Advanced Glycation in macrophages induces intracellular accumulation of 7-ketocholesterol and total sterols by decreasing the expression of ABCA-1 and ABCG-1

<p>Abstract</p> <p>Background</p> <p>Advanced glycation end products (AGE) alter lipid metabolism and reduce the macrophage expression of ABCA-1 and ABCG-1 which impairs the reverse cholesterol transport, a system that drives cholesterol from arterial wall macrophages to the liver, allowing its excretion into the bile and feces. Oxysterols favors lipid homeostasis in macrophages and drive the reverse cholesterol transport, although the accumulation of 7-ketocholesterol, 7alpha- hydroxycholesterol and 7beta- hydroxycholesterol is related to atherogenesis and cell death. We evaluated the effect of glycolaldehyde treatment (GAD; oxoaldehyde that induces a fast formation of intracellular AGE) in macrophages overloaded with oxidized LDL and incubated with HDL alone or HDL plus LXR agonist (T0901317) in: 1) the intracellular content of oxysterols and total sterols and 2) the contents of ABCA-1 and ABCG-1.</p> <p>Methods</p> <p>Total cholesterol and oxysterol subspecies were determined by gas chromatography/mass spectrometry and HDL receptors content by immunoblot.</p> <p>Results</p> <p>In control macrophages (C), incubation with HDL or HDL + T0901317 reduced the intracellular content of total sterols (total cholesterol + oxysterols), cholesterol and 7-ketocholesterol, which was not observed in GAD macrophages. In all experimental conditions no changes were found in the intracellular content of other oxysterol subspecies comparing C and GAD macrophages. GAD macrophages presented a 45% reduction in ABCA-1 protein level as compared to C cells, even after the addition of HDL or HDL + T0901317. The content of ABCG-1 was 36.6% reduced in GAD macrophages in the presence of HDL as compared to C macrophages.</p> <p>Conclusion</p> <p>In macrophages overloaded with oxidized LDL, glycolaldehyde treatment reduces the HDL-mediated cholesterol and 7-ketocholesterol efflux which is ascribed to the reduction in ABCA-1 and ABCG-1 protein level. This may contribute to atherosclerosis in diabetes mellitus.</p

Effects of isoflavone-supplemented soy yogurt on lipid parameters and atherosclerosis development in hypercholesterolemic rabbits: a randomized double-blind study

<p>Abstract</p> <p>Background</p> <p>There is increasing interest in natural treatments to control dyslipidemia and reduce the risk of cardiovascular disease. Previous studies have demonstrated the beneficial effects of soy yogurt fermented with <it>Enterococcus faecium </it>CRL 183 and of dietary isoflavones on the lipid profile. The purpose of the present study was to investigate the effects of isoflavone-supplemented soy yogurt, fermented with <it>E. faecium </it>CRL183, on lipid parameters and atherosclerosis development in rabbits with induced hypercholesterolemia.</p> <p>Methods</p> <p>Forty-eight rabbits were randomly assigned to eight groups fed on the following diets for 60 days: C - control; IY - isoflavone-supplemented soy yogurt; H - hypercholesterolemic (1.0% cholesterol wt/wt diet); HY - hypercholesterolemic plus soy yogurt; HIY - hypercholesterolemic plus isoflavone-supplemented soy yogurt; HP - hypercholesterolemic plus placebo; HI - hypercholesterolemic plus isoflavone and HE - hypercholesterolemic plus pure culture of <it>E. faecium </it>CRL 183. Serum lipids and autoantibodies against oxLDL (oxLDL Ab) were analyzed on days 0, 30 and 60 of the treatment and the atherosclerotic lesions were quantified at the end of the experiment.</p> <p>Results</p> <p>Soy yogurt, soy yogurt supplemented with isoflavones and placebo promoted significant reductions in total cholesterol level (38.1%, 27.0% and 26.6%, respectively). Significant increases in serum HDL-C concentration relative to group H were detected in animals that ingested soy yogurt, with or without the isoflavone supplement (55.2%), <it>E. faecium </it>culture (43.3%) or placebo (35.8%). Intake of soy yogurt and soy yogurt supplemented with isoflavones prevented the rise of oxLDL Ab during the study period. The extent of atherosclerosis in the thoracic and abdominal aortas was reduced in the HIY, HY and HP groups. However, when the whole aorta was analyzed, animals treated with soy yogurt supplemented with isoflavones exhibited the greatest reduction (51.4%, P < 0.05) in atherosclerotic lesion area, compared to group H.</p> <p>Conclusion</p> <p>Soy yogurt could be consumed as an alternative means of reducing the risk of cardiovascular disease by improving the lipid profile and inhibiting oxLDL Ab formation. Our findings also suggest that isoflavone supplementation may enhance the antiatherosclerotic effect of soy yogurt.</p

