Pharmacology of fibrosis and tissue injury

Abstract

Methods controlling tissue fibrosis are classified into those specifically inhibiting various metabolic aspects of collagen selectively in the injured tissue (ascorbic acid deficiency, effect of agent chelating Fe(2+), proline analogs, lathyrogens). The most promising method seems to be the blocking of crosslinks formation among collagen molecules by beta-aminopropionitrile, a competitive inhibitor of a crosslinking enzyme, lysyl oxidase. The second group of methods is called nonspecific, as they affect any stage of inflammatory process preceding the activation of fibroblasts. The importance of activated macrophages in the stimulation of fibroblast is discussed. Finally, a new concept is proposed, indicating the function of zinc ions in the control of the integrity of biomembrances, tissue reactivity to noxious agents. It is suggested that zinc may control NADPH dependent lipid peroxidation at the membrane level by inhibiting NADPH oxidase activity. The implication of these ideas to lung fibrosis induced by silica or asbestos is discussed.