Magnesium-deficient Animals Research Articles

Brain anticonvulsant protection of mice given chronic carbamazepine under various fatty acid and magnesium diet conditions

The anticonvulsant and mood stabilizer drug carbamazepine (CBZ) was evaluated for anti-seizure activity after drug pretreatment of young weaning mice given various oil-based diets. These diets had various mono-(MUFA) and poly-(PUFA) unsaturated fatty acid contents, were associated or not with magnesium deprivation, and were given over the entire experimental period (34 days). The diets included a commercial and three purified synthetic diets (n-6 PUFA, n-3 PUFA and MUFA-based chows containing 5% corn/sunflower oils 1:3, 5% rapeseed oil and 5% high oleic acid sunflower oil/sunflower oil 7:3, respectively). A 10-days CBZ treatment (50mg/kg/day fragmented in two daily intraperitoneal injections of 25mg/kg) was given 20 days after initiating diet administration and evaluations of mice was performed 4 days after arrest of CBZ in various seizure tests. In these conditions, CBZ pretreatment still exhibited anticonvulsant protection especially in magnesium-deficient animals. Ethosuximide (ESM)-like profiles under MUFA and n-3 PUFA diets and unusual GABAAergic profile under n-6 PUFA diet in magnesium-deficiency dependent audiogenic seizures (MDDAS) test as well as protection against NMDA-induced seizures in all lipid (n-3 PUFA>MUFA and n-6 PUFA) diet conditions were observed in CBZ-pretreated mice. By highlighting ESM-like and anti-NMDA mechanisms previously induced by an n-3 PUFA diet, present CBZ anticonvulsant properties suggest brain protective targets common to CBZ and n-3 PUFAs.

Phagocyte priming by low magnesium status: input to the enhanced inflammatory and oxidative stress responses

Epidemiological and experimental studies underline the role of magnesium in inflammation. Several data indicate an enhanced response of phagocytes (granulocytes, macrophages) derived from magnesium-deficient animals or cultured under low magnesium conditions to the inflammatory mediators' stimulation. On the contrary, it was pointed out that high extracellular Mg2+ concentration might partially attenuate the activation of phagocyte leukocytes. Thus, it is likely that magnesium-deficient conditions lead to the priming (pre-activation) of phagocytic cells. Magnesium status is an important modulator of the phagocyte response to immune stimuli and consequently could be implicated in a wide range of pathophysiological issues, e.g. those related to the production of radical oxygen species (ROS). It is likely that magnesium directly modulates phagocyte priming by its calcium antagonism and indirectly by its effect on the immunoinflammatory processes, the source of the priming mediators.

Features of Central Neurotransmission in Animals in Conditions of Dietary Magnesium Deficiency and After Its Correction

Magnesium is important in the regulation of neurotransmitter metabolism and the modulation of receptor function in the CNS, including neurotransmitters and receptors involved in the pathogenesis of many mental disorders. The aim of the present work was to perform a pharmacological evaluation of the central mechanisms of action of magnesium salts in the clofelin, phenamine, arecoline, nicotine, apomorphine, and 5-hydroxytryptophan tests in conditions of dietary magnesium deficiency. After reaching the magnesium deficiency state, animals were given oral (via tube) magnesium L-asparaginate and magnesium chloride lone and in combination with vitamin B(6), as well as the reference agent Magne B6. Our assessments of phenamine stereotypy in magnesium-deficient animals showed reductions in the latent period by an average of 14.89% and a significant increase in the duration of phenamine stereotypy by an average of 19.44% (from 268.23 +/- 8.17 to 320.36 +/- 19.90 min) as compared with intact rats. Studies of hyperkinesia induced by 5-hydroxytryptophan showed a two-fold reduction in its extent in the magnesium-deficient group (p </= 0.05). Administration of arecoline to magnesium-deficient animals resulted in a statistically significant increase in the latent period from a mean of 92.75 +/- 19.35 to 245.17 +/- 121.86 sec, with a reduction in the duration of tremor from an average of 1175.58 +/- 127.87 to 703.83 +/- 89.33 sec (p </= 0.05) as compared with intact rats. In terms of its influence on the hypothermic effects of clofelin and apomorphine and the convulsive effect of nicotine, there were no significant differences between the intact group and the magnesium-deficiency animals. Administration of magnesium salts compensated for the magnesium deficiency in plasma and erythrocytes, which was accompanied by recovery of measures in the phenamine, arecoline, and 5-HT tests to levels typical of intact controls. There was a tendency for magnesium L-asparaginate and magnesium chloride combined with pyridoxine to have greater activity, and the efficacies of these treatments was no less than that of reference agent Magne B6. Thus, dietary magnesium deficiency led to impairment of neurotransmission in central serotoninergic, M-cholinergic, and noradrenergic structures and administration of magnesium salts reversed these changes.

