E. Gueux

Dietary magnesium affects susceptibility of lipoproteins and tissues to peroxidation in rats.

Magnesium (Mg)-deficient and control diets were pair-fed to weanling Wistar rats for 8 days. Plasma lipoproteins were separated into various density classes by sequential preparative ultracentrifugation. The extent of lipid peroxidation was measured in terms of thiobarbituric acid reactive substances in lipoproteins and tissue homogenates before or after iron-induced lipid peroxidation. Hyperlipemia in Mg-deficient rats was accompanied by increased oxidation of very-low-density lipoproteins and low-density lipoproteins. Moreover, very-low-density lipoproteins and high-density lipoproteins from Mg-deficient rats were more susceptible to oxidative damage following iron incubation. Mg deficiency increased lipid peroxidation in liver, heart and skeletal muscles. Their homogenates were more susceptible to in vitro peroxidation. Mg deficiency has been discussed as a possible contributory factor in the development of cardiovascular disease and was associated with tissue damage and membrane alteration. These results demonstrate for the first time that Mg affects the susceptibility of lipoproteins to peroxidation and suggest that the mechanism responsible for the pathological consequences of Mg deficiency may be mediated by lipid peroxidation products.

Effect of selenium deficiency on hepatic lipid and lipoprotein metabolism in the rat

Since experimental Se deficiency results in a significant increase in plasma cholesterol concentration the present investigation was undertaken to assess further the influence of this deficiency on the expression of proteins involved in hepatic lipid metabolism. Se deficiency was induced by feeding weanling male Wistar rats on a deficient diet for 6 weeks. Hypercholesterolaemia associated with Se deficiency was related to increased 3-hydroxy-3-methylglutaryl-coA (HMG-CoA) reductase (EC 1.1.1.34) activity in liver microsomes as compared with control animals. Hepatic lipoprotein receptor levels (LDL-receptor and HDL-binding proteins, HB1 and HB2) were not significantly affected by Se deficiency, as assessed by immunoblotting. Plasma triacylglycerol concentrations tended to decrease in Se-deficient rats in concert with their reduced post-Triton secretion. There was no significant effect of Se deficiency on the hepatic synthesis of apolipoproteins. These results point to the need for further investigations into the mechanism related to the increased activity of HMG-CoA reductase and the enhanced cholesterogenesis in the liver of Se-deficient rats likely to result from this.

The effect of dietary copper on rat plasma apolipoprotein B, E plasma levels, and apolipoprotein gene expression in liver and intestine

The plasma levels of apo B and apo E, and the level of hepatic and intestinal mRNA coding for these apolipoproteins were investigated in weanling male rats pair-fed for 6 wk with a control or copperdeficient diet. Plasma cholesterol, triglycerides, and phospholipids were significantly increased, and plasma apo B and apo E levels were also markedly increased in copper-deficient rats as compared to control rats. Copper deficiency significantly increased triglyceride levels and decreased cholesterol levels in the liver. No major differences in the levels of hepatic and intestinal apo B and apo E mRNA occurred between control and copper-deficient rats. These data imply that hypertriglyceridemia dn hypercholesterolemia owing to the copper deficiency are not accompanied by modifications in the gene expression at the mRNA level in the liver and intestine of the apolipoproteins studied.

Increased Apoptosis and Free Radical Production in Thymus of Magnesium-Deficient Rats: Implications to Enhanced Thymus Involution and Immunity

Magnesium plays an important role in the maintenance of host regulatory mechanisms in inflammation and immunity. It is well known that dietary magnesium deficiency in rodents, and especially in rats, causes inflammation (for review[l,2]). This inflammatory reaction is characterized by peripheral vasodilatation, splenomegaly and leukocytosis. Elevated levels of proinflammatory cytokines and acute phase proteins have also been observed during magnesium deficiency [1,2]. On the other hand several observations on the modifications in the immune response during this deficiency have been reported [3]. Since T lymphocytes play a key role in the immune response in the present study we examined modifications occurred in the thymic gland during experimental magnesium deficiency. The thymus presents marked variations in its structure depending on the age and the condition of the organism as a whole. This organ is largest in embryos and gradually and continuously involutes throughout life. However, this process of normal or age involution may be complicated by the rapid changes of “accidental involution”[4]. Since the pioneering work of Selye (1936) it is known that following noxious stimuli, stress results in thymic involution and lymphopenia.

Study of Magnesium Absorption Using 25Mg Stable Isotope and Inductively Coupled Plasma/Mass Spectrometry Technique in Rat

Magnesium metabolism is regulated at the intestine and kidneys by controlling the fraction of Mg absorbed from the total dietary intake and by renal homeostasis (1,2). As interest in Mg dietary requirements and metabolism has grown, the need for safe and convenient techniques for measurement of Mg absorption and bioavailability has increased. Balance studies are imprecise, labor intensive, give little information on Mg metabolism and do not consider the endogenous fecal excretion (3). Although kinetic analysis has been performed with the short-lived 28Mg radioisotope, the use of radio isotopes in humans is hazardous and restricts the experiment to a few days duration and is being supplanted by stable isotope methods (4). The use of extrinsic labeling presumes that the administered isotope behaves in the same way and that its absorption is the same as that of endogenous forms of Mg. The validity of the extrinsic labeling approach is now well established (5,6,7). Stable isotopes have been analyzed by two different analytical techniques; neutron activation and mass spectrometry. Although thermal ionization mass spectrometry (TIMS) is the reference technique, inductively coupled argon plasma mass spectrometry (ICP/MS) is also being widely developed (8). ICP/MS has many advantages in stable isotope measurement and has been applied to metabolic studies of many different minerals. In the present work, the feasibility of using a Mg stable isotope and ICP/MS technique to study Mg absorption and metabolism was explored in adult rats and the optimum dosage of the isotope was investigated.