Changes in N-acetyl-beta-D-glucosaminidase activity in the urine and urinary albumin excretion in magnesium deficient rats

To discover the details of the effects of magnesium (Mg) deficiency on kidney function, the course of changes in N-acetyl-beta-D-glucosaminidase (NAG) activity in the urine and in urinary albumin excretion were examined in rats fed a Mg-deficient diet. NAG activity in the urine and urinary albumin excretion in rats fed the Mg-deficient diet significantly increased from 7 d until the end of the feeding period. We suggest that Mg-deficient diet rapidly induces kidney function insufficiency.     

Effects of gender on kidney function in magnesium-deficient rats

This study investigated the gender differences in the kidney function of magnesium (Mg)-deficient rats. Male and female rats were fed a control diet or a Mg-deficient diet for 21 d. Mg-deficient diet had no significant effect on kidney calcium (Ca) or phosphorus (P) concentration in male rats, while Ca and P concentrations in female rats were significantly higher in Mg-deficient rats than in the control rats. With regard to indicators of kidney function, no significant differences in creatinine clearance and serum urea nitrogen concentration were observed among the groups. Serum albumin concentrations were significantly lower in rats fed the Mg-deficient diet than in rats fed the control diet. In both sexes, urinary albumin excretion was significantly higher in rats fed the Mg-deficient diet than in rats fed the control diet. Gender differences had no significant influence on creatinine clearance, serum urea nitrogen concentration, serum albumin concentration and urinary albumin excretion. These results suggest that gender differences have no effect on kidney function in Mg-deficient rats under the condition used.     

Effect of Magnesium Deficiency on Various Mineral Concentrations in Rat Liver

Magnesium (Mg) deficiency is well known to affect metabolism of some trace minerals. We investigated the effect of Mg deficiency on hepatic concentration of various minerals in rats. Twelve 5-week-old male rats were divided into the groups given a control diet and an Mg-deficient diet. After 4?weeks, liver sample was collected from each rat. The concentrations of 36 minerals were simultaneously determined by a semiquantitative method of inductively coupled plasma-mass spectrometry (ICP-MS). The semiquantitative analysis showed that Mg deficiency significantly increased iron (Fe), copper (Cu), zinc (Zn), gallium (Ga), yttrium (Y), zirconium (Zr), molybdenum (Mo), rhodium (Rh), silver (Ag), and barium (Ba) concentrations, and significantly decreased scandium (Sc) and niobium (Nb) concentrations in rat liver. Then, hepatic Fe, Cu, Zn, Sc, Zr, and Mo concentrations were quantitatively measured, which indicated the similar effects as observed by the semiquantitative analysis. Additionally, the semiquantitative measurements of these minerals were highly correlated to these measurements with the quantitative method, but the measurements were not completely consistent between these analyses. The present study is the first research indicating the changes of hepatic Ga, Y, Zr, Mo, Rh, Ag, Ba, Sc, and Nb concentrations in Mg-deficient rats. The present study also indicates that the semiquantitative analysis with ICP-MS is a valid method for screening analysis to investigate various mineral concentrations in animal tissues.     

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.     

Diet-induced nephrocalcinosis and urinary excretion of albumin in female rats

This study was carried out to test the hypothesis that diet-induced nephrocalcinosis causes enhanced loss of albumin in urine, irrespective of the composition of the nephrocalcinogenic diet. Female rats were fed various purified diets for 28 days. There was a control diet (0.5% Ca, 0.04% Mg, 0.4% P, 15.1% protein, wt/wt), a low Mg (0.01% Mg), a high protein (30.2% protein) and a high P diet (0.6% P). The low Mg and high P diet induced nephrocalcinosis as demonstrated histologically and by markedly increased concentrations of kidney Ca. In rats fed the high protein diet, nephrocalcinosis was essentially absent. Group mean values of urinary excretion of albumin and plasma concentrations of urea were increased in rats fed either the low Mg or high P diet. The high protein diet did not affect urinary albumin but caused lysozymuria which was not seen in the other groups. Plasma urea was increased in rats fed the high protein diet. In individual rats, the concentration of Ca in kidney and urinary albumin excretion were positively correlated. It is suggested that nephrocalcinosis in female rats induced by either low Mg or high P intake causes kidney damage which in turn leads to increased concentrations of albumin in urine and urea in plasma.     