Cardiac fibrogenesis in magnesium deficiency: a role for circulating angiotensin II and aldosterone

Mechanisms underlying cardiac fibrogenesis in magnesium deficiency are unclear. It was reported earlier from this laboratory that serum from magnesium-deficient rats has a more pronounced stimulatory effect on cell proliferation, net collagen production, and superoxide generation in adult rat cardiac fibroblasts than serum from rats on the control diet. The profibrotic serum factors were, however, not identified. This study tested the hypothesis that circulating angiotensin II may modulate cardiac fibroblast activity in hypomagnesemic rats. Male Sprague-Dawley rats were pair-fed a magnesium-deficient (0.0008% Mg) or -sufficient (0.05%) diet for 6 days, and the effects of serum from these rats on [3H]thymidine and [3H]proline incorporation into cardiac fibroblasts from young adult rats were evaluated in the presence of losartan, an angiotensin II type 1 (AT1) receptor antagonist, and spironolactone, an aldosterone antagonist. Losartan and spironolactone markedly attenuated the stimulatory effects in vitro of serum from the magnesium-deficient and control groups, but the inhibitory effects were considerably higher in cells exposed to serum from magnesium-deficient animals. Circulating and cardiac tissue levels of angiotensin II were significantly elevated in magnesium-deficient animals (67.6% and 93.1%, respectively, vs. control). Plasma renin activity was 61.9% higher in magnesium-deficient rats, but serum angiotensin-converting enzyme activity was comparable in the two groups. Furthermore, preliminary experiments in vivo using enalapril supported a role for angiotensin II in magnesium deficiency. There was no significant difference between the groups in serum aldosterone levels. The findings suggest that circulating angiotensin II and aldosterone may stimulate fibroblast activity and contribute to a fibrogenic response in the heart in magnesium deficiency.

Synergistic effect of ofloxacin and magnesium deficiency on joint cartilage in immature rats.

Single high oral doses of fluoroquinolones (e.g., 1,200 mg of ofloxacin/kg of body weight) are chondrotoxic in juvenile rats. Characteristic cartilage lesions are detectable as early as 12 h after treatment. Since this dosing regimen does not reflect the therapeutic situation, we studied the effects of a 5- or 7-day treatment with ofloxacin at lower oral doses (10, 30, and 100 mg/kg twice a day [b.i.d.]) on joint cartilage in 4-week-old rats. We additionally investigated whether the effects of ofloxacin under these conditions are enhanced in animals kept on a magnesium-deficient diet during treatment. Knee joints were examined histologically. The concentrations of ofloxacin and magnesium were determined in plasma and cartilage. The lowest ofloxacin dose at which cartilage lesions occurred in animals on a standard diet was 100 mg/kg b.i.d. for 5 days. Peak plasma ofloxacin levels were approximately 10 mg/liter in these rats and thus were in the same range as the levels in the plasma of humans during therapy with high doses of ofloxacin. Treatment with 30 mg of ofloxacin/kg b.i.d. for 7 days caused no cartilage lesions in rats on a standard diet, but lesions did occur in 10 of 12 rats that were simultaneously fed a magnesium-deficient diet. Magnesium concentrations in bone, plasma, and cartilage from animals on an Mg(2+)-deficient diet were significantly lower than those in the controls. The concentration in plasma from animals on an Mg(2+)-deficient diet was 0.27 +/- 0.03 mmol/liter, whereas it was 0.88 +/- 0.08 mmol/liter in plasma from rats on a standard diet (means +/- standard deviations). Ofloxacin treatment did not change the total magnesium concentrations in tissues, as determined with ashed samples. The incidence of ofloxacin-induced lesions was higher in the magnesium-deficient animals, suggesting a synergistic effect. These results must be taken into account for a benefit-risk evaluation if ofloxacin is considered for use in the pediatric population.

