Biological Trace Element Research

Effect of Long-term Administration of Oral Magnesium Sulfate and Insulin to Reduce Streptozotocin-Induced Hyperglycemia in Rats: the Role of Akt2 and IRS1 Gene Expressions Abstract The effects of long-term oral administration of magnesium sulfate and insulin on hyperglycemia were investigated using Akt2 and IRS1 gene expression methods in streptozotocin-induced diabetic rats. Fifty rats were randomly divided into five experimental groups: 1, non-diabetic control (NDC); 2, Mg2+-treated non-diabetic control (Mg-NDC); 3, chronic diabetic (CD); 4, Mg2+-treated chronic diabetic (Mg-CD); and 5, insulin-treated chronic diabetic (Ins-CD). Streptozotocin was used to induce diabetes. The Mg-CD and Mg-NDC groups received 10 g/l of MgSO4 added to drinking water. The Ins-CD group received 2.5 U/kg of insulin twice a day. Blood glucose level and body weight were measured every week. The intraperitoneal glucose tolerance test (IPGTT) was performed after 16 weeks. MgSO4 administration improved the blood glucose level and IPGTT. It also increased Akt2 and IRS1 genes as well as protein expression. Insulin lowered the blood glucose level and increased IRS1 gene and protein expression, but did not affect Akt2 gene and protein expression. Glucose reduction after Mg therapy may be mediated, at least partially, via IRS1 and Akt2 genes and protein stimulation. In insulin-treated rats, insulin resistance was not significant due to the absence of Akt2 gene expression.

Diagnostic Value of Energy Dispersive Hand-Held X-ray Fluorescence Spectrometry in Determining Trace Element Concentrations in Ovine Liver Abstract There are no data available on the use of hand-held X-ray fluorescence (XRF) spectrometry to determine trace element concentrations in veterinary diagnostics. The hand-held XRF spectrometer is easy to use and does not require extensive training for the operator. In Sub-Saharan Africa with few centralised analytical laboratories equipped with expensive apparatus or mass spectrometry capabilities, trace element analysis using the hand-held XRF spectrometer provides an alternative. The objective of this study was to compare ovine hepatic copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se) and zinc (Zn) concentrations as obtained with the hand-held XRF spectrometer to those of a reference laboratory using inductively coupled plasma mass spectrometry (ICP-MS). Thirty ovine livers were obtained from an abattoir; prepared as wet blended and oven-dried samples and analysed. Bayesian correlation was used to assess the correspondence between results from the XRF and ICP-MS analyses. The oven-dried preparation procedure for XRF provided the best correlation with the ICP-MS data. The correlations for Cu and Zn were strong and the XRF method may represent a suitable substitute for ICP-MS analysis. For Mn and Fe the correlations were moderately strong and the XRF method may be suitable. For Mo, the correlation was weak and XRF cannot be recommended. Selenium could not be detected in samples prepared by either method. Hand-held XRF spectrometry was a practical method to determine liver concentrations of specific trace elements under African conditions and may significantly reduce the turn-around time of analysis, but unfortunately the apparatus is expensive.

Is There Any Relevance Between Serum Heavy Metal Concentration and BBB Leakage in Multiple Sclerosis Patients? Abstract Sharp increase in multiple sclerosis (MS) incidence rate has been observed in Iranian people. In addition, it has been suggested that increased S100B level may be useful as an indicative factor of blood-brain barrier disruption. The propose of this study was to measuring blood arsenic, lead, and cadmium concentration and serum S100B concentration in a group of healthy and multiple sclerosis patients in Tehran as the most polluted city in Iran. All subjects were interviewed regarding age, medical history, possible chemical exposure, acute or chronic diseases, smoking, and dietary habits. Blood heavy metal level was measured by an atomic absorption spectrometer (Varian model 220-Z) conjugated with a graphite furnace atomizer (GTA-110). Also, a serum S100B protein concentration was determined using a commercial ELISA kit. It was observed that all male subjects had higher blood metal level in comparison with healthy controls. Also, MS patients had higher arsenic and cadmium blood concentration in comparison with healthy individuals. Regarding the S100B concentration, it was observed that it had a significant relationship with smoking habit (P value = 0.0001). In addition, arsenic had a greater correlation (63%) with increased serum S100B biomarker level among other elements. BBB leakage was higher in multiple sclerosis than in healthy subjects due to increased S100B release. In addition with regard to the heavy metal exposure especially arsenic and cadmium, these are associated with an increased BBB disruption and it is possible to play a crucial role as a developing agent of multiple sclerosis.

