RESUMO
Magnesium supplementation may be beneficial for cancer patients due to its action as a modulator of cell proliferation and metabolism and its anti-inflammatory effect. Tumor metabolism can influence the bioavailability and absorption of nutrients, leading to an increase in the individual's nutritional needs. In this work, the effects of supplementing different dosages of magnesium chloride in mice with solid Ehrlich's tumors were investigated by analyzing their hematological, inflammatory and anthropometric biomarkers. Three dosages of magnesium chloride (MgCl2) were administered for 28 consecutive days. Animal welfare was assessed according to the criteria stipulated by the National Center for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs). The inverted grid method was used to analyze muscle strength and fatigue. Difference in expression of the Tumor Necrosis Factor (TNF-α) and the Growth Transformation Factor (TGF-ß1) genes was determined by the 2-ΔCt method. The hematological evaluation consisted of the erythrogram, white blood cell and platelet counts were used for the hematological evaluation and treatment cytotoxicity. Difference in the expression of the TNF-α and TGF-ß genes showed that the group that received a high dose of magnesium had a decrease in TNF-α and RNL, an improvement in well-being with a tendency to increase muscle strength and less tumor progression according to the days of treatment. The group that received a low dosage of magnesium had a smaller tumor volume and a more controlled tumor growth according to the days. The group that received an intermediate dosage presented cytotoxicity.
Assuntos
Cloreto de Magnésio , Neoplasias , Animais , Suplementos Nutricionais , Inflamação/tratamento farmacológico , Cloreto de Magnésio/farmacologia , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Fator de Necrose Tumoral alfaRESUMO
Previous studies reported on the broad-spectrum antiviral function of heparin. Here we investigated the antiviral function of magnesium-modified heparin and found that modified heparin displayed a significantly enhanced antiviral function against human adenovirus (HAdV) in immortalized and primary cells. Nuclear magnetic resonance analyses revealed a conformational change of heparin when complexed with magnesium. To broadly explore this discovery, we tested the antiviral function of modified heparin against herpes simplex virus type 1 (HSV-1) and found that the replication of HSV-1 was even further decreased compared to aciclovir. Moreover, we investigated the antiviral effect against the new severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and measured a 55-fold decreased viral load in the supernatant of infected cells associated with a 38-fold decrease in virus growth. The advantage of our modified heparin is an increased antiviral effect compared to regular heparin.
Assuntos
Antivirais/farmacologia , Heparina/farmacologia , Cloreto de Magnésio/farmacologia , Aciclovir/farmacologia , Adenovírus Humanos/efeitos dos fármacos , Adenovírus Humanos/fisiologia , Animais , Antivirais/química , Células CHO , Linhagem Celular Tumoral , Chlorocebus aethiops , Cricetulus , Avaliação Pré-Clínica de Medicamentos , Fibroblastos , Heparina/química , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/fisiologia , Humanos , Cloreto de Magnésio/química , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Cultura Primária de Células , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/fisiologia , Relação Estrutura-Atividade , Células Vero , Carga Viral/efeitos dos fármacos , Replicação Viral/efeitos dos fármacosRESUMO
Evidence suggest that magnesium dietary supplementation has several health benefits including lowering blood pressure, reducing insulin resistance, and improving symptoms of depression, anxiety, and migraine. Here, we aimed to study the effect of chronic magnesium supplementation on anxiety-like behavior in rats by supplementing with magnesium their drinking water for 30 days. Anxiety-like behavior was induced by subcutaneous injection of veratrin 30 min before performing elevated plus maze and open field tests to measure anxiety levels and locomotion, respectively. We quantify the concentration of magnesium in plasma and cerebrospinal fluid. We used diazepam to compare the efficacy of magnesium supplementation as an anxiolytic agent. Our results show that rats supplemented with magnesium had a statistically significant decrease in anxiety levels with not effects on locomotion and a statistically significant increase in concentration of magnesium in plasma and cerebrospinal fluid. However, the anxiolytic effect of magnesium supplementation washes-out in 12 days. We discuss the advantages of using supplemental magnesium as anxiolytic.