Plasma Magnesium, Calcium and Inorganic Phosphorus in Norwegian Semi-Domestic Female Reindeer (Rangifer tarandus tarandus) on Winter Pastures

Altogether 1645 blood plasma samples were collected from 2 reindeer (Rangifer tarandus tarandus L) herds in northern Norway (Magerøy and Sørøy), and from 2 herds in southern Norway (Filefjell and Lom) during the period from 1992 through 1995. Except for 2 subsets of samples from Lom (N = 51 and 56) all samples were collected on winter pasture between January and early March. The herds were of varying nutritional status, the Lom herd being regarded to be among the best in the country in this regard. Plasma levels of magnesium, calcium and inorganic phosphorus were measured. In addition, plasma progesterone was used as a pregnancy test, a discriminatory level of 7 nmol l-1 being chosen as indicating pregnancy. For the investigated minerals, the analysis of variance included effects for year of sampling, herd, pregnancy status, age and mineral status. Average mineral concentrations varied considerably between herds and year of sampling. The overall average (SD; min-max) concentrations of plasma Ca, Mg and P in samples collected on winter pastures were 2.42 (0.25; 0.9-3.6), 0.83 (0.17; 0.16-1.39) and 1.70 (0.47; 0.2-3.4) mmol l-1, respectively. The overall pregnancy rate was 79.8%. The frequency of subnormal plasma values within herds and years for magnesium (< or = 0.7 mmol l-1) and calcium (< or = 2.2 mmol l-1) varied between 0-61.9% and 1.4-44.9% respectively. Significant positive correlations between calcium and magnesium were found in all herds except in the Lom herd where all animals had plasma Mg values above 0.8 mmol l-1. Generally, the highest correlation coefficients were found in subsets of data with a high frequency of subnormal magnesium concentrations. Plasma magnesium showed the greatest contribution to plasma calcium variance when tested together with herd, year of sampling, pregnancy status, age and plasma inorganic phosphorus. A decrease in plasma magnesium from 1 to < 0.5 mmol l-1 was associated with a decrease in plasma calcium of approximately 15%. Mean plasma magnesium and calcium levels were significantly (p < 0.01) higher in pregnant animals than in barren females, a significant positive relationship being found between pregnancy rate and average concentrations of the same minerals when sets of observations from different herds and different years were compared. The positive correlation between plasma calcium and magnesium in herds with subnormal magnesium minima is consistent with evidence from other species reported in the literature of impaired calcium homeostasis in magnesium deficient animals.

Progressive magnesium deficiency increases mortality from endotoxin challenge: protective effects of acute magnesium replacement therapy.

