Pathogenesis of hepatic injury in endotoxemia: with special reference to phosphatidylcholine hydroperoxide accumulation

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The membrane lipid peroxidation of the liver tissue and hepatocytes was studied in order to clarify the pathogenesis of liver dysfunction in endotoxcmia. Phosphatidylcholine hydroperoxide (PCOOH) which is a specific membrane lipid oxidant was measured using high performance liquid chromatography- chemiluminescence technique. Peritonitis was induced in rats by ligation and puncture of the cecum. Blood endotoxin levels were progressively increased until 24 hours after induction of peritonitis. Hepatic PCOOH markedly increased from 740 pmol/mg to 2.628 pmol/mg after 24 hours of peritonitis, and hepatic energy charge reduced from 0.86 to 0.73. In addition, reduction of hepatic energy charge as well as increase of hepatic PCOOH was significantly suppressed by an administration of superoxide dismutase and catalase in rats with peritonitis. As hepatic tissue blood flow showed little changes throughout the experiment, an increased hepatic membranous lipid peroxidation might be one of the main causative factors for the deteriorated hepatic energy metabolism in endotoxemia. The increases of PCOOH of the hepatocytes, as well as GPT in supernatant, were achieved only when endotoxin was added to the co-culture with Kupffer cells, and not to hepatocytes alone. This evidence suggests that Kupffer cells activated by endotoxin may affect membrane lipid peroxidation of the hepatectocytes. Significant contribution of the infiltrating leukocytes and sinusoidal endothelial cells for the pathogenesis of hepatocyte injury in endotoxemia need to be further studies.