Assuntos
Ansiolíticos/farmacologia , Ansiedade , Comportamento Animal/efeitos dos fármacos , Cloreto de Magnésio/farmacologia , Animais , Ansiolíticos/administração & dosagem , Ansiedade/sangue , Ansiedade/líquido cefalorraquidiano , Ansiedade/dietoterapia , Ansiedade/tratamento farmacológico , Diazepam/farmacologia , Modelos Animais de Doenças , Magnésio/sangue , Magnésio/líquido cefalorraquidiano , Cloreto de Magnésio/administração & dosagem , Ratos , Ratos WistarRESUMO
Although incidence of clinical hypocalcemia in postpartum dairy cows is low in US dairies, subclinical hypocalcemia after calving is common and has been associated with metabolic and infectious disease. It is widespread farm practice to feed a diet rich in anions to prepartum dairy cattle to support calcium homeostasis. However, this diet is typically discontinued at parturition, when calcium needs are still high. The objective of this trial was to determine the effects of extending metabolic acidification into the first 3 d of lactation in multiparous Holstein cows with the use of magnesium chloride (MgCl2) hexahydrate drenches on blood ionized calcium concentrations. Adult Holstein cows at a commercial dairy in their second or higher lactation, with a urine pH of 6.8 or less on the day of calving, were randomly assigned to either treatment or control groups, resulting in 13 cows in the treatment group and 14 cows in the control group. Treatment cows received 480 g of oral MgCl2 hexahydrate once daily for 3 d for continued acidification starting on the day of calving, whereas cows in the control group received no treatment. Urine pH was measured daily for 5 d, starting on the day of calving (0 DIM), to assess acidification status; blood was collected on day of calving (0 DIM), 2 DIM, and 4 DIM and analyzed for ionized calcium concentrations. Differences in blood ionized calcium and urine pH over time were compared using longitudinal data analysis. Urine pH was lower in treatment cows compared with control cows at 1, 2, and 3 DIM. Blood ionized calcium concentrations were different from baseline, taken at enrollment (0 DIM) and at 2 and 4 DIM in both treatment and control cows. However, no difference was detectable between treatment and control cows at 2 or 4 DIM with respect to blood ionized calcium concentrations. Oral supplementation with MgCl2 hexahydrate resulted in the desired acidification of urine pH in the treatment group, similar to feeding of an anionic close-up diet. Continued acidification of dairy cows until 2 DIM did not result in clinically meaningful higher blood calcium concentrations compared with controls, and further research is needed, to identify physiological reasons for this finding.
Assuntos
Ração Animal , Cálcio/sangue , Bovinos/sangue , Lactação , Cloreto de Magnésio/farmacologia , Animais , Ânions/administração & dosagem , Dieta/veterinária , Feminino , Homeostase/fisiologia , Concentração de Íons de Hidrogênio , Lactação/fisiologia , Leite/química , Período Pós-Parto/metabolismo , UrinaRESUMO
The study of effects of Ca2+ and Mg2+ on antifungal activity of lactic acid bacteria (LAB) isolates and their associations revealed inducing and inhibiting effects on antifungal activity. The addition of Ca2+ essentially inhibited the antifungal effect of L. rhamnosus MDC9661 but stimulated the activity of RIN-2003-Ls, MDC9632 and MDC9633 strains, as well as their associations. Mg2+ partly increased the inhibitory activity of LAB isolates, while the addition of ions combination did not cause changes of their antifungal activity. The supplementation of Ca2+ stimulated the antifungal effect of most associations against Penicillium sp., Trichoderma viride, Geotrichum candidum, and Aspergillus flavus compared with the native conditions. The addition of Mg2+ induced the antifungal activity of RIN-2003-Ls, MDC9632, MDC9633, and INR-2010-Tsov-G-St combinations. The antifungal effects of most associations were increased in the presence of ions mixture. The natural LAB associations including VKPM B-3386, MDC9632, and MDC9633 could not suppress the growth of any tested mold; however, the supplementation of ions combination revealed their antifungal effect against all kinds of molds. The finding of substantial stimulation of the most LAB associations antifungal effect by metal ions can be basis for creation of new effective antifungal preparations by the supplementation of ions combined mixture.
Assuntos
Antifúngicos/farmacologia , Cátions Bivalentes/farmacologia , Lactobacillales/fisiologia , Antibiose , Cloreto de Cálcio/farmacologia , Fungos/efeitos dos fármacos , Cloreto de Magnésio/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Immersion euthanasia methods reported over the most recent decades for aquatic invertebrates use organic alcohols or halogenated hydrocarbons that can interfere with nuclear magnetic resonance (NMR) analysis. A rolling study design evaluated potassium chloride (KCl), magnesium chloride (MgCl2), and magnesium sulfate (MgSO4) as potential ion-based euthanasia methods for moon jellyfish (Aurelia aurita) destined for metabolomic analysis by NMR spectroscopy. Death was defined as the cessation of autonomous bell pulsing and response to external stimulus. MgCl2 applied at a dose of 142 g/L provided euthanasia within 32 sec of applications without the untoward effects observed with the other two salts. Euthanasia with KCl at the doses tested was associated with abnormal behavior and tissue degradation during dissection. MgSO4 at the doses tested resulted in abnormal behavior and failed to provide rapid euthanasia.