Influence of magnesium deficiency on the bioavailability and tissue distribution of iron in the rat

We investigated the effect of dietary magnesium (Mg) deficiency on the nutritive utilization and tissue distribution of iron (Fe). Wistar rats were fed an Mg-deficient diet (56 mg/kg) for 70 days. Absorbed Fe, Fe balance, number of the erythrocytes [red blood cells (RBC)] and leukocytes white blood cells (WBC)], hemoglobin (Hb), and Fe content were determined in samples of plasma, whole blood, skeletal muscle, heart, kidney, liver, spleen, femoral bone, and sternum obtained on experimental days 21, 35, and 70. The Mg-deficient diet significantly increased Fe absorption and Fe balance from week 5 until the end of the experimental period. This effect was accompanied by a significant decrease in the concentration of RBC and Hb from day 35, which caused the decrease in whole blood Fe seen on day 70. However, WBC were significantly increased from day 21 until the end of the experimental period. Mg deficiency significantly increased plasma and liver Fe at all three time points investigated. Spleen, heart, and kidney Fe were significantly increased only at the end of the study. However, on day 70, Fe concentration in the sternum had decreased significantly. No changes were found in skeletal muscle or femur Fe content. Mg deficiency led to increased intestinal absorption of Fe and decreased RBC counts, possibly as a result of increased fragility of the erythrocytes. Intestinal interactions between Fe and Mg, together with activation of erythropoiesis as a result of hemolysis, favored intestinal absorption of Fe. This situation gave rise to an increase in plasma Fe levels, which in turn favored Fe uptake and storage by different organs, especially the liver and spleen. However, despite the increased Fe content seen in the tissues of rats fed the Mg-deficient diet, these animals were unable to compensate for the hemolysis caused by this nutritional deficiency.     

Influence of dietary Ca, Mg, and P on cyclic-AMP excretion and kidney calcification in the rat.

A series of five experiments was conducted with young male albino rats to investigate effects of various levels of dietary Ca, P and Mg on urinary cAMP excretion and kidney calcification. Urinary cAMP excretion was shown to be directly correlated with injected parathyroid (PT) hormone dose level and to be inversely associated with dietary Ca intake. Thus, cAMP excretion may be presumed to reflect PT activity in the young rat. Magnesium deficiency tended to reduce cAMP excretion, while P excess did not affect it. Each treatment induced kidney calcification. Calcium deficiency increased cAMP excretion irrespective of Mg status, although nephrocalcinosis appeared only in the Mg-deficient animals. These data support the view that nephrocalcinosis of dietary origin in the rat is not mediated by increased PT activity.     

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-α (TNFα) 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 TNFα 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 TNFα 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 TNFα 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.     

Tumor-promoting activity of p-hydroxybenzenediazonium is accelerated in Mg-deficient rats

Tumor-promoting activity caused by the short-term administration of p-hydroxybenzenediazonium (PDQ) has been assayed in rats fed on a Mg-deficient diet as a reference model versus rats fed on a standard diet as controls. For 5 weeks groups of 20 rats, fed either on the Mg-deficient or standard diet, were treated simultaneously with PDQ. A group of 10 Mg-deficient rats remained untreated. Topical application of PDQ was followed by the appearance of macroscopic alterations in the skin, which were more evident in the Mg-deficient rats. No deaths occurred during the treatment. After 5 weeks' PDQ treatment the rats were killed and histological analyses were made. Tissues from the skin, liver, heart, kidney, lung and thymus were screened by conventional staining methods. Both the PDQ-treated Mg-deficient and PDQ-treated control rats presented tissue lesions, although to a different extent. The untreated Mg-deficient rats showed no such lesions. Mg-deficient rats treated with PDQ developed significant incipient fibrosarcomas (p<0.05) and extended hyperplasia (p<0.001), particularly in the skin, accompanied by a significant increase in the thickness of collagen (mean value: 445.4+/-47.2microm, p<0.05) compared to the control PDQ-treated group (mean values: 258.7+/-36.4microm). The overall results provide objective proof of tumor-promoting activity after 5 weeks' treatment with PDQ. Such a fast response is interpreted as being linked to the increased vulnerability of the membrane caused by Mg deficiency, which would more readily facilitate the toxic activity of p-hydroxybenzenediazonium ions.     

