Catechin reduces atherosclerotic lesion development in apo E-deficient mice: a transcriptomic study.

Much experimental evidence supports a protective role of dietary flavonoids against cardiovascular diseases. The aim of the present study was to investigate the anti-atherosclerotic effects of catechin supplemented in the diet of apoE deficient mice at a low nutritional level and to explore the mechanisms of action by a transcriptomic approach. After 6 weeks of supplementation, atherosclerotic lesions were assessed by histomorphometry and several markers of lipid, inflammation and oxidative stress status were evaluated. Analysis of the global gene expression in the aorta was carried out using pangenomic arrays. Catechin supplementation reduced the mean atherosclerotic lesion area by 32% but had no effect on total cholesterol and triacylglycerol levels in the plasma and the liver. The plasma antioxidant capacity (FRAP) and inflammatory status (serum amyloid A) were unchanged. The expression of 450 genes was significantly modified by catechin supplementation. Some of the most significantly down-regulated genes included genes coding for adhesion molecules such as CD34 and PSGL-1 known to play a key role in leukocyte adhesion to the endothelium. Other genes involved in energy metabolism, lipid metabolism and lipids trafficking such as FABP4, LPL and SCARA5 were down-regulated and may contribute to the atheroprotective effect of catechin. This work shows that transcriptomic allows characterizing the biological effects of low doses of flavonoids where common markers were not significantly affected.

Wheat germ supplementation of a low vitamin E diet in rats affords effective antioxidant protection in tissues.

BACKGROUND: Oxidative stress is implicated in the etiology of many diseases, but most of clinical trials failed to demonstrate beneficial effects of antioxidant supplementation. METHODS: In the present experiment, we assessed the mean-term effect of wheat germ supplementation, as a dietary source of vitamin E, on antioxidant protection in rat. RESULTS: Feeding rats a 20% wheat germ diet significantly increased plasma and liver vitamin E levels, compared to the low vitamin E basal diet. Concurrently, wheat germ diet consumption strongly decreased the susceptibility of heart and liver lipids to oxidation, as well as the plasma. Wheat germ feeding did not change triglycerides (TG) nor total cholesterol concentrations in plasma or liver, resulting in higher vitamin E/TG ratio compared to controls. Similar results were found with a diet in which wheat germ oil provided the same amount of vitamin E. CONCLUSIONS: Wheat germ appears thus very effective to improve antioxidant defense status, especially in tissues, irrespective of modifications of lipids status.

Apple polyphenols and fibers attenuate atherosclerosis in apolipoprotein E-deficient mice.

Atherosclerosis, which is closely linked to nutritional habits, is a major cause of mortality in Western countries. Most of the previous investigations carried out on health effects of apples have been focused on their capacity to lower lipid concentration as well as on their antioxidant effects. The aim of the present study was to investigate the antiatherosclerotic effects of apple polyphenols and fibers. A crude apple polyphenol extract and low-viscosity apple fibers isolated from cider apples were administered separately or in association with the diet of apo E-deficient mice. After 4 months of supplementation, lipemia and oxidative stress biomarkers were measured and atheroslerotic lesions assessed by histomorphometry. Total plasmatic cholesterol and triacylgycerol levels were not affected by supplementation, and hepatic cholesterol level was lower in the group supplemented with both fibers and polyphenols. Uric acid concentrations and antioxidant capacity (FRAP) in plasma were reduced in all groups supplemented with polyphenols or fibers. The mean lesion area was reduced by 17, 38, and 38%, respectively, for the polyphenol, fiber, and polyphenol + fiber groups. Apple constituents supplied at nutritional doses therefore limit the development of atherosclerotic lesions in the aorta of apo E-deficient mice. On the basis of the results, we hypothesize that apple fibers and polyphenols may play a role in preventing atherosclerosis disease by decreasing uric acid plasma level.

Inulin supplementation prevents high fructose diet-induced hypertension in rats.

BACKGROUND & AIMS: The aim of this experiment was to evaluate the potential beneficial effect of supplementation with different inulin-type fructan fractions against common features of the metabolic syndrome in a rat model of this syndrome (fructose-fed rat). METHODS: Forty Wistar rats were randomly divided into five groups and the animals received for 4 weeks either a semi-purified starch or fructose-based diet, or diets in which fructose was partially substituted with various fructans: 10 g/100 g of long-chain inulin or oligofructose, or an oligofructose-enriched inulin. After this period, blood pressure was measured and samples of blood and tissues were collected for selected biochemical analyses. RESULTS: As compared to the starch-fed group, the fructose-fed rats presented: hypertriglyceridemia, hypertension, increased susceptibility to heart peroxidation and renal damages. Long-chain inulin and oligofructose-enriched inulin supplementation prevented fructose induced elevated blood pressure, susceptibility to heart peroxidation and renal damages. All inulin-type fructans containing diets prevented fructose induced hypertriglyceridemia. CONCLUSIONS: These results suggest that supplementation with inulin-type fructans is efficient against fructose induced hypertension and that effects are most pronounced for long-chain inulin and oligofructose-enriched inulin. We hypothesize that the anti-hypertensive effect of inulin could be explained by the reduction of the high fructose induced oxidative stress.

