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Comparative angioprotective effects of magnesium compounds

Kharitonova M, Iezhitsa I, Zheltova A, Ozerov A, Spasov A, Skalny A

J Trace Elem Med Biol, 2015 Jan;29:227-34.
PMID: 25127069 DOI: 10.1016/j.jtemb.2014.06.026

Magnesium (Mg) deficiency is implicated in the development of numerous disorders of the cardiovascular system. Moreover, the data regarding the efficacy of different magnesium compounds in the correction of impaired functions due to low magnesium intake are often fragmentary and inconsistent. The aim of this study was to compare the effects of the most bioavailable Mg compounds (Mg l-aspartate, Mg N-acetyltaurate, Mg chloride, Mg sulphate and Mg oxybutyrate) on systemic inflammation and endothelial dysfunction in rats fed a low Mg diet for 74 days. A low Mg diet decreased the Mg concentration in the plasma and erythrocytes, which was accompanied by a reduced concentration of eNOs and increased levels of endothelin-1 level in the serum and impaired endothelium-dependent vasodilatation. These effects increased the concentration of proinflammatory molecules, such as VCAM-1, TNF-α, IL-6 and CRP, indicating the development of systemic inflammation and endothelial dysfunction. The increased total NO level, which estimated from the sum of the nitrate and nitrite concentrations in the serum, may also be considered to be a proinflammatory marker. Two weeks of Mg supplementation partially or fully normalised the ability of the vascular wall to effect adequate endothelium-dependent vasodilatation and reversed the levels of most endothelial dysfunction and inflammatory markers (except CRP) to the mean values of the control group. Mg sulphate had the smallest effect on the endothelin-1, TNF-α and VCAM-1 levels. Mg N-acetyltaurate was significantly more effective in restoring the level of eNOS compared to all other studied compounds, except for Mg oxybutyrate. Taken together, the present findings demonstrate that all Mg compounds equally alleviate endothelial dysfunction and inflammation caused by Mg deficiency. Mg sulphate tended to be the least effective compound.
Supplementation of selenium reduces chemical hepatocarcinogenesis in male Sprague-Dawley rats

Alwahaibi N, Mohamed J, Alhamadani A

J Trace Elem Med Biol, 2010 Apr;24(2):119-23.
PMID: 20413070 DOI: 10.1016/j.jtemb.2009.09.003

Selenium is an essential micronutrient mineral found mainly in soils and has been shown to prevent certain cancers in humans and animals. However, the dose and effects of selenium on liver cancer are controversial. The aim of this study was to investigate the effects of sodium selenite (4 mg/kg in drinking water) on chemically induced hepatocarcinogenesis in rats. Hepatocarcinogenesis was induced by a single intraperitoneal injection of diethyl nitrosamine (DEN) (200 mg/kg body weight) and 2 weeks later, the carcinogenic effect was promoted by 2-acetylaminofluorene (2-AAF) (0.02%). 44 Sprague-Dawley rats were divided into 6 groups: negative control, positive control (DEN+2-AAF), pre-selenium group (sodium selenite for 4 weeks, then DEN+2-AAF), pre-selenium control group (sodium selenite for 4 weeks, no DEN or 2-AAF), post-selenium group (sodium selenite for 8 weeks after 4 weeks of DEN injection) and post-selenium control group (sodium selenite for 8 weeks, no DEN or 2-AAF). Hematoxylin and eosin plus Gordon and Sweet's methods were used to stain liver tissues. The results showed that the number and sizes of hepatic nodules in pre- and post-selenium treatment groups significantly decreased (P<0.05) compared with the positive control. Microscopic analysis of pre- and post-selenium groups showed that the majority of nodules were hyperplastic with preserved liver architecture, whereas the positive control was full of neoplastic nodules with a completely disrupted liver architecture. Hence, pre- and post-selenium treatments can reduce the extent of liver cancer on chemically induced hepatocarcinogenesis in rats.
LNCaP prostate cancer cells are insensitive to zinc-induced senescence

