Magnesium Deficiency Alters Expression of Genes Critical for Muscle Magnesium Homeostasis and Physiology in Mice

Chronic Mg²⁺ deficiency is the underlying cause of a broad range of health dysfunctions. As 25% of body Mg²⁺ is located in the skeletal muscle, Mg²⁺ transport and homeostasis systems (MgTHs) in the muscle are critical for whole-body Mg²⁺ homeostasis. In the present study, we assessed whether Mg²⁺ deficiency alters muscle fiber characteristics and major pathways regulating muscle physiology. C57BL/6J mice received either a control, mildly, or severely Mg²⁺-deficient diet (0.1%; 0.01%; and 0.003% Mg²⁺ wt/wt, respectively) for 14 days. Mg²⁺ deficiency slightly decreased body weight gain and muscle Mg²⁺ concentrations but was not associated with detectable variations in gastrocnemius muscle weight, fiber morphometry, and capillarization. Nonetheless, muscles exhibited decreased expression of several MgTHs (MagT1, CNNM2, CNNM4, and TRPM6). Moreover, TaqMan low-density array (TLDA) analyses further revealed that, before the emergence of major muscle dysfunctions, even a mild Mg²⁺ deficiency was sufficient to alter the expression of genes critical for muscle physiology, including energy metabolism, muscle regeneration, proteostasis, mitochondrial dynamics, and excitation–contraction coupling.     

Effects of Magnesium on Cardiac Excitation-Contraction Coupling

Objective: Magnesium regulates a large number of cellular processes. Small changes in intracellular free Mg²⁺ ([Mg²⁺]_i) may have important effects on cardiac excitability and contractility. We investigated the effects of [Mg²⁺]_i on cardiac excitation-contraction coupling.

Methods: We used our ionic-metabolic model that incorporates equations for Ca²⁺ and Mg²⁺ buffering and transport by ATP and ADP and equations for MgATP regulation of ion transporters (Na⁺-K⁺ pump, sarcolemmal and sarcoplasmic Ca²⁺ pumps).

Results: Model results indicate that variations in cytosolic Mg²⁺ level might sensitively affect diastolic and systolic Ca²⁺, sarcoplasmic Ca²⁺ content, Ca²⁺ influx through L-type channels, efficiency of the Na⁺/Ca²⁺ exchanger and action potential shape. The analysis suggests that the most important reason for the observed effects is a modified normal function of sarcoplasmic Ca²⁺-ATPase pump by altered diastolic MgATP levels.

Conclusion: The model is able to reproduce qualitatively a sequence of events that correspond well with experimental observations during cardiac excitation-contraction coupling in mammalian ventricular myocytes.     

Magnesium in Obesity,Metabolic Syndrome,and Type 2 Diabetes

Magnesium (Mg²⁺) deficiency is probably the most underestimated electrolyte imbalance in Western countries. It is frequent in obese patients, subjects with type-2 diabetes and metabolic syndrome, both in adulthood and in childhood. This narrative review aims to offer insights into the pathophysiological mechanisms linking Mg²⁺ deficiency with obesity and the risk of developing metabolic syndrome and type 2 diabetes. Literature highlights critical issues about the treatment of Mg²⁺ deficiency, such as the lack of a clear definition of Mg²⁺ nutritional status, the use of different Mg²⁺ salts and dosage and the different duration of the Mg²⁺ supplementation. Despite the lack of agreement, an appropriate dietary pattern, including the right intake of Mg²⁺, improves metabolic syndrome by reducing blood pressure, hyperglycemia, and hypertriglyceridemia. This occurs through the modulation of gene expression and proteomic profile as well as through a positive influence on the composition of the intestinal microbiota and the metabolism of vitamins B1 and D.     

Magnesium VitB6 Intake Reduces Central Nervous System Hyperexcitability in Children

Objective: Ionic magnesium (Mg²⁺) depletion has long been known to cause hyperexcitability with convulsive seizures in rodents, effects that have been reversed by treatment with magnesium (Mg). Metabolic disorders and genetic alterations are suspected in this pathology, in which Mg²⁺ transport and intracellular distribution may be reduced without change in serum Mg²⁺ concentrations. We evaluated the effects of Mg²⁺/vitamin B6 regimen on the behavior of 52 hyperexcitable children (under 15 years of age) and their families.

