Sorafenib prevents liver fibrosis in a non-alcoholic steatohepatitis (NASH) rodent model
Braz. j. med. biol. res
; 48(5): 408-414, 05/2015. graf
Article
em En
| LILACS
| ID: lil-744374
Biblioteca responsável:
BR1.1
ABSTRACT
Liver fibrosis occurring as an outcome of non-alcoholic steatohepatitis (NASH) can precede the development of cirrhosis. We investigated the effects of sorafenib in preventing liver fibrosis in a rodent model of NASH. Adult Sprague-Dawley rats were fed a choline-deficient high-fat diet and exposed to diethylnitrosamine for 6 weeks. The NASH group (n=10) received vehicle and the sorafenib group (n=10) received 2.5 mg·kg-1·day-1 by gavage. A control group (n=4) received only standard diet and vehicle. Following treatment, animals were sacrificed and liver tissue was collected for histologic examination, mRNA isolation, and analysis of mitochondrial function. Genes related to fibrosis (MMP9, TIMP1, TIMP2), oxidative stress (HSP60, HSP90, GST), and mitochondrial biogenesis (PGC1α) were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Liver mitochondrial oxidation activity was measured by a polarographic method, and cytokines by enzyme-linked immunosorbent assay (ELISA). Sorafenib treatment restored mitochondrial function and reduced collagen deposition by nearly 63% compared to the NASH group. Sorafenib upregulated PGC1α and MMP9 and reduced TIMP1 and TIMP2 mRNA and IL-6 and IL-10 protein expression. There were no differences in HSP60, HSP90 and GST expression. Sorafenib modulated PGC1α expression, improved mitochondrial respiration and prevented collagen deposition. It may, therefore, be useful in the treatment of liver fibrosis in NASH.
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Texto completo:
1
Coleções:
01-internacional
Temas:
Aperfeicoar_gestao_SUS
Contexto em Saúde:
11_ODS3_cobertura_universal
/
1_ASSA2030
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2_ODS3
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8_ODS3_consumo_sustancias_psicoactivas
Base de dados:
LILACS
Assunto principal:
Custos de Cuidados de Saúde
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Transtornos Relacionados ao Uso de Substâncias
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Transtorno Depressivo Maior
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Acessibilidade aos Serviços de Saúde
Tipo de estudo:
Diagnostic_studies
Aspecto:
Determinantes_sociais_saude
Limite:
Adolescent
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Adult
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Female
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Humans
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Male
País/Região como assunto:
America do norte
Idioma:
En
Revista:
Braz. j. med. biol. res
Ano de publicação:
2015
Tipo de documento:
Article