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1.
Clin Exp Nephrol ; 24(5): 411-419, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-31912273

RESUMEN

BACKGROUND: Prothymosin alpha (ProTα) is a nuclear protein expressed in virtually all mammalian tissues. Previous studies have shown that ProTα exhibits protective effects against ischemia-induced cell death in various cell types. Recently, the 6-residue peptide P6Q (NEVDQE), the modified form of the active 6-residue core (51-56) in ProTα, has also been shown to have protective effects against retinal ischemia. However, it remains to be elucidated whether P6Q is effective against acute kidney injury (AKI). Therefore, we investigated the renoprotective effect of P6Q on cisplatin-induced AKI. METHODS: Cultured HK-2 cells were treated with cisplatin for 24 h and pretreatment with ProTα or P6Q was carried out 30 min before cisplatin treatment. Cell viability was evaluated using the MTT assay. In an in vivo study, 8-week-old male Wistar rats were divided into control, cisplatin treated, and cisplatin treated with P6Q injection groups. In the last of these, P6Q was injected intravenously before cisplatin treatment. Then, we evaluated the renoprotective effect of P6Q. RESULTS: In the study on cultured cells, pretreatment with ProTα or P6Q prevented cisplatin-induced cell death. In the in vivo study, pretreatment with P6Q significantly attenuated cisplatin-induced increase in serum creatinine and blood urea nitrogen levels, renal tubular cell injury, and apoptosis. Moreover, P6Q attenuated the mitochondrial apoptotic pathway and accelerated Akt phosphorylation after cisplatin-induced renal damage. CONCLUSION: Taken together, our findings indicate that P6Q can attenuate cisplatin-induced AKI and suppress the mitochondrial apoptotic pathway via Akt phosphorylation. These data suggest that P6Q has potential as a preventative drug for cisplatin-induced AKI.


Asunto(s)
Lesión Renal Aguda/prevención & control , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Túbulos Renales Proximales/patología , Mitocondrias/metabolismo , Lesión Renal Aguda/sangre , Lesión Renal Aguda/inducido químicamente , Animales , Antineoplásicos/farmacología , Nitrógeno de la Urea Sanguínea , Línea Celular , Cisplatino/farmacología , Creatinina/sangre , Humanos , Masculino , Péptidos/farmacología , Péptidos/uso terapéutico , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Wistar
2.
Med Sci Monit ; 23: 1464-1470, 2017 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-28343234

RESUMEN

BACKGROUND Endocan is expressed in vascular endothelial cells, and its expression is enhanced following endothelial injury via inflammatory cytokines. Subsequently, endocan is secreted into the circulation. Thus, serum endocan levels are considered a marker of endothelial injury. However, to the best of our knowledge, no data on the serum endocan levels in peritoneal dialysis (PD) patients are available. MATERIAL AND METHODS This study included 21 PD patients who underwent peritoneal equilibration test (PET) more than once between 2011 and 2015. Serum samples were collected from each patient, and the 24-h urine volume was measured at the time of PET. Serum endocan levels were measured using enzyme-linked immunosorbent assay (ELISA) at the time of the first PET, and their relationship with clinical data or the extent of urine volume decline (mL/year) was analyzed retrospectively. RESULTS Serum endocan levels were positively correlated with proteinuria level, serum creatinine level, serum tumor necrosis factor (TNF)-α level, ß2-microglobulin level, and PD drainage volume, but not with urine volume at baseline. The extent of decline in urine volume was significantly associated with serum endocan level, proteinuria level, serum creatinine level, and serum TNF-α level at baseline in a simple linear regression analysis. Moreover, multiple linear regression analysis showed that the serum endocan level and proteinuria level at baseline were independent predictors for the extent of decline in urine volume. CONCLUSIONS The results of this study indicate that serum endocan level and proteinuria level may be useful predictive markers for decreased urine volume in PD patients.


Asunto(s)
Riñón/fisiopatología , Proteínas de Neoplasias/sangre , Diálisis Peritoneal/métodos , Proteinuria/orina , Proteoglicanos/sangre , Adulto , Anciano , Biomarcadores/sangre , Creatina/sangre , Células Endoteliales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diálisis Peritoneal/efectos adversos , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/sangre , Micción/fisiología
3.
Nephrol Dial Transplant ; 31(10): 1615-23, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27190365

RESUMEN

BACKGROUND: Although histone acetylation, an epigenetic modification, has been reported to be related to the progression of various diseases, its involvement in nephrosclerosis is unclear. METHODS: Dahl salt-sensitive rats were used as a model of nephrosclerosis in this study. The rats were divided into three groups: (i) normal-salt diet group, (ii) high-salt diet group (HS), and (iii) HS administered daily with curcumin, a histone acetyltransferase inhibitor (HS+C). At 6 weeks after the treatment, the kidneys were dissected. Morphologic changes were assessed by Masson's trichrome staining. The number of macrophages, fibroblasts and the cells expressing acetylated histone H3 at Lys 9 (H3K9) were assessed by immunohistochemistry. RESULTS: Although both HS and HS+C rats revealed a marked increase in systolic blood pressure, serum creatinine was increased only in HS rats at 6 weeks. In the HS rats, nephrosclerosis was induced, accompanying a significant accumulation of macrophages and fibroblasts. The inflammation and fibrosis was markedly suppressed in the HS+C group. The level of histone acetylation at Lys 9 was enhanced in the HS rats, whereas curcumin administration suppressed the histone acetylation. Moreover, in the HS rats, interleukin-6 gene expression was associated with acetylated H3K9, as revealed by chromatin immunoprecipitation assay. CONCLUSIONS: Our results suggested that curcumin ameliorates nephrosclerosis via suppression of histone acetylation, independently of hypertension.