Methods: To assess intracellular Mg²⁺, we measured intra-erthrocyte Mg²⁺ levels (ERC-Mg). Our reference values for normal subjects were 2.46 to 2.72 mmol/L. In 30 of the 52 hyperactive children, there were low ERC-Mg values: 2.041 ± 0.279 mmol/L). Combined Mg²⁺/vitamin B6 intake (100 mg/day) for 3 to 24 weeks restored normal ERC-Mg values (2.329 ± 0.386 mmol/L).

Results: In all patients, symptoms of hyperexcitability (physical aggressivity, instability, scholar attention, hypertony, spasm, myoclony) were reduced after 1 to 6 months treatment. Other family members shared similar symptoms, had low ERC-Mg values, and also responded clinically to increased Mg²⁺/vitamin B6 intakes. Two typical families are described.

Conclusion: This open study indicates that hyperexcitable children have low ERC-Mg with normal serum Mg²⁺ values, and that Mg²⁺/vitamin B6 supplementation can restore normal ERC-Mg levels and improve their abnormal behavior.     

Vitamin C Transporters and Their Implications in Carcinogenesis

Vitamin C is implicated in various bodily functions due to its unique properties in redox homeostasis. Moreover, vitamin C also plays a great role in restoring the activity of 2-oxoglutarate and Fe²⁺ dependent dioxygenases (2-OGDD), which are involved in active DNA demethylation (TET proteins), the demethylation of histones, and hypoxia processes. Therefore, vitamin C may be engaged in the regulation of gene expression or in a hypoxic state. Hence, vitamin C has acquired great interest for its plausible effects on cancer treatment. Since its conceptualization, the role of vitamin C in cancer therapy has been a controversial and disputed issue. Vitamin C is transferred to the cells with sodium dependent transporters (SVCTs) and glucose transporters (GLUT). However, it is unknown whether the impaired function of these transporters may lead to carcinogenesis and tumor progression. Notably, previous studies have identified SVCTs’ polymorphisms or their altered expression in some types of cancer. This review discusses the potential effects of vitamin C and the impaired SVCT function in cancers. The variations in vitamin C transporter genes may regulate the active transport of vitamin C, and therefore have an impact on cancer risk, but further studies are needed to thoroughly elucidate their involvement in cancer biology.     

Erythrocyte magnesium fluxes in mice with nutritionally and genetically low magnesium status

Summary Low intracellular magnesium (Mg) contents may be observed in case of severe Mg insufficient intake or because of genetic regulation. This work was conducted to investigate the influence of intracellular Mg content on erythrocyte Mg²⁺ influx and efflux in mice with low nutritionally and genetically (MGL and MGH mice) Mg status. C57BL6 mice were fed for 2 wks a diet containing 1000 mg Mg/kg diet Mg (control group), 100 mg Mg/kg diet (Mg–marginal group) or 30 mg Mg/kg diet (Mgdeficient group), while mice with low (MGL) and high (MGH) Mg levels were fed a control diet for 2 wks. The quantification of erythrocyte Mg²⁺ influx and efflux was performed using a stable isotope of Mg. Our results showed that erythrocyte Mg²⁺ influx and efflux were respectively increased and decreased in nutritional Mg deficiency; while in genetically determined Mg status Mg²⁺ fluxes were lower in MGL mice compared to MGH mice. Moreover Mg²⁺ efflux was significantly correlated to Mg level in erythrocytes in all the mice studied (p < 0.001). In conclusion, erythrocyte Mg²⁺ influx and efflux are modulated by low Mg status, namely decreased Mg²⁺ efflux compensate for nutritional Mg deficiency, while the genetic regulation of erythrocyte Mg²⁺ content depends on modification of Mg²⁺ influx.     