Assuntos
Eutanásia Animal/métodos , Cloreto de Magnésio/administração & dosagem , Sulfato de Magnésio/administração & dosagem , Cloreto de Potássio/administração & dosagem , Cifozoários/efeitos dos fármacos , Animais , Íons/administração & dosagem , Íons/farmacologia , Cloreto de Magnésio/farmacologia , Sulfato de Magnésio/farmacologia , Cloreto de Potássio/farmacologia , Cifozoários/fisiologiaRESUMO
Magnesium (Mg) is an essential biomineral that acts as an intracellular cofactor for more than 300 enzymes. It is an important modulator of the N-methyl-D-aspartate (NMDA) receptor which is involved in memory function and depression. The purpose of this study was to compare the dose dependent effect of oral supplementation of Magnesium chloride (MgCl2), Magnesium sulphate (MgSO4) and Magnesium-L-threonate (MgT) on memory and depression-related behaviors in rats. Rats were orally administered with different doses (50 mg/kg, 100 mg/kg and 150 mg/kg) of each Mg salt. Following 28 days of oral supplementation, animals were subjected to behavioral tests. After completion of behavioral test, rats were decapitated. Brain and plasma samples were used for neurochemical and biochemical analysis. Assessment of behaviors in elevated plus maze (EPM) test and forced swim test (FST) showed that MgT more significantly improved memory of rats and decreased depression-like symptoms in healthy rats as compared to controls. Biochemical analysis indicated significant increase in plasma Mg levels dose dependently following MgT administration. This increase might be related to observe enhanced cholinergic functions and decline in oxidative stress in rats in the present study. This comparative study highlights that MgT (100mg/kg) is the most appropriate Mg salt and dose for oral treatment that strengthens cholinergic system and improves brain related functions through attenuation of oxidative burden in adult healthy rats.
Assuntos
Encéfalo/efeitos dos fármacos , Butiratos/farmacologia , Cloreto de Magnésio/farmacologia , Sulfato de Magnésio/farmacologia , Memória/efeitos dos fármacos , Acetilcolina/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Butiratos/administração & dosagem , Depressão/tratamento farmacológico , Relação Dose-Resposta a Droga , Magnésio/sangue , Cloreto de Magnésio/administração & dosagem , Sulfato de Magnésio/administração & dosagem , Masculino , Ratos WistarRESUMO
Among different RNA modifications, the helix 69 (H69) region of the bacterial ribosomal RNA (rRNA) contains three pseudouridines (Ψs). H69 is functionally important due to its location in the heart of the ribosome. Several structural and functional studies have shown the importance of Ψ modifications in influencing the H69 conformation as well as maintaining key interactions in the ribosome during protein synthesis. Therefore, a need exists to understand the influence of modified nucleosides on conformational dynamics of the ribosome under solution conditions that mimic the cellular environment. In this review on chemical probing, we provide detailed protocols for the use of dimethyl sulfate (DMS) to examine H69 conformational states and the influence of Ψ modifications under varying solution conditions in the context of both ribosomal subunits and full ribosomes. The use of DMS footprinting to study the binding of aminoglycosides to the H69 region of bacterial rRNA as a potential antibiotic target will also be discussed. As highlighted in this work, DMS probing and footprinting are versatile techniques that can be used to gain important insight into RNA local structure and RNA-ligand interactions, respectively.
