gamma-linolenic-acid and Fibrosis

To investigate the effects of Borage oil on cardiac remodeling after myocardial infarction (MI).. Male Wistar rats underwent ligation of the left coronary artery and divided into three groups: MI (control), BO-18 (18 mg/kg of borage oil) and BO-180 (180 mg/kg of borage oil). After seven days, heart was arrested in diastole and processed for histological evaluation of: MI size, LV dilation, myocyte hypertrophy, inflammatory infiltration and fibrosis in MI region and in remote region. The relative weight of the lung was used as a marker of heart failure. The MI size was comparable among groups.. Compared to control, BO treated groups showed lower weight of heart and lungs, reduced LV dilation and myocyte hypertrophy. Hemodynamic measurements were comparable. The treatment attenuated the inflammatory infiltration and fibrosis in remote myocardium.. Borage oil attenuates progression of cardiac remodeling after myocardial infarction and congestive heart failure.

Topics: Animals; Anti-Inflammatory Agents; Fibrosis; gamma-Linolenic Acid; Heart Failure; Heart Ventricles; Lung; Male; Models, Animal; Myocardial Infarction; Myocytes, Cardiac; Organ Size; Plant Oils; Rats, Wistar; Ventricular Remodeling

Fibrosis is induced by the excessive and abnormal deposition of extracellular matrix (ECM) with various growth factors in tissues. Transforming growth factor beta 1 (TGF-β1), plays a role in inducing apoptosis, modulates fibrosis, and ECM accumulation. Plasminogen activator inhibitor 1 (PAI-1) plays an important role in the development hepatic fibrosis. The overexpression of PAI-1 induces ECM accumulation, the main hallmark of chronic liver diseases. Death of hepatocytes is a characteristic feature of chronic liver disease due to various causes. The TGF-β1-mediated apoptotic pathway is regarded as a promising therapeutic target in hepatic fibrosis. Gamma-linolenic acid (GLA) is of special interest as it possesses anti-fibrosis, anti-inflammatory, and anti-cancer properties. However, the precise mechanism for GLA in chronic liver disease is not still clear. The aim of the present study was to determine whether GLA prevents hepatic PAI-1 expression and apoptosis through the inhibition of TGF-β1-mediated molecular mediators. GLA attenuated TGF-β1-stimulated PAI-1 expression, and inhibited PAI-1 promoter activity in AML12 cells. This effect was mediated by Smad3/4, the p38 pathways. We also found that GLA suppressed TGF-β1-induced apoptotic activation of the Bcl-2 family and caspase family of proteins, which resulted in the inhibition of poly-ADP-ribose polymerase 1 cleavage. GLA ameliorates the pro-fibrotic and pro-apoptotic effects of TGF-β1 in hepatocytes, suggesting GLA exerts a protective effect on hepatocytes and has a therapeutic potential for the treatment of chronic liver disease.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Cell Line; Fibrosis; gamma-Linolenic Acid; Gene Expression Regulation; Hepatocytes; Inflammation; Mice; Mitochondria; p38 Mitogen-Activated Protein Kinases; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Promoter Regions, Genetic; Protein Binding; Proto-Oncogene Proteins c-bcl-2; Serpin E2; Signal Transduction; Smad3 Protein; Smad4 Protein; Transforming Growth Factor beta1