Suppression of high lipid diet induced by atherosclerosis sarpogrelate

Abstract

Sarpogrelate (SP), a serotonin (5-HT2A) receptor antagonist, is used as an anti-platelet agent for the treatment of some vascular diseases. SP has been reported to inhibit 5-HT induced coronary artery spasm, increase in intracellular calcium and smooth muscle cells proliferation. This study was undertaken to test that SP suppresses the development of atherosclerosis due to high cholesterol diet (HCD) by decreasing blood viscosity and oxidative stress. For this purpose, 29 rabbits were divided into four groups: control group (normal diet); normal diet group with SP at the dose of 5 mg/kg/day; HCD group fed 1% cholesterol; and HCD group with SP at the dose of 5 mg/kg/day. After 90 days of the experiment, blood samples were collected and the animals were killed; the thoracic aorta was stained by the Oil Red O staining method. The results indicate that plasma levels of cholesterol, triglycerides and malondialdehyde were increased in rabbits fed HCD. Plasma viscosity and whole blood viscosity were also higher in the HCD group than that in normal diet group. Treatment with SP prevented these alterations induced by HCD whereas this agent had no significant effect in rabbits fed normal diet. Morphological examination of the aorta revealed that SP treatment prevented the formation of foam cells and atherosclerotic plaque. It is suggested that the beneficial effects of SP in atherosclerosis may be due to actions on blood viscosity, lipid levels and oxidative stress.

Fig 1

Effects of sarpogrelate on high cholesterol diet induced changes in plasma cholesterol and triglyceride levels in rabbits. Con, control; SP, sarpogrelate (5 mg/kg/day); HCD, high cholesterol (1%) diet for 90 days, *P < 0.05 versus cont; #P < 0.05 versus HCD. Each value is a mean ± SE of 4–12 animals in each group as indicated in the Methods section.

Fig 2

Effects of sarpogrelate on high cholesterol diet induced changes in plasma malondialdehyde and superoxide dismutase levels in rabbits. All abbreviations are same as in Fig. 1.

Fig 3

Effects of sarpogrelate on high cholesterol diet induced changes in whole blood and plasma viscosity in rabbits. cP – centipoise. All abbreviations are same as in Figure 1.

Fig 4

Representative illustration showing the effects of sarpogrelate on high cholesterol diet induced formation of atherosclerotic plaque in thoracic aorta of rabbits.

Fig 5

Representative illustration showing the effects of sarpogrelate on high cholesterol diet induced formation of atherosclerotic plaque in aortic arch of rabbits.

Fig 6

Representative illustration showing the effects of sarpogrelate on high cholesterol diet induced foam cells and lipid deposits in aortic arc.