Oxidised cholesterol is more hypercholesterolaemic and atherogenic than non-oxidised cholesterol in hamsters

Abstract

The present study was to test the relative hypercholesterolaemic and atherogenic potency of oxidised cholesterol (OxC) and non-oxidised cholesterol in hamsters. An OxC mixture, prepared by heating pure cholesterol (100 g) at 1608C in air for 72 h, contained 78 % cholesterol and 22 % OxC. Fifty Golden Syrian hamsters were randomly divided into five groups of ten animals and fed the control diet, a 0·05 % cholesterol diet (C-0·05), a 0·10 % cholesterol diet (C-0·1), a 0·05 % OxC mixture diet (OxC-0·05) or a 0·10 % OxC mixture diet (OxC-0·1), respectively. The OxC-0·05 and OxC-0·1 groups were more hypercholesterolaemic and had serum total cholesterol 22 and 12 % higher than the corresponding C-0·05 and C-0·1 hamsters (P, 0·05). The OxC-0·1 group demonstrated greater deposition of cholesterol and had a larger area of atherosclerotic plaque in the aorta than the corresponding C-0·1 hamsters (P, 0·05). Similarly, the aorta in the OxC-0·1 group showed greater inhibition on acetylcholine-induced relaxation compared with that in the C-0·1 hamsters. It was concluded that OxC was much more hypercholesterolaemic and atherogenic than cholesterol. Cholesterol: Cholesterol oxidation products: Oxidised cholesterol: OxysterolHuman diets contain both cholesterol and oxidised cholesterol (OxC). Cholesterol is susceptible to oxidation, forming a series of cholesterol oxidation products (COP) under various food processing conditions. The amount of COP can reach up to 10 % total cholesterol (TC) in foods 1 , particularly in Western countries where total fat intake is high and fried foods are popular 2 . More than thirty COP have been identified and reported 3,4 . The major COP include 7b-hydroxycholesterol, 7a-hydroxycholesterol, 5a-hydroxycholesterol, 7-ketocholesterol and a-epoxides 5 .COP have been extensively studied for their undesirable effects including cytotoxicity 6 , mutagenesis 7 and carcinogenesis 8 . In addition, COP have been shown to be absorbed in a similar way to cholesterol 9,10 , cause disturbance of lipid metabolism 11 and alter the cell membrane function 12,13 . Most importantly, COP could accelerate fatty streak lesion formation and promote atherosclerosis 14,15 . Human daily cholesterol intake is about 300-500 mg while that of COP could be up to 30 -50 mg, provided that 10 % cholesterol in the diet is oxidised. It is well known that high cholesterol consumption elevates plasma TC and LDL-cholesterol levels and increases the risk of CHD. However, the effect of COP in the diet on blood cholesterol is unfortunately ignored and there is very limited information concerning relative hypercholesterolaemic and atherosclerotic activity of COP and cholesterol itself 6 . The present study was therefore carried out to investigate the effect of OxC on blood cholesterol level, atherosclerotic plaque formation and endothelium function compared with that of non-oxidised cholesterol using hamsters as an animal model. Experimental methods Preparation of oxidised cholesterolPure cholesterol was purchased from Sigma Chemical Compa...

Gender-based differences in the effect of dietary cholesterol in rats

“…Serum cholesterol concentrations in control rats were within the reference ranges for male and female rats at <6 months of age, which are 1.94±0.51 μmol/mL and 2.30±0.59 μmol/mL, respectively [20]. The liver cholesterol response to feeding the rats cholesterol-enriched diets was more pronounced than serum cholesterol, as observed with other studies in rats [11][12][13], hamsters [11,21,22], and guinea pigs [21]. Cholesterol supplementation significantly increased total lipids in hepatic tissue in male and female rats.…”

Use of hamster as a model to study diet-induced atherosclerosis

“…The amount of supplemental dietary fat has ranged from 0 to 20% (w/w) [30,32,36,48,51,62,76-78,85,90,95-97], with 10% (w/w) used most frequently [31,33-35,37-43,45,47,50,52-56,59,63,65,66,79-84,88,92,94,98,99]. Ten percent saturated fatty acids (SFA) with supplemental cholesterol has been consistently reported to raise plasma total cholesterol and nHDL-C concentrations [31,38,47,50,55,62] without having adverse effects on hepatic function [51].…”

“…In the outbred strains, in contrast to that normally observed in humans, the HDL-C concentrations were equal to or slightly higher than nHDL-C concentrations. Noteworthy was the wide range of plasma cholesterol concentrations after the hamsters were fed a cholesterol- and SFA-supplemented diet, regardless of strain (Figure 1A-C) [22,24,28,30-36,38-44,47-59,61-64,66,75,77,78,80-86,88,89,92,94,96,98-100,105-114]…”

Oxidation of Cholesterol and β-Sitosterol and Prevention by Natural Antioxidants

“…COPs have been known for being cytotoxic, atherogenic, mutagenic, and carcinogenic, whereas little information is available on the biological effects of SOPs. We have studied the effect of COPs on blood cholesterol and the functioning of arteries, finding that COPs are highly hypercholesterolemic and cause atherosclerosis and endothelial dysfunction (10). We are currently studying the effect of SOPs on blood cholesterol level and cardiovascular functions.…”