Role of Pigment Epithelium-Derived Factor in Arsenic-Induced Vascular Endothelial Dysfunction in a Rat Model Abstract Water-borne arsenicosis is caused by the consumption of excess levels of inorganic arsenic from drinking water and is a worldwide public health issue. Arsenic exposure has recently attracted extensive attention due to its damage to the cardiovascular system. Vascular endothelial dysfunction (VED) is recognized as an important cause of cardiovascular diseases. Pigment epithelium-derived factor (PEDF) plays an important role in maintaining endothelial function, and our previous studies suggested that PEDF may have role in arsenic-induced damage. In the present study, we established subchronic arsenic exposure (3 months) rat model from drinking water at doses of 0, 2 mg/L, 10 mg/L, and 50 mg/L, respectively. The results showed that the endothelial cells of the aortic arch were obviously damaged, the apoptosis rate increased, the vWF and iNOS levels increased, and the NO and TNOS levels significantly decreased in the arsenic exposure groups. Regardless of serum or aortic arch endothelium, PEDF levels in the arsenic exposure groups decreased compared to the control group. The oxidative stress level and key proteins associated with apoptosis such as Fas, FasL, P53, and p-p38 were then detected to explore the detailed mechanisms. The results showed that the P53 and p-p38 levels significantly increased in the 10 mg/L and 50 mg/L groups compared to the control group. The MDA content in the arsenic exposure groups increased markedly, whereas the SOD activity decreased significantly with the increased arsenic dose. Taken together, our study is the first to find that PEDF plays a protective role in arsenic-induced endothelial dysfunction through anti-oxidation and anti-apoptosis, and p38 and P53 may be promising target proteins.

Expression Profiles of Selenium-Related Genes in Human Chondrocytes Exposed to T-2 Toxin and Deoxynivalenol Abstract The combination of excess mycotoxin exposure and selenium deficiency has been widely considered as a cause of Kashin-Beck disease (KBD). The present study aimed to investigate the expression profiles of selenium-related genes in human chondrocytes after exposure to T-2 toxin and deoxynivalenol (DON) and to preliminarily identify the potential biological functions of the identified genes. Gene expression profiling was performed on human chondrocytes treated with 0.01 μg/ml T-2 toxin and 1.0 μg/ml DON by using Affymetrix Human Gene Arrays. The 1660 selenium-related genes were derived from the Comparative Toxicogenomics Database. Gene-term enrichment analysis was conducted by the DAVID gene annotation tool. Our results showed that 69 and 191 selenium-related genes were differentially expressed after T-2 toxin and DON treatment, respectively. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these identified genes were involved in various biological functions, such as the GO terms in response to oxidative stress, cell cycle arrest, and apoptotic process and the KEGG metabolic, FoxO signaling, and p53 signaling pathways. Our results may help explain the mechanisms of interaction between mycotoxins and selenium following human chondrocyte damage and reveal the potential roles of environmental risk factors in cartilage lesions during KBD development.

