Premium
Excretion of F 2 ‐isoprostanes in bile: A novel index of hepatic lipid peroxidation
Author(s) -
Awad Joseph A.,
Morrow Jason D.
Publication year - 1995
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840220338
Subject(s) - isoprostanes , isoprostane , chemistry , lipid peroxidation , medicine , endocrinology , excretion , liver injury , oxidative stress , pharmacology , biochemistry
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 vivo. Moreover, little is known about the disposition of lipids oxidized in the liver. F 2 ‐isoprostanes are prostanoids produced by nonenzymatic free radical‐catalyzed peroxidation of arachidonic acid esterified to phospholipids. Hydrolysis of F 2 ‐isoprostanes from phospholipids by phospholipases yields free F 2 ‐isoprostanes. Excretion of F 2 ‐isoprostanes, both free and esterified to phospholipids, was measured in bile after administration of CCI 4 . The concentration of lipid‐esterified F 2 ‐isoprostanes in bile exceeded that of free F 2 ‐isoprostanes. CCI 4 , caused a dose‐dependent increase in biliary F 2 ‐isoprostane excretion that correlated better with the increase in liver F 2 ‐isoprostaes than it did with the increase in plasma F 2 ‐isoprostanes. Pretreatment with colchicine ameliorated CCI 4 ‐liver injury but did not affect baseline or CCI 4 ‐induced biliary F 2 ‐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 2 ‐isoprostanes. However, both hepatic F 2 ‐isoprostane concentrations and biliary F 2 ‐isoprostane excretion were increased only threefold. These data suggest that quantification of F 2 ‐isoprostane excretion in bile may provide a sensitive and quantitative index of hepatic lipid peroxidation. (Hepatology 1995; 22:962–968.)