Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/200377
Type: Artigo de periódico
Title: Use Of Uric Acid-lowering Agents Limits Experimental Cyclosporine Nephropathy.
Author: Mazali, Fernanda Cristina
Johnson, Richard J
Mazzali, Marilda
Abstract: 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. 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. 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. 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.
Subject: Allopurinol
Animals
Benzbromarone
Cell Proliferation
Cyclosporine
Enzyme Inhibitors
Fibrosis
Hyperuricemia
Immunohistochemistry
Kidney
Kidney Diseases
Male
Osteopontin
Random Allocation
Rats
Rats, Sprague-dawley
Uric Acid
Uricosuric Agents
Vascular Endothelial Growth Factor A
Xanthine Oxidase
Rights: fechado
Identifier DOI: 10.1159/000330274
Address: http://www.ncbi.nlm.nih.gov/pubmed/22126908
Date Issue: 2012
Appears in Collections:Unicamp - Artigos e Outros Documentos

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