Allopurinol attenuates acute kidney injury following Bothrops jararaca envenomation

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art_GOIS_Allopurinol_attenuates_acute_kidney_injury_following_Bothrops_jararaca_2017.PDF (10.35 MB)
Citações na Scopus
10
Tipo de produção
article
Data de publicação
2017
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
PUBLIC LIBRARY SCIENCE
Autores
MARTINES, Monique Silva
FERREIRA, Daniela
MALAQUE, Ceila
Citação
PLOS NEGLECTED TROPICAL DISEASES, v.11, n.11, article ID e0006024, 15p, 2017
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Snakebites have been recognized as a neglected public health problem in several tropical and subtropical countries. Bothrops snakebites frequently complicate with acute kidney injury (AKI) with relevant morbidity and mortality. To date, the only treatment available for Bothrops envenomation is the intravenous administration of antivenom despite its several limitations. Therefore, the study of novel therapies in Bothrops envenomation is compelling. The aim of this study was to evaluate the protective effect of Allopurinol (Allo) in an experimental model of Bothrops jararaca venom (BJ)-associated AKI. Five groups of Wistar rats were studied: Sham, Allo, BJ, BJ+Allo, BJ+ipAllo. BJ (0.25 mg/kg) was intravenously injected during 40'. Saline at same dose and infusion rate was administered to Sham and Allo groups. Allo and BJ+Allo groups received Allo (300 mg/L) in the drinking water 7 days prior to Saline or BJ infusion respectively. BJ+ipAllo rats received intraperitoneal Allo (25 mg/Kg) 40' after BJ infusion. BJ rats showed markedly reduced glomerular filtration rate (GFR, inulin clearance) associated with intense renal vasoconstriction, hemolysis, hemoglobinuria, reduced glutathione and increased systemic and renal markers of nitro-oxidative stress (Nitrotyrosine). Allo ameliorated GFR, renal blood flow (RBF), renal vascular resistance and arterial lactate levels. In addition, Allo was associated with increased serum glutathione as well as reduced levels of plasma and renal Nitrotyrosine. Our data show that Allo attenuated BJ-associated AKI, reduced oxidative stress, improved renal hemodynamics and organ perfusion. It might represent a novel adjuvant approach for Bothrops envenomation, a new use for an old and widely available drug.
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URI
https://observatorio.fm.usp.br/handle/OPI/25744
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Coleções
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/12
Artigos e Materiais de Revistas Científicas - LIM/13
Artigos e Materiais de Revistas Científicas - ODS/03
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