Asunto(s)
Curcumina/uso terapéutico , Histonas/metabolismo , Hipertensión/tratamiento farmacológico , Nefroesclerosis/tratamiento farmacológico , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Acetilación , Animales , Presión Sanguínea , Curcumina/farmacología , Evaluación Preclínica de Medicamentos , Epigénesis Genética/efectos de los fármacos , Expresión Génica , Hipertensión/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Riñón/efectos de los fármacos , Riñón/fisiopatología , Masculino , Factor 2 Relacionado con NF-E2/metabolismo , Nefroesclerosis/metabolismo , Ratas , Ratas Endogámicas Dahl
4.
Med Mol Morphol ; 49(3): 144-53, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26880269

RESUMEN

Long-term peritoneal dialysis causes peritoneal fibrosis, and previous reports suggest that inflammation plays a critical role in peritoneal fibrosis. Chondroitin sulfate (CS) suppresses the inflammatory response by preventing activation of nuclear factor (NF)-κB. We examined the effect of CS on the peritoneal fibrosis induced by chlorhexidine gluconate (CG) in mice. CS or water was administered daily. We divided mice into four groups: administered vehicle and water (control); administered vehicle and CS (CS); administered CG and water (CG); and administered CG and CS (CG+CS). Morphologic changes were assessed by Masson's trichrome staining. Inflammation- and fibrosis-associated factors were assessed by immunohistochemistry. Activation of NF-κB was examined by southwestern histochemistry. CS administration suppressed the progression of submesothelial thickening. The numbers of inflammation- and fibrosis-associated factors -positive cells were significantly decreased in the CG+CS group, compared to the CG group. Based on SWH, the CG+CS group contained significantly fewer NF-κB-activated cells than the CG group. Our results indicate that CS suppresses peritoneal fibrosis via suppression of NF-κB activation. These results suggest that CS has therapeutic potential for peritoneal fibrosis.


Asunto(s)
Sulfatos de Condroitina/uso terapéutico , FN-kappa B/metabolismo , Fibrosis Peritoneal/tratamiento farmacológico , Actinas/metabolismo , Animales , Quimiocina CCL2/metabolismo , Sulfatos de Condroitina/farmacología , Inmunohistoquímica , Interleucina-1beta/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones Endogámicos ICR , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Fibrosis Peritoneal/enzimología , Fibrosis Peritoneal/patología , Fibrosis Peritoneal/prevención & control , Fenotipo , Fosforilación , Proteínas Smad/metabolismo , Coloración y Etiquetado
5.
Biol Pharm Bull ; 38(2): 193-200, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25747978

RESUMEN

Long-term peritoneal dialysis therapy causes inflammation and histological changes in the peritoneal membrane. Inflammation generally activates fibroblasts and results in fibroblast-myofibroblast differentiation. Heat-shock protein 47 (HSP 47), a collagen-specific molecular chaperone, is localized in myofibroblasts and is involved in the progression of peritoneal fibrosis. Daikenchuto (DKT), a Kampo medicine, is used to prevent postoperative colon adhesion. It inhibits inflammation and HSP 47 expression in the gastrointestinal tract. We examined the effect of DKT on chlorhexidine gluconate (CG)-induced peritoneal fibrosis in mice injected with 0.1% CG dissolved in 15% ethanol. DKT was dissolved in the drinking water. Histological changes were assessed using Masson trichrome staining. Cells expressing α-smooth muscle actin (α-SMA), HSP 47, phospho-Smad 2/3, F4/80, and monocyte chemotactic protein-1 were examined immunohistochemically. Compared with the control group, the peritoneal tissues of the CG group were markedly thickened, and the number of cells expressing α-SMA, HSP 47, phospho-Smad 2/3, F4/80, and monocyte chemotactic protein-1 was significantly increased. However, these changes were inhibited in the DKT-treated group. These results indicate that DKT can prevent peritoneal fibrosis by inhibiting inflammation and HSP 47 expression.