The Study on Polymorphism of TrxR and Nrf2/HO-1 Signaling Pathway in Kaschin-Beck Disease Abstract Kaschin-Beck disease (KBD) is an endemic, chronic, and degenerative osteoarthropathy, which seriously impairs the quality of patients' life. We detected the expression of TrxR by ELISA and found that TrxR was lower in KBD than in normal control group significantly (P < 0.001); this result indicated that TrxR must be related to KBD. We retrieved cSNPs in NCBI SNP database and used three bioinformatics programmers, including SIFT, PolyPhen, and SNP3d, to help select the researched nsSNP. Then, we used PCR-RFLP to analyze the relationship between the SNP site rs5746841 in TrxR2 gene and susceptibility of KBD and detected the expression of Nrf2 and HO-1 by western blot. The results showed that the genotype of rs5746841 in 93 normal controls and 103 KBD subjects were C/C totally, but A/A and A/C were not found, which indicated preliminarily that there was no correlation between rs5746841 in TrxR2 gene and susceptibility of KBD. The expression of TrxR was lower in KBD than in normal control group significantly, while the expressions of Nrf2 and HO-1 were higher in KBD than in normal control group. These results indicated that the low expression of selenoprotein TrxR may be a candidate factor of KBD, which related to Nrf2/HO-1 signaling pathway.

Total Bioavailable Organic Selenium in Fishmeal-Based Diet Influences Growth and Physiology of Juvenile Cobia Rachycentron canadum (Linnaeus, 1766) Abstract The study examined the effects of supplemental organic selenium (Se) extracted from selenoyeast on the growth performance, glutathione peroxidase (GPx) activity, biochemical status and liver histochemistry of juvenile cobia Rachycentron canadum. Six experimental diets were prepared supplemented with Se with total concentration of 1.52 (Se-1.52), 1.93 (Se-1.93), 2.29 (Se-2.29), 2.71 (Se-2.71) and 3.14 (Se-3.14) mg/kg of total Se in the diets and a fishmeal-based control diet without Se supplementation containing 1.15 (Se-1.15) mg/kg of Se was used as control. Experimental diets were fed to the fish of six treatment groups in triplicate twice daily for 8 weeks. Juvenile cobia fed dietary Se of 1.93, 2.29 and 2.71 mg/kg showed increased final body weight (FBW), specific growth rate (SGR) and feed intake (FI) than the fish fed the control diet. Se accumulations in the muscle and liver tissue displayed a positive linear relationship with dietary Se levels. Se deficiency was apparent in fish fed the control diet and displayed reduced growth and feed efficiency. Red blood cell (RBC) counts were significantly (P < 0.05) higher in cobia fed dietary Se between 1.52 to 2.71 mg/kg than the fish fed 3.14-mg/kg Se diet. Glutathione peroxidase activity significantly (P < 0.05) declined in the group fed with control diet compared to fish fed Se-supplemental diet. Juvenile cobia fed the highest Se level (Se-3.14 mg/kg) showed toxic effects in the liver, including histopathological lesions in the liver. Based on the results obtained for FBW, SGR, tissue Se retention and haematological parameters, we conclude that optimal dietary Se requirement for juvenile cobia fed commercial diets is 2.32 mg/kg.

Ascorbic Acid Supplementation Prevents the Detrimental Effects of Prenatal and Postnatal Lead Exposure on the Purkinje Cell and Related Proteins in the Cerebellum of Developing Rats Abstract We investigated the effects of lead (Pb) and ascorbic acid co-administration on rat cerebellar development. Prior to mating, rats were randomly divided into control, Pb, and Pb plus ascorbic acid (PA) groups. Pregnant rats were administered Pb in drinking water (0.3% Pb acetate), and ascorbic acid (100 mg/kg) via oral intubation until the end of the experiment. Offspring were sacrificed at postnatal day 21, the age at which the morphology of the cerebellar cortex in developing pups is similar to that of the adult brain. In the cerebellum, Pb exposure significantly reduced Purkinje cells and ascorbic acid prevented their reduction. Along with the change of the Purkinje cells, long-term Pb exposure significantly reduced the expression of the synaptic marker (synaptophysin), γ-aminobutyric acid (GABA)–synthesizing enzyme (glutamic acid decarboxylase 67), and axonal myelin basic protein while ascorbic acid co-treatment attenuated Pb-mediated reduction of these proteins in the cerebellum of pups. However, glutamatergic N-methyl-d-aspartate receptor subtype 1 (NMDAR1), anchoring postsynaptic density protein 95 (PSD95), and antioxidant superoxide dismutases (SODs) were adversely changed; Pb exposure increased the expression of NMDAR1, PSD95, and SODs while ascorbic acid co-administration attenuated Pb-mediated induction. Although further studies are required about the neurotoxicity of the Pb exposure, the results presented here suggest that developmental Pb exposure disrupted normal development of Purkinje cells by increasing glutamatergic and oxidative stress in the cerebellum. Additionally, ascorbic acid co-treatment is beneficial in attenuating prenatal and postnatal Pb exposure–induced maldevelopment of Purkinje cells in the developing cerebellum.

