Changed Plasma Levels of Zinc and Copper to Zinc Ratio and Their Possible Associations with Parent- and Teacher-Rated Symptoms in Children with Attention-Deficit Hyperactivity Disorder

Abstract

Attention-deficit hyperactivity disorder (ADHD) is associated with alterations in the metabolism of some trace elements which may participate in the pathogenesis of this disorder. The aims of the present study were to investigate the trace element status (copper (Cu), zinc (Zn), copper to zinc ratio (Cu/Zn ratio), selenium (Se), and lead (Pb)) of ADHD children and compare them with the control group. Associations between examined elements and ratings of ADHD symptoms were also assessed. Fifty-eight ADHD children and 50 healthy children (aged 6–14 years) were included in the study. The concentrations of Cu, Zn, and Se in the plasma and Pb in the whole blood were measured by atomic absorption spectrometry. We found lower Zn level (p = 0.0005) and higher Cu/Zn ratio (p = 0.015) in ADHD children when compared with the control group. Copper levels in ADHD children were higher than those in the control group, but not significantly (p > 0.05). No significant differences in levels of Se and Pb between both groups were found. Zinc levels correlated with parent-rated score for inattention (r = −0.231, p = 0.029) as well as with teacher-rated score for inattention (r = −0.328, p = 0.014). Cu/Zn ratio correlated with teacher-rated score for inattention (r = 0.298, p = 0.015). Significant associations of Se and Pb with parent- and teacher-rated symptoms were not observed. The results of this study indicate that there are alterations in plasma levels of Cu and Zn as well as significant relationships to symptoms of ADHD.

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Protective Role of Selenium Compounds on the Proliferation, Apoptosis, and Angiogenesis of a Canine Breast Cancer Cell Line

Abstract

We herein examined the effects of different doses, forms, and compatibilities of selenium on a canine mammary gland tumor cell line, CTM1211, and explored the related mechanisms. Three selenium compounds, sodium selenite (SSE), methylseleninic acid (MSA), and methylselenocysteine (MSC), were selected for these experiments, and cyclophosphamide (CTX) served as a positive control. In the cell viability assay, the cell viability of each group at 48/72 h decreased significantly compared with the control group (p < 0.05), and the cell viability of the CTX + MSA group was lower than that of CTX and MSA groups (p < 0.05). Moreover, the inhibitory effect of selenium on cell proliferation was time-dependent but not concentration-dependent. In the cell apoptosis assay, the apoptosis values of each group increased significantly compared with the control group, and the apoptosis values of the CTX + MSA group increased the most significantly (p < 0.01). The protein and mRNA expression levels of vascular endothelial growth factor-alpha (VEGF-alpha), angiopoietin-2 (Ang-2), and hypoxia inducible factor-1 alpha (HIF-1 alpha) were downregulated in each group, while that of phosphatase and tensin homolog (PTEN) were upregulated (p < 0.05). In conclusion, these three selenium compounds, especially MSA, could significantly inhibit the viability and growth of the CTM1211 cell line, which is partly due to the induction of apoptosis and regulation of tumor angiogenesis.

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Gestational form of Selenium in Free-Choice Mineral Mixes Affects Transcriptome Profiles of the Neonatal Calf Testis, Including those of Steroidogenic and Spermatogenic Pathways

Abstract

In areas where soils are deficient in Selenium (Se), dietary supplementation of this trace mineral directly to cattle is recommended. Because Se status affects testosterone synthesis and frequency of sperm abnormalities, and the form of Se supplemented to cows affects tissue-specific gene expression, the objective of this study was to determine whether the form of Se consumed by cows during gestation would affect the expression of mRNAs that regulate steroidogenesis and/or spermatogenesis in the neonatal calf testis. Twenty-four predominantly Angus cows were assigned randomly to have individual, ad libitum, access of a mineral mix containing 35 ppm of Se in free-choice vitamin-mineral mixes as either inorganic (ISe), organic (OSe), or a 50/50 mix of ISe and OSe (MIX), starting 4 months prior to breeding and continuing throughout gestation. Thirteen male calves were born over a 3-month period (ISe, n = 5; OSe, n = 4; MIX, n = 4), castrated within 2 days of birth, and extracted testis RNA subjected to transcriptomal analysis by microarray (Affymetrix Bovine 1.0 ST arrays) and targeted gene expression analysis by real-time reverse-transcription PCR (RT-PCR) of mRNAs encoding proteins known to affect steroidogenesis and/or spermatogenesis. The form of dam Se affected (P < 0.05) the expression of 853 annotated genes, including 17 mRNAs putatively regulating steroidogenesis and/or spermatogenesis. Targeted RT-PCR analysis indicated that the expression of mRNA encoding proteins CYP2S1 (cytochrome P450, family 2, subfamily S, polypeptide 1), HSD17B7 (hydroxysteroid (17β) dehydrogenase 7), SULT1E1 (sulfotransferase family 1E, estrogen preferring, member 1), LDHA (lactate dehydrogenase A), CDK5R1 (cyclin-dependent kinase 5, regulatory subunit 1), and LEP (leptin) was affected (P < 0.05) by form of Se consumed by dams of developing bull calves, while AKR1C4 (aldo-keto reductase family 1, member C4) and CCND2 (cyclin D2) tended (P < 0.09) to be affected. Our results indicate that form of Se fed to dams during gestation affected the transcriptome of the neonatal calf testis. If these profiles are maintained throughout maturation, then the form of Se fed to dams may impact bull fertility and the development of Se form-dependent mineral mixes that target gestational development of the testis are warranted.

