Copper deficiency and lipoprotein oxidation.
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Animals↗
Biomedical subjects
E Rock
Publications and source records attributed to E Rock.
Exacerbated immune stress response during experimental magnesium deficiency results from abnormal cell calcium homeostasis.
The aim of this study was to assess the potential mechanism underlying the enhanced inflammatory processes during magnesium deficit. In this study, exacerbated response to live bacteria and platelet activating factors was shown in rats fed a magnesium-deficient diet. Peritoneal cells from these animals also showed enhanced superoxide anion production and calcium mobilising potency following in vitro stimulation. The latter effect occurred very early in the course of magnesium deficiency. These studies first showed that an abnormal calcium handling induced by extracellular magnesium depression in vivo may be at the origin of exacerbated inflammatory response.
Animals↗
Early morphological and immunological alterations in the spleen during magnesium deficiency in the rat.
Dietary magnesium deficiency in rodents, and especially in rats, causes inflammation and leads to alterations in the immune response. One of the characteristics of magnesium deficiency in the rat is a marked enlargement of the spleen. Considering the importance of the spleen for the immune response, in this study we have evaluated histological, cytological and immunological changes in this organ of rats in early stages of this deficiency. For this purpose, male weaning Wistar rats were pair-fed with either control or magnesium-deficient diet, for 2, 4 or 8 days. Results indicate that after 8 days on the deficient diet rats presented clinical signs of inflammation, splenomegalia and leukocytosis. As shown by histometrical analysis, both the red and white spleen pulps of deficient rats displayed an increased incidence of polymorphonuclear leukocytes and macrophages in all studied stages of deficiency. Concomitantly, the relative number of lymphocytes decreased. This observation was confirmed by the analysis of the cell suspension obtained from the spleen. The greater number of adherent cells in the cell suspension from deficient rats provides an additional confirmation of the increased number of macrophages in the spleen of these rats. Analysis of lymphocyte populations demonstrated a reduced proportion of CD5+ and CD8+ cells after 8 days of deficiency. The reduction in the number of CD8+ cells in deficient rats could be related to the observed decrease in IFN-gamma concentration in the spleen homogenate. In short, this study shows that magnesium deficiency causes early cytological and immunological modifications in the spleen which appeared before macroscopical changes in this organ and before clinical symptoms of inflammation. These changes could be related to the altered immune response of deficient animals.
Animals↗
Magnesium deficiency induces an hyperalgesia reversed by the NMDA receptor antagonist MK801.
The aim of this study was to determine the changes of the nociceptive thresholds in response to an acute mechanical stimulus (paw pressure) in magnesium (Mg)-deficient rats, and the involvement of the NMDA receptor in these changes. Changes in vocalization thresholds was determined after 7 days of feeding with a Mg-depleted diet. Compared with the control group, Mg-deficient rats showed a significant decrease in the vocalization thresholds (-35.8 +/- 2.5%, p < 0.001) reflecting hyperalgesia. In Mg-deprived rats, three doses (0.06, 0.12 and 0.24 mg/kg s.c.) of dizocilpine (MK801), a non-competitive NMDA receptor antagonist, significantly reversed the hyperalgesia in a dose-dependent manner for at least 48 h. No effect of MK801 was observed in the control group. These data provide evidence that Mg deficiency could constitute a new model of hyperalgesia involving NMDA receptors.
Analysis of Variance↗
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.
Animals↗
Parenteral magnesium loading test in the assessment of magnesium status in healthy adult French subjects.
Parenteral magnesium loading test has been proposed as an adequate mean to evaluate magnesium status. However, applied tests vary among different laboratories and standardized procedure is not available. In the present study, we assessed magnesium status in 32 healthy adult French subjects by magnesium loading test using MgCl2 and determination of magnesium concentrations in plasma and erythrocytes. We observed a positive correlation between plasma and erythrocyte magnesium concentrations, but there was no correlation between magnesium retention and basal urinary excretion of magnesium, and plasma or erythrocyte magnesium concentrations.
