Effects of Probucol on Blood Lipids and Paraoxonase-1 in Hypercholesterolemic Rabbits

Objective: This study aimed to investigate the effects of probucol on the concentration and expression of paraoxonase-1 in hy-percholesterolemic rabbits and try to elucidate the antiatherogenic properties of probucol. Methods: Sixteen rabbits fed with high cholesterol diet for 8 weeks were randomly divided into two groups:①high cholesterol group (n = 8) : high cholesterol diet lasting for 6 weeks;②probucol group (n = 8) ; high cholesterol diet plus 1 % probucol for 6 weeks. Control group (n = 8) was fed with normal diet for 14 weeks. The classical in-situ two steps perfusion of the liver with collagenase IV was used to isolate the parenchymal hepatocytes. The total superoxide dismutase activity and malondialdehyde and paraoxonase 1 concentration in plasma were measured at 0, 8 and 14 weeks of feeding. Reverse transcription polymerase chain reaction ( RT-PCR) was used to detect mRNA expression of PON-1 in hepatocytes. The histopathological changes of aortas were determined at the end of the study. Results: Compared with those in control group, rabbits fed with high cholesterol diet showed higher levels of plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and HDL-C, all of which were significantly reduced by probucol treatment. The plaque areas (51. 54±8. 32% ) of the aorta were ameliorated in probucol group as compared with high cholesterol group (84. 81±9. 35% ). Probucol significantly decreased the MDA concentration(9. 20±1. 31μg/ml) as compared with high cholesterol group (12. 57±1. 43μg/ml, P 0. 01), but had no effect on SOD activity. Probucol significantly increased PON-1 content and up-regulated the mRNA expression of PON-1 as compared with high cholesterol group (0. 85±0. 02μg/ml vs 0. 50±0. 01μg/ml; 0. 72±0. 01 vs 0. 46±0. 01, respectively, all P 0. 05). The PON-1 concentration was negatively associated with the MDA concentration ( r = - 0. 86, P = 0. 003) but not the level of HDL-C. Conclusions: Probucol decreased plasma lipid and MDA concentrations, and increased PON-1 concentration and its transcription in hepatocytes, which may contribute to its antiatherogenic effects.