Magnesium deficiency in pregnant rats alters methylation of specific cytosines in the hepatic hydroxysteroid dehydrogenase-2 promoter of the offspring

Prenatal under-nutrition involves changes in the epigenetic regulation of specific genes. Maternal magnesium (Mg) deficiency affects maternal glucocorticoid metabolism, but the mechanisms underlying changes in glucocorticoid homeostasis of offspring are not well understood. In this study, we investigated the effects of feeding pregnant rats a Mg-deficient diet (0.003% magnesium) on the methylation of cytosine-guanine (CpG) dinucleotides in hepatic glucocorticoid genes of neonatal offspring, compared with controls (0.082% magnesium). Methylation of CpG dinucleotides in the peroxisome proliferator-activated receptor α (Ppara), glucocorticoid receptor (Nr3c1) and 11β-hydroxysteroid dehydrogenase-2 (Hsd11b2) promoters in the liver were measured by pyrosequencing. Quantitative real-time PCR was used to assess hepatic mRNA expression of each gene. Mean methylation of the Hsd11b2 promoter in the Mg-deficient offspring (33.2%) was higher than in controls (10.4%). This was due to a specific increase at CpG dinucleotides 1 (20.0% vs. control 10.1%), 2 (58.8% vs. 17.0%), 3 (29.7% vs. 6.2%) and 4 (38.7% vs. 8.8%) (p < 0.05). Ppara and Nr3c1 methylation status and expression did not differ between the groups. No significant difference was noted between male and female pups, which were equally represented. Therefore, a Mg-deficient diet alters glucocorticoid metabolism, predicting higher hepatic intracellular glucocorticoid concentrations, and is possibly a key mechanism that induces the metabolic complications of Mg deficiency.     

Chronic magnesium deficiency decreases tolerance to hypoxia/reoxygenation injury in mouse heart

AimsMagnesium (Mg) deficiency has been reported to be associated with the development of the metabolic syndrome, cardiovascular diseases, and sudden death. We examined the influence of chronic Mg deficiency on cardiac tolerance to hypoxia/reoxygenation injury.Main methodsMice were fed an Mg-deficient diet for 4 weeks, and then their hearts were excised for Langendorff perfusion experiments. The levels of total Mg in the blood and heart were quantified by atomic absorption spectrometry.Key findingsIn Mg-deficient mice, the Mg concentration in whole blood was markedly decreased; however, that in the heart remained unchanged. When the hearts of control mice were exposed to hypoxia/reoxygenation, removal of extracellular Mg from a normal Krebs solution containing 1.2 mM Mg resulted in a significant decrease in the recovery of the tension-rate product (TRP) upon reoxygenation. In Mg-deficient mice, the recovery of TRP in the heart was reduced significantly in the absence of extracellular Mg compared to that in controls. The addition of Mg to the perfusate did not improve TRP recovery. During hypoxia/reoxygenation, cardiac damage evaluated by myocardial aspartate amino trasferase (AST) release was greater in hearts of Mg-deficient mice than in that of control mice.SignificanceThese results indicate that chronic Mg deficiency causes severe hypomagnesemia and a decrease in cardiac tolerance to hypoxia, without changing the intracellular Mg content. The decreased tolerance to hypoxia was not affected by the presence or absence of extracellular Mg, suggesting that some intracellular metabolic abnormalities develop in the cardiac myocytes of Mg-deficient mice.     

Depression-like and anxiety-related behaviour of rats fed with magnesium-deficient diet

The aims of this study were to estimate of psychomotor activity, emotional status and magnesium (Mg) content in blood of rats fed with Mg-deficient diet for 49 days; and to find out whether the combination of vitamin B6 with Mg will reveal antidepressant- and anxiolytic-like activity and reduce the length of the treatment needed to recover rats from Mg-deficient condition. To induce hypomagnesemia, seventy-nine rats were placed on a Mg-deficient diet (Mg content < or = 15 mg/kg) and demineralized water for 7 weeks. Eight control rats were fed a basal control diet. On the forty-ninth day of Mg-deficient diet, rats were treated one of the six supplementations: Mg L-aspartate alone and in combination with pyridoxine, MgCl2 x 6H2O alone and in combination with pyridoxine, Magne B6 (Mg lactate with pyridoxine) and Mg sulfate (50 mg Mg and 5 mg vitamin B6 per kg). In our study Mg-deficiency was associated with depleted intraerythrocytic (0.748 +/- 0.036 vs. 1.83 +/- 0.026 mmol/l, p < 0.001) and plasma (0.567 +/- 0.029 vs. 1.20 +/- 0.030 mmol/l, p < 0.001) Mg level compared to control rats. It was shown Mg deficiency resulted in depression-like and anxiety-related behavior in rats. Open field test result in rats including locomotor activity (number of crossed squares) and vertical activity (number of standing on hind paws), number of visiting in central squares were decreased significantly. In the elevated plus maze test, the number of visiting open arms (by 63.6%) and residence time (by 78.5%) of rats were significantly less as compared with the control group. In the forced swimming test, time immobile was significantly increased (by 70.2%) and time of swimming was decreased (by 15%) compared to control. Mg salts alone and in combination with vitamin B6 administered to Mg-deficient rats increased the Mg level in plasma and erythrocytes. Furthermore, this increase was in relation to vitamin B6 given to the animal. It was established, that the application of Mg L-aspartate and MgCl2 x 6H2O in combinations with pyridoxine led to correction of behavioural disturbances of Mg-deficient animals. Antidepressant- and anxiolytic-like activity of studied salts was comparable with those observed in Magne B6 treatment and significantly higher than in Mg sulfate treatment.     