To study the effects of endotoxin on magnesium homeostasis; to determine if progressive magnesium deficiency alters outcome from endotoxin challenge; and to evaluate the efficacy of magnesium therapy in reducing endotoxin-induced mortality. Prospective, placebo-controlled, randomized, multiexperiment studies. Research laboratory of a university hospital. Male Sprague Dawley rats (n = 299). Experiment 1 was designed to test if endotoxin alters magnesium homeostasis. Circulating total and ionized magnesium (estimated by ultrafilterable values) concentrations were determined in blood samples collected from animals after the randomized administration of placebo or 0.3, 3.0, or 30 mg/kg of endotoxin. A baseline blood sample was collected and then a second blood sample was obtained at 5, 15, 30, 60, 120, or 180 mins after endotoxin or placebo administration. In experiment 2, animals were randomized to receive magnesium-sufficient diets or magnesium-deficient diets for 6 wks. After 6 wks, the effects of the randomized administration of 3.0 mg/kg endotoxin or placebo were evaluated on mortality and analyte values (pH and blood gases, sodium, potassium, chloride, glucose, ionized calcium, hematocrit, total and ultrafilterable magnesium concentrations) in the three study groups (magnesium-sufficient, 3-wk magnesium-deficient, or 6-wk magnesium-deficient). In experiment 3, magnesium-deficient animals were randomized to receive 50 mmol/kg magnesium chloride or placebo, before or after the administration of 3.0 mg/kg of endotoxin. Baseline and 24-hr analyte determinations were performed and outcome was analyzed. Experiment 1: Significant increases (p < .05) in circulating total magnesium concentrations were found in animals that received 30 mg/kg of endotoxin, at 120 mins (0.79 +/- 0.10 vs. 0.60 +/- 0.05 mmol/L), and 180 mins (0.74 +/- 0.04 vs. 0.56 +/- 0.04 mmol/L) compared with baseline values. Similarly, significant increases (p < .05) in ionized magnesium concentrations were observed 120 and 180 mins after 3.0 and 30 mg/kg of endotoxin compared with baseline values. Experiment 2: Magnesium deficiency was strongly (p < .02) associated with increased mortality from endotoxin challenge. Endotoxin administration (3.0 mg/kg) was lethal in 10 (43%) of 23 magnesium-sufficient animals, 15 (65%) of 23 3-wk magnesium-deficient animals, and 20 (83%) of 24 6-wk magnesium-deficient animals. Experiment 3: In magnesium-deficient animals, rats treated with magnesium replacement therapy had significantly increased survival from endotoxin administration (15 [52%] of 29 vs. five [17%] of 29, p < .01) compared with placebo-treated animals. a) Endotoxin challenge causes significant increases in circulating total and ionized magnesium concentrations. b) Progressive magnesium deficiency is strongly associated with increased lethality, and magnesium replacement therapy provides significant protection from endotoxin challenge. c) These experimental results support the concept that cellular injury is probably associated with increases in circulating magnesium concentrations. Furthermore, these experimental findings suggest that magnesium deficiency predisposes to worse outcome from endotoxin challenge, and that replacement therapy in the setting of magnesium deficiency may be warranted, especially in critically ill subjects.

Hypertriglyceridemic serum from magnesium-deficient rats induces proliferation and lipid accumulation in cultured vascular smooth muscle cells

An important characteristic of hyperlipemia associated with magnesium deficiency in rats is the postprandial accumulation of triglyceride-rich lipoproteins. The present investigation was performed to determine the effect of serum from magnesium-deficient animals on cultured vascular smooth muscle cells (VSMC). Sera were obtained from control and magnesium-deficient rats fed adequate or deficient diets for 8 days. Magnesium-deficient animals were hypertriglyceridemic compared with control rats, but their total cholesterolemia was not significantly modified. Pooled sera from control and magnesium-deficient animals were added to the culture medium at various concentrations. The maximum of proliferation for both control and magnesium-deficient sera was reached when they were added at 6% to the culture medium and on day 4 after the begining of incubation. Medium containing serum from magnesium-deficient rats stimulated the cell proliferation as monitored by cell count and [ 3H]thymidine incorporation. Staining of VSMC with Oil red O and measuring lipids have shown a marked lipid accumulation (triglycerides) in cells incubated with serum obtained from magnesium-deficient animals compared with serum from control rats. These results indicate that serum from magnesium-deficient rats contains factors that stimulate proliferation of arterial medial cells and that hyperlipemia associated with magnesium-deficiency may cause lipid accumulation in vascular cells.

Protein Oxidation in Magnesium Deficient Rat Brains and Kidneys

Magnesium deficiency produces a pro-oxidant systemic inflammation in rats. The purpose of these experiments was to determine if and when there is any oxidation of cellular proteins. We have found there is a significant increase in protein oxidation products, protein carbonyls, in both the brain and the kidney within 2 to 3 weeks on a magnesium deficient diet. These changes occur prior to any detectable changes in cellular glutathione, tissue damage or dysfunction. We conclude that oxidation of cellular proteins occur early in magnesium deficiency and may contribute to the tissue damage and loss of function observed in the later stages of the deficiency. This is the first demonstration of the time course of protein oxidation product development in magnesium deficient animals.

Erythrocytes from magnesium-deficient hamsters display an enhanced susceptibility to oxidative stress.

