RESUMO
BACKGROUND: Progressive fibrous thickening of peritoneal membrane (PM) is a major complication of long-term peritoneal dialysis. TGF-ß/SMAD pathway activation, inflammation and neoangiogenesis have an important role in PM changes induced by peritoneal dialysis. Here, we investigated the effects of paclitaxel (PTX) carried in lipid core nanoparticles (LDE) on the development of peritoneal fibrosis (PF) in rats. METHODS: To induce PF, 21 male Wistar rats (300-350g) were injected with chlorhexidine gluconate for 15 consecutive days and randomly assigned to three groups: 1)PF, n = 5: no treatment; 2)LDE, n = 8: treated with LDE only, 3/3 days during 15 days; 3)LDE-PTX, n = 8: treated with PTX (4mg/kg) associated with LDE, 3/3 days during 15 days. A Control group without PF induction (n = 5) was designed, received saline solution, 3/3 days. Peritoneum function tests were performed, and anterior abdominal wall samples of the PM were collected for analyses of peritoneal thickness, immunohistochemitry, and gene expression. RESULTS: LDE-PTX treatment preserved the membrane function, maintaining the ultrafiltration rate and mass transfer of glucose at normal levels. LDE-PTX also prevented PM thickening induced by chlorhexidine gluconate injections. LDE-PTX treatment reduced the number of myofibroblasts infiltrating PM and inhibited the cell proliferation. Gene expression of fibronectin, FSP-1, VEGF, TGF-ß, and SMAD3 were reduced by LDE-PTX. CONCLUSIONS: LDE-PTX was effective to prevent development of PF and preserve the PM filtration capacity in this rat model, with clear-cut actions on pro-fibrotic mechanisms. Thus, LDE-PTX can be candidate for future clinical trials as adjuvant to peritoneal dialysis to prevent PF development, since this preparation is devoid of toxicity as shown previously.
Assuntos
Nanopartículas , Fibrose Peritoneal , Animais , Modelos Animais de Doenças , Feminino , Lipossomos , Masculino , Paclitaxel , Fibrose Peritoneal/induzido quimicamente , Fibrose Peritoneal/metabolismo , Fibrose Peritoneal/prevenção & controle , Peritônio/patologia , Ratos , Ratos Wistar , Fator de Crescimento Transformador beta/metabolismoRESUMO
INTRODUÇÃO: A Insuficiência Renal Crônica (IRC) tem incidência alarmante neste século. A diálise peritoneal, uma das modalidades de terapia renal pode ter complicações, e entre estas a fibrose peritoneal, que ocorre com o decorrer dos anos nestes pacientes. Sua forma mais grave é a chamada peritonite esclerosante encapsulante, levando à mudança de terapia dialítica. OBJETIVO: Estudar a influência do uso do captopril na fibrose peritoneal induzida em ratos pelo uso de solução de glicose a 4,25 %. MÉTODOS: Estudo prospectivo controlado, em ratos Wistar não urêmicos. Foram estudados 20 animais. Os animais foram submetidos diariamente à punção abdominal, sendo infundida solução de diálise peritoneal com glicose a 4,25% na dose de 10 ml/100 g de peso. Os animais foram divididos em 2 grupos: experimental e controle. O grupo experimental recebeu captopril na dose de 30 mg/kg/dia por gavagem. O grupo controle não recebeu nenhuma droga. Foram acompanhados por 21 e 49 dias. Ao final do período foram submetidos à procedimento cirúrgico para retirada de peritônio parietal e visceral. As amostras obtidas foram analisadas histologicamente, usando-se coloração Hematoxilina - Eosina e Sirius Red, para avaliação do grau de fibrose. RESULTADOS: A análise mostrou que a intensidade da fibrose, a espessura do peritônio e o número de células não atingiram diferença estatisticamente significante entre os grupos experimental e controle. CONCLUSÃO: O estudo mostrou que o uso do captopril não foi capaz de alterar a intensidade da fibrose peritoneal induzida pelo uso de solução de diálise em ratos.
