Effect of pentoxifylline on the fibrogenic functions of cultured rat liver fat-storing cells and myofibroblasts

The effects of pentoxifylline (PTX) an analogue of the methylxanthine theobromine, on basic fibrogenic reactions of cultured fat-storing cells and myofibroblasts (MFB), the cell types most important for the excessive production of extracellular matrix components in fibrosing liver, were studied. The proliferation of MFB (i.e activated, transdifferentiated fat-storing cells) was more dose-dependently inhibited by pentoxifylline than that of unactivated fat-storing cells (ED(50) 50 mu g/mL). In addition, PTX retarded the transdifferentiation of fat-storing cells into smooth muscle alpha-actin positive MFB, a 50% reduction in actin-positive cells being reached with concentrations of 0.5 mg PTX/mL medium. The transdifferentiation associated decrease in retinyl palmitate of cultured fat-storing cells was delayed by PTX. The synthesis of [S-35] sulfate-labeled glycosaminoglycans (GAG) and total and cellular fibronectin was not significantly reduced by treatment of MFB with PTX up to 1.0 mg/mL. It is concluded that PTX reduces the transdifferentiation of fat-storing cells to MFB and the proliferation of MFB, but leaves the synthesis of extracellular matrix: components GAG and fibronectin unaffected. The effect of PTX on the former reactions might account for the reported antifibrogenic properties of this drug in experimental hepatic fibrogenesis.