Assuntos
Escherichia coli/genética , Impressão Molecular/métodos , Pseudouridina/química , RNA Ribossômico 16S/química , RNA Ribossômico 23S/química , Compostos de Anilina/química , Antibacterianos/farmacologia , Fracionamento Celular/métodos , DNA Complementar/biossíntese , DNA Complementar/química , DNA Complementar/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Gentamicinas/farmacologia , Hidroliases/genética , Hidroliases/metabolismo , Ligantes , Cloreto de Magnésio/farmacologia , Neomicina/farmacologia , Conformação de Ácido Nucleico , Fatores de Terminação de Peptídeos/genética , Fatores de Terminação de Peptídeos/metabolismo , Pseudouridina/genética , Pseudouridina/metabolismo , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , RNA Ribossômico 23S/genética , RNA Ribossômico 23S/metabolismo , Transcrição Reversa , Subunidades Ribossômicas Maiores de Bactérias/química , Subunidades Ribossômicas Maiores de Bactérias/efeitos dos fármacos , Subunidades Ribossômicas Maiores de Bactérias/genética , Subunidades Ribossômicas Maiores de Bactérias/metabolismo , Subunidades Ribossômicas Menores de Bactérias/química , Subunidades Ribossômicas Menores de Bactérias/efeitos dos fármacos , Subunidades Ribossômicas Menores de Bactérias/genética , Subunidades Ribossômicas Menores de Bactérias/metabolismo , Ribossomos/química , Ribossomos/efeitos dos fármacos , Ribossomos/genética , Ribossomos/metabolismo , Ésteres do Ácido Sulfúrico/químicaRESUMO
BACKGROUND AND PURPOSE: Streptococcus pneumoniae is the most common cause of bacterial meningitis in adults and is characterized by high lethality and substantial cognitive disabilities in survivors. Here, we have studied the capacity of an established therapeutic agent, magnesium, to improve survival in pneumococcal meningitis by modulating the neurological effects of the major pneumococcal pathogenic factor, pneumolysin. EXPERIMENTAL APPROACH: We used mixed primary glial and acute brain slice cultures, pneumolysin injection in infant rats, a mouse meningitis model and complementary approaches such as Western blot, a black lipid bilayer conductance assay and live imaging of primary glial cells. KEY RESULTS: Treatment with therapeutic concentrations of magnesium chloride (500 mg·kg-1 in animals and 2 mM in cultures) prevented pneumolysin-induced brain swelling and tissue remodelling both in brain slices and in animal models. In contrast to other divalent ions, which diminish the membrane binding of pneumolysin in non-therapeutic concentrations, magnesium delayed toxin-driven pore formation without affecting its membrane binding or the conductance profile of its pores. Finally, magnesium prolonged the survival and improved clinical condition of mice with pneumococcal meningitis, in the absence of antibiotic treatment. CONCLUSIONS AND IMPLICATIONS: Magnesium is a well-established and safe therapeutic agent that has demonstrated capacity for attenuating pneumolysin-triggered pathogenic effects on the brain. The improved animal survival and clinical condition in the meningitis model identifies magnesium as a promising candidate for adjunctive treatment of pneumococcal meningitis, together with antibiotic therapy.
Assuntos
Cloreto de Magnésio/administração & dosagem , Meningite Pneumocócica/tratamento farmacológico , Streptococcus pneumoniae/efeitos dos fármacos , Estreptolisinas/metabolismo , Animais , Proteínas de Bactérias/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/microbiologia , Modelos Animais de Doenças , Feminino , Cloreto de Magnésio/farmacologia , Meningite Pneumocócica/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Neuroglia/efeitos dos fármacos , Neuroglia/microbiologia , Ratos , Ratos Sprague-Dawley , Streptococcus pneumoniae/isolamento & purificação , Taxa de SobrevidaRESUMO
The neurologic manifestations of neonatal hyperbilirubinemia in the central nervous system (CNS) exhibit high variations in the severity and appearance of motor, auditory and cognitive symptoms, which is suggestive of a still unexplained selective topography of bilirubin-induced damage. By applying the organotypic brain culture (OBC: preserving in vitro the cellular complexity, connection and architecture of the in vivo brain) technique to study hyperbilirubinemia, we mapped the regional target of bilirubin-induced damage, demonstrated a multifactorial toxic action of bilirubin, and used this information to evaluate the efficacy of drugs applicable to newborns to protect the brain. OBCs from 8-day-old rat pups showed a 2-13 fold higher sensitivity to bilirubin damage than 2-day-old preparations. The hippocampus, inferior colliculus and cerebral cortex were the only brain regions affected, presenting a mixed inflammatory-oxidative mechanism. Glutamate excitotoxicity was appreciable in only the hippocampus and inferior colliculus. Single drug treatment (indomethacin, curcumin, MgCl2) significantly improved cell viability in all regions, while the combined (cocktail) administration of the three drugs almost completely prevented damage in the most affected area (hippocampus). Our data may supports an innovative (complementary to phototherapy) approach for directly protecting the newborn brain from bilirubin neurotoxicity.
