Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-11-01T21:08:44Z No. of bitstreams: 1 ViniciusBarretoGarcia_DISSERT.pdf: 3420241 bytes, checksum: 521464fbb3b5ad4dcf8800370812b249 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-11-07T00:13:01Z (GMT) No. of bitstreams: 1 ViniciusBarretoGarcia_DISSERT.pdf: 3420241 bytes, checksum: 521464fbb3b5ad4dcf8800370812b249 (MD5) / Made available in DSpace on 2017-11-07T00:13:01Z (GMT). No. of bitstreams: 1 ViniciusBarretoGarcia_DISSERT.pdf: 3420241 bytes, checksum: 521464fbb3b5ad4dcf8800370812b249 (MD5) Previous issue date: 2017-06-23 / A Doen?a Hep?tica Alco?lica (DHA) corresponde a diversas patologias hep?ticas revers?veis e irrevers?veis que ocorrem em resposta ? ingest?o do etanol, dentre elas a esteato-hepatite alco?lica que, embora revers?vel, ainda n?o possui terapia farmacol?gica espec?fica. O objetivo deste estudo foi avaliar os efeitos hepatoprotetores do carvedilol (CARV) em ratos com esteato-hepatite alco?lica. Para isso, ratos Wistar foram divididos em 5 grupos: controle negativo, controle positivo, CARV 1mg, CARV 3mg e CARV 5mg (5 animais por grupo ? sendo os grupos CARV duplicados). Durante 28 dias consecutivos os animais foram submetidos ? gavagem oral de solu??o salina (NaCl 0,9% - controle negativo) ou solu??o alco?lica a 30%, 7g/kg (grupo controle positivo e grupos CARV). Os grupos CARV recebiam a dose respectiva do f?rmaco por gavagem 1h antes da solu??o alco?lica. O sangue dos animais foi coletado via pun??o card?aca para dosagem de triglicer?deos (TG) e transaminases hep?ticas (AST e ALT) e as amostras hep?ticas foram submetidas ? an?lise colorim?trica do malonalde?do (MDA), mieloperoxidase (MPO) e glutationa reduzida (GSH), ? an?lise imuno-enzim?tica (ELISA) das citocinas Interleucina 1 beta (IL-1?), fator de necrose tumoral alfa (TNF-?) e interleucina 10 (IL-10), ? PCR quantitativa em tempo real (RT-qPCR) dos genes pr?-col?genos I e III, Fator Nuclear ?B (NF- ?B) e TNF-? e ? an?lise histopatol?gica por Hematoxilina e Eosina, Picro-Sirius, Imuno-histoqu?mica para COX-2, RANK, RANKL, IBA-1, ICAM-1, SOCS-1, SOD-1 e GPx-1 e imunofluoresc?ncia para IL-1? e NF- ?B. Todas as t?cnicas utilizadas demonstraram que o efeito hepatoprotetor do carvedilol se d? por meio da regula??o que ele desempenha sobre as C?lulas de Kupffer e C?lulas Estreladas, levando a respostas anti-inflamat?rias, antioxidantes e anti-fibr?ticas. / Alcoholic liver disease (DHA) corresponds to several reversible and irreversible liver diseases that occur in response to ethanol intake, among them alcoholic steatohepatitis which, although reversible, does not have specific pharmacological therapy yet. The aim of this study was to evaluate the hepatoprotective effects of carvedilol (CARV) in rats with alcoholic steatohepatitis. Therefore, Wistar rats were divided into 5 groups: negative control, positive control, CARV 1mg, CARV 3mg and CARV 5mg (5 animals per group - the CARV groups being duplicated). During 28 consecutive days the animals were submitted to oral gavage of saline solution (NaCl 0.9% - negative control) or alcohol solution at 30%, 7g / kg (positive control group and CARV groups). The CARV groups received a more adequate dose to the drug by gavage 1h before the alcoholic solution. The blood of the animals was collected via cardiac puncture for the determination of triglycerides (TG) and hepatic transaminases (AST and ALT), and as hepatic samples were submitted to colorimetric analysis of malonaldehyde (MDA), myeloperoxidase (MPO) and reduced glutathione (GSH), immunoenzymatic analysis (ELISA) of the cytokines Interleukin 1 beta (IL-1?), tumor necrosis factor alpha (TNF-?) and interleukin-10 (IL-10), real-time quantitative PCR (RT-qPCR) of Pro-collagen I and III genes, Nuclear Factor ?B (NF-?B) and TNF-? and hertopathological analysis by Hematoxylin and Eosin, Picro-Sirius, Immunohistochemistry for COX-2, RANK, RANKL, IBA-1, ICAM -1, SOCS-1, SOD-1 and GPx-1 and immunofluorescence for IL-1? and NF-?B. All techniques demonstrated that the hepatoprotective effect of carvedilol occurs through the regulation it plays on as Kupffer Cells and Star Cells, leading to anti-inflammatory, antioxidant and anti-fibrotic responses.