Utilization of magnesium during hypokinesia and magnesium supplementation in healthy subjects

ObjectiveThe incompleteness of electrolyte utilization during hypokinesia and electrolyte supplementation is the defining factor of electrolyte metabolic changes, yet the effect of electrolyte supplementation and HK upon electrolyte utilization is poorly understood. To determine the influence of magnesium (Mg²⁺) supplementation and hypokinesia (diminished movement) on magnesium utilization, we investigated the use of Mg²⁺ supplementation to establish its effect upon muscle Mg²⁺ content and Mg2²⁺ losses.MethodsThis study was conducted in 40 physically healthy male volunteers during a pre-experimental period of 30 d and an experimental period of 364 d. Subjects were equally divided into four groups: unsupplemented control subjects (UCSs), unsupplemented experimental subjects (UESs), supplemented control subjects (SCSs), and supplemented experimental subjects (SESs). A daily supplementation of 3.0 mmol of magnesium-chloride per kilogram of body weight was given to subjects in the SCS and SES groups.ResultsMuscle Mg²⁺ content decreased (P < 0.05) and plasma Mg²⁺ concentration and Mg²⁺ loss in urine and feces increased (P < 0.05) in the SES and UES groups compared with their pre-experimental levels and values in their respective control groups (SCS and UCS). Muscle Mg²⁺ content decreased more (P < 0.05) and plasma Mg²⁺ concentration and Mg²⁺ loss in urine and feces increased more (P < 0.05) in the SES group than in the UES group.The muscle Mg²⁺ content and plasma Mg²⁺ level and Mg²⁺ losses did not change in the control groups.ConclusionDaily Mg²⁺ supplementation during prolonged hypokinesia decreases more muscle Mg²⁺ content and Mg²⁺-deficient muscle increases more Mg²⁺ loss in healthy subjects indicating lower Mg²⁺ utilization with than without Mg²⁺ supplementation.     

Effects of paraquat on Mg2+-ATPase activity in rat liver

Intraperitoneal injection of paraquat (70 mg/kg) elicited a significant decrease of 20% in activity of Mg²⁺-ATPase in hepatic mitochondria, which is always surrounded by a high concentration of oxygen, in rats. The decrease of mitochondrial Mg²⁺-ATPase activity was completely abolished by pretreatment with vitamin E, which is a scavenger of oxygen radicals. On the other hand, paraquat administration did not change the Mg²⁺-ATPase activity in endoplasmic reticulum, which exists in an anaerobic condition in living cells. When liver microsomes were incubated with 1 mM paraquat under aerobic conditions, the Mg²⁺-ATPase activity was decreased by 42%. The decrease of Mg²⁺-ATPase activity was completely eliminated by pretreatment with vitamin E. Furthermore, lipid peroxidation in microsomes was tremendously increased by the addition of 1 mM paraquat under aerobic conditions. The increase of lipid peroxidation was completely abolished by preadministration of vitamin E in rats. The results suggest that the inhibition of Mg²⁺-ATPase activity induced by paraquat may be mediated by active oxgen, which is produced by the reaction of paraquat radicals; molecular oxygen may be involved in the induction of hepatic cell injury.     

The influence of hardness components (Ca2+ and Mg2+) in water on the uptake and concentration of cadmium in a simulated freshwater ecosystem.

To determine whether hardness components in water influenced uptake and concentration of Cd in members of a simulated freshwater ecosystem, an alga (Nitella flexilis), a rooted plant (Elodea canadensis), infusoria snails (Ampullaria paludosa), catfish (Corydoras punctatus), and guppies (Lebistes reticulatus) were cultured together for 1, 6, and 12 hr; and 1, 2, 3, 7, 11, 14 and 21 days in hard (total Ca²⁺ and Mg²⁺ approximately 150 ppm) or soft (total Ca²⁺ and Mg²⁺ 0 ppm) water containing an initial concentration of 0.1 ppm Cd-115. At the end of each of the 10 different exposure periods, specimens of each species were rinsed in distilled water, digested in nitric acid, plated on 2-in. stainless steel planchettes and dried. The amount of radioactivity indicated that the initial rate of Cd uptake by these organisms was faster in hard water than in soft water; however, the total concentration of Cd was greater in those organisms cultured in soft water than those in hard water.     

