Evidence for a Possible Role of Lipid Peroxidation in Experimental Liver Fibrosis

Abstract

Liver fibrosis represents a common stage of several conditions of chronic active liver diseases, leading eventually to cirrhosis. Knowledge of the biology and of the pathobiology of fibrogenetic processes in mammalian liver has advanced significantly in the last decade, and we are beginning to understand the complex molecular network of cytokine-mediated cellular interactions which play a major role in the modulation of extracellular matrix deposition. Evidence, coming from both clinical and experimental studies, indicates that liver oxidative injury and, in particular, lipid peroxidation of polyunsaturated fatty acids of biological membranes, are often associated with liver fibrosis. In our laboratory we have shown that lipid peroxidation is associated with the development of the most commonly used experimental model of liver fibrosis, chronic administration of carbon tetrachloride (CCl4) to rats. Moreover, in the same experimental model, vitamin E supplementation, a procedure known to prevent lipid peroxidative processes, can afford significant protection against the production of aldehydic end-products of lipid peroxidation, as well as against the development of liver necrosis and collagen deposition. These effects of vitamin E seem also to be related to a decreased expression of transforming growth factor β1 (TGFβ1), the best known pro-fibrogenic cytokine. Finally,in vitro studies indicate that lipid peroxidation can modulate collagen synthesis by fibroblasts and, more important, by fat-storing cells. Thus, we suggest the possibility that, because of their activity on some transmembrane signalling systems and other cellular functions, aldehydic end-products of lipid peroxidation might act as molecular mediators in the process of liver fibrosis consequent on oxidative injuries.