Adult↗
Functional alterations in sarcoplasmic reticulum membranes of magnesium-deficient rat skeletal muscle as consequences of free radical-mediated process.
Free radical-induced physiopathologies are generally thought to be mediated by membrane injuries. Using a pro-oxidant model induced by dietary magnesium deficiency, we have recently shown that skeletal muscle lesions occurred with a rise in the calcium level and enhanced free radical production. In this study, we investigated the physicochemical and biochemical properties of sarcoplasmic reticulum membranes isolated from hind limb muscles of weanling male rats pair fed magnesium-deficient or control diets for 12 d. The calcium-induced calcium efflux from preloaded vesicles was increased in membranes isolated from Mg-deficient rat muscle. In agreement with this latter observation, we demonstrated increased ryanodine binding affinity of the calcium channel. The Ca2(+)-ATPase activity of the pump was shown to be reduced. The viscosity state of the membranes, assessed by 1,6-diphenyl-1,3,5-hexatriene fluorescence anisotropy, was significantly increased in Mg-deficient membranes. Moreover, these membranes demonstrated an increased content of protein carbonyls as compared with controls. These functional as well as structural changes are closed to those described in sarcoplasmic reticulum membranes oxidatively modified in vitro. Together, these data fitted well with the concept that free radical-induced membrane damages resulting in calcium overload may be at the origin of skeletal muscle lesion during Mg-deficiency.
Animals↗
Diets deficient in selenium and vitamin E affect plasma lipoprotein and apolipoprotein concentrations in the rat.
The present study examined the effects of Se, vitamin E and combined Se and vitamin E deficiencies in rats on plasma lipid, lipoprotein and apolipoprotein (apo) concentrations. Deficiencies were induced by feeding rats the respective diets for 6 weeks. The study shows that Se deficiency results in increased concentrations of plasma cholesterol and apo E. Both could be explained by an increase in the HDL1 fraction. Vitamin E deficiency alone had no significant effect on plasma lipid, lipoprotein and apo concentrations. Se deficiency in combination with vitamin E deficiency leads to an increase in plasma LDL and apo B concentrations. These results point to the need for further investigations on the mechanism by which Se deficiency affects lipoprotein metabolism.
Animals↗
Commentary on magnesium deficiency and nitric oxide.
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Animals↗
Dietary magnesium deficiency in rats enhances free radical production in skeletal muscle.
Recent studies suggest that free radicals may be involved in tissue injuries induced by magnesium deficiency. The aim of the present study was to assess the effect of magnesium deficiency on free radical production of skeletal muscle tissue. Male Wistar rats were pair-fed from weaning for 12 d either control or Mg-deficient diets containing 960 or 40 mg magnesium/kg diet, respectively. In the Mg-deficient rats, hypomagnesemia was accompanied by significantly lower magnesium and greater calcium concentrations in skeletal muscle tissue. Electron microscopy of skeletal muscle tissue revealed ultrastructural changes, including swelling mitochondria and disorganization of the sarcoplasmic reticulum network. Using the spin-trapping technique, we showed that significantly more hydroxyl radicals were generated in muscle homogenates of Mg-deficient rats. Moreover, the amount of spin trap adducts was increased in the presence of exogenous iron in both groups. In agreement with these observations, a greater concentration of thiobarbituric acid-reactive substances and a lower concentration of thiol groups were found in skeletal muscle of the Mg-deficient group compared with controls. These results strongly support the hypothesis that free radical-mediated injury could contribute to skeletal muscle lesions resulting from magnesium deficiency.
Animals↗
Anemia in copper-deficient rats: role of alterations in erythrocyte membrane fluidity and oxidative damage.
