Use of Uric Acid-Lowering Agents Limits Experimental Cyclosporine Nephropathy

dc.creatorMazali, FC
dc.creatorJohnson, RJ
dc.creatorMazzali, M
dc.date2012
dc.date2014-07-30T19:07:28Z
dc.date2015-11-26T16:55:29Z
dc.date2014-07-30T19:07:28Z
dc.date2015-11-26T16:55:29Z
dc.date.accessioned2018-03-28T23:42:52Z
dc.date.available2018-03-28T23:42:52Z
dc.identifierNephron Experimental Nephrology. Karger, v. 120, n. 1, n. E12, n. E19, 2012.
dc.identifier1660-2129
dc.identifierWOS:000302403600002
dc.identifier10.1159/000330274
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/73030
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/73030
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1277135
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionBackground: Hyperuricemia frequently complicates cyclosporine (CsA) therapy. Previous studies have shown that hyperuricemia exacerbates interstitial and vascular lesions in the cyclosporine model. We tested the hypothesis that normalization of uric acid could prevent the development of cyclosporine toxicity. Methods: CsA nephropathy was induced by administering CsA (15 mg/kg/day) for 7 weeks to rats on a low salt diet (CsA group). The effect of preventing hyperuricemia was determined by concomitant treatment with a xanthine oxidase inhibitor, allopurinol (CsAALP), or with a uricosuric, benzbromarone (CsABENZ), in drinking water. Control groups included vehicle-treated rats. Results: CsA-treated rats developed mild hyperuricemia with arteriolar hyalinosis, tubular atrophy, striped interstitial fibrosis, increased cell proliferation and decreased VEGF expression. Treatment with allopurinol or benzbromarone limited renal disease, with reduced interstitial fibrosis, cell proliferation, macrophage infiltration, osteopontin expression and arteriolar hyalinosis, in association with restoration of VEGF expression. Both drugs provided comparable protection. Conclusions: An increase in uric acid exacerbates CsA nephropathy in the rat. Concomitant treatment with allopurinol or benzbromarone reduced the severity of renal disease. The similar protection observed with both drugs suggests that the effect is associated more with lowering uric acid levels than the antioxidant effect of allopurinol. Copyright (C) 2011 S. Karger AG, Basel
dc.description120
dc.description1
dc.descriptionE12
dc.descriptionE19
dc.descriptionNIH [HL-68607, DK-52121, HL-79352]
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionNIH [HL-68607, DK-52121, HL-79352]
dc.descriptionFAPESP [04/05026-9, 07/055084-3]
dc.languageen
dc.publisherKarger
dc.publisherBasel
dc.publisherSuíça
dc.relationNephron Experimental Nephrology
dc.relationNephron Exp. Nephrol
dc.rightsfechado
dc.rightshttp://www.karger.com/Services/RightsPermissions
dc.sourceWeb of Science
dc.subjectCyclosporine
dc.subjectUric acid
dc.subjectArteriolar hyalinosis
dc.subjectTubulointerstitial fibrosis
dc.subjectAzathioprine-antilymphocyte Globulin
dc.subjectRenal-allograft Recipients
dc.subjectIndependent Mechanism
dc.subjectProspective Trial
dc.subjectAngiotensin-ii
dc.subjectBlood-pressure
dc.subjectHyperuricemia
dc.subjectNephrotoxicity
dc.subjectTransplantation
dc.subjectGout
dc.titleUse of Uric Acid-Lowering Agents Limits Experimental Cyclosporine Nephropathy
dc.typeArtículos de revistas


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