Rosiglitazona, agonista do PPAR-y "Peroxisome Proliferator-Activated Receptor-y" reverte a nefrotoxicidade induzida pelo tenofovir-DF / The peroxisome proliferator-activated receptor-y agonist rosiglitazone reverses tenofovir-induced nephrotoxicity

AUTOR(ES)

Alexandre Braga Libório

DATA DE PUBLICAÇÃO

2008

RESUMO

Objective: To characterize the mechanisms of tenofovir disoproxil fumarate (TDF)- induced nephrotoxicity and the protective effects of rosiglitazone (RSG), a peroxisome proliferator-activated receptor-y agonist. Methods: Rats were treated for 30 days with one of two TDF doses (50 or 300 mg/kg of food), to which RSG (92 mg/kg of food) was added for the last 15 days. Biochemical parameters were measured, and renal tissue was extracted for immunoblotting. Results: Mean daily ingestion was comparable among all the treated groups. Highdose TDF induced severe renal failure accompanied by reduced expression of endothelial nitric-oxide synthase and intense renal vasoconstriction. All of these features were ameliorated by RSG administration. Low-dose TDF did not alter the glomerular filtration rate but induced significant phosphaturia, proximal tubular acidosis and polyuria, as well as reducing urinary concentrating ability. These alterations were caused by specific downregulation of the sodium-phosphorus cotransporter, sodium/hydrogen exchanger 3 and aquaporin 2. No Fanconis syndrome was identified (proteinuria was normal and there was no glycosuria). Treatment with RSG reversed TDF-induced tubular nephrotoxicity, normalizing urinary biochemical parameters and membrane transporter protein expression. Conclusion: These findings have potential clinical applications in patients presenting with TFV-induced nephrotoxicity, especially in those presenting with hypophosphatemia or a reduction in glomerular filtration rate.

ASSUNTO(S)

hiv capacidade de concentração renal drug induced abnormalities hiv antiretrovirais/ efeitos adversos renal failure anormalidades induzidas por drogas antiretroviral/adverse effects renal concentration ability phosphate metabolism disturbs peroxisome proliferators activated receptor distúrbios do metabolismo do fósforo ratos insuficiência renal rats receptores ativados por proliferador de peroxissomo

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