Pathogenetic role of magnesium deficiency in ophthalmic diseases

Magnesium is one of the most important regulatory cation involved in several biological processes. It is important for maintaining the structural and functional integrity of several vital ocular tissues such as cornea, lens and retina. The magnesium content of lens, especially in its peripheral part, is higher than that in aqueous and vitreous humor. Magnesium has also been shown to play critically important role in retinal functions. Magnesium plays significant role as a cofactor for more than 350 enzymes in the body and regulates neuroexcitability and several ion channels. Membrane associated ATPase functions that are crucial in regulating the intracellular ionic environment, are magnesium-dependent. Moreover, the enzymes involved in ATP production and hydrolysis are also magnesium-dependent. Magnesium deficiency by interfering with ATPase functions causes increased intracellular calcium and sodium and decreases intracellular potassium concentration. Such ionic imbalances in turn alter the other cellular enzymatic reactions and form the basis of the association of magnesium deficiency with ophthalmic diseases such as cataract. In presence of magnesium deficiency, an imbalance between mediators of vasoconstriction and vasorelaxation may underlie the vasospasm, which is one of the pathogenic factors in primary open angle glaucoma. Furthermore, magnesium deficiency is also a contributing factor in increased oxidative stress and inducible NOS stimulation that can further contribute in the initiation and progression of ocular pathologies such as cataract, glaucoma and diabetic retinopathy. In this paper we review the association of disturbances of magnesium homeostasis with several ophthalmic diseases.     

Role of magnesium in hypertension

Magnesium affects blood pressure by modulating vascular tone and reactivity. It acts as a calcium channel antagonist, it stimulates production of vasodilator prostacyclins and nitric oxide and it alters vascular responses to vasoactive agonists. Magnesium deficiency has been implicated in the pathogenesis of hypertension with epidemiological and experimental studies demonstrating an inverse correlation between blood pressure and serum magnesium levels. Magnesium also influences glucose and insulin homeostasis, and hypomagnesemia is associated with metabolic syndrome. Although most epidemiological and experimental studies support a role for low magnesium in the pathophysiology of hypertension, data from clinical studies have been less convincing. Furthermore, the therapeutic value of magnesium in the management of hypertension is unclear. The present review addresses the role of magnesium in the regulation of vascular function and blood pressure and discusses the implications of magnesium deficiency in experimental and clinical hypertension, in metabolic syndrome and in pre-eclampsia.     

Magnesium metabolism and its disorders

Magnesium is the fourth most abundant cation in the body and plays an important physiological role in many of its functions. Magnesium balance is maintained by renal regulation of magnesium reabsorption. The exact mechanism of the renal regulation is not fully understood. Magnesium deficiency is a common problem in hospital patients, with a prevalence of about 10%. There are no readily available and easy methods to assess magnesium status. Serum magnesium and the magnesium tolerance test are the most widely used. Measurement of ionised magnesium may become more widely available with the availability of ion selective electrodes.Magnesium deficiency and hypomagnesaemia can result from a variety of causes including gastrointestinal and renal losses. Magnesium deficiency can cause a wide variety of features including hypocalcaemia, hypokalaemia and cardiac and neurological manifestations. Chronic low magnesium state has been associated with a number of chronic diseases including diabetes, hypertension, coronary heart disease, and osteoporosis. The use of magnesium as a therapeutic agent in asthma, myocardial infarction, and pre-eclampsia is also discussed.Hypermagnesaemia is less frequent than hypomagnesaemia and results from failure of excretion or increased intake. Hypermagnesaemia can lead to hypotension and other cardiovascular effects as well as neuromuscular manifestations. Causes and management of hypermagnesaemia are discussed.     

