Modulation of extracellular matrix by nutritional hepatotrophic factors in thioacetamide-induced liver cirrhosis in the rat

Autor(es)

Guerra, R. R. ^[1] ; Trotta, M. R. ^[1] ; Parra, O. M. ^[1] ; Avanzo, J. L. ^[2] ; Bateman, A. ^[3] ; Aloia, T. P. A. ^[1] ; Dagli, M. L. Z. ^[2] ; Hernandez-Blazquez, F. J. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Vet & Zootecn, Dept Cirurgia, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med Vet & Zootecn, Dept Patol, Sao Paulo - Brazil

^[3] McGill Univ, Royal Victoria Hosp, MUHC, Dept Med, Montreal, PQ H3A 2T5 - Canada

• Tipo de documento: Artigo Científico
• Fonte: Brazilian Journal of Medical and Biological Research; v. 42, n. 11, p. 1027-1034, NOV 2009.
• Citações Web of Science: 5

Resumo

Nutritional substances associated to some hormones enhance liver regeneration when injected intraperitoneally, being denominated hepatotrophic factors (HF). Here we verified if a solution of HF (glucose, vitamins, salts, amino acids, glucagon, insulin, and triiodothyronine) can revert liver cirrhosis and how some extracellular matrices are affected. Cirrhosis was induced for 14 weeks in 45 female Wistar rats (200 mg) by intraperitoneal injections of thioacetamide (200 mg/kg). Twenty-five rats received intraperitoneal HF twice a day for 10 days (40 mL.kg(-1).day(-1)) and 20 rats received physiological saline. Fifteen rats were used as control. The HF applied to cirrhotic rats significantly: a) reduced the relative mRNA expression of the genes: Col-alpha 1 (-53%), TIMP-1 (-31.7%), TGF-beta 1 (-57.7%), and MMP-2 (-41.6%), whereas Plau mRNA remained unchanged; b) reduced GGT (-43.1%), ALT (-17.6%), and AST (-12.2%) serum levels; c) increased liver weight (11.3%), and reduced liver collagen (-37.1%), regenerative nodules size (-22.1%), and fibrous septum thickness. Progranulin protein (immunohistochemistry) and mRNA (in situ hybridization) were found in fibrous septa and areas of bile duct proliferation in cirrhotic livers. Concluding, HF improved the histology and serum biochemistry of liver cirrhosis, with an important reduction of interstitial collagen and increased extracelullar matrix degradation by reducing profibrotic gene expression. (AU)

• Processo FAPESP: 04/10972-0 - Efeito dos fatores hepatotroficos sobre a quantidade e distribuicao do colageno no figado de ratas (wistar) com cirrose induzida experimentalmente por tioacetamida.
• Beneficiário: Mauricio de Rosa Trotta
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 04/10971-4 - Uso de fatores hepatotróficos para o tratamento da cirrose hepática experimentalmente induzida por tioacetamida em fígado de Ratas Wistar
• Beneficiário: Francisco Javier Hernandez Blazquez
• Modalidade de apoio: Auxílio à Pesquisa - Regular