The Variable Regulatory Effect of Arsenic on Nrf2 Signaling Pathway in Mouse: a Systematic Review and Meta-analysis Abstract Arsenic is known to cause oxidative damage. Nuclear factor E2-relate factor-2 (Nrf2) can resist this toxicity. Scholars demonstrated that Nrf2 pathway was activated by arsenic. In contrast, other articles established arsenic-induced inhibition of Nrf2 pathway. To resolve the contradiction and elucidate the mechanism of Nrf2 induced by arsenic, 39 publications involving mouse models were identified through exhaustive database retrieval and were analyzed. The pooled results suggested that arsenic obviously elevated transcription and translation levels of Nrf2 and its downstream genes, NAD(P)H dehydrogenase 1 (NQO1), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and GST-glutathione-S-transferase1/2 (GSTO1/2). Arsenic increased the level of reactive oxygen species (ROS), but reduced the level of glutathione (GSH). Subgroup analysis between arsenic and control groups showed that the levels of Nrf2 and its downstream genes are greater in high dose than that in the low dose, higher in short-term exposure than long term, female subjects tolerated better than males, higher in mice than the rats, and greater in other organs than the liver. However, the contents of genes of Nrf2 pathway between the arsenic and control groups were lower in rats than in mice and were less for long-term exposure than the short term (P < 0.05). Conclusively, a variable regulation of arsenic on Nrf2 pathway is noted. Higher dose and short-term exposure of female mice organs except for liver promoted Nrf2 pathway. On the other hand, arsenic inhibited Nrf2 pathway for long-term exposure on rats.

GM1 Ameliorates Lead-Induced Cognitive Deficits and Brain Damage Through Activating the SIRT1/CREB/BDNF Pathway in the Developing Male Rat Hippocampus Abstract Developmental lead (Pb) exposure involves various serious consequences, especially leading to neurotoxicity. In this study, we examined the possible role of monosialoganglioside (GM1) in lead-induced nervous impairment in the developing rat. Newborn male Sprague-Dawley rat pups were exposed to lead from birth for 30 days and then subjected to GM1 administration (0.4, 2, or 10 mg/kg; i.p.) or 0.9% saline. The results showed that developmental lead exposure significantly impaired spatial learning and memory in the Morris water maze test, reduced GM1 content, induced oxidative stress, and weakened the antioxidative systems in the hippocampus. However, co-treatment with GM1 reversed these effects. Moreover, GM1 counteracted lead-induced apoptosis by decreasing the expression of Bax, cleaved caspase-3, and by increasing the level of Bcl-2 in a dose-dependent manner. Furthermore, we found that GM1 upregulated the expression of SIRT1, CREB phosphorylation, and BDNF, which underlie learning and memory in the lead-treated developing rat hippocampus. In conclusion, our study demonstrated that GM1 exerts a protective effect on lead-induced cognitive deficits via antioxidant activity, preventing apoptosis, and activating SIRT1/CREB/BDNF in the developing rat hippocampus, implying a novel potential assistant therapy for lead poisoning.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com