Beneficial effects of Oltipraz, nuclear factor - erythroid - 2 - related factor 2 (Nrf2), on renal damage in unilateral ureteral obstruction rat model

ABSTRACT Introduction: We investigated whether Oltipraz (OPZ) attenuated renal fibrosis in a unilateral ureteral obstruction (UUO) rat model. Materials and Methods: We randomly divided 32 rats into four groups, each consisting of eight animals as follows: Rats in group 1 underwent a sham operation and received no treatment. Rats in group 2 underwent a sham operation and received OPZ. Rats in group 3 underwent unilateral ureteral ligation and received no treatment. Group 4 rats were subjected to unilateral ureteral ligation plus OPZ administration. Transforming growth factor beta-1 (TGF-β1), E-cadherin, nitric oxide (NO) and hydroxyproline levels were measured. Histopathological and immunohistochemical examinations were carried out. Results: TGF-β1, NO and E-cadherin levels in the UUO group were significantly higher than the sham group and these values were significantly different in treated groups compared to the UUO group. In rats treated with UUO + OPZ, despite the presence of mild tubular degeneration and less severe tubular necrosis, glomeruli maintained a better morphology when compared to the UUO group. Expressions of α-SMA in immunohistochemistry showed that the staining positivity decreased in the tubules of the OPZ-treated group. Conclusions: While the precise mechanism of action remains unknown, our results demonstrated that OPZ exerted a protective role in the UUO-mediated renal fibrosis rat model highlighting a promising therapeutic potency of Nrf2-activators for alleviating the detrimental effects of unilateral obstruction in kidneys.

effect of microwave radiation on osteogenesis and osteolysis of rats in the hypergravity condition and the role of Rana sylvatica Le conte oil as a radioprotector

Microwave Thermotherapy has been gradually used in radiotherapy and it is reported that microwave radiation increases bone demineralization rate independently of temperature. Furthermore, it becomes more and more widespread that the damage caused by the synergistic effect of microwave radiation and hypergravity. The experiment was designed to investigate the effect of microwave radiation on osteogenesis and osteolysis of rats in the hypergravity condition and to observe the role of Rana sylvatica Le conte oil as a radioprotector. Wistar rats were exposed to microwave radiation of 200mW/cm[2] power density and +6G hypergravity, and the concentrations of osteocalcin, calcitionin, calcium, phosphorus, and hydroxyproline and the activity of alkaline phosphatase were detected in serum. The serum concentrations of osteocalcin and calcitionin and the activity of alkaline phosphatase decreased, while the calcium, phosphorus and hydroxyproline concentrations increased after the synergistic effect of microwave radiation and hypergravity. Rana sylvatica Le conte oil intervention inhibited significantly the decrease of osteocalcin concentration and restrained significantly the increases of hydroxyproline and calcium concentrations in serum. These results imply that the synergistic effect of microwave radiation and hypergravity inhibits osteogenesis and enhances osteolysis in rats causing bone metabolic disturbance, while the injury resulted from microwave radiation and hypergravity could be protected by intervention with Rana sylvatica Le conte oil and it provides an original direction in the investigation of radioprotectors

Serum hyaluronic acid level: Correlation with quantitative measurement of hepatic fibrosis in a cirrhotic rat model / 대한간학회지

BACKGROUNDS/AIMS: The serum level of hyaluronic acid (HA) has been suggested as a useful serologic marker for hepatic fibrosis. However, the relationship between serum HA levels and quantitative markers of fibrosis from liver tissue has not been reported. The aim of this study was to determine the correlation between serum HA level and quantitative measurement of hepatic fibrosis in a cirrhotic rat model. METHODS: Cirrhosis was produced by common bile duct ligation (BDL) in adult Sprague-Dawley rats. The animals were classified into four groups: (1) G1, sham operated (n=5); (2) G2, BDL for 2 weeks (n=6); (3) G3, BDL for 3 weeks (n=6); and (4) G4, BDL for 4 weeks (n=6). Hepatic fibrosis was analyzed histomorphologically using the Batts and Ludwig scoring system. Serum HA level and hepatic hydroxyproline content were quantified. The gene expressions in the liver of procollagen, collagen, and transforming growth factor-beta (TGF-beta) were measured by reverse transcriptase-polymerase chain reaction. RESULTS: In groups G1, G2, G3, and G4, the Batts and Ludwig scores (mean+/-SD) were 0, 1.3+/-0.5, 2.6+/-0.5, and 3.4+/-0.5, respectively (P<0.05), serum HA levels were 12.5+/-3.2, 30.0+/-4.3, 228.6+/-157.7, and 391.3+/-207.7 ng/mL (P<0.05), and the concentration of hydroxyproline was 12.4+/-2.8, 17.6+/-3.8, 17.9+/-2.4, and 33.4+/-3.4 microgram/g liver tissue, and it was significantly higher in group G4 than in the other groups (P<0.05). The gene expressions of collagen, procollagen, and TGF-beta1 in the liver were also significantly higher in group G4 compared with the other groups (P<0.05). Direct linear correlations were observed between serum HA level and hepatic hydroxyproline content, hepatic gene expressions of collagen, procollagen, TGF-beta1, and histomorphological grade of hepatic fibrosis (P<0.001). CONCLUSIONS: These results indicate that serum HA is a useful and noninvasive serologic marker for the evaluation of advanced hepatic fibrosis.