Effects of Cd, Zn and Cd + Zn Combination on ATPase Activitiy in the Gill and Muscle of Tilapia (Oreochromis niloticus)

This study investigated the responses of Na⁺/K⁺-ATPase, Mg²⁺-ATPase and Ca²⁺-ATPase in the gill and muscle of a freshwater fish Oreochromis niloticus exposed to 1 μg/mL of Cd and Zn and their mixture for different periods (0, 7, 14, 21 and 28 days). At the end of experimental periods, the activities Na⁺/K⁺-ATPase, Mg²⁺-ATPase and Ca²⁺-ATPase in gill tissues and only Ca²⁺-ATPase activity in muscle tissues were measured. Gill Na⁺/K⁺-ATPase activity generally decreased following single metal exposures, whereas their combinations increased its activity. Gill Ca²⁺-ATPase activity decreased relative to the control at most exposure times for single exposures of Zn and Cd, as well as for the combined exposure. There was no gill Ca²⁺-ATPase activity after 28 days of exposure to Zn and Cd combined. Mg²⁺-ATPase activity was not affected significantly in gill tissue by exposure to Zn and Cd individually or in combination. Muscle Ca²⁺-ATPase activity also decreased significantly following metal exposure, but not as greatly as in the gill tissue. Tissue protein levels were mostly unaffected by metal exposures. This study showed that certain ATPases are highly sensitive to metal exposure whether the metals are essential or non essential, and suggests using gill tissue Na⁺/K⁺-ATPase and Ca²⁺-ATPase as sensitive biomarkers in metal contaminated waters.     

EFFECT OF EXTRACELLULAR Mg CONCENTRATION ON ELECTRICALLY INDUCED CONTRACTIONS OF RAT VAS DEFERENS IN VITRO

Contraction of smooth muscles of the vas deferens plays an important role in the propulsion of sperm into the pelvic urethra. This study examined the influence of external Mg²⁺ concentration on reactivity of the rat vas deferens to electrical stimulation in vitro. Vasa deferentia isolated from adult male rats were set up in tissue baths containing physiological salt solution at 37°C and were stimulated electrically. Thereafter, increasing concentrations of Mg²⁺ were added to the bath and their effects on electrically evoked contractions were recorded. The effect of external Mg²⁺ depletion on evoked contractions was also examined. External Mg²⁺ depletion enhanced the contractile response to electrical stimulation while increasing external Mg²⁺ concentration inhibited the contractions. The inhibitory effect of Mg²⁺ was partially reversed by increasing extracellular Ca²⁺ concentration and was not additive with nifedipine. The results indicate that reactivity of the vas deferens to electrical stimulation is modulated by extracellular Mg²⁺ concentration. The possible relevance of these data to sperm transport through the vas deferens is discussed.     

Hypomagnesemia Is a Risk Factor for Infections after Kidney Transplantation: A Retrospective Cohort Analysis

Introduction: Magnesium (Mg²⁺) deficiency is a common finding in the early phase after kidney transplantation (KT) and has been linked to immune dysfunction and infections. Data on the association of hypomagnesemia and the rate of infections in kidney transplant recipients (KTRs) are sparse. Methods: We conducted a single-center retrospective cohort study of KTRs transplanted between 2005 and 2015. Laboratory data, including serum Mg²⁺ (median time of the Mg²⁺ measurement from KT: 29 days), rate of infections including mainly urinary tract infections (UTI), and common transplant-related viral infections (CMV, polyoma, EBV) in the early phase after KT were recorded. The primary outcome was the incidence of infections within one year after KT, while secondary outcomes were hospitalization due to infection, incidence rates of long-term (up to two years) infections, and all-cause mortality. Results: We enrolled 376 KTRs of whom 229 patients (60.9%) suffered from Mg²⁺ deficiency defined as a serum Mg²⁺ < 0.7 mmol/L. A significantly higher incidence rate of UTIs and viral infections was observed in patients with versus without Mg²⁺ deficiency during the first year after KT (58.5% vs. 47.6%, p = 0.039 and 69.9% vs. 51.7%, p < 0.001). After adjustment for potential confounders, serum Mg²⁺ deficiency remained an independent predictor of both UTIs and viral infections (odds ratio (OR): 1.73, 95% CI: 1.04–2.86, p = 0.035 and OR: 2.05, 95% CI: 1.23–3.41, p = 0.006). No group differences according to Mg²⁺ status in hospitalizations due to infections and infection incidence rates in the 12–24 months post-transplant were observed. In the Cox regression analysis, Mg²⁺ deficiency was not significantly associated with all-cause mortality (HR: 1.15, 95% CI: 0.70–1.89, p = 0.577). Conclusions: KTRs suffering from Mg²⁺ deficiency are at increased risk of UTIs and viral infections in the first year after KT. Interventional studies investigating the effect of Mg²⁺ supplementation on Mg²⁺ deficiency and viral infections in KTRs are needed.     

