Myocardial magnesium depletion during cyclosporine treatment, associated with reciprocal calcium overload, can be prevented by plentiful dietary magnesium supply.
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Animals↗
Biomedical subjects
H G Classen
Publications and source records attributed to H G Classen.
Influence of high and low dietary magnesium levels on functional, chemical and morphological parameters of 'old' rats.
The effect of dietary magnesium deficiency has so far been studied preferentially in rapidly growing rodents or in adult animals. Since magnesium deficiency frequently occurs in elderly persons too, magnesium- and calcium-deficient diets were offered during 32 and 64 days to 'old' rats (34 months old, spontaneous mortality of 15 per cent). The calcium-deficient diet (2.5 per cent of the requirement) was well tolerated and no profound biochemical disturbances were noted. In contrast, dietary magnesium deficiency (12.5 per cent of the requirement) induced loss of body weight, formation of erythema, severe hypomagnesaemia and increase of tissue calcium levels. No seizures were noted and mortality did not increase, in contrast to growing magnesium-deficient rats. Histologically, age effects were present in bone tissues of old rats, however no additional dietary effects became visible. Tensile strength of femur and rib did not reveal treatment-related changes. Fourteen days preloading with high dietary magnesium increased plasma magnesium and also skeletal concentrations, although to an only small degree. Nevertheless, time until the appearance of erythema in 50 per cent of the rats subsequently fed the magnesium-deficient diet was significantly delayed.
Aging↗
Potentiation of magnesium-deficiency-induced foetotoxicity by concomitant iron deficiency and its prevention by adequate supply via drinking water.
Magnesium (Mg) and iron (Fe) deficiency frequently develop during pregnancy. Therefore these factors were studied alone (Mg-L, resp. Fe-L) or in combination (Mg-L/Fe-L) on 16 female and 8 male adult fertile Sprague-Dawley rats. The animals were offered a basal diet containing 30 per cent and 17 per cent of the rat's requirement for magnesium and iron, respectively, starting 21 days before mating (2:1) until 49 days after mating. Offspring were also kept on this regimen during a 3-week lactation period and 7 days post weaning. Drinking water was either enriched with 101 ppm Fe2+ (ferrous gluconate): Mg-L, or 365 ppm magnesium (magnesium-L-aspartate hydrochloride trihydrate, MAH): Fe-L, or with any: Mg-L/Fe-L or with both electrolytes: Controls. Fertility remained unaffected under these conditions. Clinically, Fe-L induced iron deficiency and growth retardation of offspring. Pronounced reproductive toxicity was elicited by Mg-L and was even potentiated by Mg-L/Fe-L. In the parental generation, too, adverse effects of Mg-L were aggravated by Mg-L/Fe-L despite the fact that no iron accumulation occurred. Bioavailability of iron was not impaired by magnesium as MAH. With respect to human pregnancy magnesium supplementation has higher priority over iron supplements. To improve tolerance and compliance both minerals are suggested to be taken simultaneously.
Administration, Oral↗
Increase of streptozocin toxicity by magnesium deficiency in the diabetic rat model.
To study interactions between magnesium (Mg) and diabetes mellitus, female SD-rats weighing ca. 230 g were rendered Mg-deficient by offering a diet providing only 20% of the rat's requirement. After 14 days the animals were injected 75 mg streptozocin (STZ) per kg body weight intraperitoneally. Placebo-treated controls received the same diet, however their drinking-water was enriched with 20 mmol/l Mg as the magnesium-L-aspartate hydrochloride. Mg deficiency remarkably increased STZ-induced lethality from 3.8% to 61.1% on day 35. Pronounced hyperglycemia and necrosis of pancreatic beta cells also suggest an increased effect of STZ on the pancreas during Mg deficiency. The underlying mechanisms are discussed. Food consumption was decreased in Mg-deficient animals and steeply increased 7 days following STZ treatment. Similarly consumption of drinking-water also increased. Since diabetic rats lost body weight, relative and absolute Mg intake via food or drinking-water increased. In this way further Mg depletion of diabetic rats was prevented.
Animals↗
Interactions between magnesium and iron. In vitro studies.
In vitro experiments were performed to study the effects of magnesium (Mg) on the absorption of iron (Fe), which have been reported in the literature. Both poorly soluble Mg compounds (Mg oxide and Mg trisilicate) and a readily soluble Mg salt (Mg aspartate hydrochloride trihydrate) were studied along with ferrous gluconate. The influence of the addition of Mg aspartate hydrochloride, Mg oxide and Mg trisilicate on the pH of aqueous acidic solutions was examined initially. As expected, the Mg salts employed as antacids (Mg oxide and Mg trisilicate) were found to have a potent neutralising effect, while after the addition of Mg aspartate hydrochloride the pH value was only slightly shifted toward the alkaline side. These findings suggest that Mg aspartate hydrochloride--unlike Mg oxide and Mg trisilicate--has no appreciable influence on Fe absorption, as the availability of Fe salts in the intestinal tract is pH dependent. A procedure simulating the physiological variations of the pH value in the gastrointestinal tract was used to determine the Fe and Mg content in the supernatant after the addition of the above Fe and Mg salts to aqueous solutions. The addition of poorly water-soluble Mg compounds was shown to result in a drastic reduction in the amount of Fe contained in the supernatant. These data are in agreement with those reported in the literature. However, no decrease in the amount of dissolved Fe was noted in the presence of Mg aspartate hydrochloride. These findings confirm that poorly water-soluble Mg compounds have a high capacity to adsorb Fe and, thus, interfere with Fe absorption.(ABSTRACT TRUNCATED AT 250 WORDS)
Aspartic Acid↗
Cyclosporin induces magnesium deficiency in rats and thereby aggravates its own nephrotoxicity: benefit of magnesium supplementation.
