Excretion of F2-isoprostanes in bile: A novel index of hepatic lipid peroxidation

✍ Scribed by Joseph A. Awad; Jason D. Morrow

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 728 KB
• Volume: 22
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840220338

✦ Synopsis

Lipid peroxidation is believed to be an important mechanism of liver injury caused by some xenobiotics. However, it has been difficult to demonstrate and quantify this process in uiuo. Moreover, little is known about the disposition of lipids oxidized in the liver. Fz-isoprostanes are prostanoids produced by nonenzymatic free radical-catalyzed peroxidation of arachidonic acid esterified to phospholipids. Hydrolysis of Fz-isoprostanes from phospholipids by phospholipases yields free F,-isoprostanes. Excretion of Fz-isoprostanes, both free and esterified to phospholipids, was measured in bile after administration of CCL. The concentration of lipid-esterified F2-isoprostanes in bile exceeded that of free F,-isoprostanes. CCl, caused a dose-dependent increase in biliary Fp-isoprostane excretion that correlated better with the increase in liver F2-isoprostanes than it did with the increase in plasma F2-isoprostanes. Pretreatment with colchicine ameliorated CCIJiver injury but did not affect baseline or CCL,-induced biliary Fp-isoprostane excretion. Administration of diquat to selenium-deficient rats, which causes hepatic and renal necrosis, was associated with a 13-fold elevation of plasma F,-isoprostanes. However, both hepatic Fz-isoprostane concentrations and biliary F,-isoprostane excretion were increased only threefold. These data suggest that quantification of FPisoprostane excretion in bile may provide a sensitive and quantitative index of hepatic lipid peroxidation.