MARIANA MACIEL TORRES

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2
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Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina

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Agora exibindo 1 - 4 de 4
  • conferenceObject
    THE COMBINATION OF PROBIOTICS AND PREBIOTICS SUPPLEMENTATION IMPROVES LIPID METABOLISM, NAFLD AND OBESITY IN OB/OB MICE
    (2015) STEFANO, J. T.; TORRES, M. M.; PEREIRA, I. V. A.; JIMENEZ, D.; MUNTANELLI, B.; MALTA, F. M.; COGLIATI, B.; PINHO, J. R. R.; CARRILHO, F. J.; OLIVEIRA, C. P.
  • conferenceObject
    INTRATUMORAL INJECTION OF S-NITROSO-N-ACETYLCYSTEINE (SNAC) IN A RODENT MODEL OF NON-ALCOHOLIC STEATOHEPATITIS (NASH)-RELATED HEPATOCELLULAR CARCINOMA (HCC)
    (2014) STEFANO, J. T.; TORRES, M. M.; PEREIRA, I. V. A.; COGLIATI, B.; OLIVEIRA, M. G. de; CHAMMAS, C.; CARRILHO, F. J.; OLIVEIRA, C. P.
  • article 20 Citação(ões) na Scopus
    Sorafenib prevents liver fibrosis in a non-alcoholic steatohepatitis (NASH) rodent model
    (2015) STEFANO, J. T.; PEREIRA, I. V. A.; TORRES, M. M.; BIDA, P. M.; COELHO, A. M. M.; XERFAN, M. P.; COGLIATI, B.; BARBEIRO, D. F.; MAZO, D. F. C.; KUBRUSLY, M. S.; D'ALBUQUERQUE, L. A. C.; SOUZA, H. P.; CARRILHO, F. J.; OLIVEIRA, C. P.
    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 (PGC1 alpha) 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 PGC1 alpha 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 PGC1 alpha expression, improved mitochondrial respiration and prevented collagen deposition. It may, therefore, be useful in the treatment of liver fibrosis in NASH.
  • conferenceObject
    Sorafenib improves liver mitochondrial dysfunction attenuating liver fibrosis in non-alcoholic steatohepatitis (NASH) model
    (2012) STEFANO, Jose Tadeu; PEREIRA, Isabel V.; COELHO, Ana Maria M.; XERFAN, Mariana P.; BARBEIRO, Denise F.; TORRES, Mariana Maciel; BIDA, Patricia Martins; MAZO, Daniel F.; COGLIATI, Bruno; SOUZA, Heraldo Possolo; D'ALBUQUERQUE, Luiz C.; CARRILHO, Flair J.; OLIVEIRA, Claudia P.
    Background/Aim: Mitochondria dysfunction in liver may play an important role in the induction of NASH and fibrosis. Recent evidences have shown that kinase inhibitors are able to inhibit angiogenesis, a key mechanism in fibrosis development. We investigated the role of sorafenib as an antifibrotic agent in a rodent model of NASH. Methods: Adult Sprague-Dawley rats, weighing 250-300g, were fed a choline-deficient high fat diet (CDHFD)(35% total fat, 54% trans fatty acid enriched) and simultaneously exposed to diethylnitrosamine (DEN)(100 mg/Kg) in drinking water during 6 weeks to induce NASH and fibrosis. Sorafenib group (n=10) received sorafenib 2.5 mg/kg/day; NASH group (n=10) received CDHFD plus DEN by daily gavage. Control group (n=4) was fed a standard diet. After this period the animals were sacrificed and liver tissues were collected for histologic examination, mRNA isolation and analysis of mitochondrial function. Genes related to fibrosis [matrix metalloproteinases-9 (MMP-9), tissue inhibitor of matrix metalloproteinases 1 and 2 (TIMP-1 and 2)], oxidative stress [Heat Shock Protein 60 and 90 (HSP-60 and 90)] and mitochondrial biogenesis [peroxisome proliferator-activated receptorgamma co-activator 1 α (PGC-1 α )] were evaluated by RT-qPCR method. Liver mitochondrial oxidation and phosphorylation activities were measured by polarographic method. Results: Sorafenib treatment restored the liver mitochondrial function almost similar with control group, and increased RCR and state 3 respiration in comparison to NASH group (Table 1). Besides, sorafenib upregulated PGC-1 α (p<0,001), a gene related to mitochondrial biogenesis. In the other side, TIMP-2 gene expression also was upregulated (p=0,026). There was no difference in expression of HSP-60 (p=0,447), HSP-90 (p=0,141), TIMP-1 (p=0,623) and MMP-9 (p=0,623) between both groups. All of the animals treated with sorafenib showed a significant lost weight and a decreased of fibrosis score in comparison to control (p<0.05). Conclusions: 1) Treatment with sorafenib reduced fibrosis in a rodent model of NASH; 2)Sorafenib increased mRNA expression of PGC-1α and TIMP-2. 3) Sorafenib treatment improves liver mitochondrial dysfunction. Considering that PGC1 α coordinates gene expression that stimulates mitochondrial biogenesis and the TIMP-2 abrogates endothelial cell proliferation and blocks angiogenesis, sorafenib could be used in the treatment of liver fibrosis and prevent fibrosis in this model.