Enterolactone Induces G1-phase Cell Cycle Arrest in Nonsmall Cell Lung Cancer Cells by Downregulating Cyclins and Cyclin-dependent Kinases

Flaxseed is a rich source of the plant lignan secoisolariciresinol diglucoside (SDG), which is metabolized into mammalian lignans enterodiol (ED) and enterolactone (EL) in the digestive tract. The anticancer properties of these lignans have been demonstrated for various cancer types, but have not been studied for lung cancer. In this study, we investigated the anticancer effects of EL for several nonsmall cell lung cancer (NSCLC) cell lines of various genetic backgrounds. EL inhibited the growth of A549, H441, and H520 lung cancer cells in concentration- and time-dependent manners. The antiproliferative effects of EL for lung cancer cells were not due to enhanced cell death, but rather due to G₁-phase cell cycle arrest. Molecular studies revealed that EL decreased mRNA or protein expression levels of the G₁-phase promoters cyclin D1, cyclin E, cyclin-dependent kinases (CDK)-2, -4, and -6, and p-cdc25A; decreased phosphorylated retinoblastoma (p-pRb) protein levels; and simultaneously increased levels of p21^WAF1/CIP1, a negative regulator of the G₁ phase. The results suggest that EL inhibits the growth of NSCLC cell lines by downregulating G₁-phase cyclins and CDKs, and upregulating p21^WAF1/CIP1, which leads to G₁-phase cell cycle arrest. Therefore, EL may hold promise as an adjuvant treatment for lung cancer therapy.     

Differential effects of ca2+ on proliferation of stomach,colonic, and pancreatic cancer cell lines in vitro

Calcium intake inhibits growth of colon cancer in vivo, the mechanisms of which are not fully elucidated. The objective of this study was to determine whether Ca²⁺ directly affects the growth of colon cancer cells in vitro and to compare the effects of Ca²⁺ on the growth of several gastroenteropancreatic cancer cells, including mouse colon cancer (MC‐26), human colon cancer (Lo Vo and WIDR), human gastric cancer (AGS and SII), and human pancreatic cancer (PANC‐1 and MIA) cells. All tumor cell lines tested grew in medium containing low concentration (approx 0.16 mM) of Ca²⁺. Higher concentrations of Ca²⁺ significantly inhibited the growth of all three colon cancer cell lines tested but had no significant effect on proliferation of the stomach and pancreatic cancer cell lines. Growth of AGS cells, in the presence of 0.1 or 0.5 mMEGTA (resulting in the loss of the extracellular Ca²⁺) was similar to that observed in the absence of EGTA, indicating that AGS cells were relatively insensitive to loss of extracellular Co²⁺. In the presence of TMB‐8, an inhibitor of intracellular Ca²⁺ release, the growth of colonic cancer cell lines was inhibited in a dose‐dependent manner, indicating that a minimum basal level of intracellular Ca²⁺ was required for continued proliferation of colon cancer cells. The stomach cancer cell lines (AGS) was once again less sensitive to the effects of TMB‐8 than were the colon cancer cells, indicating an inherent difference in Ca²⁺ requirements and sensitivity to Ca²⁺ for growth of different gastroenteropancreatic cancer cells in vitro. These results further demonstrate that in contrast to normal cells, all tumor cells tested can continue to proliferate in the presence of low concentrations of extracellular Ca²⁺ (approx <0.16 mM) and that higher concentrations of Ca²⁺ specifically and directly inhibit growth of human and mouse colon cancer cells. The latter results may provide an additional explanation for the mechanism by which intake of dietary calcium decreases the risk of developing colon cancers.     

