Prevention of Liver Cell Damage Following Lipid Peroxidation by Depression of Lysophosphatide Formation

Abstract

In hepatocytes cytotoxic events induced by haloalkanes or acute iron-overload exhibit neither a quantitative nor a temporal correlation to lipid peroxidation (Ungemach 1987). This is contradictory to the unicausal theory of liver cell necrosis as a direct consequence of the peroxidative destruction of polyunsaturated fatty acids in biological membranes. Thus, secondary toxicological mechanisms have been postulated (Recknagel 1983). As a relevant secondary pathological mechanism an autocatalytic activation of phospholipase A₂ could be demonstrated which is triggered by lipid peroxidation and finally produces cytolytic amounts of lysophosphatides in the plasma membrane (Ungemach 1987). If this concept of phospholipase A₂ activation represents a significant lipid peroxidation-dependent cytotoxic mechanism, it has to be assumed that under conditions of phospholipase A inhibition or suppression of the formation of critical lysophosphatide concentrations the late membrane damage of hepatocytes may be prevented.