Effect of selenium deficiency on tissue taurine concentration and urinary taurine excretion in the rat

The purpose of this study was to determine the effect of selenium deficiency on tissue taurine levels and urinary taurine excretion. Weanling male Sprague-Dawley rats were fed selenium-deficient or selenium-adequate diets for 20 weeks. As selenium deficiency developed, urinary taurine excretion increased in selenium-deficient rats compared to controls. At 12 weeks, the selenium-deficient rats excreted 1.7-fold more taurine than control rats. At the same time plasma glutathione peroxidase was 1.2% of control and plasma glutathione was 226% of control. At 20 weeks, renal taurine was decreased but renal glutathione was increased in selenium-deficient rats compared to controls. Feeding the experimental diet for 6 weeks without methionine supplementation caused a fall in urinary taurine excretion. However, there was no difference between selenium-deficient and control rats. These results indicate that selenium deficiency affects renal handling of taurine in the rat when dietary sulfur amino acids are not restricted.     

Effect of various levels of supplementation with sodium pivalate on tissue carnitine concentrations and urinary excretion of carnitine in the rat

In previous studies, sodium pivalate has been administered to rats in their drinking water (20 mmoles/L; equivalent to 0.3% of the diet) as a way to lower the concentration of carnitine in tissues and to produce a model of secondary carnitine deficiency. Although this level of supplementation results in a marked decrease in carnitine concentration in a variety of tissues, it does not produce the classical signs of carnitine deficiency (i.e., decreased fatty acid oxidation and ketogenesis). The present study was designed (1) to determine if increasing the level of pivalate supplementation (0.6, 1.0% of the diet) would further reduce the concentrations of total and free carnitine in rat tissues without altering growth or food intake, and (2) to examine the effect of length of feeding (4 vs. 8 weeks) on these variables. Male, Sprague-Dawley rats were randomly assigned to either a control (0.2% sodium bicarbonate) or experimental diet (0.3, 0.6, 1.0% sodium pivalate) for either four or eight weeks. Animals (n = 6/group) were housed in metabolic cages; food and water were provided ad libitum throughout the study. Supplementation with sodium pivalate did not alter water intake or urine output. Ingestion of a diet containing 1.0% pivalic acid decreased food intake (g/day; P < 0.05), final body weight (P < 0.007), and growth rate (P < 0.001) after four weeks. The concentration of total carnitine in plasma, heart, liver, muscle, and kidney was reduced in all experimental groups (P < 0.001), regardless of level of supplementation or length of feeding. The concentration of free carnitine in heart, muscle, and kidney was also reduced (P < 0.001) in rats treated with pivalate for either four or eight weeks. The concentration of free carnitine in liver was reduced in animals supplemented with pivalate for eight weeks (P < 0.05), but no effect was observed in livers from rats treated for four weeks. Excretion of total carnitine and short chain acylcarnitine in urine was increased in pivalate supplemented rats throughout the entire feeding period (P < 0.001). Free carnitine excretion was increased during Weeks 1 and 2 (P < 0.01), but began to decline during Week 3 in experimental groups. During Weeks 6 and 8, free carnitine excretion in pivalate supplemented rats was less than that of control animals (P < 0.01). In summary, no further reduction in tissue carnitine concentration was observed when rats were supplemented with sodium pivalate at levels greater than 0.3% of the diet. Food intake (g/day) and growth were decreased in rats fed a diet containing 1.0% sodium pivalate. These data indicate that maximal lowering of tissue carnitine concentrations is achieved by feeding diets containing 0.3% sodium pivalate or less.     