Influence of a probiotic soy product on fecal microbiota and its association with cardiovascular risk factors in an animal model

<p>Abstract</p> <p>Background</p> <p>Previous work showed that daily ingestion of an aqueous soy extract fermented with <it>Enterococcus faecium </it>CRL 183 and <it>Lactobacillus helveticus </it>416, supplemented or not with isoflavones, reduced the total cholesterol and non-HDL-cholesterol levels, increased the high-density lipoprotein (HDL) concentration and inhibited the raising of autoantibody against oxidized low-density lipoprotein (ox-LDL Ab) and the development of atherosclerotic lesions.</p> <p>Objective</p> <p>The aim of this study was to characterize the fecal microbiota in order to investigate the possible correlation between fecal microbiota, serum lipid parameters and atherosclerotic lesion development in rabbits with induced hypercholesterolemia, that ingested the aqueous soy extract fermented with <it>Enterococcus faecium </it>CRL 183 and <it>Lactobacillus helveticus </it>416.</p> <p>Methods</p> <p>The rabbits were randomly allocated to five experimental groups (n = 6): control (C), hypercholesterolemic (H), hypercholesterolemic plus unfermented soy product (HUF), hypercholesterolemic plus fermented soy product (HF) and hypercholesterolemic plus isoflavone-supplemented fermented soy product (HIF). Lipid parameters and microbiota composition were analyzed on days 0 and 60 of the treatment and the atherosclerotic lesions were quantified at the end of the experiment. The fecal microbiota was characterized by enumerating the <it>Lactobacillus </it>spp., <it>Bifidobacterium </it>spp., <it>Enterococcus </it>spp., Enterobacteria and <it>Clostridium </it>spp. populations.</p> <p>Results</p> <p>After 60 days of the experiment, intake of the probiotic soy product was correlated with significant increases (P < 0.05) on <it>Lactobacillus </it>spp., <it>Bifidobacterium </it>spp. and <it>Enterococcus </it>spp. and a decrease in the Enterobacteria population. A strong correlation was observed between microbiota composition and lipid profile. Populations of <it>Enterococcus </it>spp., <it>Lactobacillus </it>spp. and <it>Bifidobacterium </it>spp. were negatively correlated with total cholesterol, non-HDL-cholesterol, autoantibodies against oxidized LDL (oxLDL Ab) and lesion size. HDL-C levels were positively correlated with <it>Lactobacillus </it>spp., <it>Bifidobacterium </it>spp., and <it>Enterococcus </it>spp. populations.</p> <p>Conclusion</p> <p>In conclusion, daily ingestion of the probiotic soy product, supplemented or not with isoflavones, may contribute to a beneficial balance of the fecal microbiota and this modulation is associated with an improved cholesterol profile and inhibition of atherosclerotic lesion development.</p

Vitamin C and Vitamin E in Prevention of Nonalcoholic Fatty Liver Disease (NAFLD) in Choline Deficient Diet Fed Rats

AIM: Oxidative stress has been implicated in the pathogenesis of Nonalcoholic Fatty Liver Disease (NAFLD). Vitamin C and vitamin E are known to react with reactive oxygen species (ROS) blocking the propagation of radical reactions in a wide range of oxidative stress situations. The potential therapeutic efficacy of antioxidants in NAFLD is unknown. The aim of this study was to evaluate the role of antioxidant drugs (vitamin C or vitamin E) in its prevention. METHODS: Fatty liver disease was induced in Wistar rats by choline-deficient diet for four weeks. The rats were randomly assigned to receive vitamin E (n = 6) – (200 mg/day), vitamin C (n = 6) (30 mg/Kg/day) or vehicle orally. RESULTS: In the vehicle and vitamin E-treated rats, there were moderate macro and microvesicular fatty changes in periportal area without inflammatory infiltrate or fibrosis. Scharlach stain that used for a more precise identification of fatty change was strong positive. With vitamin C, there was marked decrease in histological alterations. Essentially, there was no liver steatosis, only hepatocellular ballooning. Scharlach stain was negative. The lucigenin-enhanced luminescence was reduced with vitamin C (1080 ± 330 cpm/mg/minx10(3)) as compared to those Vitamin E and control (2247 ± 790; 2020 ± 407 cpm/mg/minx10(3), respectively) (p < 0.05). Serum levels of aminotransferases were unaltered by vitamin C or vitamin E. CONCLUSIONS: 1) Vitamin C reduced oxidative stress and markedly inhibited the development of experimental liver steatosis induced by choline-deficient diet ; 2)Vitamin E neither prevented the development of fatty liver nor reduced the oxidative stress in this model