Hepatic Pathological Changes Due to Hydroxyalkenals

Abstract

The nonenzymatic autoxidation of polyunsaturated fatty acids is known to cause increased formation of alkenals, alk-2-enals, malonaldehyde and 4-hydroxyalkenals (1–3). A number of alkenals are formed during microsomal lipid peroxidation and some of these alkenals, such as the hydroxyalkenals, are effective nonradical products which could be responsible for part of the effects associated with lipid peroxidation (4–10). Esterbauer et al and Benedetti et al have demonstWed that alkenals are produced during stimulated (ADP-Fe⁺² or NADPH-Fe⁺²) microsomal lipid peroxidation and that these alkenals (in particular 4-hydroxyalkenals) could be responsible for part of the destructive effects caused by lipid peroxidation on cells and cell constituents (5,6). Cytotoxic alkenals originating due to lipid peroxidation were shown to damage cellular membranes of red blood cells, inhibit protein synthesis, and decreased the activity of membrane bound enzymes such as microsomal glucose-6-phosphatase, cytochrome P-450, and aminopyrine N-demethylase (7–13). Further investigations have determined that alkenal compounds may play an important role in liver injury caused by CC1₄ and BrCC1₃ (14,15). Alkenal groups are formed in phospholipids of liver microsomas as a consequence of the peroxidative cleavage of phospholipid-bound unsaturated fatty acids after in vivo intoxication with CC1₄ and BrCC1₃ (14).