This study was designed to make precise the nature and the mechanism of the anemia induced by dietary copper (Cu) deficiency. Male Wistar rats were pair fed from weanling for 6 wk either a Cu-deficient or a control diet. The reduced red blood cell (RBC) 51Cr survival indicates an increased destruction of RBC during Cu deficiency. 1,6-Diphenyl-1,3,5-hexatriene fluorescence polarization studies revealed an increase in the fluidity of erythrocyte membranes from deficient rats. The reduced cholesterol-to-phospholipid ratio was consistent with the increased fluidity. Other results indicate an increased vulnerability of RBC to hemolysis in dilute hydrogen peroxide and an increased formation of lipid peroxidation products. Before exposure to free radical stress, electron spin resonance studies in intact RBC revealed decreased correlation time of 16-doxyl-stearic acid, confirming a more fluid membrane in RBC from Cu-deficient rats. After in vitro peroxidation, RBC from Cu-deficient rats showed a more ordered state of membrane lipids compared with controls. Together, these studies demonstrate the hemolytic nature of the anemia. The shortened survival of erythrocytes apparently results from changes in membrane fluidity and enhanced susceptibility to peroxidation.
Anemia↗
Magnesium deficiency in rats induces a rise in plasma nitric oxide.
Magnesium deficiency in rats leads to an oxidative stress involving an increased production of radical oxygen species. The present study was designed to examine the effect of experimental magnesium deficiency on plasma nitric oxide (NO) level and nitric oxide synthases (NOS) activities in rats. The data show that the concentration of NO is markedly increased in plasma of magnesium-deficient rats. This rise in plasma NO results from activation of inducible nitric oxide synthase (iNOS) rather than of the constitutive form (cNOS) of the enzyme. These data are in agreement with previous observations indicating that inflammation occurs during magnesium-deficiency and provide an additional cause of oxidative lesions through formation of peroxynitrite from nitric oxide and superoxide anion.
Animals↗
Glycogen hyperaccumulation in white muscle fibres of RN- carrier pigs. A biochemical and ultrastructural study.
1. The dominant RN- gene affects meat quality of pigs by increasing the glycogen content of muscle. Glycogen localization was studied in Longissimus dorsi muscle from RN- carrier pigs (RN- pigs) and rn+ rn+ homozygous pigs (rn+ pigs). 2. Ultrastructural study showed an excess of glycogen in the sarcoplasm of white fibres from RN- pigs as compared to rn+ pigs. 3. Lysosome-enriched fractions extracted from muscles contained 6% of the tissue glycogen content in both types of pigs. The distribution of the glycogen particles between sarcoplasm and lysosomes appeared to be similar in both RN- and rn+ pig tissues. 4. White fibres from RN- pigs with an increased glycogen level showed two ultrastructural alterations: the sarcoplasmic compartment was abnormally enlarged and a large proportion of mitochondria was morphologically modified. 5. The RN- gene seems, therefore, to be associated with alterations in the glycolytic metabolism, in the distribution of proteic compartments and in the oxidative metabolism of white muscle fibres.
Acetylglucosaminidase↗
Fluidity state of lymphocyte plasma membrane in malignant hyperthermia susceptible pigs and humans.
Recent studies suggest that abnormalities occur at the lipid level in malignant hyperthermia susceptible humans and pigs. To test this hypothesis, we first investigated the physical state of plasma membranes of lymphocytes isolated from normal and malignant hyperthermia susceptible swine. In halothane-challenged pigs, malignant hyperthermia susceptibility was also assessed by ryanodine binding assay on purified sarcoplasmic reticulum membranes. The results clearly show that plasma membrane of lymphocytes from malignant hyperthermic pigs are significantly more fluid than controls. We then attempted to apply the same methodology to lymphocytes prepared from human patients previously diagnosed by the halothane and caffeine contracture test. In that case, there was no clear relationship between malignant hyperthermia susceptibility and the fluidity state of lymphocyte plasma membranes.
Animals↗
Magnesium and ageing. I. Experimental data: importance of oxidative damage.
