Protective effect of deferiprone on hemin-induced oxidation of low and high density lipoproteins

Abstract

Oxidative modification of low density lipoproteins (LDL) and high density lipoproteins (HDL) play a major role in the pathogenesis of atherosclerosis. The hemin, iron compound is an oxidant that can be detected in thalassemic patients at high level. This is importantly a prerequisite for the development of atherosclerosis with vascular complications in the patients. Deferiprone (L1) is an oral iron chelator used to treat the patients having excessive plasma iron. The objective of this study is to investigate the effect of L1 on hemin-induced oxidation of low and high density lipoproteins and the effect of L1 on U937 derived macrophage uptake of heminoxidized low density lipoprotein. In vitro study was conducted by adding the L1 at the concentrations of 5, 10, 50, 100, and 500 .M into the LDL and HDL prior to oxidation induction using the hemin with the incubation period of 24 h. The degree of the lipoprotein oxidation was determined by thiobarbituric acid reactive substances (TBARs) formation. The levels of alpha-tocopherol and lipid composition were measured by HPLC. The results showed that the L1 at all tested concentrations have the protective effect on the hemin-oxidized LDL and HDL by inhibition of TBARs formation approximately 50-80% and almost 100% in LDL and HDL, respectively at time 9 and 24 h of incubation. However, the L1 could not preserve the alpha-tocopherol both in hemin-oxidized LDL and HDL. In addition, the L1 at the concentration of 500 muM could protect the decrease of cholesteryl arachidonate and cholesteryl linoleate level. However, L1 did not affect macrophage uptake of hemin oxidized LDL. This study was concluded that L1 possessed an antioxidative activity both in LDL and HDL oxidation induced by hemin.