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Animals↗
Erythema formation in magnesium-deficient albino rats. A non-invasive model for the screening of anti-inflammatory agents and oral mineral supplements.
The enteral bioavailability of magnesium firmly bound to a fire-proof, inert SiO2-Al2O3 matrix (ground magnesia boats) was studied in magnesium-deficient albino Sprague-Dawley rats, with and without blocking gastric hydrochloric acid secretion with omeprazole. Magnesium was absorbed, although to a small degree, also at anacidity. Pronounced erythema, developing after only some days in hypomagnesemic hypercalcemic rats, are proposed as a non-invasive model for the screening of antiinflammatory substances. Using this model significant protective effects were proven for cromoglycate, polyenthylene glycol 400, and omeprazole; the latter, however, seems more likely to act via a magnesium-sparing mechanism.
Animals↗
In vitro magnesium absorption and the role of intestinal motility.
Magnesium (Mg) is known as an inhibitor of spontaneously contracting muscular tissues. To increase extracellular Mg in vivo, high doses of Mg must be given orally. Therefore, we investigated the effect of different doses of Mg given from the mucosal side of the small intestine of rats. According to the model of Trendelenburg, a system for the perfusion of isolated small intestine was developed, which allows the simultaneous recording of absorption and muscle contractions. Increasing doses of Mg were applied serosally or intraluminally. Intramulinal Mg did not affect intestinal motility. In contrast, increasing concentrations of serosal Mg resulted in a 50% inhibition of motility at 2.9 mmol/l Mg. This indicates no influence on intestinal motility of high doses of Mg acting from the mucosal side. In further studies, the addition of citric acid or taurocholic acid did not alter Mg absorption. Serosally applied amiloride (1 mmol/l) inhibited absorption, but also resulted in complete loss of motility. Since in this model passive diffusion is the most important mechanism of Mg transport, a direct influence of amiloride on Mg absorption can be excluded. From these data, we conclude that intestinal motility influences absorption--also of ions in aqueous solution--and should therefore be taken into account in absorption studies.
Amiloride↗
Pharmacokinetics of magnesium salts.
Due to the widespread use of magnesium (Mg) in human medicine, interest in quantitative enteral absorption rates arose more than 100 years ago. The introduction of the AAS technique and of radioisotopes has stimulated research. Slowly exchanging compartments have not, however, been accessible up until now, and the exact mechanism(s) of enteral Mg absorption is still unclear; hence, the fate of orally administered Mg cannot be followed in detail. The capacity of skeletal Mg stores varies with exogenous Mg supply, consumption, excretion and age. In otherwise healthy subjects, urine Mg levels correlate with exogenous supply. Neglecting the fact that exogenous Mg exchanges with deep Mg stores to a considerable degree, it makes sense to qualitatively study the availability of Mg compounds by relating the amount administered to the amount excreted in the urine, especially after filling deep compartments. Since renal Mg excretion patterns are known to change when tubular reabsorption capacity is exceeded or when pH alterations occur, these parameters must be monitored and taken into account at the quantitative evaluation of data.
Bone and Bones↗
In-vivo monitoring of corticomedullary nephrocalcinosis in rats using computerized tomography.
An in-vivo method, computerized tomography (CT), was used to monitor nephrocalcinosis in female rats. CT density data correlated well with renal Ca content measured by atomic absorption spectrophotometry. In-vivo CT measurements revealed that the severity of nephrocalcinosis may change spontaneously with time. Manifest calcifications may exhibit spontaneous regression and are probably affected positively by high dietary Mg, in contrast to increased Ca. It is concluded that CT is a suitable and reliable non-invasive in vivo method to follow up time-dependent alterations in kidney calcifications in rats.
Animals↗
[The clinical importance of magnesium. 2. The indications for supplementation and therapy].
Mg deficiency is characterized by diverse secondary electrolyte alterations. Extracellularly, hypocalcemia is a particular feature, which may be explained by increased resistance of bone towards parathormone. Intracellularly, decreased concentrations of Mg and K and increased amounts of Na and Ca are found in contractile organelles. At increased Mg levels, concentration of parathormone may decrease, leading to hypocalcemia. Calcium-antagonistic effects are observed in smooth muscle, the myocardium and the end-plate of skeletal muscles. Hence, Mg may be prescribed either to correct a deficit or to utilize its pharmacologic effects. Dosaging still needs to be optimized.