Magnesium status may be compromised with ageing for two reasons: insufficient intake (magnesium deficiency) or alterations in magnesium metabolism (magnesium depletion). There is a large volume of literature suggesting that magnesium deficit contributes to the ageing process and to the vulnerability to age-related diseases. One of the biological changes associated with ageing is an increase in free radical formation with subsequent damage to cellular processes. Prime targets of the more reactive free radicals are unsaturated lipids in cell membranes, amino acids in proteins, and nucleotides in DNA. The accumulation of unrepaired oxidative damage products may be a major factor in cellular ageing. Magnesium-deficient animals show an increased susceptibility to an in vivo oxidative stress and their tissues are more susceptible to in vitro peroxidation. Moreover, the protective properties of various antioxidant drugs and nutrients suggest that free radicals are involved in the injury process of magnesium deficiency. The consequences on stress susceptibility, defective membrane functions and perturbation of intracellular calcium metabolism, inflammation, cardiovascular diseases including atherosclerosis and ischaemia/reoxygenation injury, diabetes, fibrosis, immune dysfunction and other diseases associated with ageing are presented and discussed.
Aging↗
31P NMR and freeze fracture studies of sarcoplasmic reticulum membranes from normal and malignant hyperthermic pigs: effect of halothane and dantrolene.
The effects of halothane and dantrolene on sarcoplasmic reticulum membranes isolated from normal and malignant hyperthermia pig muscle have been investigated using 31P NMR and freeze fracture electron microscopy. The dynamical and structural changes are estimated from the second moment, as calculated from 31P NMR spectra. For both membranes, addition of halothane induces a similar decrease in the spectral second moment. At high concentration of halothane, freeze fracture replicas show small unilamellar vesicles or mixed micelles, uniformly sprayed in the case of malignant hyperthermia membranes but mainly aggregated for the normal ones. The effect of halothane on both membranes is partially inhibited by adding dantrolene. These results suggest that (i) the malignant hyperthermia syndrome is not directly related to the polar heads of phospholipids and (ii) dantrolene counteracts unspecifically the disturbing effect of halothane at the lipid level.
Animals↗
Membrane properties of the sarcolemma and sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia. Action of halothane.
The role of sarcolemma and sarcoplasmic reticulum in malignant hyperthermia was studied by the esr technique using the trapezius muscle membrane of both normal and genetically susceptible pigs. Normal and malignant hyperthermia membranes from sarcolemma as well as from sarcoplasmic reticulum did not show significant differences near the polar heads of the phospholipidic bilayer. In contrast, the fluidity and activation energy of normal membranes differed from those in malignant hyperthermia; in both sarcolemma and sarcoplasmic reticulum the mobility of the label was greater than the controls. The presence of halothane was examined, by inducing this disease anesthetically. The drug effect confirmed the above results, i.e. the disease affects mainly the hydrophobic core of the lipid bilayer of both sarcolemma and sarcoplasmic reticulum membranes.
Animals↗
Mitochondrial nucleotide translocase from skeletal muscle of halothane sensitive pigs: an electrophoretic study.
ATP translocation into mitochondria isolated from halothane-sensitive pig (HP) muscle was dramatically reduced compared with normal pigs (NP). To determine if this was due to a decreased amount of ATP translocase in the mitochondrial membranes, or a structural modification of this protein, an electrophoretic study was undertaken. Total proteins and purified translocase preparations from (NP) and (HP) mitochondria were analyzed by SDS gel electrophoresis. In the two types of mitochondria no significant differences were observed either in the amount of ATP translocase or in the molecular weight. Also, neither nonequilibrium pH gradient gel electrophoresis nor the analysis of peptides produced by limited proteolysis revealed any structural difference between the two types of protein. On the basis of these results, the depressed translocase activity observed in (HP) mitochondria cannot be explained by a reduced amount of the nucleotide translocase, nor a structural alteration of this protein. Possible inhibition of (HP) translocase activity by Ca2+ accumulation or by other mechanisms is discussed.
Animals↗