RESUMO
Grape is one of the most popular and widely cultivated fruits in the world. Although grape skin and seeds are waste product of the winery and grape juice industry, these wastes contain large amounts of phytochemicals such as flavonoids, phenolic acids, and anthocyanidins, which play an important role as chemopreventive and anticancer agents. We evaluated efficacies of grape skin and seeds on hepatic injury induced by dimethylnitrosamine (DMN) in rats. Treatment with DMN significantly increased levels of serum alanine transaminase, aspartate transaminase, alkaline phosphatase, and bilirubin. Diet supplementation with grape skin or seeds (10% daily for 4 weeks) prevented these elevations. The grape skin and seeds also restored serum albumin and total protein levels, and reduced the hepatic level of hydroxyproline and malondialdehyde. Furthermore, grape skin and seeds reduced DMN-induced collagen accumulation, as estimated by histological analysis of liver tissue stained with Sirius red. Grape skin and seeds also reduced hepatic stellate cell activation, as assessed by alpha-smooth muscle actin staining. In conclusion, grape skin and seeds exhibited in vivo hepatoprotective and antifibrogenic effects against DMN-induced liver injury, suggesting that grape skin and seeds may be useful in preventing the development of hepatic fibrosis.
Assuntos
Animais , Ratos , Actinas , Alanina Transaminase , Fosfatase Alcalina , Antocianinas , Antineoplásicos , Aspartato Aminotransferases , Bilirrubina , Colágeno , Dieta , Suplementos Nutricionais , Dimetilnitrosamina , Fibrose , Flavonoides , Frutas , Células Estreladas do Fígado , Hidroxiprolina , Fígado , Cirrose Hepática , Malondialdeído , Músculos , Fenol , Sementes , Albumina Sérica , Pele , Vitis , ResíduosRESUMO
Abstract In many clinical situations which cause thymic involution and thereby result in immune deficiency, T cells are the most often affected, leading to a prolonged deficiency of T cells. Since only the thymic-dependent T cell production pathway secures stable regeneration of fully mature T cells, seeking strategies to enhance thymic regeneration should be a key step in developing therapeutic methods for the treatment of these significant clinical problems. This study clearly shows that receptor activator of NF-kappaB ligand (RANKL) stimulates mouse thymic epithelial cell activities including cell proliferation, thymocyte adhesion to thymic epithelial cells, and the expression of cell death regulatory genes favoring cell survival, cell adhesion molecules such as ICAM-1 and VCAM-1, and thymopoietic factors including IL-7. Importantly, RANKL exhibited a significant capability to facilitate thymic regeneration in mice. In addition, this study demonstrates that RANKL acts directly on the thymus to activate thymus regeneration regardless of its potential influences on thymic regeneration through an indirect or systemic effect. In light of this, the present study provides a greater insight into the development of novel therapeutic strategies for effective thymus repopulation using RANKL in the design of therapies for many clinical conditions in which immune reconstitution is required.
Assuntos
Animais , Masculino , Camundongos , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Ciclofosfamida/farmacologia , Regulação para Baixo/efeitos dos fármacos , Células Epiteliais/citologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Molécula 1 de Adesão Intercelular/genética , Interleucina-7/genética , Camundongos Endogâmicos C57BL , Ligante RANK/farmacologia , RNA Mensageiro/genética , Receptor Ativador de Fator Nuclear kappa-B/genética , Regeneração/efeitos dos fármacos , Timo/citologia , Regulação para Cima/efeitos dos fármacos , Molécula 1 de Adesão de Célula Vascular/genética , Proteína X Associada a bcl-2/genética , Proteína bcl-X/genéticaRESUMO
Highly specific and sensitive immunoassay method for soluble human recombinant interleukin-6 (hu rlL-6) was established by two different immunization methods. One is conventional method by Freund's adjuvant method and the other is special method which is directly injected to mouse spleen. Among seven established monoclonal antibodies (mAbs), two typical monoclonal antibodies, designated YB3 (IgG1) and NY2 (IgM), were further characterized. These mAbs highly bound to IL-6, however did not show cross reactivity with IL-1B and IL-2. As the results of ELISA inhibition assay and western blotting method, it was further identified that YB3 and NY2 had high binding specificity with IL-6. And the limiting detection amount of rlL-6 for YB3 was 5 ng/ml and for NY2 was 0.5 ng/ml. Furthermore, N-glycosylated human rlL-6 was also bound to YB3 on ELISA. On the other hand YB-3 furtherly recognized N-glycosylated human rlL-6 by sandwich ELISA method. These mAbs may be of use to diagnose the gynecopathy which contains abortion and preterm labor.