JOSE TADEU STEFANO
Projetos de Pesquisa
Unidades Organizacionais
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
Agora exibindo 1 - 5 de 5
- Ischemic Preconditioning-Like Effect of Polyunsaturated Fatty Acid-Rich Diet on Hepatic Ischemia/Reperfusion Injury(2011) COELHO, Ana Maria Mendonca; MACHADO, Marcel Cerqueira Cesar; TAKAHASHI, Hilton Kenji; SAMPIETRE, Sandra N.; STEFANO, Jose Tadeu; LEITE, Andre Zonetti A.; CURI, Rui; D'ALBUQUERQUE, Luiz A. CarneiroAim The aim of this study was to investigate a possible preconditioning effect of oral diet enriched with polyunsaturated fatty acids (PUFAs) on liver ischemia/reperfusion (I/R) injuries. Methods Wistar male rats were fed a standard diet or polyunsaturated fatty acid-rich diet (PRD) enriched with (GII) or without (GIII) omega-3 PUFA. Rats were submitted to partial liver ischemia during 1 h and evaluated in pre- and post-I/R conditions. In pre-I/R condition, livers were collected for determination of fatty acid composition, liver mitochondrial function, malondialdehyde (MDA) content, and histological analysis. Four hours after liver reperfusion serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), serum levels of tumor necrosis factor-alpha, interleukin-6, interleukin-10, and prostaglandin-E2, liver mitochondrial function, MDA content, and histology were evaluated. Results In the pre-I/R condition, GII and GIII groups had an increase on PUFA content and exhibited slight increased macrosteatosis and microsteatosis in the liver. After 4 h of reperfusion, PRD-fed rats showed a marked decrease on steatosis, diminished necrosis, an increase in MDA formation, and mitochondrial uncoupling. We also observed a marked decrease in plasma levels of cytokines and ALT and AST activities in post-I/R condition in PRD groups. Conclusion In this experimental model in the rat, PRD has a preconditioning effect protecting the liver from I/R injury and should be object of future clinical studies.
- Microsomal triglyceride transfer protein and nonalcoholic fatty liver disease(2011) PEREIRA, Isabel V. A.; STEFANO, Jose T.; OLIVEIRA, Claudia P. M. S.Nonalcoholic fatty liver disease is currently one of the most common forms of liver disease, covering cases from simple steatosis without inflammation, to cases of steatohepatitis and fibrosis, and may lead to liver cirrhosis and hepatocellular carcinoma. The pathophysiology of nonalcoholic fatty liver disease is based on multiple events; changes in the secretion of lipoproteins can lead to steatosis. Liver lipid secretion is mediated by apoB100 and microsomal triglyceride transfer protein (MTP). The pharmacological suppression of MTP is suggested as a possible treatment for hyperlipidemia, although the upregulation of this protein can be a treatment for nonalcoholic steatohepatitis.
- Survivin expression patterns could reflect different roles in hepatocarcinogenesis, especially in non-alcoholic fatty liver disease-related hepatocellular carcinoma(2011) STEFANO, Jose T.; OLIVEIRA, Claudia P.; CARRILHO, Flair J.; ALVES, Venancio A. F.
- S-Nitroso-N-acetylcysteine induces de-differentiation of activated hepatic stellate cells and promotes antifibrotic effects in vitro(2011) STEFANO, J. T.; COGLIATI, B.; SANTOS, F.; LIMA, V. M. R.; MAZO, D. C.; MATTE, U.; ALVARES-DA-SILVA, M. R.; SILVEIRA, T. R.; CARRILHO, F. J.; OLIVEIRA, C. P. M. S.Nitric oxide (NO) has been shown to act as a potent antifibrogenic agent by decreasing myofibroblast differentiation. S-Nitroso-N-acetylcysteine (SNAC), a NO donor, attenuates liver fibrosis in rats, but the cellular and molecular mechanisms on liver myofibroblast-like phenotype still remain unknown. Here, we investigate the antifibrotic effects of SNAC on hepatic stellate cells, the major fibrogenic cell type in the liver. A murine GRX cell line was incubated with SNAC (100 mu M) or vehicle (control group) for 72 h. Cell viability was measured by MTT colorimetric assay and the conversion of myofibroblast into quiescent fat-storing cell phenotype was evaluated by Oil-Red-O staining. TGF beta-1, TIMP-1, and MMP-13 levels were measure in the supernatant by ELISA. Profibrogenic- and fibrolytic-related gene expression was quantified using real-time qPCR. SNAC induced phenotype conversion of myofibroblast-like phenotype into quiescent cells. SNAC decreased gene and protein expression of TGF beta-1 and MMP-2 compared to control groups. Besides, SNAC down-regulated profibrogenic molecules and up-regulated MMP-13 gene expression, which plays a key role in the degradation of interstitial collagen in liver fibrosis. In conclusion, these findings demonstrate that SNAC efficiently can modulate the activation and functionality of murine hepatic stellate cells and could be considered as an antifibrotic treatment to human liver fibrosis.
- Decreased immunoexpression of survivin could be a potential marker in human non-alcoholic fatty liver disease progression?(2011) STEFANO, Jose T.; OLIVEIRA, Claudia P. M. S. de; CORREA-GIANNELLA, Maria L.; SOARES, Ibere C.; KUBRUSLY, Marcia S.; BELLODI-PRIVATO, Marta; MELLO, Evandro S. de; LIMA, Vicencia M. R. de; CARRILHO, Flair J.; ALVES, Venancio A. F.Background/aim Regulation of apoptosis in non-alcoholic fatty liver disease (NAFLD) has been a theme of growing debate. Although no other study assessed the role of survivin in NAFLD, its expression has been reported in hepatic carcinogenesis because of other aetiological factors with relevant discrepancies. The aim of this study was to assess the pattern of survivin immunoexpression by tissue microarray along the whole spectrum of NAFLD, including non-alcoholic steatohepatitis (NASH)-related hepatocelular carcinoma (HCC). Methods Liver biopsies from 56 patients with NAFLD were evaluated: 18 with steatosis, 21 non-cirrhotic NASH, 10 NASH-related cirrhosis, seven NASH-related HCC, as compared with 71 HCC related to other causes and with 12 normal livers. Results Survivin immunoexpression in NAFLD was restricted to cytoplasm and was found to be progressively lower in advanced stages, including cirrhosis and HCC: steatosis vs NASH-related cirrhosis (P=0.0243); steatosis vs NASH-related HCC (P=0.0010); NASH vs NASH-related cirrhosis (P=0.0318); and NASH vs NASH-related HCC (P=0.0007), thus suggesting a deregulation of apoptosis from NAFLD towards HCC. Interestingly, survivin immunoreactivity in NASH-related HCC was also found to be significantly lower than in HCC related to other causes (P < 0.05). Remarkably, nuclear staining for survivin was not detected in any case of NAFLD, contrasting to its presence in all other cases of HCC. Conclusions Survivin immunoexpression in NASH-related HCC is herein originally found substantially different than in HCC related to other causes, thus requiring further studies to elucidate the role of survivin in human NAFLD progression.