4-hydroxy-2,3-alkenals as molecular mediators of oxidative stress in the pathogenesis of liver fibrosis (review).
4-hydroxy-2,3-alkenals (HAKs) are major end products of oxidative decomposition of omega-3 and omega-6 polyunsaturated fatty acids of membrane phospholipids, a process usually referred to as lipid peroxidation. These reactive aldehydic compounds have been unequivocally detected in vivo in either clinical or experimental conditions of chronic liver damage, suggesting an involvement of lipid peroxidation processes, elicited by either reactive oxygen intermediates (ROI) or by pro-oxidant agents, in the pathogenesis of liver fibrosis. Literature data provided by experimental studies with animal models of liver fibrosis or by studies performed on primary culture of human hepatic stellate cells (hHSC), which are known to play a major role in liver fibrogenesis, indicate that HAKs may sustain at molecular level the fibrogenic development of chronic liver diseases. These compounds may act as ultimate mediators of oxidative stress able to up-regulate the synthesis of extracellular matrix components and of growth factors, chemokines and cytokines, as well as to modulate functional responses of hepatic cell types involved in the progression of chronic liver diseases and to sustain chronic hepatitis.
Parola
M
M
Dipartimento di Medicina e Oncologia Sperimentale, Universita degli Studi di Torino, I-10125 Torino, Italy.
Robino
G
G
Dianzani
M U
MU
D000475:Alkenes / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology* / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress
D000475:Alkenes; D005231:Fatty Acids, Unsaturated