Previous studies in our laboratory have indicated a role for free radical participation in magnesium deficiency cardiomyopathy. We have demonstrated the ability of various antioxidant drugs and nutrients to protect against magnesium deficiency-induced myocardial injury. In this study, we have examined erythrocytes from normal and magnesium-deficient animals and compared their susceptibility to an in vitro oxidative stress. Syrian male hamsters were placed on either magnesium-deficient or magnesium-supplemented diets. Animals from each group also received vitamin E in doses of 10 and 25 mg as subcutaneous implants. Erythrocytes obtained after 14 days on the diet were exposed to an exogenous hydroxyl (.OH) radical generating system (dihydroxyfumarate not equal to Fe3+ ADP) at 37 degrees C for 20 min. Erythrocyte crenation was observed and quantified by scanning electron microscopy. Lipid peroxidation, hemolysis (%), and intracellular glutathione levels were determined. In addition, serum lipid changes and membrane phospholipids were characterized. Our data demonstrate that erythrocytes from magnesium-deficient animals are more susceptible to free radical injury, supporting our hypothesis that magnesium deficiency reduces the threshold antioxidant capacity.

Magnesium-deficiency elevates circulating levels of inflammatory cytokines and endothelin.

We have developed two rodent models of diet-induced magnesium-deficiency in which histologically defined cardiac lesions can be induced within two to three weeks. During the development of these lesions, the magnesium-deficient animals exhibit circulating cytokine levels which are indicative of a generalized inflammatory state. Dramatic elevations of the macrophage-derived cytokines, IL-1, IL-6, and TNF-alpha together with significantly elevated levels of the endothelial cell-derived cytokine, endothelin, were detected in the plasma of these animals. We believe that the pathophysiological effects caused by the action of these cytokines may play a role in the promotion of cardiovascular pathology associated with magnesium deficiency.

Canine renal and systemic hemodynamic measurements after 4 weeks of a magnesium deficient diet.

To probe renal hemodynamic measurements in relation to simultaneous systemic hemodynamic measurements in normal, adult, conscious dogs on a magnesium-deficient diet, 6 experimental animals were given 4 weeks of a magnesium-deficient diet compared to 9 animals whose dietary magnesium was normal. Systemic hemodynamics were estimated using a thermodilution catheter, and renal hemodynamics were estimated by standard renal clearance techniques. Electrolytes and hormones were also surveyed in these same animals at the time of hemodynamic measurements. Heart rate was significantly higher in magnesium-deficient dogs, but there were no other systemic hemodynamic differences between the two groups of dogs. Renal blood flow, effective renal plasma flow, and urinary osmolality were significantly higher in the magnesium-deficient animals. Whole-blood ionized calcium and potassium, serum magnesium, and fractional excretion of magnesium were lower in the magnesium-deficient dogs. We conclude that the renal circulation is more sensitive than the systemic circulation to disturbances in magnesium balance. Disturbances of other electrolytes accompanying magnesium deficiency were also confirmed.

Changes in the erythrocyte membrane during magnesium deficiency

Several parameters were investigated to assess the properties of the erythrocyte membrane from male rats of initial weight 85 g that were subjected to dietary magnesium depletion for four weeks. The ghost membranes from these cells had an increased fluidity compared with controls, as monitored by fluorescence polarization using the probe diphenylhexatriene. Intract erythrocytes from the same rats had a reduced osmotic fragility to hypotonic salin solutions and measurement of intracellular/extracellular ratios suggested an increased permeability to the loss of cellular magnesium and potassium, and the gain of sodium, in magnesium-deficient animals. The significance of these membrane changes in relation to the anaemia that develops during magnesium deficiency is uncertain, but they may be the primary lesion underlying disturbances in cellular metabolism.

Influence of Magnesium Deficiency on Liver Collagen after Carbon Tetrachloride or Ethanol Administration to Rats

