S-nitroso-N-acetylcysteine attenuates liver fibrosis in experimental nonalcoholic steatohepatitis

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Citações na Scopus
23
Tipo de produção
article
Data de publicação
2013
Título da Revista
ISSN da Revista
Título do Volume
Editora
DOVE MEDICAL PRESS LTD
Autores
OLIVEIRA, Marcelo G. de
COGLIATI, Bruno
SOUZA, Gabriela F. P. de
RABELO, Fabiola
Citação
DRUG DESIGN DEVELOPMENT AND THERAPY, v.7, p.553-563, 2013
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
S-Nitroso-N-acetylcysteine (SNAC) is a water soluble primary S-nitrosothiol capable of transferring and releasing nitric oxide and inducing several biochemical activities, including modulation of hepatic stellate cell activation. In this study, we evaluated the antifibrotic activity of SNAC in an animal model of nonalcoholic steatohepatitis (NASH) induced in Sprague-Dawley rats fed with a choline-deficient, high trans fat diet and exposed to diethylnitrosamine for 8 weeks. The rats were divided into three groups: SNAC, which received oral SNAC solution daily; NASH, which received the vehicle; and control, which received standard diet and vehicle. Genes related to fibrosis (matrix metalloproteinases [MMP]-13, -9, and -2), transforming growth factor beta-1 [TGF beta-1], collagen-1 alpha, and tissue inhibitors of metalloproteinase [TIMP-1 and -2] and oxidative stress (heat-shock proteins [HSP]-60 and -90) were evaluated. SNAC led to a 34.4% reduction in the collagen occupied area associated with upregulation of MMP-13 and -9 and downregulation of HSP-60, TIMP-2, TGF beta-1, and collagen-1 alpha. These results indicate that oral SNAC administration may represent a potential antifibrotic treatment for NASH.
Palavras-chave
S-nitroso-N-acetylcysteine, fibrogenesis, NASH, diethylnitrosamine
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