Wong PF, Abubakar S

J Trace Elem Med Biol, 2008;22(3):242-7.
PMID: 18755400 DOI: 10.1016/j.jtemb.2008.03.008

Prostate cancer is an age-related disease that is linked to the inability of prostate cells to accumulate zinc following transformation. It is shown in the present study that the basal percentage of normal prostate cells expressing senescence-associated beta-galactosidase (SA-beta-gal) is higher than that of the cancer cells. In the presence of high zinc in the cell culture medium, the percentage of normal prostate cells expressing the SA-beta-gal increased but not that of the cancer cells. Increased intracellular zinc occurs in the prostate cancer cells treated with supraphysiologic concentration of zinc but it does not induce senescence or decrease the telomerase activities in these cells. Senescence, however, occurred when the prostate cancer cells DNA is damaged by irradiation. These findings suggest that prostate cancer cells are insensitive to the senescence-inducing effects of zinc but the cancer cells retain the capacity to undergo senescence through other pathways.
Fulltext A literature review on beneficial role of vitamins and trace elements: Evidence from published clinical studies

Taheri S, Asadi S, Nilashi M, Ali Abumalloh R, Ghabban NMA, Mohd Yusuf SY, et al.

J Trace Elem Med Biol, 2021 Sep;67:126789.
PMID: 34044222 DOI: 10.1016/j.jtemb.2021.126789

COVID-19 is a kind of SARS-CoV-2 viral infectious pneumonia. This research aims to perform a bibliometric analysis of the published studies of vitamins and trace elements in the Scopus database with a special focus on COVID-19 disease. To achieve the goal of the study, network and density visualizations were used to introduce an overall picture of the published literature. Following the bibliometric analysis, we discuss the potential benefits of vitamins and trace elements on immune system function and COVID-19, supporting the discussion with evidence from published clinical studies. The previous studies show that D and A vitamins demonstrated a higher potential benefit, while Selenium, Copper, and Zinc were found to have favorable effects on immune modulation in viral respiratory infections among trace elements. The principles of nutrition from the findings of this research could be useful in preventing and treating COVID-19.
The influence of selenium status on body composition, oxidative DNA damage and total antioxidant capacity in newly diagnosed type 2 diabetes mellitus: A case-control study

Othman FB, Mohamed HJBJ, Sirajudeen KNS, Noh MFBM, Rajab NF

J Trace Elem Med Biol, 2017 Sep;43:106-112.
PMID: 28065595 DOI: 10.1016/j.jtemb.2016.12.009

Selenium is involved in the complex system of defense against oxidative stress in diabetes through its biological function of selenoproteins and the antioxidant enzyme. A case-control study was carried out to determine the association of plasma selenium with oxidative stress and body composition status presented in Type 2 Diabetes Mellitus (T2DM) patient and healthy control. This study involved 82 newly diagnosed T2DM patients and 82 healthy controls. Plasma selenium status was determined with Graphite Furnace Atomic Absorption Spectrometry. Body Mass Index, total body fat and visceral fat was assessed for body composition using Body Composition Analyzer (TANITA). Oxidative DNA damage and total antioxidant capacity were determined for oxidative stress biomarker status. In age, gender and BMI adjustment, no significant difference of plasma selenium level between T2DM and healthy controls was observed. There was as a significant difference of Oxidative DNA damage and total antioxidant capacity between T2DM patients and healthy controls with tail DNA% 20.62 [95% CI: 19.71,21.49] (T2DM), 17.67 [95% CI: 16.87,18.56] (control); log tail moment 0.41[95% CI: 0.30,0.52] (T2DM), 0.41[95% CI: 0.30,0.52] (control); total antioxidant capacity 0.56 [95% CI: 0.54,0.58] (T2DM), 0.60 [95% CI: 0.57,0.62] (control). Waist circumference, BMI, visceral fat, body fat and oxidative DNA damage in the T2DM group were significantly lower in the first plasma selenium tertile (38.65-80.90μg/L) compared to the second (80.91-98.20μg/L) and the third selenium tertiles (98.21-158.20μg/L). A similar trend, but not statistically significant, was observed in the control group.
Monitoring of salt iodisation programme in Iran; Health outcomes, shortages and perspective