Asunto(s)
Fibrosis Peritoneal/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Actinas/metabolismo , Animales , Antígenos de Diferenciación/metabolismo , Quimiocina CCL2/metabolismo , Clorhexidina/análogos & derivados , Proteínas del Choque Térmico HSP47/metabolismo , Masculino , Medicina Kampo , Ratones Endogámicos ICR , Panax , Fibrosis Peritoneal/inducido químicamente , Fibrosis Peritoneal/metabolismo , Fibrosis Peritoneal/patología , Peritoneo/efectos de los fármacos , Peritoneo/metabolismo , Peritoneo/patología , Fitoterapia , Extractos Vegetales/farmacología , Proteína Smad2/metabolismo , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Zanthoxylum , Zingiberaceae
6.
BMC Res Notes ; 17(1): 155, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38840123

RESUMEN

BACKGROUND AND OBJECTIVE: Aspartame (L-aspartyl L-phenylalanine methyl ester) is an artificial sweetener widely used as a sugar substitute. There are concerns regarding the effects of high aspartame doses on the kidney owing to oxidative stress; however, whether the maximum allowed dose of aspartame in humans affects the kidneys remains unknown. Therefore, in this study, we investigated whether the maximum allowed dose of aspartame in humans affects the kidneys. METHODS: In this study, animals were fed a folate-deficient diet to mimic human aspartame metabolism. Eight-week-old ICR mice were divided into control (CTL), 40 mg/kg/day of aspartame-administered (ASP), folate-deficient diet (FD), and 40 mg/kg/day of aspartame-administered with a folate-deficient diet (FD + ASP) groups. Aspartame was administered orally for eight weeks. Thereafter, we evaluated aspartame's effect on kidneys via histological analysis. RESULTS: There were no differences in serum creatinine and blood urea nitrogen levels between the CTL and ASP groups or between the FD and FD + ASP groups. There was no histological change in the kidneys in any group. The expression of superoxide dismutase and 4-hydroxy-2-nonenal in the kidney did not differ between the CTL and ASP groups or the FD and FD + ASP groups. CONCLUSION: Our findings indicate that the allowed doses of aspartame in humans may not affect kidney function or oxidative states.


Asunto(s)
Aspartame , Riñón , Ratones Endogámicos ICR , Estrés Oxidativo , Edulcorantes , Animales , Aspartame/farmacología , Riñón/efectos de los fármacos , Riñón/metabolismo , Edulcorantes/farmacología , Edulcorantes/administración & dosificación , Ratones , Masculino , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/metabolismo , Superóxido Dismutasa/metabolismo , Nitrógeno de la Urea Sanguínea
7.
Drugs R D ; 17(3): 389-396, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28547536

RESUMEN

BACKGROUND AND OBJECTIVE: We compared the hemoglobin-maintaining effects between continuous erythropoietin receptor activator (CERA) and darbepoetin-α (DA) in patients with chronic kidney disease (CKD) during the 3 months before dialysis initiation. METHODS: This study was conducted with 37 CERA-administered patients and 26 DA-administered patients who had initiated dialysis at a participating facility between January 2012 and December 2014. We investigated clinical laboratory data 3 months before and at dialysis initiation, and compared these data between the CERA and DA groups. RESULTS: No significant differences in hemoglobin level or reticulocyte count were found between the two groups 3 months before dialysis initiation. However, at dialysis initiation, the hemoglobin level (CERA 9.82 ± 1.52 vs. DA 8.79 ± 1.07 g/dL; P = 0.003) and the reticulocyte count (CERA 5.21 ± 2.95 vs. DA 3.15 ± 1.62 × 104/µL; P = 0.004) were significantly higher in the CERA group than in the DA group. Moreover, the extent of changes in the erythropoietin resistance index during the 3 months before dialysis initiation was significantly increased in the DA group compared with the CERA group. CONCLUSIONS: Our results suggest that CERA may be more effective than DA in maintaining hemoglobin levels in patients with CKD during 3 months before dialysis initiation.


Asunto(s)
Darbepoetina alfa/uso terapéutico , Eritropoyetina/uso terapéutico , Hematínicos/uso terapéutico , Polietilenglicoles/uso terapéutico , Insuficiencia Renal Crónica/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Femenino , Hemoglobinas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/fisiopatología , Recuento de Reticulocitos , Factores de Tiempo
8.
Intern Med ; 53(9): 1023-7, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24785897

RESUMEN

We herein report the case of a 21-year-old woman with refractory adult-onset Still's disease who developed central venous catheter-related methicillin-resistant Staphylococcus aureus sepsis during aggressive immunosuppressive therapy. She subsequently experienced septic pulmonary embolism (SPE) and sacroiliitis during treatment with intravenous vancomycin and was successfully treated with long-term oral linezolid therapy. This case suggests that the occurrence of methicillin-resistant Staphylococcus aureus infection in immunosuppressive patients can trigger severe clinical manifestations such as SPE and septic sacroiliitis and that linezolid is suitable for treating such conditions.


Asunto(s)
Acetamidas/administración & dosificación , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Oxazolidinonas/administración & dosificación , Embolia Pulmonar/etiología , Sacroileítis/etiología , Infecciones Estafilocócicas/etiología , Enfermedad de Still del Adulto/complicaciones , Antiinfecciosos/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Linezolid , Imagen por Resonancia Magnética , Embolia Pulmonar/tratamiento farmacológico , Embolia Pulmonar/microbiología , ARN Ribosómico 23S , Sacroileítis/tratamiento farmacológico , Sacroileítis/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Factores de Tiempo , Tomografía Computarizada por Rayos X , Adulto Joven
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