Assuntos
Bilirrubina/toxicidade , Encefalopatias Metabólicas/patologia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encefalite/patologia , Hiperbilirrubinemia/complicações , Animais , Sobrevivência Celular/efeitos dos fármacos , Curcumina/farmacologia , Indometacina/farmacologia , Inflamação/patologia , Cloreto de Magnésio/farmacologia , Modelos Biológicos , Fármacos Neuroprotetores/farmacologia , Técnicas de Cultura de Órgãos , Estresse Oxidativo , RatosRESUMO
BACKGROUND: Opioid effectiveness to treat cancer pain is often compromised by the development of tolerance and the occurrence of undesirable side effects, particularly during long-term treatment. Hence, the search for more efficient analgesics remains a necessity. The main goal of this study was to relieve neuropathic symptoms associated with tumour growth by administering the non-opioid analgesic dipyrone (DIP) alone or in combination with magnesium chloride (MgCl2 ), an adjuvant that blocks the NMDA receptor channel. METHODS: Mice were inoculated with a melanoma cell line (B16-BL6) in the left thigh and two protocols were used to evaluate the effect of DIP (270 mg/kg), MgCl2 (200 mg/kg), or the combination DIP-MgCl2 . In the therapeutic protocol the drugs, alone or combined, were administered once tumour had promoted increased nociception. In the preventive protocol, drugs were administered prior to the appearance of the primary tumour. Tumour growth was assessed with a caliper and nociception was determined using behavioural tests. RESULTS: DIP promoted antinociception only at the beginning of both protocols due to the development of tolerance. The combination DIP-MgCl2 improved the antinociceptive effect, avoiding tolerance and reducing tumour growth in the preventive treatment, more efficiently than each compound alone. CONCLUSIONS: These results suggest that DIP-MgCl2 may represent a safe, affordable and accessible option to reduce tumour growth and to treat cancer pain avoiding the risk of tolerance, without the typical complications of opioids agents, particularly when long-term treatment is required. SIGNIFICANCE: This study shows a non-opioid analgesic combined with an adjuvant as a therapeutic option to treat cancer pain. The avoidance of antinociceptive tolerance when repeated administration is required, as well as tumor growth reduction, are additional advantages to be considered.
Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Dor do Câncer/tratamento farmacológico , Dipirona/farmacologia , Cloreto de Magnésio/farmacologia , Analgésicos/administração & dosagem , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Dor do Câncer/psicologia , Dipirona/administração & dosagem , Progressão da Doença , Combinação de Medicamentos , Tolerância a Medicamentos , Cloreto de Magnésio/administração & dosagem , Masculino , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Medição da Dor/efeitos dos fármacosRESUMO
Magnesium salts are components of many dietary supplements used in treatment or prevention of magnesium deficiency. Hypomagnesemia usually results from an improper lifestyle, including unbalanced diet. Isolated hepatocytes of animals or humans are the preferred model used to study the in vitro effects of exogenous factors on cellular metabolic changes. The aim of this study was to evaluate the content of saturated, monounsaturated and polyunsaturated fatty acids and their esters in isolated rat hepatocytes influenced by different magnesium concentrations. The isolated rat hepatocytes were used as the test material. Hepatocytes were prepared in culture medium (Hepatocyte Medium) + MgCl(2) solution to concentrations of 2 mM/dm(3) MgCl(2), 4 mM/dm(3) MgCl(2). After incubation with different concentrations of magnesium ions, changes in the content of fatty acids and their esters were found for the whole hepatocytes and hepatocyte membranes. Despite changes in the fatty acid content in the whole hepatocytes and their membranes, there were no changes in the coefficient of degree of saturation of fatty acids when different concentrations of MgCl2 were used.
Assuntos
Ácidos Graxos/análise , Hepatócitos/química , Cloreto de Magnésio/farmacologia , Animais , Células Cultivadas , Masculino , Ratos , Ratos WistarRESUMO
Breast cancer is the most common malignancy and also the second leading cause of cancer death among women and also in women that have a high mortality. Previous studies showed that magnesium (Mg) has cytotoxic effects on malignant cell lines. However, the anti-cancer effects of Mg on MCF-7 breast cancer cells are uncertain. This study was aimed at the comparison of the cytotoxic effect of Mg salt (MgCl2) and cisplatin on MCF-7 cells and fibroblasts (as normal cells). After treatment with various concentrations of MgCl2, and cisplatin as a positive control for 24 and 48 hours (h), cytotoxicity activity was measured by MTT assay. In addition, apoptosis was determined by annexin V/propidium iide assay. Both cisplatin and the MgCl2 exhibited dose-dependent cytotoxic effects in the MCF-7 cell line, although the LD50 of the Mg was significantly higher when compared to cispaltin (40 µg/ml vs. 20 µg/ml). Regarding annexin V/propidium results, treatment of MCF-7 cells with LD50 concentrations of cisplatin and Mg showed 59% and 44% apoptosis at 24h, respectively. Finally, the results indicated that Mg has cytotoxic effects on MCF-7 cells, but less than cisplatin as a conventional chemotherapeutic agent. However, regarding the side effects of chemotherapy drugs, it seems that Mg can be considered as a supplement for the treatment of breast cancer.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Cloreto de Magnésio/farmacologia , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Combinada , Feminino , Citometria de Fluxo , Humanos , Células MCF-7RESUMO
Addition of MgCl2 to the culture medium has been found to dramatically increase the activity of Bacillus deramificans pullulanase expressed by Brevibacillus choshinensis. The specific activity of the pullulanase obtained from medium supplemented with MgCl2 was also higher than that obtained in culture medium without added magnesium ions. In this work, the mechanism of this increase was studied. When cultured in medium without added magnesium ions, B. choshinensis mainly produced a thermolabile, inactive form of pullulanase. The addition of magnesium ions led to the production of a thermostable, active form of pullulanase. Circular dichroism assays revealed considerable differences in secondary structure between the active and inactive pullulanase forms. Transmission electron microscopy suggested that magnesium ion addition inhibits the shedding of cell wall protein (HWP) layers from the cell surface. Quantitative real-time PCR showed that magnesium ion addition represses transcription of HWP. Because the pullulanase gene and HWP have identical promoters, pullulanase gene transcription was also inhibited. These results suggest that when pullulanase is expressed slowly, it tends to fold into an active form.
Assuntos
Bacillus/enzimologia , Bacillus/genética , Brevibacillus/metabolismo , Parede Celular/metabolismo , Glicosídeo Hidrolases/metabolismo , Cloreto de Magnésio/farmacologia , Brevibacillus/genética , Parede Celular/ultraestrutura , Dicroísmo Circular , Microscopia Eletrônica de Transmissão , Regiões Promotoras Genéticas/genética , Dobramento de Proteína , Reação em Cadeia da Polimerase em Tempo RealRESUMO
AIM: This study evaluated the efficacy of oral magnesium supplementation in the reduction of plasma glucose levels in adults with prediabetes and hypomagnesaemia. METHODS: A total of 116 men and non-pregnant women, aged 30 to 65 years with hypomagnesaemia and newly diagnosed with prediabetes, were enrolled into a randomized double-blind placebo-controlled trial to receive either 30 mL of MgCl2 5% solution (equivalent to 382 mg of magnesium) or an inert placebo solution once daily for four months. The primary trial endpoint was the efficacy of magnesium supplementation in reducing plasma glucose levels. RESULTS: At baseline, there were no significant statistical differences in terms of anthropometric and biochemical variables between individuals in the supplement and placebo groups. At the end of follow-up, fasting (86.9 ± 7.9 and 98.3 ± 4.6 mg/dL, respectively; P = 0.004) and post-load glucose (124.7 ± 33.4 and 136.7 ± 23.9 mg/dL, respectively; P = 0.03) levels, HOMA-IR indices (2.85 ± 1.0 and 4.1 ± 2.7, respectively; P = 0.04) and triglycerides (166.4 ± 90.6 and 227.0 ± 89.7, respectively; P = 0.009) were significantly decreased, whereas HDL cholesterol (45.6 ± 10.9 and 46.8 ± 9.2 mg/dL, respectively; P = 0.04) and serum magnesium (1.96 ± 0.27 and 1.60 ± 0.26 mg/dL, respectively; P = 0.005) levels were significantly increased in those taking MgCl2 compared with the controls. A total of 34 (29.4%) people improved their glucose status (50.8% and 7.0% in the magnesium and placebo groups, respectively; P < 0.0005). CONCLUSION: Our results show that magnesium supplementation reduces plasma glucose levels, and improves the glycaemic status of adults with prediabetes and hypomagnesaemia.