Ma ZF, Zhang Y, Zhou H, Pan B

J Trace Elem Med Biol, 2019 May;53:135.
PMID: 30910196 DOI: 10.1016/j.jtemb.2019.02.012
Dysregulation of metallothionein and zinc aggravates periodontal diseases

Aziz J, Rahman MT, Vaithilingam RD

J Trace Elem Med Biol, 2021 Jul;66:126754.
PMID: 33831799 DOI: 10.1016/j.jtemb.2021.126754

BACKGROUND: Periodontitis (PD) is a multifaceted inflammatory disease connected to bacterial infection that results in the destruction of tooth supporting structures and eventually tooth loss. Given their involvement in infection and inflammation, both metallothionein (MT) and zinc (Zn) might play vital roles in the development and progression of PD. More specifically, both MT and Zn are heavily involved in regulating immune functions, controlling bacterial infection, balancing inflammatory responses, and reducing oxidative stress, all of which are associated with the pathogenesis of PD.
OBJECTIVE: This review paper will explore the physiological functions of MT and Zn and hypothesise how dysregulation could negatively affect periodontal health, leading to PD.
FINDINGS: Bacterial lipopolysaccharide (LPS) derived from periodontal pathogens, namely P. gingivalis initiates the acute phase response, thus upregulating the expression of MT which leads to the subsequent deficiency of Zn, a hallmark of periodontal disease. This deficiency leads to ineffective NETosis, increases the permeability of the gingival epithelium, and disrupts the humoral immune response, collectively contributing to PD. In addition, the presence of LPS in Zn deficient conditions favours M1 macrophage polarisation and maturation of dendritic cells, and also inhibits the anti-inflammatory activity of regulatory T cells. Collectively, these observations could theoretically give rise to the chronic inflammation seen in PD.
CONCLUSION: A disrupted MT and Zn homeostasis is expected to exert an adverse impact on periodontal health and contribute to the development and progression of PD.
Protective potential of cerium oxide nanoparticles in diabetes mellitus

Chai WF, Tang KS

J Trace Elem Med Biol, 2021 Jul;66:126742.
PMID: 33773280 DOI: 10.1016/j.jtemb.2021.126742

BACKGROUND: Diabetes mellitus (DM) is a non-communicable metabolic disease which is closely related to excessive oxidative stress after constant exposure to high plasma glucose. Although the current antidiabetic medications are effective in lowering blood glucose, these medications do not prevent or reverse the disease progression. Thus, there is a crucial need to explore new therapeutic interventions that could address this shortcoming. As cerium oxide nanoparticles (CONPs) possess antioxidant property, this agent may be used as a treatment option for the management of DM.
PURPOSE: This review aims to provide a critical evaluation of the pharmacological and antidiabetic effects of CONPs in cell and animal models. The roles of CONPs in attenuating DM complications are also presented in this report.
METHODS: We conducted a literature search in the PubMed database using the keywords "cerium oxide", "cerous oxide", "ceria", "nanoceria", and "diabetes" from inception to December 2020. The inclusion criteria were primary source articles that investigated the role of CONPs in DM and diabetic complications.
RESULTS: We identified 47 articles from the initial search. After the thorough screening, only 31 articles were included in this study. We found that CONPs can attenuate parameters that are related to DM and diabetic complications in various animals and cell culture models.
CONCLUSION: CONPs could potentially be used in the treatment of those with DM and complications caused by the disease.
Low magnesium diet alters distribution of macroelements and trace elements in tissues and organs of female rats

Zheltova AA, Kharitonova MV, Iezhitsa IN, Serebryansky EP, Evsyukov OY, Spasov AA, et al.