硫酸镁在产科麻醉中的研究进展

镁离子是人体内最丰富的阳离子之一,在机体许多的细胞功能中都发挥重要作用,参与体内多种重要的生物合成过程。硫酸镁是一种传统药物,在预防和治疗母亲与胎儿相关的各种疾病如妊娠高血压综合征、先兆子痫、子痫发作及先兆早产中的作用越来越受到重视,能够降低产妇及胎儿的发病率和死亡率。随着研究的不断深入,人们发现其在麻醉领域中的作用愈加突出,能够与全身麻醉药、局部麻醉药、麻醉镇痛药等产生协同作用,可作为术中安全的麻醉辅助用药。本文阐述了硫酸镁对于产科麻醉医生的重要性,硫酸镁在产科麻醉中的应用,并查找其在妊娠高血压疾病、早产儿的神经保护、麻醉辅助镇痛、预防应激反应以及稳定血流动力学等方面应用的最新证据。     

Selected organopathies caused by experimental magnesium deficiency

A role of enzyme mediated metabolic processes is discussed. Unfavourable effect of magnesium deficiency on the functioning of various organs may lead to extensive and irreversible morphological changes of focal character. Basing on the results of several experiments and own experience, the author discusses an effect of low-magnesium diet on histological, histochemical, and microscopic lesions to the myocardium, skeletal musculature, liver, and pancreas. Magnesium deficiency predisposes to myocardial necrosis which simulates electrolyte-steroid-cardiomyopathy by necrosis (ESCN). Low-magnesium diet decreases resistance of the animals to various types of stress such as: cooling, immobilization, and noise. Insignificant degree of the lesions to skeletal musculature produced by magnesium deficiency and no progress in these lesions during the experiment may depend upon relatively stable magnesium reserve in the muscles. Low-magnesium diet increases the number of so-called Ito cells in the liver. It is probable that these cells together with hepatocytes contribute to the formation of collagen fibres. Magnesium deficiency may lead to the abnormal digestion of nutrients in the pancreas, interfering with exocytosis of zymogen granules. Supplementation of the diet with magnesium may prevent various organopathies.     

A clinical approach to common electrolyte problems: 4. Hypomagnesemia.

Magnesium plays a critical role in many cell functions. Hypomagnesemia may occur because of decreased intake or absorption, internal redistribution or increased loss of this element through either renal or nonrenal routes. Manifestations of magnesium deficiency include alterations in calcium, phosphate and potassium homeostasis along with cardiac disorders such as malignant ventricular arrhythmias refractory to conventional therapy, enhanced sensitivity to digoxin and, possibly, coronary artery vasospasm and sudden death. Other features of magnesium deficiency include a host of neuromuscular and neuropsychiatric disorders. In this review we detail mechanisms that may lead to magnesium deficiency, summarize the clinical features of the deficiency and provide a clinical approach to the diagnosis and treatment of this electrolyte disorder.     

Role of Magnesium in Oxidative Stress in Individuals with Obesity

Adipose tissue is considered an endocrine organ that promotes excessive production of reactive oxygen species when in excess, thus contributing to lipid peroxidation. Magnesium deficiency contributes to the development of oxidative stress in obese individuals, as this mineral plays a role as an antioxidant, participates as a cofactor of several enzymes, maintains cell membrane stability and mitigates the effects of oxidative stress. The objective of this review is to bring together updated information on the participation of magnesium in the oxidative stress present in obesity. We conducted a search of articles published in the PubMed, SciELO and LILACS databases, using the keywords ‘magnesium’, ‘oxidative stress’, ‘malondialdehyde’, ‘superoxide dismutase’, ‘glutathione peroxidase’, ‘reactive oxygen species’, ‘inflammation’ and ‘obesity’. The studies show that obese subjects have low serum concentrations of magnesium, as well as high concentrations of oxidative stress marker in these individuals. Furthermore, it is evident that the adequate intake of magnesium contributes to its appropriate homeostasis in the body. Thus, this review of current research can help define the need for intervention with supplementation of this mineral for the prevention and treatment of disorders associated with this chronic disease.     

