RESUMO
OBJECTIVE: To test the effects of peginterferon in an unrecoverable model of bile-duct ligation (BDL) induced liver fibrosis. MATERIAL AND METHODS: Thirty-seven Wistar rats were divided into five groups: group 1, BDL + peginterferon (n = 8); group 2, BDL (n = 8); group 3, sham + peginterferon (n = 7); group 4, sham (n = 7); and group 5, control group (n = 7). Peginterferon-alpha 2b (50 microgr/kg) or saline (1 mL/kg) was administered intraperitonealy every week for four weeks. Serum biochemical markers, liver tissue oxidative stress, collagen and transforming growth factor-beta (TGF-beta) levels were examined after four weeks. Liver slides were stained by hematoxylin and eosin and Masson trichrome\Gomory reticulum staining. RESULTS: The levels of tissue collagen, TGF-beta, biochemical markers (AST, ALT, bilirubins, alkaline phosphates, gamma-glutamyl transpeptidase) and oxidative stress markers (Malondialdehyde, luminal, lucigenin) of the BDL group were higher than the sham operated and control groups (all-p < 0.001). Peginterferon improved malondialdehyde, luminal and glutathione levels in the BDL + peginterferon group (p < 0.05). Histopathological examination of the BDL groups showed stage-3 fibrosis, while all the control groups were normal. Peginterferon showed no improvement in fibrosis either histologically, or biochemically. CONCLUSIONS: Peginterferon improved levels of malondialdehyde, glutathione and luminal in the rat model of BDL induced liver fibrosis. Peginterferon however,showed no anti-fibrotic effects in this model and therefore may not be a useful treatment for liver fibrosis.
Assuntos
Interferon-alfa/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Fígado/patologia , Polietilenoglicóis/uso terapêutico , Animais , Ductos Biliares , Colágeno/metabolismo , Modelos Animais de Doenças , Glutationa/metabolismo , Interferon alfa-2 , Interferon-alfa/farmacologia , Ligadura , Fígado/efeitos dos fármacos , Fígado/metabolismo , Cirrose Hepática/etiologia , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Polietilenoglicóis/farmacologia , Ratos , Ratos Wistar , Proteínas Recombinantes , Fator de Crescimento Transformador beta/metabolismo , Resultado do TratamentoRESUMO
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a prevalent condition associated with obesity and insulin resistance (IR). Leptin plays a key role in the control of energy balance, and insulin sensitivity. In this study, we aimed to examine whether serum leptin levels correlate with insulin resistance, oxidative stress parameters and the severity of histological changes in NAFLD. METHODS: Fifty-two patients (M/F: 28/24) with no alcohol intake and biopsy-proven diagnosis of NAFLD were studied. Serum leptin levels were measured by radioimmunoassay. HOMA (homeostasis model assessment) IR index was calculated. Comparisons between the patients with NAFLD and non-alcoholic steatohepatitis (NASH) were performed using the Student's t test. Multivariate regression analysis and the area under the receiver operating characteristic (ROC) curve were used to identify the independent predictors for NASH. RESULTS: We found no association between serum leptin, fasting insulin levels, and oxidative stress parameters. ROC curve and multiple regression analysis revealed no association between the severity of histological changes and serum leptin levels. During six months followed-up period only NASH group with elevated leptin levels had significant reductions of ALT and AST values (p = 0.03, and 0.005, respectively). CONCLUSION: Our findings show a preventive effect of leptin against progressive liver injury in NAFLD.