The effects of magnesium deficiency on liver collagen after the administration of a hepatotoxic substance were investigated. Rats, fed a control or magnesium-deficient diet (0.040 g/kg), received six CCl4 or mineral oil injections administered at 2-d intervals starting from the first day of diet treatment. They were killed 3 or 12 d after the last injection. Between postinjection d 3 and 12, no change of magnesium concentration in liver was observed in the deficient rats. Three days after the end of treatment liver calcium in the magnesium-deficient CCl4-treated rats was higher than in any other group. Liver collagen of untreated control rats and untreated magnesium-deficient rats was not significantly different. In control and magnesium-deficient animals receiving CCl4 treatment, the liver collagen levels were significantly higher than in untreated rats. The magnesium-deficient rats receiving CCl4 have higher liver collagen than the controls receiving CCl4. In a second experiment the effect of suboptimum intake of magnesium (0.120 g/kg) combined with the ingestion of ethanol was studied in rats given a solution of ethanol in water for 55 d as their only source of fluid. Mortality occurred in the magnesium-deficient rats receiving ethanol, and body weights of these rats were lower than those of animals in the other three groups. The collagen concentration in liver was higher in magnesium-deficient rats consuming ethanol than in any other groups. The synergistic action between magnesium deficiency and ethanol therefore appears to be analogous to that observed with CCl4.

Elevated circulating immunoreactive calcitonin in the magnesium-deficient normocalcemic rat.

Previous studies indicate that magnesium, like calcium, stimulates the release of calcitonin (CT) from the thyroid gland. On the other hand, C-cell hyperplasia has been noted in magnesium-deficient dogs and rats. To explore further possible interrelationships between magnesium and CT, 21-day-old Sprague-Dawley male rats fed a control diet (0.043% Mg and 0.47 Ca) were match-fed with rats given either a control low calcium diet (0.043% Mg and 0.15% Ca) or a low magnesium-low calcium diet (0.001% Mg and 0.15% Ca). The low calcium content in the magnesium-deficient diet prevented the development of hypercalcemia characteristic of the magnesium-deficient rat. After 17 days, animals were killed by decapitation. Blood was obtained from some animals in the basal state and in other animals 1 min postpentagastrin or 1 min postmagnesium chloride infusion. No significant difference was found in the serum calcium level in the three groups, while the mean serum immunoreactive CT (iCT) level was significantly higher in magnesium-deficient rats both before and after pentagastrin. An acute iv infusion of MgCl2 resulted in significant increases in serum iCT in both the control and magnesium-deficient animals. The results of this study demonstrate that basal serum iCT levels and their response to pentagastrin are increased in magnesium-deficient, normocalcemic animals. The further increase in serum iCT after magnesium infusion in magnesium-depleted animals appears paradoxical and indicates that the relationship between extracellular magnesium and iCT release is not a simple feedback mechanism. It is possible that the increase in circulating iCT may be a response to extracellular-intracellular differences in magnesium concentration. Alternatively, the increased C-cell activity may be secondary to some unknown metabolic alteration induced by magnesium deficiency, rather than to magnesium deficiency per se.

Influence of magnesium deficiency and soy protein on magnesium and zinc status in rats

Female weanling Sprague-Dawley rats were fed casein or soy protein isolate based diets containing approximately 800 or 200 mg Mg/kg diet. Magnesium deficiency was reflected in reduced femur, carcass and plasma magnesium but not in hepatic concentration. Zinc concentration in bone was decreased in magnesium deficient animals. Plasma alkaline phosphatase and hemoglobin were depressed by magnesium deficiency. The enzyme levels were lowest in rats fed soy protein. The adverse effects on magnesium and zinc status were more pronounced than had previously been reported in response to mild magnesium deficiency for a shorter period of time.

Magnesium deficiency and myocardial infarct size in the dog

Although epidemiologic data suggest a relation between myocardial infarction death rates and dietary intake of magnesium, there are no experimental studies reflecting such a phenomenon. It is now reported that beagle dogs kept on a severely magnesium-deficient diet for 100 days develop a larger infarct than do control animals. Control animals were either kept on the same diet as experimental animals with supplementary magnesium, or were fed standard dog chow. The control groups were indistinguishable and were therefore pooled. Infarction was produced by occlusion of the left anterior descending coronary artery for 1 hour followed by 4 hours of reperfusion. Slices of ventricular myocardium, 5 mm thick, were made from the apex to the base. Ischemic muscle, considered to be the muscle at risk, was delineated by a microsphere-autoradiographic method, and necrotic muscle was delineated by tetrazolium stain. Involved areas were measured by planimetry, and these integrated to produce the volume. The volumes of muscle made ischemic were similar in the experimental and control groups. The volumes of necrotic muscle, however, were less in the control than in the experimental animals. The ratio of necrotic muscle volume to the volume of muscle at risk was greater in the experimental animals than in the control animals by a factor of almost two (p less than 0.004). These experiments indicate that, under the conditions used here, animals fed a magnesium-deficient diet develop a larger infarct than do control animals. This could occur either through decreased postocclusion collateral flow or increased vulnerability of the ischemic muscle in magnesium-deficient animals. Although these experiments cannot rule out an effect on postocclusion collateral flow, they do suggest that electrolyte abnormalities related to magnesium deficiency are of such a character as to increase myocardial vulnerability to injury.