Effects of magnesium deficiency on photosynthesis and carbohydrate partitioning

Magnesium nutrition is often forgotten, while its absence adversely affects numerous functions in plants. Magnesium deficiency is a growing concern for crop production frequently observed in lateritic and leached acid soils. Competition with other cations (Ca²⁺, Na⁺, and K⁺) is also found to be an essential factor, inducing magnesium deficiency in plants. This nutrient is required for chlorophyll formation and plays a key role in photosynthetic activity. Moreover, it is involved in carbohydrate transport from source-to-sink organs. Hence, sugar accumulation in leaves that results from the impairment of their transport in phloem is considered as an early response to Mg deficiency. The most visible effect is often recorded in root growth, resulting in a significant reduction of root/shoot ratio. Carbohydrate accumulation in source leaves is attributed to the unique chemical proprieties of magnesium. As magnesium is a nutrient with high mobility in plants, it is preferentially transported to source leaves to prevent severe declines in photosynthetic activity. In addition, Mg is involved in the source-to-sink transport of carbohydrates. Hence, an inverse relationship between Mg shortage and sugar accumulation in leaves is often observed. We hereby review all these aspects with a special emphasis on the role of Mg in photosynthesis and the structural and functional effects of its deficiency on the photosynthetic apparatus.     

Role of dietary magnesium in cardiovascular disease prevention, insulin sensitivity and diabetes

PURPOSE OF REVIEW: This review summarizes the evidence for benefits of magnesium on metabolic abnormalities, inflammatory parameters, and cardiovascular risk factors and related-potential mechanisms. Controversy due to contrasting results in the literature is also discussed. RECENT FINDINGS: Increased dietary magnesium intake confers protection against the incidence of diabetes, metabolic syndrome, hypertension, and cardiovascular disease. It ameliorates insulin resistance, serum lipid profiles, and lowers inflammation, endothelial dysfunction, oxidative stress, and platelet aggregability. Magnesium acts as a mild calcium antagonist on vascular smooth muscle tone, and on postreceptor insulin signaling; it is critically involved in energy metabolism, fatty acid synthesis, glucose utilization, ATPase functions, release of neurotransmitters, and endothelial cell function and secretion. Prospective studies, however, have found only a modest effect for dietary magnesium on incident pathologies. Furthermore, magnesium supplementation on glucose metabolism, blood lipid levels, and ischemic heart disease has given inconsistent results. SUMMARY: There is strong biological plausibility for the direct impact of magnesium intake on metabolic and cardiovascular risk factors, but in-vivo magnesium deficiency might play only a modest role. Reverse causality, the strong association between magnesium and other beneficial nutrients, or the possibility that people who choose magnesium-rich foods are more health-conscious may be confounding factors.     

Magnesium contents of leukemic lymphocytes

In this study, magnesium concentrations were measured in lymphocytes from patients with acute myeloblastic leukemia (AML), chronic megalositer leukemia (KML) and acute lymphoblastic leukemia (ALL) before and after chemotherapy management, and results were compared with those of control subjects. Magnesium concentrations were higher in the patient groups compared with control values. However, no meaningful differences were found among magnesium concentrations of the patient groups themselves. Similarly, no statistically meaningful differences were found between lymphocyte magnesium concentrations before and after chemotherapy management in the patient groups. In the inter-correlation analysis, we observed no correlations between pre- and post-magnesium concentrations in patients' lymphocytes. It has been suggested that magnesium concentrations of leukemic lymphocytes might increase due to the high ATP requirement of the leukemic cells since magnesium is known to play an important part as a cofactor in most of the energy-producing reactions.     

Role of magnesium in alleviation of aluminium toxicity in plants

Magnesium is pivotal for activating a large number of enzymes; hence, magnesium plays an important role in numerous physiological and biochemical processes affecting plant growth and development. Magnesium can also ameliorate aluminium phytotoxicity, but literature reports on the dynamics of magnesium homeostasis upon exposure to aluminium are rare. Herein existing knowledge on the magnesium transport mechanisms and homeostasis maintenance in plant cells is critically reviewed. Even though overexpression of magnesium transporters can alleviate aluminium toxicity in plants, the mechanisms governing such alleviation remain obscure. Possible magnesium-dependent mechanisms include (i) better carbon partitioning from shoots to roots; (ii) increased synthesis and exudation of organic acid anions; (iii) enhanced acid phosphatase activity; (iv) maintenance of proton-ATPase activity and cytoplasmic pH regulation; (v) protection against an aluminium-induced cytosolic calcium increase; and (vi) protection against reactive oxygen species. Future research should concentrate on assessing aluminium toxicity and tolerance in plants with overexpressed or antisense magnesium transporters to increase understanding of the aluminium-magnesium interaction.     

