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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 8
Affiliation:
[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
Total Affiliations: 3
Document type: Journal article
Source: Brazilian Journal of Medical and Biological Research; v. 42, n. 11, p. 1027-1034, NOV 2009.
Web of Science Citations: 5
Abstract

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)