Efeitos antifibróticos do extrato de Curatella americana L. sobre as células estreladas hepáticas

Abstract

Hepatic fibrosis is characterized as a healing process in which hepatic stellate cells (HSCs) are activated in response to liver damage and begin to express a myofibroblast-like phenotype. The Curatella americana L., a plant commonly found in the Cerrado region, presents antioxidant activity already demonstrated by our group. In this context, the objective of this study was to investigate the effect of the hydromethanolic extract of the inner stem bark of Curatella americana L. on parameters associate the activation of HSCs in response to oxidative stress. For this we used the GRX line as the HSC model and the cultures were treated with different concentrations (10 ug/mL to 5000 ug/mL) of extract added to the culture medium by different time periods according to the objective of the experiment. The antioxidant capacity of the extract was evaluated, in vitro, by the quantification of lipid peroxidation (TBARS). Intracellular ROS level was determined by using fluorescent probe dichlorodihydrofluorescein diacetate (DCFH-DA). Cytotoxicity was assessed by MTT, density by staining with sulforhodamine B, proliferation by counting viable cells with trypan blue. Adhesion and cell migration were evaluated in a static cytometer. Results demonstrated that the extract was able to protect the lipid of the induced damage, by the action of hydrogen peroxide, in all concentrations tested. However, at high concentrations it also acts as a pro-oxidant, increasing the basal production of ROS and reducing cell viability. At concentrations of up to 2000 μg/mL the extract does not altered the cell viability, however it modified the rate of proliferation, motility and migratory capacity of the cells. These data suggest that the extract of Curatella americana L. exerts a double effect on the redox status in the HSCs depending on the concentration used, acting as antioxidant and preventing the activation of these cells or as a prooxidant and directing the cells activated for apoptosis.