In vivo antioxidant activity of procyanidin-rich extracts from grape seed and pine (Pinus maritima) bark in rats.

BACKGROUND: In vitro evidence exists for the potential antioxidant benefits of procyanidin-rich extracts, but in vivo studies are scarce. We have evaluated the effects of selected procyanidin-rich extracts on oxidative stress in rats in condition of prolonged consumption of these compounds and also after single administration i.e. in postprandial conditions. METHODS: Rats were fed for 8 weeks with diets supplemented with either a grape seed extract (GE), a pine bark extract (PE), or a high-degree polymerized pine bark extract (HPE). An additional study was performed in order to assess the postprandial effect of these extracts on plasma antioxidant capacity. The ferric-reducing antioxidant power (FRAP) and thiobarbituric acid-reactive substances (TBARS) were determined in plasma. For lipid peroxidation study of heart tissue, homogenates were prepared and TBARS were measured after lipid peroxidation induced by FeSO4-ascorbate. RESULTS: After 8 weeks of dietary treatment, total antioxidant capacity in plasma was significantly higher in the GE and PE groups as compared with the other two groups. Plasma TBARS concentrations and heart susceptibility to peroxidation were not significantly different between the groups. In the postprandial state, by comparing plasma antioxidant capacity 2 hours after ingestion of the different procyanidin-rich extracts (500 mg/kg body weight), we observed that FRAP values were higher in the procyanidin-rich extracts groups as compared with the control group. Moreover, plasma FRAP concentration was significantly higher in the GE group as compared with the other groups. CONCLUSION: The results of the present experiment constitute positive evidence for an in vivo antioxidant effect at the plasma level of procyanidin-containing plant extracts.

Caffeic acid inhibits oxidative Stress and reduces hypercholesterolemia induced by iron overload in rats.

The effects of caffeic acid, a major phenolic compound of the diet, on oxidative stress and cholesterolemia are studied in rats submitted to oxidative stress by iron overload. Male Wistar rats were fed semi-synthetic diets containing regular (50 mg/kg diet) or high (2000 mg/kg) doses of iron with and without caffeic acid (6460 mg/kg) for 4 weeks. The high doses of iron induced an increase of lipid oxidation in the liver, as measured by thiobarbituric acid-reactive substances (TBARS), and an increase of cholesterolemia. Caffeic acid fully prevented the pro-oxidant effects of high iron doses (p < 0.001). It also reduced lipid peroxidation in rats fed the low iron dose (p < 0.05). Caffeic acid also increased vitamin E levels in plasma (2.74 micromol/L to 4.09 micromol/L for normal diet; p < 0.001; 2.78 micromol/L to 4.94 micromol/L for iron supplemented diet p < 0.001). Iron-induced hypercholesterolemia was inhibited by caffeic acid (1.07 g/L to 0.82 g/L; p < 0.001). These results demonstrate the antioxidative capacity of caffeic acid, a highly bioavailable polyphenol, in an in vivo model of oxidative stress.

Lyophilized carrot ingestion lowers lipemia and beneficially affects cholesterol metabolism in cholesterol-fed C57BL/6J mice.

BACKGROUND: Several lines of evidence indicate that diet rich in fruit and vegetable can protect against cardiovascular diseases by acting on cholesterol metabolism and on oxidative stress. AIM OF THE STUDY: The aim of this study was to assess whether daily carrot consumption (provided as lyophilized powder) could differentially influence the consequences of cholesterol supplementation on lipid metabolism and oxidative stress in C57BL/6J mice. METHODS: Fourteen mice were randomized in four groups. Mice were fed either control diets (without or with 0.25% cholesterol added) or lyophilized carrot enriched diets (20% wt/wt without or with 0.25 % cholesterol added) for 4 weeks. Cholesterol and triglycerides in plasma and in liver were measured at the end of the experimental period. Fecal excretion of sterols was evaluated. Vitamin E and carotenoid concentrations were also determined. Several biomarkers relative to oxidative stress such as FRAP (Ferric Reducing Ability of Plasma) and isoprostanes were investigated. RESULTS: Feeding the carrot diet resulted in a decrease of cholesterol (-41%) and triglycerides (-49 %) in plasma and in the liver (-41% and -39%, respectively) in animals fed cholesterol-supplemented diets. Carrot diet induced an increase of total neutral sterols fecal excretion, which inhibits digestive cholesterol absorption. Carrot diet increased antioxidant status in cholesterol-fed mice as related by the 16% higher FRAP values. Although vitamin E was not affected by carrot diet, vitamin E/TG ratio was significantly higher in animals fed carrot diets. The carrot diet induced an increase of vitamin E in the heart in both cholesterol-free and cholesterol-supplemented mice suggesting a higher protection of this tissue. CONCLUSION: This study shows that carrot ingestion decreases lipemia and improves antioxidant status in mice. Such results suggest that carrot intake may exert a protective impact against CVD linked to atherosclerosis. It is likely that these effects could be due to the synergistic effect of fiber and associated antioxidants.

Effects of sulphate- and bicarbonate-rich mineral waters on net and fractional intestinal absorption and urinary excretion of magnesium in rats.