Intravenous Magnesium Sulfate With and Without EDTA as a Magnesium Load Test—Is Magnesium Deficiency Widespread?

Serum/plasma measurements do not reflect magnesium deficits in clinical situations, and magnesium load tests are used as a more accurate method to identify magnesium deficiency in a variety of disease states as well as in subclinical conditions. The objective of this study was to determine if people are indeed magnesium deficient or if the apparent magnesium deficiency is due to the composition of the infusate used in the load test. Magnesium load tests were performed on seven patients using three different Mg solution infusions-a Mg-EDTA (ethylene diamine tetraacetic acid)-nutrient cocktail used in EDTA chelation therapy containing several components including vitamins and minerals, and the same cocktail without EDTA and an infusion of an identical amount of magnesium in normal saline solution. There was no significant difference in the amount of magnesium retained in the 24 h after infusion among the three infusates. All infusates resulted in very high magnesium retention compared to previous published magnesium load studies. Magnesium deficiency may be widespread, and the relationship of Mg deficiency to related diseases requires further study.     

Magnesium: nutrition and metabolism

Magnesium is an essential mineral that is needed for a broad variety of physiological functions. The usual daily magnesium uptake with a western diet is sufficient to avoid deficiency but seems not to be high enough to establish high normal serum magnesium concentrations that are protective against various diseases. Changes in magnesium homeostasis mainly concern the extracellular space, as the intracellular magnesium concentration is well regulated and conserved. The extracellular magnesium concentration is primarily regulated by the kidney, the mechanisms of this regulation have been elucidated recently. Due to the growing knowledge about the regulation of extra- and intracellular magnesium concentrations and the effects of changed extracellular magnesium levels the use of magnesium in therapy gains more widespread attention.     

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.     

Magnesium deficiency in the Japanese quail

Morphological effects of magnesium deficiency on liver cells and general aspects of its influence on the metabolism were investigated in young quails. Magnesium deficiency was characterized by a depressed growth, a high mortality rate, a decrease in hematocrit and magnesium and calcium plasma concentrations. Magnesium deficiency reduced the magnesium concentration in heart by 44%, but did not affect the concentration in liver. Ultrastructural aspect of liver parenchymal cells revealed that the number of mitochondria per cell section was decreased and the average area of a mitochondrion was greater in deficient quails than in control animals. The significance of these morphological changes was discussed in relation to disturbances in energy metabolism of these organelles. From these results, japanese quail appeared as an interesting experimental model for studies on metabolic disturbances in magnesium deficiency.     

Magnesium deficiency inhibits biosynthesis of blood glutathione and tumor growth in the rat

Previously we found that blood glutathione (GSH) levels increase in response to tumor growth in the rat and that this increase is not prevented with zinc deficiency. We also found that zinc deficiency which inhibited tumor growth did not prevent this increase in blood GSH. Therefore, the objectives of this study were to determine the effects of another nutritional modification, namely magnesium deficiency, on blood GSH status and on tumor growth. Magnesium was selected because it is an obligatory cofactor in GSH synthesis and in all biosynthetic reactions involving ATP. To this end, magnesium- and zinc-deficient rats with and without tumors were compared to pair-fed control rats with and without tumors. After 32 days of depletion, the rats were killed, and blood samples were analyzed for nonprotein sulfhydryls (SH) and specifically for GSH. The key finding was that in magnesium-deficient rats with or without tumors, blood GSH levels were low and SH levels were normal indicating a decrease in GSH biosynthesis. In contrast, zinc deficiency affected SH and GSH in parallel. Thus, these two deficiencies must act by different mechanisms. The zinc data verified our earlier results obtained with a different tumor type and rat strain, for blood GSH levels increased in tumor-bearing rats fed control diets, and zinc deficiency did not prevent this increase. Depletion of magnesium or zinc was equally effective in inhibiting tumor growth. These results provide in vivo evidence of a magnesium requirement for GSH biosynthesis in rat erythrocytes. Further, the results suggest that magnesium deficiency may inhibit tumor growth by limiting GSH synthesis from SH precursors.     