Dietary boron modified the effects of magnesium and molybdenum on mineral metabolism in the cholecalciferol-deficient chick

The metabolic effects of dietary boron, magnesium, and molybdenum on mineral metabolism in the cholecalciferol-deficient chick, with emphasis on growth cartilage histology, were studied. One-day-old cockerel chicks were assigned to groups in a fully-crossed, three factor, 2 x 2 x 2 design. The basal diet was based on ground corn, high-protein casein, and corn oil and contained 125 IU cholecalciferol (inadequate), 0.465 mg B, 2.500 mg Mg, and 0.420 mg Mo/kg. The treatments were the supplementation of the basal diet with B at O or 3; Mg at 300 (inadequate) or 500 (adequate); and Mo at 0 or 20 mg/kg. At d 25, B depressed mortality, alleviated the cholecalciferol-deficiency induced distortion of the marrow sprouts (MS) of the proximal tibial epiphysial plate, and elevated the numbers of osteoclasts within the MS. Adequate Mg exacerbated the cholecalciferol-deficiency induced bone lesions. Mo widened the MS markedly. In Mg-deficient chicks, B elevated plasma Ca and Mg concentrations and growth, but inhibited initiation of cartilage calcification; B had the opposite effect in Mg-adequate chicks. An interaction among B, Mg, and Mo affected plasma uric acid and glucose concentrations. B may function to modify mineral metabolism in cholecalciferol deficiency, suppressing bone anabolism in concurrent Mg deficiency and bone catabolism in concurrent Mg adequacy.     

Effect of Mg nutriture on the dynamics of administered 25Mg exchange in vivo in the rat

The effect of Mg nutriture on Mg exchange and interorgan distribution was studied in adult rats ten days after a single I.P. dose of (25)Mg ( approximately 5 mg). First the effects of level of Mg intake (0.25, 0.05, or 0.01% Mg) on standard measures of Mg nutriture were studied for 62d to fully document the Mg status of the adult rats. The Mg-deficient diet led to a reduction in plasma, erythrocyte and urine Mg concentration but the only tissues affected were kidney and bone; no outward signs of deficiency were observed. At this point, the 4 remaining rats from each diet group received a single dose of (25)Mg and were killed 10d later. Unlike measures of total Mg content, Mg restriction was observed to significantly alter the distribution of isotope within the soft tissue compartment. The proportion of retained isotope accumulated by soft tissues other than skeletal muscle increased. Because this was not true for skeletal muscle, exogenous (25)Mg label was diverted to more metabolically active tissues during Mg restriction. The apparent Mg exchangeable pool (MgEP) size, determined by in vivo stable isotope dilution, reflected this difference in skeletal muscle (25)Mg accumulation; MgEP size was 39% lower in Mg restricted (0.01% Mg) compared to control (0.05% Mg) rats. The pool of exchangeable Mg in bone was also reduced by Mg restriction but, unlike the soft tissue compartment, the reduction in bone exchangeable Mg was quantitatively similar to the reduction in total Mg content.     

The characterization of central neuromediation in rats fed with magnesium-deprived diet before and after magnesium replenishment

