Oxidative tyrosylation of high density lipoprotein impairs biliary sterol secretion in rats

The oxidation of low density lipoprotein plays a central role in the pathogenesis of atherosclerosis. Oxidative modification could also occur in high density lipoprotein (HDL), which may alter reverse cholesterol transport. It has recently been proposed that myeloperoxidase-generated tyrosyl radical may modify HDL. In the present study we have examined whether the oxidative tyrosylation of HDL by peroxidase may alter biliary cholesterol secretion and bile acid transformation. HDL was modified by exposure to L-tyrosine, H2O2 and peroxidase labelled with [14C]cholesterol and injected i.v. into rats with bile diversion. A reduced excretion of radioactivity (14-20%) was recovered in the bile of animals administered with tyrosylated HDL at the different periods of collection. Both labelled cholesterol (14.3%, P < 0.05) and bile acids (18.9%, P < 0.05) were decreased in these rats, similarly to results obtained from malondialdehyde-modified HDL. Consequently, this kind of oxidative modification resulted in a loss of the hepatobiliary systems capacity to normally process HDL.