INTRODUCTION: Chronic renal failure has alarming incidence all over the world in this century. Among the modalities of dialytic treatment, peritoneal dialysis has a major spot. This method of dialytictreatment may present complications, and among those is peritoneal fibrosis. It occurs in patients submitted to peritoneal dialysis along years. It's most dangerous form is sclerosing encapsulant peritonitis, wich leads to a need of change in modality and many times lead to death. OBJECTIVE: Study the influence of using captopril on the peritoneal fibrosis induced in rats using solution with glucoses 4.25%. METHODS: Prospective controlled study in 20 non-uremic Wistar rats. The animals received a peritoneal infusion of 10 ml/100g of peritoneal dialysis solution glucose 4.25% on a daily basis. The animals were divided in two groups: experimental and control. The experimental group received captopril 30 mg/kg/d, by a gastric tube. The control group did not receive any drug. The follow-up was 21 and 49 days. At the end, one surgical procedure was performed to get histological samples of visceral and parietal peritoneum. The samples were analyzed using Hematoxylin Eosin and Sirius Red, to evaluate the severity of the fibrosis. RESULTS: The analysis showed that the intensity of the fibrosis, the peritoneal thickness and the cell number in experimental and control groups were not statistically significant different in experimental and control groups. CONCLUSION: Our findings indicate that captopril do not decrease the intensity of fibrosis on the peritoneal membrane that happens on rats on peritoneal dialysis.
Assuntos
Animais , Masculino , Ratos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Captopril/uso terapêutico , Glucose/administração & dosagem , Diálise Peritoneal , Fibrose Peritoneal/prevenção & controle , Fibrose Peritoneal/induzido quimicamente , Ratos WistarRESUMO
INTRODUCTION: Chronic renal failure has alarming incidence all over the world in this century. Among the modalities of dialytic treatment, peritoneal dialysis has a major spot. This method of dialytic treatment may present complications, and among those is peritoneal fibrosis. It occurs in patients submitted to peritoneal dialysis along years. It's most dangerous form is sclerosing encapsulant peritonitis, wich leads to a need of change in modality and many times lead to death. OBJECTIVE: Study the influence of using captopril on the peritoneal fibrosis induced in rats using solution with glucoses 4.25%. METHODS: Prospective controlled study in 20 non-uremic Wistar rats. The animals received a peritoneal infusion of 10 ml/100g of peritoneal dialysis solution glucose 4.25% on a daily basis. The animals were divided in two groups: experimental and control. The experimental group received captopril 30 mg/kg/d, by a gastric tube. The control group did not receive any drug. The follow-up was 21 and 49 days. At the end, one surgical procedure was performed to get histological samples of visceral and parietal peritoneum. The samples were analyzed using Hematoxylin Eosin and Sirius Red, to evaluate the severity of the fibrosis. RESULTS: The analysis showed that the intensity of the fibrosis, the peritoneal thickness and the cell number in experimental and control groups were not statistically significant different in experimental and control groups. CONCLUSION: Our findings indicate that captopril do not decrease the intensity of fibrosis on the peritoneal membrane that happens on rats on peritoneal dialysis.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Captopril/uso terapêutico , Glucose/administração & dosagem , Diálise Peritoneal , Fibrose Peritoneal/prevenção & controle , Animais , Masculino , Fibrose Peritoneal/induzido quimicamente , Ratos , Ratos WistarRESUMO
PURPOSE: To investigate the influence of using simvastatin on the peritoneal fibrosis induced in rats using peritoneal dialysis solution with glucoses 4.25%. METHODS: Prospective controlled study in 20 non-uremic Wistar rats. The animals received a peritoneal infusion of 10 ml/100 g of peritoneal dialysis solution glucose 4.25% on a daily basis. The animals were divided in two groups: experimental and control. The experimental group received simvastatin 4 mg/kg/d, by a gastric tube. The control group did not receive any drug. The follow-up was 21 and 49 days. At the end, one surgical procedure was performed to get histological samples of visceral and parietal peritoneum. The samples were analyzed using Hematoxylin Eosin and Sirius Red, to evaluate the severity of the fibrosis. RESULTS: The analysis showed that the intensity of the fibrosis, the peritoneal thickness and the cell number in experimental and control groups were not statistically significant different in experimental and control groups. CONCLUSION: The simvastatin do not decrease the intensity of fibrosis on the peritoneal membrane that happens on rats on peritoneal dialysis.
