ABSTRACT
PURPOSE: Diabetes is the leading cause of end-stage renal failure. The present study was undertaken to characterize the effects of Corni Fructus on diabetic nephropathy in streptozotocin-induced diabetic rats and their mechanisms. MATERIALS AND METHODS: Streptozotocin-diabetic rats were orally administrated with Corni Fructus at a dose of 100, 200 or 400 mg/kg body mass for 40 days. RESULTS: Corni Fructus-treated diabetic rats showed significant decreases of blood glucose, urinary protein levels and water consumption. Corni Fructus also reduced serum total cholesterol, total triglyceride and low-density lipoprotein cholesterol levels, and showed a tendency of enhancing high-density lipoprotein cholesterol level. Levels of serum albumin and creatinine in diabetic rats were also significantly reduced by Corni Fructus administration at a dose of 200 and 400 mg/kg body mass compared with non-treated diabetic rats. Corni Fructus increased catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidose (GSH-px) activities in the kidneys of diabetic rats. Furthermore, Corni Fructus treatment enhanced renal peroxisome proliferator-activated receptor-gamma (PPARgamma) expression in diabetic rats. CONCLUSION: These results demonstrated that Corni Fructus may have the potential to protect the animals from diabetic nephropathy by amelioration of oxidative stress and stimulation of PPARgamma expression.
Subject(s)
Animals , Male , Rats , Blotting, Western , Body Weight/drug effects , Catalase/metabolism , Cornus/chemistry , Diabetes Mellitus, Experimental/drug therapy , Glucose Tolerance Test , Glutathione/metabolism , Hypoglycemic Agents/therapeutic use , Malondialdehyde/metabolism , Plant Extracts/therapeutic use , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , Superoxide Dismutase/metabolismABSTRACT
BACKGROUND: We evaluated the effects of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) on the production of tumor necrosis factor-alpha (TNF-alpha) and expression of nuclear factor-kappaB (NF-kappaB) in stimulated THP-1 cells, a human monocyte cell line. MATERIALS AND METHODS: We evaluated the cytotoxic effect of 15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), one of natural PPAR-gamma ligands, using commercial cell proliferation assay. Cells were pretreated with 15d-PGJ(2) and then stimulated with lipopolysaccharide (LPS) or lipoteichoic acid (LTA). The amount of TNF-alpha was measured by using commercial ELISA method. NF-kappaB activation was evaluated by Western blot analysis. RESULTS: 15d-PGJ(2) showed dose-dependent cytotoxic effect on the tested cells after 4 hr of treatment. Stimulation of cells by LPS or LTA induced TNF-alpha production. TNF-alpha production was markedly decreased in the cells pretreated with 15d-PGJ(2) compared to cells treated only with LPS or LTA in a dose-dependent manner. Pretreatment of 15d-PGJ(2) reduced LPS or LTA induced NF-kappaB expression in the nuclear extracts of THP-1 cells. CONCLUSION: 15d-PGJ(2) pretreatment decreased TNF-alpha production from the THP-1 cells stimulated by LPS or LTA, and this assumed to be associated with inhibition of NF-kappaB activation.
Subject(s)
Humans , Blotting, Western , Cell Line , Cell Proliferation , Enzyme-Linked Immunosorbent Assay , Ligands , Lipopolysaccharides , Monocytes , NF-kappa B , Peroxisomes , Teichoic Acids , Tumor Necrosis Factor-alphaABSTRACT
PURPOSE: This study was performed to demonstrate a correlation among urinary 15d-PGJ2, proinflammatory cytokines (i.e. IL-23, IL-6, and TGF-beta1), and CRP, and to determinate the contributors to prognostic score and proteinuria in IgAN patients. METHODS: Fifty-four patients with biopsy-proven IgAN were enrolled. For comparison with IgAN, five MCD patients were also enrolled. Immunohistochemical staining for PPAR-gamma in kidney tissue and measurements of urinary IL-6, IL-23, TGF-beta1, 15d-PGJ2 and serum CRP were performed RESULTS: There was no difference according to PPAR-gamma staining. 15d-PGJ2 was negatively correlated with urinary IL-23, TGF-beta1, and CRP. Among proinflammatory cytokines and CRP, there were positive relationships with each other except for IL-23 and CRP. TGF-beta1 in the group having proteinuria more than 3 g/day was statistically higher than that in the sole hematuria group. However, in multivariate regression analysis, not a single relation was found between TGF-beta1 and proteinuria. Prognostic score was correlated with IL-6, IL-23, TGF-beta1, CRP, 15d-PGJ2, and 24hr proteinuria. 24hr proteinuria was correlated with IL-6 and 15d-PGJ2. In multivariate regression analysis, CRP, 15d-PGJ2, and 24hr proteinuria contributed to prognostic score, and only 15d-PGJ2 contributed to 24hr proteinuria. Last, urinary 15d-PGJ2 in IgAN was higher than that in MCD. CONCLUSION: Endogenous 15d-PGJ2 was associated with inflammation and might be considered as a material which could delay the damage of kidney in IgAN. In the future, larger cohort and long-term follow-up studies are needed to demonstrate the role of 15d-PGJ2 as prognostic indicator or marker of kidney damage.