Pro-inflammatory and oxidative effects of noncrystalline uric acid in human mesangial cells: contribution to hyperuricemic glomerular damage

dc.contributor.authorConvento, M. S. [UNIFESP]
dc.contributor.authorPessoa, E. [UNIFESP]
dc.contributor.authorDalboni, Maria Aparecida [UNIFESP]
dc.contributor.authorBorges, F. T. [UNIFESP]
dc.contributor.authorSchor, N. [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:06:06Z
dc.date.available2016-01-24T14:06:06Z
dc.date.issued2011-02-01
dc.description.abstractHyperuricemia 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.en
dc.description.affiliationFed Univ São Paulo UNIFESP, Dept Med, Div Nephrol, BR-04023900 São Paulo, Brazil
dc.description.affiliationUnifespFed Univ São Paulo UNIFESP, Dept Med, Div Nephrol, BR-04023900 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFinanciadora de Estudos e Projetos (FINEP)
dc.description.sponsorshipFundacao Oswaldo Ramos (FOR)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.format.extent21-27
dc.identifierhttp://dx.doi.org/10.1007/s00240-010-0282-5
dc.identifier.citationUrological Research. New York: Springer, v. 39, n. 1, p. 21-27, 2011.
dc.identifier.doi10.1007/s00240-010-0282-5
dc.identifier.issn0300-5623
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/33401
dc.identifier.wosWOS:000286664000003
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofUrological Research
dc.rightsAcesso restrito
dc.rights.licensehttp://www.springer.com/open+access/authors+rights?SGWID=0-176704-12-683201-0
dc.subjectReactive oxygen speciesen
dc.subjectNoncrystalline uric aciden
dc.subjectCyclooxygenase 2en
dc.subjectMesangial cellsen
dc.subjectLipopolysaccharideen
dc.titlePro-inflammatory and oxidative effects of noncrystalline uric acid in human mesangial cells: contribution to hyperuricemic glomerular damageen
dc.typeArtigo
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