Alcohol-induced vascular damage of brain is ameliorated by administration of magnesium

Ethanol ingestion can cause irreversible neuronal and vascular damage in the brain and stroke-like events. Using an intact in vivo rat brain (pial) model, TV image-intensification, cultured cerebral vascular muscle cells, digital-image analysis, and a novel Mg²⁺ ion-selective electrode to measure extracellular ionized Mg²⁺, studies were designed to determine whether: 1) perivascular or systemic administration (IV or intra-arterial) of magnesium aspartate HCl (MgA) exert vasodilator effects on arterioles (65–130 μm o.d.) and venules (60–135 μm); 2) nonvasodilator doses of MgA could modify vascular spasms induced by BaCl₂ and ethanol; 3) nonvasodilator doses of MgA could ameliorate or prevent the cerebral vascular damage induced by high doses of ethanol; and 4) ethanol depletes cerebral vascular muscle of intracellular Mg ions ([Mg²⁺]_i). Perivascular application of MgA (0.01–100 μmol) produced dose-dependent vasodilatation of cerebral arterioles and venules; arterioles yielded greater vasodilator responses compared to venules. Nonvasodilator doses of Mg (1.0, 4.0 μmol/min), administered IV or intra-arterially, into a branch of the internal carotid artery, prevented: 1) the spasmogenic actions of ethanol and Ba²⁺; and 2) the vasculotoxic actions (rupture of postcapillary venules and focal hemorrhages) of ethanol. In addition, ethanol depleted cerebral vascular muscle cells of [Mg²⁺]_i; blood levels of ionized Mg²⁺ rose after IP ethanol. Despite the fact that systemic infusion of low nonvasodilator doses did not result in dilatation of the pial arterioles and venules, plasma total and ionized Mg rose 18–230%, depending upon doses of MgA and time of plasma sampling. These data support the idea that Mg²⁺ can act as a local vasodilator on brain microvessels and possess antispasmodic properties on brain arterioles and venules. In addition, our results indicate that Mg may posses some unique cerebral vascular protective properties against the vasculotoxic effects of ethanol. Lastly, these findings suggest ethanol-induced cerebrovasospasm and vascular damage appear to be associated with a rapid loss of [Mg²⁺]_i from cerebral vascular muscle cells.     

Continuous osmotic minipump infusion of alcohol into brain decreases brain [Mg2+] and brain bioenergetics and enhances susceptibility to hemorrhagic stroke: An in vivo 31P-NMR study

³¹P-NMR spectroscopic studies were performed in vivo on brains of rats chronically infused for 7 and 14 days with 30% ethanol (in the third cerebral ventricle). Peripheral blood alcohol concentration (BAC) rose to between 16.5–30.5 mg/dl. Brain intracellular free Mg²⁺ ([Mg²⁺]_i) fell 33–39%, brain mitochondrial cytosolic phosphorylation potential (CPP) fell 31–48%, and brain phosphocreatine (PCr) fell approximately 15%; however, neither brain intracellular free hydrogen ion concentration (pHi) nor brain intracellular inorganic phosphate (Pi) were affected significantly by the chronic release of ethanol from the brain implants. Correlations were found between [Mg²⁺]_i and [PCr] and between [Mg²⁺]_i and CPP. Although brain free [MgADP] was not affected, [MgATP] fell by almost 20% accompanied by a 35–40% rise in free [ADP]. Interestingly, 14-day surgical implantation of 0.9% sterile saline into the third cerebral ventricle was associated with a 20% fall in brain [Mg²⁺]_i and a 35% fall in CPP; however, PCr, ATP, or pHi was not significantly altered. Systemic administration of 4 g/kg ethanol into the 7- and 14-day chronic ethanol animals resulted in a 9- and 12-fold increase in hemorrhagic stroke mortality compared to naive, control rats. Eating habits, grooming, gait and arterial blood pressure were not affected by the chronic brain implantation of ethanol. These data lend support to the notion, primarily based on epidemiologic evidence, that chronic exposure to alcohol can pose a high risk for hemorrhagic stroke. Our alcohol pump-implanted rats also might provide a new model of slow, moderate alcohol intoxication.     

Effects of Elevated Atmospheric CO<Subscript>2</Subscript> and O<Subscript>3</Subscript> on Hill Activity and Ca<Superscript>2+</Superscript>/Mg<Superscript>2+</Superscript>-ATPase Activity of <Emphasis Type="Italic">Pinus tabulaeformis</Emphasis> Carr.

