The Effect of α-Tocopherol on Copper Binding to Low Density Lipoprotein

authors:

avatar Mohammad Ali Ghaffari 1 , * , avatar Mohammad Reza Saffari 2 , avatar Taibeh Ghiasvand 1

Department of Biochemistry, School of Medicine, Ahwaz Jundishapour University of Medical Sciences, Ahwaz, Iran
Department of Biochemistry and Nutrition, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Iranian Journal of Pharmaceutical Research: Vol.5, issue 3; 209-214
published online: November 20, 2010
article type: Research Article
received: June 21, 2005
accepted: May 21, 2006
DOI: https://doi.org/10.22037/ijpr.2010.677

how to cite: Ghaffari M A, Saffari M R, Ghiasvand T. The Effect of α-Tocopherol on Copper Binding to Low Density Lipoprotein. Iran J Pharm Res. 2006;5(3):e128287. https://doi.org/10.22037/ijpr.2010.677.

Abstract

The oxidative modification of low density lipoprotein (LDL) may play an important role in atherogenesis. Antioxidants that can prevent LDL oxidation may act as antiatherogens. Our understanding of the mechanism of LDL oxidation and factors that determine its susceptibility to oxidation is still incomplete. Copper is a candidate for oxidizing LDL in atherosclerotic lesions. The binding of copper ions to LDL is usually thought to be a prerequisite for LDL oxidation by copper. Therefore we investigated the effect of α-tocopherol (as a major fat soluble antioxidant) on copper bound to LDL and furthermore effect of this binding on the susceptibility of LDL to oxidative modification.
 
 
In this study LDL was isolated from EDTA-plasma (1 mg EDTA/ml blood) by ultracentrifugation using a single-step discontinuous gradient. Then α-tocopherol was added to LDL and incubated for 1 h at 37° C. The oxidation rate of LDL was estimated by thiobarbitoric acid reactive substances (TBARS) after CuSO4 addition. Finally, the effect of α-tocopherol on formation of LDL-copper complex by gel filtration was studied.
 
 
Our results showed that α-tocopherol (dose dependently) suppressed the formation of TBARS and LDL-copper complex. The α-tocopherol with concentrations of 10, 50 and 100 µM reduced susceptibility of LDL to oxidative modification approximately by 2, 13 and 21 percent, respectively. Furthermore, addition of α-tocopherol to the LDL and CuSO4 mixture containing before hand prevented the formation of LDL-copper complex, approximately by 30 percent.
 
 
In conclusion we found that α-tocopherol with inhibition of copper binding to LDL may decrease the susceptibility of LDL oxidation to this ion and thus could play a role in prevention of atherosclerosis.