Tratamiento de la enfermedad de Paget con olpadronato. Su eficacia terapeutica en respondedores parciales al pamidronato oral / Treatment of Paget's disease with olpadronate. Its efficacy in partial responders to oral pamidronate

Se estudió la eficacia del olpadronato, un nuevo bisfosfonato producto de la dimetilación del pamidronato, en 37 pacientes con enfermedad de Paget de (X + 1DS) 68 + 8 anos de edad. La población estaba constituida por: 12 pacientes sin tratamiento específico previo (STP) y 25 pacientes que habían recibido tratamientos anteriores (CTP) hasta (X + 1DS) 11+8 meses previos al inicio del estudio. La fosfatasa alcalina (FA) inicial en ambos grupos fue: 36 + 20 UKA y 43 + 30 UKA, respectivamente (rango normal: 5 a 15 IKA). La dosis diaria utilizada fue: 127 + 34mg por vía oral durante 3.5 + 2.4 meses (rango: 0.5 a 13 meses). Siete pacientes recibieron 2 ciclos de tratamiento. Todos los pacientes STP y 21 pacientes CTP normalizaron los valores de FA e hidroxiprolina urinaria (remisión completa). En 1 paciente CTP el olpadronato no fue efectivo y en 3 pacientes CTP la hidroxiprolina se normalizó pero no la FA aunque descendió en un 60 por ciento de los valores iniciales (remisión parcial). Se comparó la eficacia del olpadronato respecto del pamidronato en 14 pacientes CTP que habían sido previamente tratados con varios ciclos de pamidronato durante un período de 6.6 + 4.2 años y que no habían conseguido normalizar la FA. Doce de los 14 pacientes normalizaron la FA con el tratamiento con olpadronato y todos alcanzaron valores de hidroxiprolina normales. Conclusión: El olpadronato en dosis de 100 a 200 mg/día por vía oral es bien tolerado y eficaz en el tratamiento de la enfermedad de Paget aún en aquellos pacientes parcialmente respondedores al pamidronato.

Sensibilidad de los marcadores del remodelamiento óseo: su modificación en la menopausia, ante la terapia estrogénica de reemplazo y ante una enfermedad metabólica generalizada / Markers of bone turnover, their sensibility to bone remodeling: changes in menopause, in hormone replacement therapy and in a metabolic bone disease

Evalua una batería de marcadores bioquímicos específicos y sensibles para predecir cambios en la velocidad del remodelamiento óseo. Se estudió a mujeres sanas pre y postmenospáusicas y en estas últimas a su vez se evaluó los cambios producidos después de 90 días de una terapia hormonal de reemplazo. Respecto de los marcadores bioquímicos de formación, la FA total aumentó en las postmenospáusicas respecto del grupo premenospáusico (P < 0,0001), al igual que la BGP (1 < 0,01); en cambio, la FA ósea no registró cambios significativos. Luego de la terapia hormonal de reemplazo ninguno de estos marcadores registraron cambios significativos. Todos los marcadores de resorción aumentaron en als mujeres postmenospáusicas. Los convencionales tales como el calcio urinario/creatinina y la hidroxiprolina con un p < 0,01 y p < 0,006 respectivamente. Los nuevos marcadores de resorción presentaron los siguientes cambios: Pyr p < 0,001; 72 por ciento; D-Pyr p < 0,003, 27 por ciento y Crosslaps p < 0,003, 70 por ciento de aumento respectivamente. Ante la terapia estrogénica, si bien los marcadores convencionales no mostraron diferencias significativas respecto del nivel basal, la Pyr disminuyó significativamente en un 15 por ciento (p < 0,03), la D-Pyr en un 15 por ciento (p < 0,04) y los Crosslaps en un 39 por ciento (p < 0,001). También se investigó la precisión diagnóstica de los marcadores bioquímicos en pacientes con un remodelamiento óseo aumentado, como es el caso de enfermedades celíacas. Estas se compararon con los normales que presentaban igual estado estrogénico observándose distintos comportamientos entre pre y postmenospáusicas. La BGP aumentó sólo en las celíacas premenospáusicas (p < 0,003). La FA total en los dos grupos estrogénicos (p < 0,0001 y p < 0,005 respectivamente), al igual que la FA ósea (p < 0,0003 y p< 0,0004, respectivamente). El marcador de resorción D-Pyr no presentó diferencias significativas en ninguno de los dos grupos, la Pyr sílo en las premenopáusicas (p < 0,01). La hidroxiprolina aumentó en ambos (p < 0,04 y p < 0,004, respectivamente), al igual que los Crosslaps (p < 0,001 para los dos grupos estrogénicos)