associated with many tubular anomalies that may be due to down regulation of a variety of ion transporters. Because rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist induces the expression of many of these same transporters, we tested if the nephrotoxicity can be ameliorated by its use. High doses of TDF caused severe renal failure in rats accompanied by a reduction in endothelial nitric-oxide synthase and intense renal vasoconstriction; all of which were significantly improved by rosiglitazone treatment. Low-dose TDF did not alter glomerular filtration rate but produced significant phosphaturia, proximal tubular acidosis, polyuria and a reduced urinary concentrating ability. These alterations were caused by specific downregulation of the sodium-phosphorus cotransporter, sodium/hydrogen exchanger 3 and aquaporin 2. A Fanconi's-like syndrome was ruled out as there was no proteinuria or glycosuria. Rosiglitazone reversed TDF-induced tubular nephrotoxicity, normalized urinary biochemical parameters and membrane transporter protein expression. These studies suggest that rosiglitazone treatment might be useful in patients presenting with TFV-induced nephrotoxicity especially in those with hypophosphatemia or reduced glomerular filtration rate.


Assuntos
Adenina/análogos & derivados , Nefropatias/tratamento farmacológico , Organofosfonatos/efeitos adversos , Tiazolidinedionas/uso terapêutico , Adenina/efeitos adversos , Animais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Taxa de Filtração Glomerular/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Hipofosfatemia/tratamento farmacológico , Hipofosfatemia Familiar/tratamento farmacológico , Nefropatias/induzido quimicamente , Masculino , Proteínas de Membrana Transportadoras/efeitos dos fármacos , Ratos , Ratos Wistar , Inibidores da Transcriptase Reversa/efeitos adversos , Rosiglitazona , Tenofovir , Tiazolidinedionas/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA