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1.
J Neuroinflammation ; 17(1): 99, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32241292

RESUMO

BACKGROUND: Bladder-related pain symptoms in patients with bladder pain syndrome/interstitial cystitis (BPS/IC) are often accompanied by depression and memory deficits. Magnesium deficiency contributes to neuroinflammation and is associated with pain, depression, and memory deficits. Neuroinflammation is involved in the mechanical allodynia of cyclophosphamide (CYP)-induced cystitis. Magnesium-L-Threonate (L-TAMS) supplementation can attenuate neuroinflammation. This study aimed to determine whether and how L-TAMS influences mechanical allodynia and accompanying depressive symptoms and memory deficits in CYP-induced cystitis. METHODS: Injection of CYP (50 mg/kg, intraperitoneally, every 3 days for 3 doses) was used to establish a rat model of BPS/IC. L-TAMS was administered in drinking water (604 mg·kg-1·day-1). Mechanical allodynia in the lower abdomen was assessed with von Frey filaments using the up-down method. Forced swim test (FST) and sucrose preference test (SPT) were used to measure depressive-like behaviors. Novel object recognition test (NORT) was used to detect short-term memory function. Concentrations of Mg2+ in serum and cerebrospinal fluid (CSF) were measured by calmagite chronometry. Western blot and immunofluorescence staining measured the expression of tumor necrosis factor-α/nuclear factor-κB (TNF-α/NF-κB), interleukin-1ß (IL-1ß), and N-methyl-D-aspartate receptor type 2B subunit (NR2B) of the N-methyl-D-aspartate receptor in the L6-S1 spinal dorsal horn (SDH) and hippocampus. RESULTS: Free Mg2+ was reduced in the serum and CSF of the CYP-induced cystitis rats on days 8, 12, and 20 after the first CYP injection. Magnesium deficiency in the serum and CSF correlated with the mechanical withdrawal threshold, depressive-like behaviors, and short-term memory deficits (STMD). Oral application of L-TAMS prevented magnesium deficiency and attenuated mechanical allodynia (n = 14) and normalized depressive-like behaviors (n = 10) and STMD (n = 10). The upregulation of TNF-α/NF-κB signaling and IL-1ß in the L6-S1 SDH or hippocampus was reversed by L-TAMS. The change in NR2B expression in the SDH and hippocampus in the cystitis model was normalized by L-TAMS. CONCLUSIONS: Normalization of magnesium deficiency by L-TAMS attenuated mechanical allodynia, depressive-like behaviors, and STMD in the CYP-induced cystitis model via inhibition of TNF-α/NF-κВ signaling and normalization of NR2B expression. Our study provides evidence that L-TAMS may have therapeutic value for treating pain and comorbid depression or memory deficits in BPS/IC patients.


Assuntos
Butiratos/uso terapêutico , Cistite/complicações , Hiperalgesia/tratamento farmacológico , Deficiência de Magnésio/tratamento farmacológico , Transtornos da Memória/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Animais , Butiratos/farmacologia , Ciclofosfamida/efeitos adversos , Cistite/induzido quimicamente , Cistite/metabolismo , Cistite/fisiopatologia , Modelos Animais de Doenças , Feminino , Hiperalgesia/etiologia , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatologia , Deficiência de Magnésio/complicações , Deficiência de Magnésio/metabolismo , Deficiência de Magnésio/fisiopatologia , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismo , Transtornos da Memória/fisiopatologia , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/metabolismo
2.
Plant Mol Biol ; 101(6): 551-560, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31621003

RESUMO

KEY MESSAGE: At least eight MGT genes were identified in citrus and PtrMGT5 plays important role in maintaining Mg homeostasis in citrus by getting involved in the Mg absorption and transport. Magnesium (Mg) is an essential macronutrient for plant growth and development, and the magnesium transporter (MGT) genes participate in mediate Mg2+ uptake, translocation and sequestration into cellular storage compartments. Although several MGT genes have been characterized in various plant species, a comprehensive analysis of the MGT gene family in citrus is still uncharacterized. In this study, eight PtrMGT genes were identified through genome-wide analyses. Phylogenetic analyses revealed that PtrMGT genes were classified into five distinct subfamilies. A quantitative RT-PCR analysis showed that eight PtrMGT genes were expressed in all of the detected tissues and they mainly expressed in the vegetative organs. Expression analyses revealed the PtrMGT genes responded to various Mg deficiency stresses, including absolute Mg deficiency and antagonistic Mg deficiency which caused by low pH or Al toxicity. PtrMGT5, which localizes to the plasma membrane and was transcriptionally active, was functionally characterized. PtrMGT5 overexpression considerably enhanced absolute Mg deficiency and antagonistic Mg deficiency tolerance in transgenic Arabidopsis plants, which was accompanied by increased fresh weight and Mg content, whereas opposite changes were observed when PtrMGT5 homolog in Valencia Orange callus was knocked down. Taken together, PtrMGT5 plays important role in maintaining Mg homeostasis in citrus by getting involved in the Mg absorption and transport.