Mineral deficiency symptoms of the oil palm

Summary Young oil palms in sand culture experiment developed symptoms of nitrogen, potassium and magnesium deficiencies involving a homogeneous yellowing, a marginal yellowing and an orange chlorosis respectively. All these deficiencies resulted in poor growth and a reduced root development. A further experiment showed that Little Leaf Disease was caused by boron deficiency. Magnesium and potassium deficiency symptoms were also induced in this experiment. Sulphur deficiency symptoms, consisting of a yellowing of the young leaves, an interveinal chlorosis and necrosis, were induced in a factorial sand culture experiment and a second missing element trial. Insufficient available nitrogen, potassium, magnesium and boron all have an adverse effect on the production of inflorescences.It is considered that Plant Failure disease is caused by a poorly developed rooting system which may result from magnesium, boron and, possibly, potassium deficiencies.No evidence has been obtained to support the view that Confluent Orange Spotting is caused by potassium deficiency.     

Magnesium and the inflammatory response: potential physiopathological implications

The purpose of this review is to summarize experimental findings showing that magnesium modulates cellular events involved in inflammation. Experimental magnesium deficiency in the rat induces after a few days a clinical inflammatory syndrome characterized by leukocyte and macrophage activation, release of inflammatory cytokines and acute phase proteins, excessive production of free radicals. Increase in extracellular magnesium concentration, decreases inflammatory response while reduction in the extracellular magnesium results in cell activation. Because magnesium acts as a natural calcium antagonist, the molecular basis for inflammatory response is probably the result of modulation of intracellular calcium concentration. The priming of phagocytic cells, the opening calcium channel and activation of N-methyl-d-aspartate (NMDA) receptors, the activation of nuclear factor-kappa B (NFkappaB) have been considered as potential mechanisms. Moreover, magnesium deficiency induces a systemic stress response by activation of neuro endocrinological pathways. As nervous and immune systems interact bidirectionally, the roles of neuromediators have also been considered. Magnesium deficiency contributes to an exaggerated response to immune stress and oxidative stress is the consequence of the inflammatory response. Inflammation contributes to the pro-atherogenic changes in lipoprotein metabolism, endothelial dysfunction, thrombosis, hypertension and explains the aggravating effect of magnesium deficiency on the development of metabolic syndrome. Further studies are still needed to assess more accurately the role of magnesium in immune response in humans, but these experimental findings in animal models suggest that inflammation is the missing link to explain the role of magnesium in many pathological conditions.     

Magnesium Protects Cognitive Functions and Synaptic Plasticity in Streptozotocin-Induced Sporadic Alzheimer’s Model

Alzheimer’s disease (AD) is characterized by profound synapse loss and impairments of learning and memory. Magnesium affects many biochemical mechanisms that are vital for neuronal properties and synaptic plasticity. Recent studies have demonstrated that the serum and brain magnesium levels are decreased in AD patients; however, the exact role of magnesium in AD pathogenesis remains unclear. Here, we found that the intraperitoneal administration of magnesium sulfate increased the brain magnesium levels and protected learning and memory capacities in streptozotocin-induced sporadic AD model rats. We also found that magnesium sulfate reversed impairments in long-term potentiation (LTP), dendritic abnormalities, and the impaired recruitment of synaptic proteins. Magnesium sulfate treatment also decreased tau hyperphosphorylation by increasing the inhibitory phosphorylation of GSK-3β at serine 9, thereby increasing the activity of Akt at Ser473 and PI3K at Tyr458/199, and improving insulin sensitivity. We conclude that magnesium treatment protects cognitive function and synaptic plasticity by inhibiting GSK-3β in sporadic AD model rats, which suggests a potential role for magnesium in AD therapy.