Assuntos
Glicemia/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Cloreto de Magnésio/uso terapêutico , Deficiência de Magnésio/tratamento farmacológico , Estado Pré-Diabético/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Cloreto de Magnésio/administração & dosagem , Cloreto de Magnésio/farmacologia , Deficiência de Magnésio/metabolismo , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/metabolismoRESUMO
The differing bioavailability of magnesium salts remains an open question, both at the cellular and systemic level. However, this issue is relevant for identifying the most effective magnesium supplement. We compared the effects of three widely used magnesium salts: MgSO4, MgCl2 and Mg pidolate, on the proliferation of four human cell types: promyelocytic leukaemia HL60, osteoblast-like Saos-2 and U-2 OS, and endothelial cells from the umbilical vein. The three magnesium salts had no effect on endothelial and leukemic cell growth, but magnesium pidolate impaired cell growth in osteoblast-like cells. In particular, in Saos-2 cells, 1 mM pidolate induced a slight accumulation of cells in the G0/G1 phase of the cell cycle and, in parallel, an early rise in intracellular calcium and a late decrease in intracellular magnesium content. Interestingly, when cultured in 5 mM magnesium pidolate, Saos-2 cells grew as fast as the controls. Moreover, intracellular magnesium and calcium concentrations did not vary. These results suggest a lower bioavailability of magnesium pidolate in osteoblast-like cells.
Assuntos
Cloreto de Magnésio/farmacologia , Sulfato de Magnésio/farmacologia , Ácido Pirrolidonocarboxílico/farmacologia , Disponibilidade Biológica , Cálcio/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Humanos , Magnésio/metabolismo , Cloreto de Magnésio/química , Sulfato de Magnésio/química , Ácido Pirrolidonocarboxílico/química , Sais/química , Sais/farmacologia , Relação Estrutura-AtividadeRESUMO
Deep sea water (DSW), originally pumped from the Pacific Rim off the coast of Hualien County (Taiwan), and its mineral constituents, were concentrated by a low-temperature vacuum evaporation system to produce a hardness of approximately 400,000 mg/L of seawater mineral concentrate. The primary composition of this seawater mineral concentrate was ionic magnesium (Mg²âº), which was approximately 96,000 mg/L. Referring to the human recommended daily allowance (RDA) of magnesium, we diluted the mineral concentrate to three different dosages: 0.1 × DSW (equivalent to 3.75 mg Mg²âº/kg DSW); 1 × DSW (equivalent to 37.5 mg Mg²âº/kg DSW); and 2 × DSW (equivalent to 75 mg Mg²âº/kg DSW). Additionally, a magnesium chloride treatment was conducted for comparison with the DSW supplement. The study indicated that 0.1 × DSW, 1 × DSW and 2 × DSW decreased the systolic and diastolic pressures in spontaneous hypertensive rats in an eight-week experiment. DSW has been shown to reduce serum lipids and prevent atherogenesis in a hypercholesterolemic rabbit model. Our results demonstrated that 1 × DSW and 2 × DSW significantly suppressed the serum cholesterol levels, reduced the lipid accumulation in liver tissues, and limited aortic fatty streaks. These findings indicated that the antiatherogenic effects of DSW are associated with 5'-adenosine monophosphate-activated protein kinase (AMPK) stimulation and the consequent inhibition of phosphorylation of acetyl-CoA carboxylase (ACC) in atherosclerotic rabbits. We hypothesize that DSW could potentially be used as drinking water because it modulates blood pressure, reduces lipids, and prevents atherogenesis.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Acetil-CoA Carboxilase/metabolismo , Água Potável/química , Água do Mar/química , Animais , Aorta/metabolismo , Aterosclerose/etiologia , Aterosclerose/prevenção & controle , Pressão Sanguínea , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Hipercolesterolemia/complicações , Hipercolesterolemia/terapia , Lipídeos/sangue , Magnésio , Cloreto de Magnésio/farmacologia , Masculino , Minerais/química , Coelhos , Ratos , Ratos Endogâmicos SHR , TaiwanRESUMO
OBJECTIVE: Streptomyces hygroscopicus ATCC29253 has attracted much interests due to its capacity of producing various secondary metabolites with strong bioactivities, including immunosuppressant rapamycin, nigericin, hexaenes, elaiophylin and hygrocins. OBJECTIVE: To investigate biosynthetic pathway of these metabolites and construct high-yield strains by genetic engineering, establishment of a highly efficient genetic manipulation system is critically required in this strain. METHODS: We tested the effects of conjugation media and donor strains on conjugal transfer from Escherichia coli to S. hygroscopicus ATCC29253 and other Streptomycetes. RESULTS: We found that both casamino acid and MgCl2 supplemented in conjugation media improved conjugation frequency in S. hygroscopicus ATCC29253. A random experiment led to the disclosure of an optimal combination of casamino acid and MgCl2 by which the conjugation frequency in S. hygroscopicus reached 1.5 x 10(-4). Meanwhile, we also found significant changes in conjugation frequencies of S. lividans, S. albus and S. avermitilis when casamino acid was supplemented in conjugation media. CONCLUSION: Casamino acid has significant influence on conjugation frequency in not only S. hygroscopicus ATCC29253 but also other Streptomyces such as S. lividans, S. albus and S. avermitilis.