Assuntos
Magnésio/metabolismo , Poncirus/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Deficiência de Magnésio/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Poncirus/genética
3.
Am J Physiol Renal Physiol ; 317(4): F825-F838, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31364380

RESUMO

Hypomagnesemia is associated with reduced kidney function and life-threatening complications and sustains hypokalemia. The distal convoluted tubule (DCT) determines final urinary Mg2+ excretion and, via activity of the Na+-Cl- cotransporter (NCC), also plays a key role in K+ homeostasis by metering Na+ delivery to distal segments. Little is known about the mechanisms by which plasma Mg2+ concentration regulates NCC activity and how low-plasma Mg2+ concentration and K+ concentration interact to modulate NCC activity. To address this, we performed dietary manipulation studies in mice. Compared with normal diet, abundances of total NCC and phosphorylated NCC (pNCC) were lower after short-term (3 days) or long-term (14 days) dietary Mg2+ restriction. Altered NCC activation is unlikely to play a role, since we also observed lower total NCC abundance in mice lacking the two NCC-activating kinases, STE20/SPS-1-related proline/alanine-rich kinase and oxidative stress response kinase-1, after Mg2+ restriction. The E3 ubiquitin-protein ligase NEDD4-2 regulates NCC abundance during dietary NaCl loading or K+ restriction. Mg2+ restriction did not lower total NCC abundance in inducible nephron-specific neuronal precursor cell developmentally downregulated 4-2 (NEDD4-2) knockout mice. Total NCC and pNCC abundances were similar after short-term Mg2+ or combined Mg2+-K+ restriction but were dramatically lower compared with a low-K+ diet. Therefore, sustained NCC downregulation may serve a mechanism that enhances distal Na+ delivery during states of hypomagnesemia, maintaining hypokalemia. Similar results were obtained with long-term Mg2+-K+ restriction, but, surprisingly, NCC was not activated after long-term K+ restriction despite lower plasma K+ concentration, suggesting significant differences in distal tubule adaptation to acute or chronic K+ restriction.


Assuntos
Hipopotassemia/metabolismo , Deficiência de Magnésio/metabolismo , Ubiquitina-Proteína Ligases Nedd4/biossíntese , Animais , Dieta , Regulação para Baixo , Túbulos Renais Distais/metabolismo , Magnésio/sangue , Deficiência de Magnésio/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ubiquitina-Proteína Ligases Nedd4/genética , Fosforilação , Potássio/sangue , Deficiência de Potássio/metabolismo , Membro 3 da Família 12 de Carreador de Soluto/biossíntese , Membro 3 da Família 12 de Carreador de Soluto/genética
4.
Int Urol Nephrol ; 51(8): 1443-1449, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31264087

RESUMO

OBJECTIVE: To explore the short-term variation in bone metabolic markers and the characteristics of hungry bone syndrome (HBS) after parathyroidectomy (PTX) with forearm autotransplantation in uremic patients with secondary hyperparathyroidism (SHPT) and to provide a basis for the pathogenesis, diagnosis and treatment of metabolic bone disease in SHPT. METHODS: A total of 115 patients with SHPT receiving PTX from July 2015 to December 2017, hospitalized at the First Affiliated Hospital of Nanjing Medical University, were enrolled in our study. We retrospectively analyzed the baseline clinical data, the levels of bone metabolism markers before and on the third day after PTX, and the risk factors predicting HBS. RESULTS: Preoperative baseline data showed that the levels of bone metabolic markers such as bone metabolism-regulating hormones: iPTH, calcitonin (CT); bone formation markers: phosphatase (ALP), osteocalcin (OC); bone resorption markers: type I collagen cross-linked N-telopeptides (NTX), type I collagen cross-linked C-telopeptides (CTX), tartrate-resistant acid phosphatase 5b (TRAP-5b) were all increased compared to normal levels. The levels of postoperative serum iPTH, CT, CTX and TRAP-5b decreased significantly compared to preoperative levels, while the levels of OC and ALP increased significantly. Of the 115 patients, 101 (87.8%) developed HBS after PTX. High preoperative serum ALP and low preoperative serum calcium level independently predicted the occurrence of HBS. Younger preoperative age, high preoperative serum ALP and iPTH level independently predicted the severity of HBS. CONCLUSIONS: In severe SHPT, both bone formation and resorption were active, which suggested the presence of high-turnover bone diseases characterized by up-regulation of osteoclasts-osteoblasts functionally coupling activation in the patients. PTX could promote osteoblast activity and reduce osteoclast activity. HBS was common after PTX. Preoperative higher serum ALP and lower calcium were independent predictors of the occurrence of HBS. Younger patients with higher preoperative ALP and PTH may need to closely monitor serum calcium levels and intensive calcium supplementation after PTX.


Assuntos
Doenças Ósseas/diagnóstico , Osso e Ossos/metabolismo , Hiperparatireoidismo Secundário/cirurgia , Hipocalcemia/diagnóstico , Hipofosfatemia/diagnóstico , Deficiência de Magnésio/diagnóstico , Paratireoidectomia , Complicações Pós-Operatórias/diagnóstico , Diálise Renal , Adulto , Doenças Ósseas/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Hiperparatireoidismo Secundário/etiologia , Hipocalcemia/metabolismo , Hipofosfatemia/metabolismo , Deficiência de Magnésio/metabolismo , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/metabolismo , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Estudos Retrospectivos , Síndrome
5.
Int J Mol Sci ; 20(13)2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31248059

RESUMO

Magnesium (Mg) deficiency is one of the major constraining factors that limit the yield and quality of agricultural products. Uniform seedlings of the Citrus sinensis were irrigated with Mg deficient (0 mM MgSO4) and Mg sufficient (1 mM MgSO4) nutrient solutions for 16 weeks. CO2 assimilation, starch, soluble carbohydrates, TBARS content and H2O2 production were measured. Transcriptomic analysis of C. sinensis leaves was performed by Illumina sequencing. Our results showed that Mg deficiency decreased CO2 assimilation, but increased starch, sucrose, TBARS content and H2O2 production in C. sinensis leaves. A total of 4864 genes showed differential expression in response to Mg deficiency revealed by RNA-Seq and the transcriptomic data were further validated by real-time quantitative PCR (RT-qPCR). Gene ontology (GO) enrichment analysis indicated that the mechanisms underlying Mg deficiency tolerance in C. sinensis may be attributed to the following aspects: a) enhanced microtubule-based movement and cell cycle regulation; b) elevated signal transduction in response to biotic and abiotic stimuli; c) alteration of biological processes by tightly controlling phosphorylation especially protein phosphorylation; d) down-regulation of light harvesting and photosynthesis due to the accumulation of carbohydrates; e) up-regulation of cell wall remodeling and antioxidant system. Our results provide a comprehensive insight into the transcriptomic profile of key components involved in the Mg deficiency tolerance in C. sinensis and enrich our understanding of the molecular mechanisms by which plants adapted to a Mg deficient condition.


Assuntos
Citrus sinensis/genética , Regulação da Expressão Gênica de Plantas , Deficiência de Magnésio/genética , Folhas de Planta/genética , Transcriptoma , Transporte Biológico , Citrus sinensis/metabolismo , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Ontologia Genética , Sequenciamento de Nucleotídeos em Larga Escala , Magnésio/metabolismo , Deficiência de Magnésio/metabolismo , Fenótipo , Folhas de Planta/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Análise de Sequência de RNA , Transdução de Sinais
6.
Inflammopharmacology ; 27(4): 649-661, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31172335

RESUMO

Magnesium deficiency (MgD) can cause inflammation in human body. The known mechanisms of inflammation caused by MgD include activation of phagocytic cells, opening of calcium channels, activation of the N-methyl-D-aspartate (NMDA) receptor, and activation of nuclear factor (NF)-κB. In addition, MgD causes systemic stress response through neuroendocrinological pathways. The inflammation caused by MgD can result in pro-atherogenic changes in the metabolism of lipoproteins, endothelial dysfunction, and high blood pressure. Studies suggest that magnesium may play an important role in the pathophysiology of some inflammatory diseases. Several clinical trials and laboratory studies have been done on the functional role of magnesium. In this study, we review some inflammatory diseases, in which the magnesium has a role in their pathophysiology. Among these diseases, diabetes, asthma, preeclampsia, atherosclerosis, heart damage, and rheumatoid arthritis have been highlighted.


Assuntos
Inflamação/metabolismo , Magnésio/metabolismo , Animais , Humanos , Deficiência de Magnésio/metabolismo , NF-kappa B/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo
7.
Int J Mol Sci ; 20(9)2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-31035385

RESUMO

Several drugs including diuretics and proton-pump inhibitors can cause magnesium loss and hypomagnesemia. Magnesium and drugs use the same transport and metabolism pathways in the body for their intestinal absorption, metabolism, and elimination. This means that when one or more drug is taken, there is always a potential risk of interaction with the magnesium status. Consequently the action of a drug may be adversely affected by magnesium (e.g., magnesium, calcium, and zinc can interfere with the gastrointestinal absorption of tetracycline antibiotics) and simultaneously the physiological function of minerals such as magnesium may be impaired by a drug (e.g., diuretics induce renal magnesium loss). Given the ever-increasing number of drugs on the market and the frequency with which they are used, greater attention must be paid in daily medical and pharmaceutical practice focused in particular on the adverse effects of drug therapy on magnesium status in order to minimize the potential risk to the health of patients.


Assuntos
Magnésio/metabolismo , Animais , Humanos , Absorção Intestinal/efeitos dos fármacos , Deficiência de Magnésio/metabolismo , Inibidores da Bomba de Prótons/uso terapêutico , Canais de Cátion TRPM/metabolismo , Tetraciclina/metabolismo
8.
FASEB J ; 33(6): 7192-7201, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30848940

RESUMO

Hypomagnesemia (blood Mg2+ concentration <0.7 mM) is a common electrolyte disorder in patients with type 2 diabetes (T2D), but the etiology remains largely unknown. In patients with T2D, reduced blood Mg2+ levels are associated with an increased decline in renal function, independent of glycemic control and hypertension. To study the underlying mechanism of this phenomenon, we investigated the renal effects of hypomagnesemia in high-fat-diet (HFD)-fed mice. In mice fed a low dietary Mg2+, the HFD resulted in severe hypomagnesemia within 4 wk. Renal or intestinal Mg2+ wasting was not observed after 16 wk on the diets. Despite the absence of urinary or fecal Mg2+ loss, the HFD induced a reduction in the mRNA expression transient receptor potential melastatin type 6 in both the kidney and colon. mRNA expression of distal convoluted tubule (DCT)-specific genes was down-regulated by the LowMg-HFD, indicating atrophy of the DCT. The low dietary Mg2+ resulted in severe HFD-induced proximal tubule phospholipidosis, which was absent in mice on a NormalMg-HFD. This was accompanied by albuminuria, moderate renal damage, and alterations in renal energy metabolism, including enhanced gluconeogenesis and cholesterol synthesis. In conclusion, this study shows that hypomagnesemia is a consequence of diet-induced obesity and insulin resistance. Moreover, hypomagnesemia induces major structural changes in the diabetic kidney, including proximal tubular phospholipidosis, providing a novel mechanism for the increased renal decline in patients with hypomagnesemic T2D.-Kurstjens, S., Smeets, B., Overmars-Bos, C., Dijkman, H. B., den Braanker, D. J. W., de Bel, T., Bindels, R. J. M., Tack, C. J. J., Hoenderop, J. G. J., de Baaij, J. H. F. Renal phospholipidosis and impaired magnesium handling in high-fat-diet-fed mice.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Túbulos Renais Distais/metabolismo , Túbulos Renais Proximais/metabolismo , Deficiência de Magnésio/metabolismo , Magnésio/metabolismo , Obesidade/metabolismo , Fosfolipídeos/metabolismo , Albuminúria/etiologia , Animais , Atrofia , Líquidos Corporais/química , Metabolismo Energético , Fezes/química , Resistência à Insulina , Túbulos Renais Distais/patologia , Túbulos Renais Proximais/patologia , Magnésio/administração & dosagem , Magnésio/farmacocinética , Deficiência de Magnésio/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica , Obesidade/complicações , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase em Tempo Real , Canais de Cátion TRPM/biossíntese , Canais de Cátion TRPM/genética
9.
Nutrients ; 11(3)2019 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-30884817

RESUMO

Mg2+ deficiency may be involved in lifestyle-related diseases, including hypertension, cardiovascular diseases, and diabetes mellitus. Dietary Mg2+ is absorbed in the intestine mediated through transcellular and paracellular pathways. However, there is little research into what factors upregulate Mg2+ absorption. We searched for food constituents that can increase the expression levels of Mg2+ transport carriers using mouse colonic epithelial MCE301 cells. Cyanidin, an anthocyanidin found in black beans and berries, increased the mRNA levels of Mg2+ transport carriers including transient receptor potential melastatin 6 (TRPM6) channel and cyclin M4 (CNNM4). The cyanidin-induced elevation of Mg2+ transport carriers was blocked by GW6471, a peroxisome proliferator-activated receptor α (PPARα) inhibitor, but not by PPARγ, PPARδ, and protein kinase A inhibitors. Cyanidin-3-glucoside showed similar results to cyanidin. Cyanidin increased the protein levels of TRPM6 and CNNM4, which were distributed in the apical and lateral membranes, respectively. The nuclear localization of PPARα and reporter activities of Mg2+ transport carriers were increased by cyanidin, which were inhibited by GW6471. The cyanidin-induced elevation of reporter activity was suppressed by a mutation in a PPAR-response element. Fluorescence measurements using KMG-20, an Mg2+ indicator, showed that Mg2+ influx and efflux from the cells were enhanced by cyanidin, and which were inhibited by GW6471. Furthermore, cyanidin increased paracellular Mg2+ flux without affecting transepithelial electrical resistance. We suggest that cyanidin increases intestinal Mg2+ absorption mediated by the elevation of TRPM6 and CNNM4 expression, and may constitute a phytochemical that can improve Mg2+ deficiency.


