Navegando por Palavras-chave "Noncrystalline uric acid"

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    Noncrystalline uric acid inhibits proteoglycan and glycosaminoglycan synthesis in distal tubular epithelial cells (MDCK)
    (Associação Brasileira de Divulgação Científica, 2010-10-01) Borges, Fernanda Teixeira [UNIFESP]; Dalboni, Maria Aparecida [UNIFESP]; Michelacci, Yara Maria [UNIFESP]; Schor, Nestor [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Hyperuricemia is associated with renal stones, not only consisting of uric acid (UrAc) but also of calcium oxalate (CaOx). Glycosaminoglycans (GAGs) are well-known inhibitors of growth and aggregation of CaOx crystals. We analyzed the effect of noncrystalline UrAc on GAG synthesis in tubular distal cells. MDCK (Madin-Darby canine kidney) cells were exposed to noncrystalline UrAc (80 µg/mL) for 24 h. GAGs were labeled metabolically and characterized by agarose gel electrophoresis. The expression of proteoglycans and cyclooxygenase 2 (COX-2) was assessed by real-time PCR. Necrosis, apoptosis and prostaglandin E2 (PGE2) were determined by acridine orange, HOESCHT 33346, and ELISA, respectively. CaOx crystal endocytosis was evaluated by flow cytometry. Noncrystalline UrAc significantly decreased the synthesis and secretion of heparan sulfate into the culture medium (UrAc: 2127 ± 377; control: 4447 ± 730 cpm) and decreased the expression of perlecan core protein (UrAc: 0.61 ± 0.13; control: 1.07 ± 0.16 arbitrary units), but not versican. Noncrystalline UrAc did not induce necrosis or apoptosis, but significantly increased COX-2 and PGE2 production. The effects of noncrystalline UrAc on GAG synthesis could not be attributed to inflammatory actions because lipopolysaccharide, as the positive control, did not have the same effect. CaOx was significantly endocytosed by MDCK cells, but this endocytosis was inhibited by exposure to noncrystalline UrAc (control: 674.6 ± 4.6, CaOx: 724.2 ± 4.2, and UrAc + CaOx: 688.6 ± 5.4 geometric mean), perhaps allowing interaction with CaOx crystals. Our results indicate that UrAc decreases GAG synthesis in MDCK cells and this effect could be related to the formation of UrAc and CaOx stones.
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    Pro-inflammatory and oxidative effects of noncrystalline uric acid in human mesangial cells: contribution to hyperuricemic glomerular damage
    (Springer, 2011-02-01) Convento, M. S. [UNIFESP]; Pessoa, E. [UNIFESP]; Dalboni, Maria Aparecida [UNIFESP]; Borges, F. T. [UNIFESP]; Schor, N. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Hyperuricemia is associated with cardiovascular and renal diseases, as glomerulosclerosis. Noncrystalline uric acid induces deleterious effects on endothelial and vascular smooth muscle cells. in the present study, we analyzed the damage induced by UA on human mesangial cells (HMC), the potential mechanism involved in this injury, and its consequences during infection. HMC were exposed to noncrystalline UA (8 mg/dl) and/or lipopolysaccharide (LPS, 100 mu g/ml) for 24 h. in the experiments of cellular viability, HMC were exposed to 8-50 mg/dl of UA. Necrosis was assessed by acridine orange and ethidium bromide. Reactive oxygen species (ROS) were analyzed by 2',7'-dichlorofluorescein. Prostaglandin E2 (PGE2) was evaluated by ELISA. Cyclooxygenase 2 (COX-2) expression was assessed by real-time PCR. UA induced necrosis only at supraphysiological concentrations. Nevertheless, it significantly increased ROS production at 8 mg/dl. LPS increased necrosis and ROS production. Interestingly, the association between UA and LPS decreased ROS and necrosis. UA associated or not with LPS induced COX-2 expression and PGE2 increases in HMC. Results suggest that UA has pro- and anti-oxidant effects in HMC. During infections, it acts like scavenger increasing cellular viability, but alone it can induce ROS production and cellular death in higher concentrations. Additionally, UA has direct pro-inflammatory effects inducing COX-2 expression and PGE2 synthesis. It is concluded that elevated concentrations of uric acid potentially contributes to glomerular damage.