Assuntos
Soluções para Diálise/efeitos adversos , Glucose/efeitos adversos , Diálise Peritoneal/efeitos adversos , Fibrose Peritoneal/prevenção & controle , Sinvastatina/uso terapêutico , Animais , Contagem de Células , Colágeno/análise , Masculino , Fibrose Peritoneal/induzido quimicamente , Fibrose Peritoneal/patologia , Estudos Prospectivos , Ratos , Ratos Wistar , Fatores de TempoRESUMO
PURPOSE: To investigate the influence of using simvastatin on the peritoneal fibrosis induced in rats using peritoneal dialysis solution with glucoses 4.25%. METHODS: Prospective controlled study in 20 non-uremic Wistar rats. The animals received a peritoneal infusion of 10 ml/100 g of peritoneal dialysis solution glucose 4.25% on a daily basis. The animals were divided in two groups: experimental and control. The experimental group received simvastatin 4 mg/kg/d, by a gastric tube. The control group did not receive any drug. The follow-up was 21 and 49 days. At the end, one surgical procedure was performed to get histological samples of visceral and parietal peritoneum. The samples were analyzed using Hematoxylin Eosin and Sirius Red, to evaluate the severity of the fibrosis. RESULTS: The analysis showed that the intensity of the fibrosis, the peritoneal thickness and the cell number in experimental and control groups were not statistically significant different in experimental and control groups. CONCLUSION: The simvastatin do not decrease the intensity of fibrosis on the peritoneal membrane that happens on rats on peritoneal dialysis.
OBJETIVO: Investigar a influência do uso da sinvastatina na fibrose peritoneal induzida em ratos pelo uso de solução de diálise peritoneal rica em glicose. MÉTODOS: Estudo prospectivo controlado, em ratos Wistar não urêmicos. Foram estudados 20 animais. Os animais foram submetidos diariamente à punção abdominal, sendo infundida solução de diálise peritoneal com glicose a 4,25% na dose de 10 ml/100 g de peso. Os animais foram divididos em dois grupos: experimental e controle. O grupo experimental recebeu sinvastatina na dose de 4 mg/kg/dia por gavagem. O grupo controle não recebeu nenhuma droga. Foram acompanhados por 21 e 49 dias. Ao final do período foram submetidos à procedimento cirúrgico para retirada de peritônio parietal e visceral. As amostras obtidas foram analisadas histologicamente, usando-se coloração Hematoxilina - Eosina e Sirius Red, para avaliação do grau de fibrose. RESULTADOS: A análise mostrou que a intensidade da fibrose, a espessura do peritônio e o número de células não atingiram diferença estatisticamente significante entre os grupos experimental e controle. CONCLUSÃO: A sinvastatina não foi capaz de alterar a intensidade da fibrose peritoneal induzida pelo uso de solução de diálise em ratos.
Assuntos
Animais , Masculino , Ratos , Soluções para Diálise/efeitos adversos , Glucose/efeitos adversos , Diálise Peritoneal/efeitos adversos , Fibrose Peritoneal/prevenção & controle , Sinvastatina/uso terapêutico , Contagem de Células , Colágeno/análise , Estudos Prospectivos , Fibrose Peritoneal/induzido quimicamente , Fibrose Peritoneal/patologia , Ratos Wistar , Fatores de TempoRESUMO
BACKGROUND: Peritoneal washing out with physiological solution with different substances added is useful in peritoneal infections, but the effect of enzymatic detergents, such as quaternary didecyl-dimethyl ammonium compounds (DDAC), used in the sterilization of surgical material is unknown. We undertook this study to determine histological changes (inflammation, fibrosis and new vessel formation) in the peritoneum of Wistar rats after the application of physiological solution or DDAC. METHODS: The minimum inhibitory concentration (MIC) of DDAC for E. coli (512 µg/ml) and E. faecalis (128 µg/ml) was determined. Sixty-three Wistar rats weighing 200 ± 20 g were studied. They were divided into three groups: control: 7 rats were instilled with 3 ml of physiological solution in peritoneal cavity; groups 1 and 2 were instilled with 3 ml of MIC for E. coli and E. faecalis, respectively. These groups were divided into four subgroups of seven animals. In every rat, 1 cm(2) of peritoneum was obtained at 2, 7, 14, and 21 days for histological study with hematoxylin-eosin. Ten fields were evaluated. The data obtained were analyzed with the Mann-Whitney test. RESULTS: There were no significant differences in inflammation, fibrosis and new vessel formation with the physiological solution vs. DDAC at 2, 7, 14, and 21 days (p >0.05), except for inflammation at 2 days in group 2 (p = 0.026), which remitted. CONCLUSIONS: There was no significant difference in changes in rat peritoneum after physiological solution or DDAC application.