Assuntos
Antocianinas/farmacologia , Proteínas de Transporte de Cátions/efeitos dos fármacos , Magnésio/metabolismo , PPAR alfa/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Animais , Linhagem Celular , Colo/citologia , Células Epiteliais/metabolismo , Glucosídeos/farmacologia , Mucosa Intestinal/citologia , Deficiência de Magnésio/metabolismo , Camundongos , Oxazóis/metabolismo , RNA Mensageiro/metabolismo , Canais de Cátion TRPM/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismo , Regulação para Cima
10.
Brain Res Bull ; 144: 149-157, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30500564

RESUMO

Magnesium (Mg2+) is an essential mineral for maintaining biological functions. One major action of Mg2+ in the brain is modulating the voltage-dependent blockade of N-methyl-d-aspartate type glutamate receptors, thereby controlling their opening, which is crucial for synaptic plasticity. Therefore, Mg2+ has been shown to play critical roles in learning and memory, and synaptic plasticity. However, the effects of dietary Mg2+ deficiency (MgD) on learning and memory and the morphology of neurons contributing to memory performance have not been examined in depth. Here, we show that MgD impairs hippocampus-dependent memories in mice. Mice fed an MgD diet showed deficits in hippocampus-dependent contextual fear, spatial and social recognition memories, although they showed normal amygdala- and insular cortex-dependent conditioned taste aversion memory, locomotor activity, and emotional behaviors such as anxiety-related and social behaviors. However, MgD mice showed normal spine density and morphology of hippocampal neurons. These findings suggest that MgD impairs hippocampus-dependent memory without affecting the morphology of hippocampal neurons.


Assuntos
Deficiência de Magnésio/metabolismo , Memória/efeitos dos fármacos , Memória/fisiologia , Animais , Ansiedade/fisiopatologia , Condicionamento Clássico/fisiologia , Espinhas Dendríticas , Suplementos Nutricionais , Medo/fisiologia , Ácido Glutâmico/farmacologia , Hipocampo/efeitos dos fármacos , Aprendizagem/fisiologia , Magnésio/metabolismo , Deficiência de Magnésio/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Plasticidade Neuronal/fisiologia , Neurônios/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Reconhecimento Psicológico , Transmissão Sináptica/fisiologia
11.
Magnes Res ; 31(2): 39-48, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30398154

RESUMO

Given a possible anti-inflammatory role of magnesium in endothelial cells, the aim of this study was to investigate the effects of magnesium on human umbilical vein endothelial cell (HUVEC) viability, gene expression, and the pro-inflammatory response caused by a bacterial endotoxin (LPS). HUVECs were cultured at three different concentrations of magnesium sulphate (0.1 mM; control-1 mM; 5 mM) for 72 hours. Exposing the cells to LPS reduced cell viability in culture with low magnesium, but high magnesium protected the HUVECs from LPS-induced cell death. LPS-treated HUVECs cultured in low magnesium showed up-regulation of mRNA expression for pro-inflammatory factors and the expression of cytokine proteins, including IL-2, IL-3, IL-8, IL-15 and MCP-1. This was associated with greater adhesion of monocytes to the cells. In contrast, high magnesium decreased the expression of inflammatory factors and cytokines. The study found that LPS activation of the expression of many pro-inflammatory factors is exacerbated in the presence of low magnesium concentration whilst a high magnesium concentration partly inhibited the inflammatory response to LPS.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Inflamação/tratamento farmacológico , Deficiência de Magnésio/metabolismo , Magnésio/farmacologia , Monócitos/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Monócitos/metabolismo , Relação Estrutura-Atividade
12.
Isr Med Assoc J ; 20(9): 533-538, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30221864

RESUMO

BACKGROUND: Magnesium is an essential intracellular cation. Magnesium deficiency is common in the general population and its prevalence among patients with cirrhosis is even higher. Correlation between serum levels and total body content is poor because most magnesium is intracellular. Minimal hepatic encephalopathy is a subclinical phase of hepatic encephalopathy with no overt symptoms. Cognitive exams can reveal minor changes in coordination, attention, and visuomotor function, whereas language and verbal intelligence are usually relatively spared. OBJECTIVES: To assess the correlation between intracellular and serum magnesium levels and minimal hepatic encephalopathy. METHODS: Outpatients with a diagnosis of compensated liver cirrhosis were enrolled in this randomized, double-blinded study. Patients were recruited for the study from November 2013 to January 2014, and were randomly assigned to a control (placebo) or an interventional (treated with magnesium oxide) group. Serum and intracellular magnesium levels were measured at enrollment and at the end of the study. Cognitive function was assessed by a specialized occupational therapist. RESULTS: Forty-two patients met the inclusion criteria, 29 of whom were included in this study. Among these, 83% had abnormal cognitive exam results compatible with minimal hepatic encephalopathy. While only 10% had hypomagnesemia, 33.3% had low levels of intracellular magnesium. Initial intracellular and serum magnesium levels positively correlated with cognitive performance. CONCLUSIONS: Magnesium deficiency is common among patients with compensated liver cirrhosis. We found an association between magnesium deficiency and impairment in several cognitive function tests. This finding suggests involvement of magnesium in the pathophysiology of minimal hepatic encephalopathy.


