Elyett Gueux

Inflammatory response following acute magnesium deficiency in the rat

The importance of inflammatory processes in the pathology of Mg deficiency has been recently reconsidered but the sequence of events leading to the inflammatory response remains unclear. Thus, the purpose of the present study was to characterize more precisely the acute phase response following Mg deficiency in the rat. Weaning male Wistar rats were pair-fed either a Mg-deficient or a control diet for either 4 or 8 days. The characteristic allergy-like crisis of Mg-deficient rats was accompanied by a blood leukocyte response and changes in leukocytes subpopulations. A significant increase in interleukin-6 (IL-6) plasma level was observed in Mg-deficient rats compared to rats fed a control diet. The inflammatory process was accompanied by an increase in plasma levels of acute phase proteins. The concentrations of alpha2-macroglobulin and alpha1-acid glycoprotein in the plasma of Mg-deficient rats were higher than in control rats. This was accompanied in the liver by an increase in the level of mRNA coding for these proteins. Moreover, Mg-deficient rats showed a significant increase in plasma fibrinogen and a significant decrease in albumin concentrations. Macrophages found in greater number in the peritoneal cavity of Mg-deficient rats were activated endogenously and appeared to be primed for superoxide production following phorbol myristate acetate stimulation. A high plasma level of IL-6 could be detected as early as day 4 for the Mg-deficient diet. Substance P does not appear to be the initiator of inflammation since IL-6 increase was observed without plasma elevation of this neuropeptide. The fact that the inflammatory response was an early consequence of Mg deficiency suggests that reduced extracellular Mg might be responsible for the activated state of immune cells.

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.

Increased phagocytosis and production of reactive oxygen species by neutrophils during magnesium deficiency in rats and inhibition by high magnesium concentration.

Recent studies underline the importance of the immunoinflammatory processes in the pathology of Mg deficiency. Neutrophils possess a superoxide anion-generating NADPH oxidase and its inappropriate activation may result in tissue damage. The aim of the present study was to assess the effect of experimental Mg deficiency in the rat on polymorphonuclear leucocytes (PMN) activity and the role of increasing extracellular Mg. Weaning male Wistar rats were fed either a Mg-deficient or a control diet for 8 d. In Mg-deficient rats, the characteristic inflammatory response was accompanied by a marked increase in the number of PMN. Higher plasma interleukin 6 and NO concentrations and increased lipid peroxidation in the heart were found in Mg-deficient rats as compared with control rats. As shown by chemiluminescence studies, basal neutrophil activity from Mg-deficient rats was significantly elevated when compared with neutrophils from control rats. Moreover, the chemiluminescence of PMN from Mg-deficient rats was significantly higher than that of control rats following phorbol myristate acetate or opsonized zymosan activation. PMN from Mg-deficient rats also showed an increased activity of phagocytosis in comparison with neutrophils from control animals. Increasing extracellular Mg concentration in the incubating medium of PMN (0.8 v. 8.0 mM) decreased the chemiluminescence activity of PMN from control rats following opsonized zymosan activation. Chemiluminescence activities of PMN from Mg-deficient rats following phorbol myristate acetate or opsonized zymosan challenge were also decreased by high extracellular Mg concentration. From this work, it appears that PMN activation is an early consequence of Mg deficiency and that high extracellular Mg concentration inhibits free radicals generation.

Accelerated thymus involution in magnesium-deficient rats is related to enhanced apoptosis and sensitivity to oxidative stress

Experimental Mg deficiency leads to alterations in the immune response. Reduction of thymus weight and histological changes were previously observed in Mg-deficient rats after several weeks on a deficient diet, suggesting that functions of this immune organ may be affected by Mg deficiency. More recently, changes in the immune system during early Mg deficiency were shown. Thus, in the present study we examined modifications in the thymus during the early stages of Mg deficiency in weanling rats. From our results, it appears that Mg deficiency accelerates thymus involution. The assessment of apoptosis (enumeration of apoptotic cells on the basis of morphological criteria and intranucleosomal degradation of genomic DNA) showed greater values in thymuses from Mg-deficient rats as compared with controls. This was observed very early, since a significant difference was shown on the second day of deficiency, before reduced weight of thymus, which was recorded in the later period. These results indicate the relationship of accelerated thymus involution with an active process of cell death. Mg deficiency led to histological changes in the thymus. In the early stage of deficiency (second day) the presence of inflammatory cells was shown, suggesting that the inflammatory process was already occurring in the tissue studied. Later (eighth day) an increased proportion of epithelial reticular cells in the cortex was shown, indicating a remodelling process occurring in this period. Enhanced susceptibility to peroxidation also occurred very early during Mg deficiency. It may be hypothesized that disturbances in Mg status of short duration could have cellular effects with various deleterious consequences.