Calcium↗
[Clinical significance of magnesium. 1: Distribution in the organism, evaluation of current supply].
The most important compartments of Mg metabolism are described: Bone Mg stores correlate closely with serum Mg, which latter depends mainly on intestinal absorption and excretion, predominantly via the kidneys. Since intracellular Mg is mainly bound, the overall intracellular Mg concentration depends largely on the amount of available ligands such as ATP. Serum Mg reflects the Mg content of bone stores. The frequency at which hyper- or hypomagnesemia occurs depends largely on the precision with which the normal range is established. Recommendations for the sampling of serum are made.
Biological Availability↗
Hypothesis: the effect of oral nitrite on blood pressure in the spontaneously hypertensive rat. Does dietary nitrate mitigate hypertension after conversion to nitrite?
Increasing doses of nitrite (3.7-14.8 mg/kg BW) were administered via intragastric intubation to 64 spontaneously hypertensive Sprague-Dawley rats. Systemic blood pressure, measured in conscious animals with the tail cuff method, significantly decreased in a dose-related manner 16 and 32 minutes later, and pulse rate slightly increased. Since orally ingested nitrate may be partially converted to nitrite, it seems worthwhile to study correlations between dietary nitrate and blood pressure in experimental animals and man.
Administration, Oral↗
Nephrocalcinosis without functional renal impairment in rats subjected to subacute moderate magnesium deficiency, and intervention studies on the mobilization of calcium deposits.
Female Sprague-Dawley rats (100-120 g) were kept for 12 d on diets containing 250, 1500, or 9000 ppm Mg. Then subgroups were loaded with water, frusemide or magnesium and urine was collected over 6 h. Moderately Mg-deficient diet (250 ppm) induced moderate hypomagnesaemia (62.3% of controls), but did not result in hypercalcaemia or the formation of typical erythema. Nevertheless, pronounced nephrocalcinosis developed, as shown by increased renal wet and dry weight and elevated tissue concentrations of Ca, P and Mg, the calculous deposits probably consisting to a large extent of Ca3 (PO4)2. Despite these alterations, renal function remained unimpaired in Mg-deficient rats, as shown by normal urinary creatinine excretion and the unaffected ability of the kidneys to concentrate urine. Loading with water, frusemide or Mg increased urinary excretion of calcium in all three diet groups to a similar extent; hence no significant proof can be given that calculous deposits are mobilized under these conditions. Since comparable conditions may also be present under clinical conditions in man, special care should be given to maintain optimal Mg balance.
Animals↗
Forty years of "drug research".
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Biotechnology↗
Age-dependent accumulation of cadmium in rats exposed to contaminated drinking water; interactions with zinc and copper and subcellular Cd distribution in kidney cells.
One of each pair of female sister rats aging 1, 4, 7 or 10 months was exposed during 3 months to 31.5 mg/L Cd (as CdCl2) in its drinking water and sacrificed immediately after Cd exposure together with its untreated sister. Concentrations of Cd, Zn and Cu were measured in the kidneys (medulla and cortex), the liver, the duodenum and the uterus. Furthermore, the subcellular distribution of Cd was measured in renal tissue. The accumulation of metal ions, defined as the difference between Cd-treated and untreated rats, was pronounced in all tissues except the uterus and was significantly decreased at increasing age. Multivariate analysis of variance revealed significant interaction with Zn and Cu. Higher Cd accumulation in the tissues of young animals probably depends on the higher consumption of contaminated drinking water per kilogram of body weight. High concentrations of Cd detected in cell nuclei may be due to the similarity between Cd2+ and Ca2+.
Aging↗
Magnesium in pregnant women and the newborn.
In this article the importance of Mg for pregnant women and fetal outcome is reviewed. The physiological changes of Mg-containing body fluids and of tissues are discussed. Mg supplementation during pregnancy seems to be necessary and the efficacy on maternal health and on the newborn are reported. Serum Mg levels decrease during pregnancy and there is a 25% increase of renal Mg excretion. Mg supplementation has a positive effect, with reduced incidence of hospital admission and preterm labour, while the gestational age of the fetus is longer. Convulsions may occur in newborns with hypomagnesaemia. Hypermagnesaemia of the newborn following MgSO4 infusions to toxaemic mothers has been reported.
Female↗
Kinetic studies on nitrite and nitrate in rats by ion-pair chromatography.
A highly sensitive and specific ion-pair chromatographic method is presented for the simultaneous determination of nitrite (NO2-) and nitrate (NO3-) in plasma. The detection limits are 2 mumol NO2-/l and 8 mumol NO3-/l with recovery rates of 98-99%. The applicability of this method to clinical medicine is demonstrated using NO2- -loaded rats as a biological model: following intravenous infusion or intragastric application of NO2-, blood levels of NO2-, NO3- and methemoglobin are measured during 2-64 min. The kinetic data obtained reflect the complex metabolism of NO2- and NO3- in living organisms.
Animals↗