Assuntos
Transtornos Cognitivos/complicações , Encefalopatia Hepática/complicações , Cirrose Hepática/complicações , Deficiência de Magnésio/complicações , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/metabolismo , Método Duplo-Cego , Feminino , Encefalopatia Hepática/metabolismo , Humanos , Cirrose Hepática/metabolismo , Deficiência de Magnésio/metabolismo , Óxido de Magnésio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos
13.
Plant Signal Behav ; 13(9): e1500068, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30153078

RESUMO

Magnesium (Mg), an essential element for plants is easily leached in acidic and sandy soils. Magnesium deficiency induces the initiation and elongation of root hairs, which allows the plant roots to acquire more Mg under Mg-limited conditions. However, the signals involved in the regulatory cascade leading to the induction of root hair development under Mg deficiency are largely unknown to date. Recent studies have revealed that many chemical signal molecules such as ethylene, nitric oxide, auxin, reactive oxygen, and calcium regulate the root hair development induced owing to Mg deficiency. This mini-review intends to briefly discuss the role of these chemical signals in the induction of root hair development under Mg-deficient conditions.


Assuntos
Deficiência de Magnésio/metabolismo , Raízes de Plantas/metabolismo , Cálcio/metabolismo , Etilenos/metabolismo , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos/metabolismo , Magnésio/metabolismo , Raízes de Plantas/fisiologia
14.
Sci Rep ; 8(1): 12705, 2018 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-30139942

RESUMO

Grass carp (223.85-757.33 g) were fed diets supplemented with magnesium (73.54-1054.53 mg/kg) for 60 days to explore the impacts of magnesium deficiency on the growth and intestinal structural integrity of the fish. The results demonstrated that magnesium deficiency suppressed the growth and damaged the intestinal structural integrity of the fish. We first demonstrated that magnesium is partly involved in (1) attenuating antioxidant ability by suppressing Nrf2 signalling to decrease antioxidant enzyme mRNA levels and activities (except CuZnSOD mRNA levels and activities); (2) aggravating apoptosis by activating JNK (not p38MAPK) signalling to upregulate proapoptotic protein (Apaf-1, Bax and FasL) and caspase-2, -3, -7, -8 and -9 gene expression but downregulate antiapoptotic protein (Bcl-2, IAP and Mcl-1b) gene expression; (3) weakening the function of tight junctional complexes (TJs) by promoting myosin light chain kinase (MLCK) signalling to downregulate TJ gene expression [except claudin-7, ZO-2b and claudin-15 gene expression]. Additionally, based on percent weight gain (PWG), against reactive oxygen species (ROS), against caspase-9 and claudin-3c in grass carp, the optimal dietary magnesium levels were calculated to be 770.38, 839.86, 856.79 and 811.49 mg/kg, respectively.


Assuntos
Carpas/metabolismo , Deficiência de Magnésio/metabolismo , Magnésio/metabolismo , Animais , Antioxidantes/metabolismo , Mucosa Intestinal/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
15.
Diabetologia ; 61(9): 2030-2042, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29987474

RESUMO

AIMS/HYPOTHESIS: Hypomagnesaemia (blood Mg2+ <0.7 mmol/l) is a common phenomenon in individuals with type 2 diabetes. However, it remains unknown how a low blood Mg2+ concentration affects lipid and energy metabolism. Therefore, the importance of Mg2+ in obesity and type 2 diabetes has been largely neglected to date. This study aims to determine the effects of hypomagnesaemia on energy homeostasis and lipid metabolism. METHODS: Mice (n = 12/group) were fed either a low-fat diet (LFD) or a high-fat diet (HFD) (10% or 60% of total energy) in combination with a normal- or low-Mg2+ content (0.21% or 0.03% wt/wt) for 17 weeks. Metabolic cages were used to investigate food intake, energy expenditure and respiration. Blood and tissues were taken to study metabolic parameters and mRNA expression profiles, respectively. RESULTS: We show that low dietary Mg2+ intake ameliorates HFD-induced obesity in mice (47.00 ± 1.53 g vs 38.62 ± 1.51 g in mice given a normal Mg2+-HFD and low Mg2+-HFD, respectively, p < 0.05). Consequently, fasting serum glucose levels decreased and insulin sensitivity improved in low Mg2+-HFD-fed mice. Moreover, HFD-induced liver steatosis was absent in the low Mg2+ group. In hypomagnesaemic HFD-fed mice, mRNA expression of key lipolysis genes was increased in epididymal white adipose tissue (eWAT), corresponding to reduced lipid storage and high blood lipid levels. Low Mg2+-HFD-fed mice had increased brown adipose tissue (BAT) Ucp1 mRNA expression and a higher body temperature. No difference was observed in energy expenditure between the two HFD groups. CONCLUSIONS/INTERPRETATION: Mg2+-deficiency abrogates HFD-induced obesity in mice through enhanced eWAT lipolysis and BAT activity.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Deficiência de Magnésio/metabolismo , Obesidade/etiologia , Células 3T3-L1 , Animais , Resistência à Insulina/fisiologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Magnésio , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real
16.
Adv Chronic Kidney Dis ; 25(3): 267-273, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29793666