Inulin attenuates atherosclerosis in apolipoprotein E-deficient mice

Effects of different inulin-type fructan fractions were studied on atherosclerotic plaque formation in male apo E-deficient mice. Thirty-two mice were randomly divided into four groups and received either a semi-purified sucrose-based diet (control group), or diets in which sucrose was replaced in part by various inulin-type fructans (10 g/100 g): long-chain inulin, oligofructose, or an oligofructose-enriched inulin for 16 weeks. The presence of atherosclerotic plaques was assessed by histomorphometry in the aortic sinus. The apo E-deficient mice fed long-chain inulin or an oligofructose-enriched inulin had about 35 % and 25 % less atherosclerotic lesion area compared with the control group, respectively. Feeding long-chain inulin significantly reduced plasma cholesterol concentrations (P<0.001), and the three inulin-type fructans reduced triacylglycerol (TAG) concentrations compared with the control group (P<0.001). Both the long-chain inulin and an oligofructose-enriched inulin significantly lowered hepatic cholesterol concentrations compared with the control diet (P<0.05). Hepatic TAG concentrations were significantly lower in all three groups fed the fructan-supplemented diets v. the control group (P<0.0001). The results of the present study suggest that inhibition of atherosclerotic plaque formation is more potent in the presence of long-chain inulin, either alone or in combination with oligofructose (an oligofructose-enriched inulin), and that this probably is related to changes in lipid metabolism.

Enhanced tumor necrosis factor-α production following endotoxin challenge in rats is an early event during magnesium deficiency

Magnesium (Mg) plays an essential role in fundamental cellular reactions and the importance of the immuno-inflammatory processes in the pathology of Mg deficiency has been recently reconsidered. The purpose of the present study was to assess the effect of different stages of Mg deficiency on endotoxin response and tumor necrosis factor-alpha (TNF alpha) production. Weaning male Wistar rats were pair fed either a Mg-deficient or a control diet. At day 7, lipopolysaccharide (LPS) induced no lethal effects in control rats but resulted in 70% mortality in Mg-deficient rats within 3 h. The vulnerability of Mg-deficient rats to LPS was associated with higher TNF alpha plasma values. Mg-deficient animals that received magnesium supplementation before endotoxin challenge had significantly increased survival. At day 2, control and Mg-deficient rats were also subjected to endotoxin challenge with or without magnesium pre-treatment. A significant increase in TNF alpha plasma level was observed in Mg-deficient rats compared to rats fed the control diet. Mg-deficient rats that received magnesium replacement therapy before endotoxin challenge had significantly lower TNF alpha plasma values than those receiving saline before endotoxin. Thus, the results of this experiment suggest that the activated or primed state of immune cells is an early event occurring in Mg deficiency.

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 α-tocopherol and a significantly lowered α-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 estradlol-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.

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.

Female rats are protected against oxidative stress during copper deficiency

Background: Copper deficiency induces a dramatic decrease of superoxide dismutase activity and leads to alteration of antioxidant defense systems. Methods and Objective: Experiments were conducted in weanling male, intact and ovariectomized female rats, fed either a copper-adequate or copper-deficient diet for seven weeks, in order to determine whether endogenous estrogen could modulate oxidative stress and the severity of copper-deficiency. Results: Feeding male rats a copper-deficient diet induced typical signs of copper deficiency, such as decreased hepatic copper, growth retardation, anemia, heart hypertrophy, pancreas atrophy and hypercholesterolemia. Furthermore, copper deficiency increased the amount of lipid peroxidation products in the heart, liver and pancreas following in vitro iron induction. Although levels of hepatic copper in copper-deficient females were similar to those of their male counterparts, the females were partially protected from the adverse effects of the deficiency (no growth retardation, less severe anemia, lesser extent of lipid peroxidation). Thus, female rats are provided with a greater degree of protection against oxidative damage than males. However, females did not appear to be protected against pancreas atrophy, heart enlargement and hypercholesterolemia induced by copper deficiency. This observed partial protection of females was lost after ovariectomy as shown by decreased body weight and hematocrit, heart enlargement and higher tissue peroxidation in ovariectomized females compared to intact females. Conclusions: The results suggest that the partial protection of copper deficient females is related to the antioxidant properties of estrogens. The protective action of estrogen against oxidative stress is of particular importance when antioxidant defenses are decreased as shown in this experimental model.

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.