Suboptimal intake of magnesium in rats. Effects during growth and gestation

To investigate the interaction of magnesium depletion and source of protein and the effect of this interaction on growth, female weanling Sprague-Dawley rats were fed diets based on 20% casein or 20% soy protein isolate which contained eithe adequate (800 mg/kg) or suboptimal (200 mg/kg) levels of magnesium. The initial suboptimal level of approximately 100 mg/kg magnesium was increased to approximately 200 mg/kg magnesium on day 6 of the study. The nutritional stress of rapid growth resulted in clinical signs of deficiency including audiogenic seizures in the animals fed the casein diet which was low in magnesium. Some clinical manifestations of deficiency persisted through almost all of the 6-week growth period. The lower nutritional quality of soy protein isolate and/or the components of soy which depress mineral bioavailability resulted in a higher rate of alopecia and skin sores in the rats fed the soy low magnesium diet than in those fed the casein low magnesium one. Growth retardation in the magnesium deficient animals occurred during the post-weaning growth phase. Gestational weight gain was also depressed by low magnesium intake to a greater extent than has been previously reported in response to a mild magnesium restriction. Because of recent reports of suboptimal intakes of magnesium by humans, further research of combined effects of subacute magnesium deficiency and utilization of foods containing soy protein is needed.

Calcium homeostasis and bone pathology in magnesium deficient rats

Calcium homeostasis and bone pathology were studied in weanling rats fed a low (70 ppm) magnesium diet for 2-21 days. The rats developed significant, progressive hypercalcemia after 6 days on the diet. The increase in blood calcium was accompanied by progressive hypoactivity of the parathyroid gland (PTG), as determined by histologic and morphometric analyses. Thus hyperactivity of the PTG could not have been responsible for the hypercalcemia observed. Histologic examination of femora and humeri from magnesium-deficient rats showed progressive subperiosteal hyperplasia, consisting of undifferentiated osteoprogenitor cells and fibrous tissue, after 7 days of deficiency. The presence of unmineralized osteoid tissue in the metaphyses indicated that mineralization was not proceeding normally. The alterations in differentiation of osteoprogenitor cells, together with the failure of mineralization, resulted in significantly lower rates of bone formation (as measured by fluorochrome labeling) in the magnesium-deficient rats. Basophilic cementing lines and inactive osteocytes in the cortices of bones from magnesium-deficient rats indicated that bone resorption was also severely reduced in magnesium deficiency. We postulate that bone magnesium depletion (66% by day 21) has a direct negative effect on osteoblastic and osteocytic activity, and may explain, in part, the decreased responsiveness of bone to parathyroid hormone (PTH) that has been observed in magnesium-deficient animals.

Divalent Cation Transport by Rat Cecum and Colon in Calcium and Magnesium Deficiency

SummaryThe effects of calcium and magnesium deficiency on net divalent cation movements of large intestine were studied in growing rats by in vivo perfusion of cecum and colon. Magnesium-deficient rats and controls were perfused with 0.4, 0.8, and 1.2 mM calcium in saline; large intestinal calcium movements were similar in both diet groups despite hypercalcemia in magnesium-deficient animals. In a separate study, calcium-deficient rats and controls were perfused with 0, 0.25, and 2.5 mM magnesium in saline; large intestinal magnesium movements were the same in both diet groups. Thus, large intestinal calcium transport in the rat, which adapts to calcium or vitamin D deficiency, does not respond to magnesium restriction, and large intestinal magnesium transport is not affected by calcium deficiency. These findings suggest that effects of magnesium and calcium restriction on fecal excretion of divalent cations in balance studies are not mediated by large intestinal adaptation.We thank Duane Miller and Helen...