The main photo-physiological characteristics of Pinus tabulaeformis Carr. were analyzed in open-top chambers under elevated carbon dioxide and ozone concentrations. The results indicated that the leaves net photosynthetic rates (p < 0.05), Hill activity, Ca²⁺/Mg²⁺-ATPase activity, soluble sugar and starch contents all increased under elevated carbon dioxide concentration in whole growing season. While under elevated ozone concentration, the leaves net photosynthetic rates, Hill activity, Ca²⁺/Mg²⁺-ATPase activity, soluble sugar and starch contents all decreased. Under elevated carbon dioxide and ozone concentration, the leaves net photosynthetic rates, Hill activity, soluble sugar and starch contents all increased, but Ca²⁺-ATPase activity increased during the earlier growing season, decreased in later growing season, while Mg²⁺-ATPase activity responded contrarily.     

Role of brain [Mg2+]i in alcohol-induced hemorrhagic stroke in a rat model: A 31P-NMR in vivo study

One hundred percent of anesthetized rats administered 6.6 gm/kg of ethanol IP died within 10–35 min of alcohol injection; upon autopsy of the brain all demonstrated profound subarachnoid and intracranial bleeding, clear signs of hemorrhagic stroke. Pretreatment of rats with 4 μmol/min MgCl₂, but not saline, via IV administration (for 30–45 min), prevented hemorrhagic stroke in all animals so treated with 6.6 gm/kg ethanol. Administration of the stroke dose of alcohol resulted in rapid (within 3–5 min) and marked deficits in whole brain intracellular free Mg ([Mg²⁺⁺]_i) as observed by in vivo ³P-NMR spectroscopy. Intracellular pH (pH_i) and the phosphocreatine [PCr]/[ATP] ratio also fell following a significant fall in brain [Mg²⁺]_i). Brains of rats that exhibited strokelike events, upon death and autopsy, demonstrated continued and marked intracellular acidosis with progressive fall in the [PCr]/[ATP] ratio and elevation of inorganic phosphate (P_i) and [H⁺]i; these events were not accompanied by any rises in systemic arterial blood pressure. Rats pretreated with MgCl₂ exhibited relatively stable brain [Mg²⁺]_i, and essentially unchanged pHi, [PCr], [ATP], or [P_i] following alcohol administration, although such animals exhibited threefold alterations in plasma Mg²⁺, as measured by ion selective electrodes. These observations suggest that high alcohol ingestion can result in severe vasospasm, ischemia, and rupture of blood vessels probably as a consequence of depletion of brain [Mg₂₊]_i, events that can be prevented by Mg²⁺ pretreatment.     

Sesame Oil Therapeutically Ameliorates Cardiac Hypertrophy by Regulating Hypokalemia in Hypertensive Rats

Background: Hypokalemia and hypertension are common manifestations of preclinical cardiovascular conditions that have a predictive value for cardiovascular morbidity and mortality. Cardiac hypertrophy, an important risk factor in heart failure, is attributed to long‐term hypokalemia and hypertension. Sesame oil is rich in nutrients and possesses potent antihypertensive activities. Methods: We investigated the therapeutic potential of sesame oil using a hypertensive model created by subcutaneously injecting deoxycorticosterone acetate (DOCA; 15 mg/mL/kg in mineral oil; twice weekly for 5 weeks) and supplementing with 1% sodium chloride drinking water (DOCA/salt) to uninephrectomized rats. Sesame oil was administered by oral gavage (0.5 or 1 mL/kg/d for 7 days) after 4 weeks of DOCA/salt treatment. Systolic blood pressure (SBP) and diastolic blood pressure (DBP), electrocardiography (ECG), and K⁺ and Mg²⁺ levels were assessed 24 hours after the last dose of sesame oil. Heart tissue was collected for histologic analysis. Results: Sesame oil effectively reduced the SBP/DBP and ECG abnormalities and increased the serum levels of K⁺ and Mg²⁺ while limiting the urinary excretion of K⁺ in DOCA/salt‐induced hypertensive rats. In addition, sesame oil decreased the heart mass, the thickness of the left ventricle, and the diameter of cardiomyocytes, indicating the regression of left ventricular hypertrophy in the hypertensive rats. Conclusion: We demonstrate that sesame oil therapeutically ameliorates cardiac hypertrophy by regulating hypokalemia in hypertensive rats.