Assuntos
Aminoácidos/farmacologia , Conjugação Genética , Sirolimo/metabolismo , Streptomyces/genética , Cloreto de Magnésio/farmacologia , Streptomyces/metabolismoRESUMO
Drinking deep seawater (DSW) with high levels of magnesium (Mg) decreased serum lipids in animal studies. Therefore the effects of drinking DSW on blood lipids and its antioxidant capacity in hypercholesterolemic subjects were investigated. DSW was first prepared by a process of filtration and reverse osmosis, and then the concentrated DSW with high levels of Mg was diluted as drinking DSW. Forty-two hypercholesterolemic volunteers were randomly divided into three groups: reverse osmotic (RO) water, DSW (Mg: 395 mg/L, hardness 1410 ppm), and magnesium-chloride fortified (MCF) water (Mg: 386 mg/L, hardness 1430 ppm). The subjects drank 1050 mL of water daily for 6 weeks, and blood samples were collected and analyzed on weeks 0, 3, and 6. Drinking DSW caused a decrease in blood total cholesterol levels and this effect was progressively enhanced with time. Serum low-density lipoprotein-cholesterol (LDL-C) was also decreased by DSW. Further, total cholesterol levels of subjects in the DSW group were significantly lower than those in the MCF water or RO water groups. Compared with week 0, the DSW group had higher blood Mg level on weeks 3 and 6, but the Mg levels were within the normal range in all three groups. DSW consumption also lowered thiobarbituric acid-reactive substances (TBARS) values in serum. In conclusion, DSW was apparently effective in reducing blood total cholesterol and LDL-C, and also in decreasing lipid peroxidation in hypercholesterolemic subjects.
Assuntos
Anticolesterolemiantes/farmacologia , Antioxidantes/farmacologia , LDL-Colesterol/sangue , Colesterol/sangue , Hipercolesterolemia/tratamento farmacológico , Magnésio/farmacologia , Água do Mar/química , Adulto , Feminino , Filtração , Humanos , Hipercolesterolemia/sangue , Cloreto de Magnésio/farmacologia , Masculino , Pessoa de Meia-Idade , Osmose , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Sucrose synthase (SUS) catalyzes the reversible conversion of sucrose and a nucleoside diphosphate into the corresponding nucleoside diphosphate-glucose and fructose. In Arabidopsis, a multigene family encodes six SUS (SUS1-6) isoforms. The involvement of SUS in the synthesis of UDP-glucose and ADP-glucose linked to Arabidopsis cellulose and starch biosynthesis, respectively, has been questioned by Barratt et al. [(2009) Proc Natl Acad Sci USA 106:13124-13129], who showed that (i) SUS activity in wild type (WT) leaves is too low to account for normal rate of starch accumulation in Arabidopsis, and (ii) different organs of the sus1/sus2/sus3/sus4 SUS mutant impaired in SUS activity accumulate WT levels of ADP-glucose, UDP-glucose, cellulose and starch. However, these authors assayed SUS activity under unfavorable pH conditions for the reaction. By using favorable pH conditions for assaying SUS activity, in this work we show that SUS activity in the cleavage direction is sufficient to support normal rate of starch accumulation in WT leaves. We also demonstrate that sus1/sus2/sus3/sus4 leaves display WT SUS5 and SUS6 expression levels, whereas leaves of the sus5/sus6 mutant display WT SUS1-4 expression levels. Furthermore, we show that SUS activity in leaves and stems of the sus1/sus2/sus3/sus4 and sus5/sus6 plants is â¼85% of that of WT leaves, which can support normal cellulose and starch biosynthesis. The overall data disprove Barratt et al. (2009) claims, and are consistent with the possible involvement of SUS in cellulose and starch biosynthesis in Arabidopsis.