RESUMO

As with other electrolytes, magnesium homeostasis depends on the balance between gastrointestinal absorption and kidney excretion. Certain drugs used commonly in patients with CKD can decrease gastrointestinal ingestion and kidney reclamation, and potentially cause hypomagnesemia. Other magnesium-containing drugs such as laxatives and cathartics can induce hypermagnesemia, particularly in those with impaired glomerular filtration and magnesium excretion. In this review, we will discuss the potential magnesium complications associated with a range of commonly encountered drugs in the care of CKD patients, discuss the potential mechanisms, and provide basic clinical recommendations.


Assuntos
Homeostase/efeitos dos fármacos , Deficiência de Magnésio/induzido quimicamente , Magnésio/metabolismo , Doenças Metabólicas/induzido quimicamente , Insuficiência Renal Crônica/tratamento farmacológico , Agentes Urológicos/efeitos adversos , Biomarcadores/metabolismo , Humanos , Deficiência de Magnésio/metabolismo , Doenças Metabólicas/metabolismo , Insuficiência Renal Crônica/complicações , Agentes Urológicos/uso terapêutico
17.
Adv Chronic Kidney Dis ; 25(3): 281-290, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29793668

RESUMO

Vascular calcification (VC) is associated with elevated cardiovascular mortality rates in patients with CKD. Recent clinical studies of patients with advanced CKD have observed an association between low serum magnesium (Mg) levels on one hand and elevated VC and cardiovascular mortality on the other. These findings have stimulated interest in understanding Mg's impact on CKD in general and the associated VC in particular. In vitro and preclinical in vivo data indicate that Mg has the potential to protect vascular smooth muscle cells against calcification via several different molecular mechanisms. Accordingly, data from pilot interventional studies in the clinic suggest that oral Mg supplementation reduces VC in patients with CKD. The present review provides an overview of our current understanding of the impact of Mg on the development of VC in patients with CKD.


Assuntos
Deficiência de Magnésio/fisiopatologia , Magnésio/metabolismo , Insuficiência Renal Crônica/fisiopatologia , Calcificação Vascular/fisiopatologia , Biomarcadores/metabolismo , Humanos , Magnésio/uso terapêutico , Deficiência de Magnésio/tratamento farmacológico , Deficiência de Magnésio/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Agentes Urológicos/metabolismo , Agentes Urológicos/uso terapêutico , Calcificação Vascular/etiologia , Calcificação Vascular/metabolismo , Calcificação Vascular/prevenção & controle
18.
Inflamm Bowel Dis ; 24(10): 2198-2210, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-29788266

RESUMO

Background: Magnesium (Mg) is essential for human health and is absorbed mainly in the intestine. In view of the likely occurrence of an Mg deficit in inflammatory bowel disease (IBD) and the documented role of Mg in modulating inflammation, the present study addresses whether Mg availability can affect the onset and progression of intestinal inflammation. Methods: To study the correlation between Mg status and disease activity, we measured magnesemia by atomic absorption spectroscopy in a cohort of IBD patients. The effects of dietary Mg modulation were assessed in a murine model of dextran sodium sulfate (DSS)-induced colitis by monitoring magnesemia, weight, fecal occult blood, diarrhea, colon length, and histology. Expression of the transient receptor potential melastatin (TRPM) 6 channel was assessed by real-time reverse transcription polymerase chain reaction and immunohistochemistry in murine colon tissues. The effect of Mg on epithelial barrier formation/repair was evaluated in human colon cell lines. Results: Inflammatory bowel disease patients presented with a substantial Mg deficit, and serum Mg levels were inversely correlated with disease activity. In mice, an Mg-deficient diet caused hypomagnesemia and aggravated DSS-induced colitis. Colitis severely compromised intestinal Mg2+ absorption due to mucosal damage and reduction in TRPM6 expression, but Mg supplementation resulted in better restoration of mucosal integrity and channel expression. Conclusions: Our results highlight the importance of evaluating and correcting magnesemia in IBD patients. The murine model suggests that Mg supplementation may represent a safe and cost-effective strategy to reduce inflammation and restore normal mucosal function.