Magnesium (Mg) intake is below the recommended daily allowances in many developed countries. Mg-rich mineral waters can provide significant amounts of energy-free Mg and thus help to meet Mg requirements. We assessed the effects of different Mg-rich mineral waters on overall intestinal Mg absorption and urinary Mg excretion in 40 rats split into four groups: one received distilled water, another a solution of MgCl(2) and the others two different mineral waters, sulphated water (Hépar) and carbonated water (Badoit) mixed with the diet and as drinking water, for four weeks. The rats were given 3 mg of (26)Mg orally and 0.5 mg of (25)Mg intravenously. They were placed in metabolic cages, and diet consumption, and faeces and urine excretion were monitored during the last four days of the experiment. The rats were then sacrificed and blood was sampled. Mg levels in the diet, faeces, urine and biological samples were measured by atomic absorption spectrometry. Mg stable isotope measurements were performed by ICP/MS. Mg-rich mineral waters significantly increased net intestinal absorption of Mg by more than 30%, but the proportions of both apparent and true intestinal absorption of Mg were similar in all four groups. Thus, net and fractional retention of Mg were similar in the three Mg-supplemented groups. In conclusion, both types of Mg-rich mineral waters studied similarly increased both absorption and urinary excretion of Mg with no positive effect on the overall retention of Mg, probably because the Mg status of the rats was already satisfactory.

Oligofructose protects against the hypertriglyceridemic and pro-oxidative effects of a high fructose diet in rats.

Recent findings indicate that in addition to its hyperlipemic effect, a high fructose diet has a pro-oxidant effect in rats compared with a starch-based diet. Oligofructose (OFS) has already been shown to decrease plasma lipids in rats. We assessed the impact of fructose on oxidative stress by supplementing a high fructose diet with OFS. Rats were fed either a high fructose diet or a starch-based diet, with or without supplementation of 10 g/100 g oligofructose for 4 wk. Regardless of the type of carbohydrate, OFS in the diet produced an enlargement of the cecum and led to a significant increase in the SCFA cecum pool. Fructose feeding was associated with significantly higher insulin plasma concentrations (+63%) in the control groups, whereas insulin plasma concentrations did not differ in rats fed the fructose diet supplemented with OFS. Plasma leptin concentration was significantly lower (approximately 50%) in the OFS-supplemented fructose group compared with the other three groups. Fructose feeding in rats also significantly increased plasma (P < 0.001) and liver (P < 0.001) triglyceride (TG) concentrations and the addition of OFS prevented the TG accumulation induced by fructose in the liver (P < 0.05) and hyperlipemia (P < 0.05). OFS consumption prevented (P < 0.05) the lower plasma vitamin E/TG ratio in rats fed the fructose diet. Control rats fed the fructose diet had high plasma TBARS values compared with rats fed the starch diet, whereas TBARS values remained unchanged when rats were supplemented with OFS. Control rats fed the fructose diet had higher TBARS urine values and higher heart tissue susceptibility to peroxidation compared with rats fed the starch diet, and this effect was significantly reduced by OFS consumption. Further studies are required to identify the mechanisms underlying the protective effect of OFS against the pro-oxidant effect of fructose. However, the potential nutritional benefits of OFS supplementation in fructose-rich diets are suggested.

Metabolic syndrome in the rat: females are protected against the pro-oxidant effect of a high sucrose diet.

Metabolic syndrome is more prevalent in men than in women. In an experimental dietary model of metabolic syndrome, the high-fructose-fed rat, oxidative stress has been observed in males. Given that estradiol has been documented to exert an antioxidant effect, we investigated whether female rats were better protected than males against the adverse effects of a high-sucrose diet, and we studied the influence of hormonal status in female rats. Males and females were first fed a sucrose-based or starch-based diet for 2 weeks. In the males, the plasma triglyceride (TG)-raising effect of sucrose was accompanied by significantly lowered plasma alpha-tocopherol and a significantly lowered alpha-tocopherol/TG ratio (30%), suggesting that vitamin E depletion may predispose lipoproteins to subsequent oxidative stress. In males, after exposure of heart tissue homogenate to iron-induced lipid peroxidation, thiobarbituric reactive substances were significantly higher in the sucrose-fed than in the starch-fed rats. In contrast, in sucrose-fed females, neither a decrease in vitamin E/TG ratio nor an increased susceptibility of heart tissue to peroxidation was observed, despite both a significantly decreased heart superoxide dismutase activity (14%) and a significant 3-fold increase in plasma nitric oxide concentration compared with starch-fed females. The influence of hormonal status in female rats was then assessed using intact, ovariectomized, or estradiol-supplemented ovariectomized female rats fed the sucrose or starch diet for 2 weeks. After exposure of heart tissue to iron-induced lipid peroxidation, higher susceptibility to peroxidation was found only in ovariectomized females fed the sucrose diet compared with the starch group and not in intact females or ovariectomized females supplemented with estradiol. Thus, estrogens, by their effects on antioxidant capacity, might explain the sexual difference in the pro-oxidant effect of sucrose diet resulting in metabolic syndrome in rats.