Excretion of F2-isoprostanes in bile: a novel index of hepatic lipid peroxidation.
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. F2-isoprostanes are prostanoids produced by nonenzymatic free radical-catalyzed peroxidation of arachidonic acid esterified to phospholipids. Hydrolysis of F2-isoprostanes from phospholipids by phospholipases yields free F2-isoprostanes. Excretion of F2-isoprostanes, both free and esterified to phospholipids, was measured in bile after administration of CCl4. The concentration of lipid-esterified F2-isoprostanes in bile exceeded that of free F2-isoprostanes. CCl4 caused a dose-dependent increase in biliary F2-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 CCl4-liver injury but did not affect baseline or CCl4-induced biliary F2-isoprostane excretion. Administration of diquat to selenium-deficient rats, which causes hepatic and renal necrosis, was associated with a 13-fold elevation of plasma F2-isoprostanes. However, both hepatic F2-isoprostane concentrations and biliary F2-isoprostane excretion were increased only threefold. These data suggest that quantification of F2-isoprostane excretion in bile may provide a sensitive and quantitative index of hepatic lipid peroxidation.
Awad
J A
JA
Division of Gastroenterology, Vanderbilt University, Nashville, TN 37232, USA.
Morrow
J D
JD
D000818:Animals; D001646:Bile / Q000378:metabolism*; D002251:Carbon Tetrachloride / Q000494:pharmacology; D003078:Colchicine / Q000494:pharmacology; D015237:Dinoprost / Q000378:metabolism*; D004178:Diquat / Q000494:pharmacology; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000172:deficiency
D008054:Lipid Peroxides; D004178:Diquat; D015237:Dinoprost; D002251:Carbon Tetrachloride; D012643:Selenium; D003078:Colchicine