Assuntos
Colite Ulcerativa/complicações , Colite/prevenção & controle , Doença de Crohn/complicações , Dieta , Hipocalcemia/metabolismo , Deficiência de Magnésio/congênito , Magnésio/administração & dosagem , Canais de Cátion TRPM/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Estudos de Casos e Controles , Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Colite Ulcerativa/metabolismo , Colite Ulcerativa/fisiopatologia , Doença de Crohn/metabolismo , Doença de Crohn/fisiopatologia , Sulfato de Dextrana/toxicidade , Feminino , Seguimentos , Humanos , Hipocalcemia/etiologia , Hipocalcemia/patologia , Magnésio/metabolismo , Deficiência de Magnésio/etiologia , Deficiência de Magnésio/metabolismo , Deficiência de Magnésio/patologia , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Prognóstico , Canais de Cátion TRPM/genética , Adulto Jovem
19.
Nutrients ; 10(3)2018 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-29510564

RESUMO

In type 2 diabetes mellitus (T2D), the handling of magnesium is disturbed. Magnesium deficiency may be associated with a higher risk of coronary heart disease (CHD). We investigated the associations between (1) dietary magnesium intake; (2) 24 h urinary magnesium excretion; and (3) plasma magnesium concentration with prevalent CHD in T2D patients. This cross-sectional analysis was performed on baseline data from the DIAbetes and LifEstyle Cohort Twente-1 (DIALECT-1, n = 450, age 63 ± 9 years, 57% men, and diabetes duration of 11 (7-18) years). Prevalence ratios (95% CI) of CHD by sex-specific quartiles of magnesium indicators, as well as by magnesium intake per dietary source, were determined using multivariable Cox proportional hazard models. CHD was present in 100 (22%) subjects. Adjusted CHD prevalence ratios for the highest compared to the lowest quartiles were 0.40 (0.20, 0.79) for magnesium intake, 0.63 (0.32, 1.26) for 24 h urinary magnesium excretion, and 0.62 (0.32, 1.20) for plasma magnesium concentration. For every 10 mg increase of magnesium intake from vegetables, the prevalence of CHD was, statistically non-significantly, lower (0.75 (0.52, 1.08)). In this T2D cohort, higher magnesium intake, higher 24 h urinary magnesium excretion, and higher plasma magnesium concentration are associated with a lower prevalence of CHD.


Assuntos
Doença das Coronárias/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Dieta , Deficiência de Magnésio/epidemiologia , Magnésio/administração & dosagem , Estado Nutricional , Idoso , Biomarcadores/sangue , Biomarcadores/urina , Doença das Coronárias/diagnóstico , Doença das Coronárias/metabolismo , Doença das Coronárias/prevenção & controle , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Magnésio/sangue , Magnésio/urina , Deficiência de Magnésio/diagnóstico , Deficiência de Magnésio/metabolismo , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Prevalência , Fatores de Proteção , Recomendações Nutricionais , Fatores de Risco
20.
J Nutr Biochem ; 56: 35-47, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29454997

RESUMO

The liver is the organ that responds to nutritional disturbances including magnesium deficiency. The present study evaluated cellular responses to magnesium deficiency using model cells of the liver, namely, HepG2 cells as hepatocytes, RAW264.7 cells as Kupffer cells and human umbilical vein endothelial cells (HUVECs) as vascular endothelial cells; we examined effects of culture with magnesium deficient medium on cell responses in individual types of cells as well as interactive responses among cells. Metabolomic analyses indicated that magnesium deficiency differentially affected the cellular content of metabolites among HepG2 cells, RAW264.7 cells and HUVECs. The cellular content of the metabolites in HepG2 cells and HUVECs was also affected by the conditioned medium from RAW264.7 cells cultured with the magnesium-deficient media. The changes in HUVECs partly resembled those of the livers of magnesium-deficient rats previously described. RNA-seq analyses indicated that magnesium deficiency modulated the expression levels of molecules related to the ubiquitin-proteasome pathway and oxidative stress/antioxidant response in HepG2 cells and RAW264.7 cells, respectively. Furthermore, when HUVECs were co-cultured with RAW264.7 cells, lipopolysaccharide-induced expression of interleukin (IL)-1ß and IL-6 was enhanced by magnesium deficiency, depending on the presence of RAW264.7 cells. The present study reveals that magnesium deficiency affects cellular metabolism in HepG2 liver cells, RAW264.7 macrophages and HUVECs, and that the modulation of cellular responses to extracellular magnesium deficiency in HUVECs depends on the presence of RAW264.7 cells. The complex responses in individual cells and through cell interactions partly explain the regulatory reaction to magnesium deficiency in the liver.


Assuntos
Células Endoteliais/citologia , Hepatócitos/citologia , Macrófagos/citologia , Deficiência de Magnésio/metabolismo , Animais , Antioxidantes/química , Comunicação Celular , Células Endoteliais/metabolismo , Células Hep G2 , Hepatócitos/metabolismo , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Macrófagos do Fígado/citologia , Lipopolissacarídeos , Fígado/metabolismo , Macrófagos/metabolismo , Metabolômica , Camundongos , Células RAW 264.7
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