J Trace Elem Med Biol, 2017 Jan;39:36-42.
PMID: 27908421 DOI: 10.1016/j.jtemb.2016.07.002

The aim of the present study was to assess whether dietary magnesium deficiency can alter distribution of macroelements and trace elements in different organs and tissues. Experiments were carried out on 12 adult female Wistar rats, which were fed either a diet with low Mg content (≤20mgkg(-1) of diet) (LMgD) or a diet with daily recommended Mg content (≈500mgkg(-1)) as control group (CG) for 70 days. On the 70th day of the experiment heart, aorta, femoral skeletal muscle, forebrain, cerebellum, pituitary gland, thyroid gland, ovaries, uterus, liver, kidneys, and spleen were taken for analysis of mineral content. Concentrations of Fe and Ca were measured by inductively coupled plasma-atomic emission spectrometry, and levels of Na, K, Mg, Co, Cu, Zn, Ni, Se, I were determined by inductively coupled plasma mass spectrometry. On the 70th day, LMgD led to significant reduction of Mg level in red blood cells, plasma, aorta, uterus and thyroid gland compared to CG as well as resulted in significant decrease of Mg/Ca ratio in kidneys, spleen and ovaries. Contrary to this, an increase of Mg/Ca ratio was found in cerebellum of LMgD group. Significant decrease of K concentration was shown in aorta of LMgD animals compared to CG whereas myocardial K concentration was increased in LMgD group. Na level was two-fold higher in skeletal muscles of rats that received LMgD in comparison to CG (p=0.006). Increased concentrations of Fe in ovaries and uterus were found in LMgD. Mg restriction did not affect Zn concentration in any of tasted tissues. Se level was higher in spleen and lower in uterus of LMgD animals compared to CG. MgD was accompanied by increased level of Co in skeletal muscles and decreased its level in kidneys and uterus. LMgD feeding was associated with decreased concentrations of Ni in heart, thyroid gland, spleen, uterus and Co in heart, aorta, liver, kidneys, spleen and ovaries. The changes of Mg, K, Co content were accompanied by dramatic (10-fold) decrease of I concentration in aorta of LMgD animals. LMgD causes decrease of I content in ovaries and increase of I level in uterus vs CG. Thus, distribution of macroelements (Ca, Na, K) was weakly affected by Mg restriction that led to the most evident alterations of Co and Ni tissue levels. Moreover, mineral balance of uterus seems to be the most susceptible to low Mg intake. Hypomagnesaemia resulted in significant changes of 5 studied trace elements (Fe, Se, Cu, Ni and Co).
Protective effect of magnesium acetyltaurate against NMDA-induced retinal damage involves restoration of minerals and trace elements homeostasis

Jafri AJA, Arfuzir NNN, Lambuk L, Iezhitsa I, Agarwal R, Agarwal P, et al.

J Trace Elem Med Biol, 2017 Jan;39:147-154.
PMID: 27908408 DOI: 10.1016/j.jtemb.2016.09.005

