Efeitos hepatoprotetores do carvedilol em modelo de esteato-hepatite alcoólica induzida em ratos wistar

Abstract

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-1β), tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10), real-time quantitative PCR (RT-qPCR) of Pro-collagen I and III genes, Nuclear Factor κB (NF-κB) and TNF-α 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-1β and NF-κB. 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.