Magnesium (Mg) has been proposed to take part in biochemical dysregulation contributing to psychiatric disorders. The aims of this study was to estimate acute behavioural responses to clonidine (0.1 mg/kg i.p.), d-amphetamine (5 mg/kg, i.p), arecoline (15 mg/kg i.p), nicotine (6 mg/kg i.p.), apomorphine (1.5 mg/kg i.p.) and L-5-hydroxytryptophan (300 mg/kg i.p.) in rats fed with Mg-deprivated diet for 49 days and then treated with organic and inorganic Mg salts (50 mg Mg per kg) ether alone or in combination with pyridoxine (5 mg vitamin B6 per kg). In our study Mg-deficient rats were more sensitive to d-amphetamine-induced motor stereotypes compared with control rats; time of onset of the stereotypies insignificantly decreased by 14.89% and duration of the stereotypies significantly increased by 19.44% (320.36 +/- 19.90 vs. 268.23 +/- 8.17 minutes; p = 0.043). Mg deficiency did not modulate sensitivity to nicotine-induced seizure. The time between nicotine injection and emergence of clonic seizure (seizure latency) in the controls and Mg-deficient rats were 0.80 +/- 0.26 and 0.96 +/- 0.21 minutes respectively. Duration of the seizures in the controls and Mg-deficient rats were 64.93 +/- 7.20 and 79.32 +/- 8.13 minutes. In our study, Mg deficiency did not affect on clonidine- and apomorphine-induced hypothermia. Clonidine produced similar decreases in rectal temperature in controls and Mg-deficient group. In experiments using apomorphine, values of hypothermia were similar to those observed with clonidine. Mg deficiency antagonized 5-hydroxytryptophan-induced head-twitch response. The number of head twitches produced by 5-hydroxytryptophan was significantly (p = 0.49) decreased: twofold in magnesium-deficient rats (1.23 +/- 0.44 per minute) as compared with controls (2.42 +/- 0.52 per minute). Arecoline-induced tremor was comparably less expressed in Mg-deficient rats than in controls. The time between arecoline injection and time of onset of the tremor in the controls and Mg-deficient rats were 92.75 +/- 19.35 and 245.17 +/- 121.86 seconds respectively (p < or = 0.035). Duration of the tremors in the controls and Mg-deficient rats were 1175.58 +/- 127.87 and 703.83 +/- 89.33 seconds (p = 0.015). Magnesium salts (Mg chloride, Mg L-aspartate alone and in combination with B6) were administered through gastric tube during twenty days up to complete compensation oferythrocyte and plasma Mg levels in all experimental groups. In our study administration of Mg salts resulted in normalization of acute behavioural responses in Mg-deficient rats to d-amphetamine, arecoline, and L-5-hydroxytryptophan. Behavioural responses in rats treated with both Mg chloride and Mg L-aspartate in combinations with B6 were comparable with those observed in MagneB6 treatment.     

Maternal Magnesium Deficiency in Mice Leads to Maternal Metabolic Dysfunction and Altered Lipid Metabolism with Fetal Growth Restriction

Inadequate magnesium (Mg) intake is a widespread problem, with over 50% of women of reproductive age consuming less than the Recommended Dietary Allowance (RDA). Because pregnancy increases the requirement for Mg and the beneficial effects of magnesium sulfate for preeclampsia/eclampsia and fetal neuroprotection are well described, we examined the outcomes of Mg deficiency during pregnancy. Briefly, pregnant Swiss Webster mice were fed either control or Mg-deficient diets starting on gestational day (GD) 6 through euthanasia on GD17. Mg-deficient dams had significantly reduced weight gain and higher plasma adipokines, in the absence of inflammation. Livers of Mg-deficient dams had significantly higher saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) and lower polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) (P < 0.0001) and arachidonic acid (AA) (P < 0.0001). Mechanistically, Mg deficiency was accompanied by enhanced desaturase and elongase mRNA expression in maternal livers along with higher circulating insulin and glucose concentrations (P < 0.05) and increased mRNA expression of Srebf1 and Chrebp, regulators of fatty acid synthesis (P < 0.05). Fetal pups exposed to Mg deficiency were growth-restricted and exhibited reduced survival. Mg-deficient fetal livers showed lower MUFAs and higher PUFAs, with lower desaturase and elongase mRNA expression than controls. In addition, DHA concentrations were lower in Mg-deficient fetal brains (P < 0.05). These results indicate that Mg deficiency during pregnancy influences both maternal and fetal fatty acid metabolism, fetal growth and fetal survival, and support better understanding maternal Mg status before and during pregnancy.     

High arsenic intake raises kidney copper and lowers plasma copper concentrations in rats

The effect of high arsenic intake on copper metabolism was investigated. Male rats aged 6 wk had free access to purified diets containing either 0 or 100 mg As/kg diet and demineralized water for a period of 2 wk. Arsenic was added to the diet in the form of NaAsO₂. The high-arsenic diet decreased feed and water intake and body weight gain, but significantly increased liver weight. Kidney weight was not affected. Arsenic feeding drastically elevated kidney copper concentration, but significantly reduced copper concentration in plasma. Both true absorption and biliary excretion of copper were decreased significantly in rats fed the high-arsenic diet. True copper absorption was lowered essentially through the lower copper intake in the rats fed arsenic. It is speculated that arsenic feeding primarily leads to copper accumulation in the kidney, followed by a decrease in feed intake and thus in true, absolute copper absorption, a decrease in plasma copper concentration, and a decrease in biliary copper excretion.