Glutamate-mediated excitotoxicity involving N-methyl-d-aspartate (NMDA) receptors has been recognized as a final common outcome in pathological conditions involving death of retinal ganglion cells (RGCs). Overstimulation of NMDA receptors results in influx of calcium (Ca) and sodium (Na) ions and efflux of potassium (K). NMDA receptors are blocked by magnesium (Mg). Such changes due to NMDA overstimulation are also associated with not only the altered levels of minerals but also that of trace elements and redox status. Both the decreased and elevated levels of trace elements such as iron (Fe), zinc (Zn), copper (Cu) affect NMDA receptor excitability and redox status. Manganese (Mn), and selenium (Se) are also part of antioxidant defense mechanisms in retina. Additionally endogenous substances such as taurine also affect NMDA receptor activity and retinal redox status. Therefore, the aim of this study was to evaluate the effect of Mg acetyltaurate (MgAT) on the retinal mineral and trace element concentration, oxidative stress, retinal morphology and retinal cell apoptosis in rats after-NMDA exposure. One group of Sprague Dawley rats received intravitreal injection of vehicle while 4 other groups similarly received NMDA (160nmolL(-1)). Among the NMDA injected groups, 3 groups also received MgAT (320nmolL(-1)) as pre-treatment, co-treatment or post-treatment. Seven days after intravitreal injection, rats were sacrificed, eyes were enucleated and retinae were isolated for estimation of mineral (Ca, Na, K, Mg) and trace element (Mn, Cu, Fe, Se, Zn) concentration using Inductively Coupled Plasma (DRC ICP-MS) techniques (NexION 300D), retinal oxidative stress using Elisa, retinal morphology using H&E staining and retinal cell apoptosis using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Intravitreal NMDA injection resulted in increased concentration of Ca (4.6 times, p<0.0001), Mg (1.5 times, p<0.01), Na (3 times, p<0.0001) and K (2.3 times, p<0.0001) compared to vehicle injected group. This was accompanied with significant increase of Ca/Mg and Na/K ratios, 3 and 1.27 times respectively, compared to control group. The trace elements such as Cu, Fe and Zn also showed a significant increase amounting to 3.3 (p<0.001), 2.3 (p<0.0001) and 3 (p<0.0001) times respectively compared to control group. Se was increased by 60% (p<0.005). Pre-treatment with MgAT abolished effect of NMDA on minerals and trace elements more effectively than co- and post-treatment. Similar observations were made for retinal oxidative stress, retinal morphology and retinal cell apoptosis. In conclusion, current study demonstrated the protective effect of MgAT against NMDA-induced oxidative stress and retinal cell apoptosis. This effect of MgAT was associated with restoration of retinal concentrations of minerals and trace elements. Further studies are warranted to explore the precise molecular targets of MgAT. Nevertheless, MgAT seems a potential candidate in the management of diseases involving NMDA-induced excitotoxicity.
The protective effect of nano calcium produced from freshwater clam shells on the histopathological overview of the liver and kidneys of mice exposed to mercury toxins

Srie Rahayu SY, Aminingsih T, Fudholi A

J Trace Elem Med Biol, 2022 May;71:126963.
PMID: 35231878 DOI: 10.1016/j.jtemb.2022.126963

BACKGROUND AND AIM: Freshwater clam shells nanoparticles powder is one of the uses of freshwater clams that can manufacture instant granular mineral supplements. This product can be used as a supplement to detoxify heavy metal toxins, such as Mercury. Mercury is an element that is detectable in all environmental media. Adults and children receive the most Mercury from food, air, and water intake. The majority of Mercury in the environment comes from the waste from mining activities and the metal industry. Mercury was found widely in the biosphere and is known as a dangerous hepatotoxicant. This study aimed to describe the hepatoprotective role of nano minerals (Ca, Mg, and Zn) produced from freshwater clam shells against mercury acetate poisoning in mice.
MATERIAL AND METHODS: The mice were divided randomly into a control group (aqua bidest and mercury acetate) and an experimental group for this purpose. The experimental mice group was given orally nano Ca supplementation in three dose groups (9 mg, 18 mg, and 27 mg/200 g animal body weight) once a day for 21 consecutive days. The mice are then given mercury acetate (1300 µg/200 g animal body weight intraperitoneally) on the 21st day. One hour after giving the nano Ca supplement, the mice's blood was taken. Liver and kidney were autopsied two days later to check quantitative and qualitative changes caused by mercury concentrations in liver and kidney histopathologies.
RESULTS: The results demonstrated the importance of nano Ca supplementation before mercury acetate induction, which has been shown to reduce necrotic depletion and hepatocyte degeneration.
CONCLUSION: Nano Ca supplementation has decreased the concentration of Hg in the blood of mice so that it can be used as a potential health supplement to detoxify mercury toxins.

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