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The Prevention Effect of Selenium on Prevalence of Children Kaschin-Beck Disease in Active Endemic Areas in Qinghai Plateau

Abstract

Selenium deficiency is an important environmental risk factor of Kaschin-Beck disease (KBD), and appropriate selenium supplement can reduce the prevalence of KBD. Guide and Xinghai counties, active endemic areas of KBD in Qinghai Plateau, are characteristic with low level of selenium. The aim of this article was to explore the relationship between selenium content and prevalence of children KBD in some active endemic areas from Guide and Xinghai counties. The historical data of KBD were collected, including the detectable rates of KBD and selenium contents of the hair of children, and then the relationship between the prevalence of KBD and selenium contents of hair was analyzed. In KBD endemic areas of Guide County, the detectable rates of X-ray and metaphysic lesion were declined from 25.00 and 16.96 % in 2000 to 13.75 and 13.75 % in 2010, respectively. Similarly, in KBD endemic areas of Xinghai County, the detectable rates of X-ray and metaphysic lesion were declined from 46.51 and 40.31 % in 2000 to 10.64 and 8.51 % in 2010, respectively. The selenium contents of hair in Xinghai county were increased from 130.01 ± 48.08 μg/kg in 2003 to 211.8 ± 86.64 μg/kg in 2010(t = 2.98, P < 0.05); the selenium content of hair in Guide County were increased from 142.30 ± 62.02 μg/kg in 2003 to 182.09 ± 78.46 μg/kg in 2010 (t = 3.12, P < 0.05). There was a negative correlation between the prevalence of KBD and selenium contents of hair (r = −0.785). There was a close relationship between selenium content and prevalence of KBD. Selenium could reduce the prevalence of KBD, so it is very necessary to supplement selenium appropriately for KBD prevention.

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Effect of Zinc Supplementation on Antioxidant Defenses and Oxidative Stress Markers in Patients Undergoing Chemotherapy for Colorectal Cancer: a Placebo-Controlled, Prospective Randomized Trial

Abstract

The study aimed to investigate the effect of oral zinc supplementation on antioxidant defenses and oxidative stress markers during chemotherapy for colorectal cancer. Twenty-four patients who had undergone surgical resection of colorectal cancer participated in this placebo-controlled, prospective randomized study. The supplementation was started in the perioperative period, in which 10 patients received 70 mg of zinc (zinc group, n = 10) and 14 patients received placebo (placebo group, n = 14) for 16 weeks. Approximately 45 days after surgical resection of tumor, all patients received a chemotherapeutic regimen (capecitabine, capecitabine combined with oxaliplatin or 5-fluorouracil). Vitamin C, vitamin E, antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), and lipid peroxidation markers malondialdehyde (MDA) and 8-isoprostane were determined before the first, second, third, and fourth chemotherapy cycles. Compared with the placebo group, the zinc group presented higher SOD values before the first, second, and fourth chemotherapy cycles and lower GPx values before the third cycle. There were no statistical differences between the study groups in vitamin C, vitamin E, MDA, or 8-isoprostane plasma values. Longitudinal analysis revealed decreased vitamin E concentration in the placebo group before the second and fourth cycles as compared with the initial values. Zinc supplementation during chemotherapy cycles increased SOD activity and maintained vitamin E concentrations. Although no effect of zinc supplementation on oxidative stress markers was observed, the increase in SOD activity indicates a production of stable free radicals, which may have a positive effect in cancer treatment.

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Zinc Chloride and Lead Acetate-Induced Passive Avoidance Memory Retention Deficits Reversed by Nicotine and Bucladesine in Mice

Abstract

It is very important to investigate the neurotoxic effects of metals on learning and memory processes. In this study, we tried to investigate the effects and time course properties of oral administration of zinc chloride (25, 50, and 75 mg/kg, for 2 weeks), lead acetate (250, 750, 1,500, and 2,500 ppm for 4, 6 and 8 weeks), and their possible mechanisms on a model of memory function. For this matter, we examined the intra-peritoneal injections of nicotine (0.25, 0.5, 1, and 1.5 mg/kg) and bucladesine (50, 100, 300, and 600 nM/mouse) for 4 days alone and in combination with mentioned metals in the step-through passive avoidance task. Control animals received saline, drinking water, saline, and DMSO (dimethyl sulfoxide)/deionized water (1:9), respectively. At the end of each part of studies, animals were trained for 1 day in step-through task. The avoidance memory retention alterations were evaluated 24 and 48 h later in singular and combinational studies. Zinc chloride (75 mg/kg) oral gavage for 2 weeks decreased latency times compared to control animals. Also, lead acetate (750 ppm oral administrations for 8 weeks) caused significant lead blood levels and induced avoidance memory retention impairments. Four-days intra-peritoneal injection of nicotine (1 mg/kg) increased latency time compared to control animals. Finally, findings of this research showed that treatment with intra-peritoneal injections of nicotine (1 mg/kg) and/or bucladesine (600 nM/mouse) reversed zinc chloride- and lead acetate-induced avoidance memory retention impairments. Taken together, these results showed the probable role of cholinergic system and protein kinase A pathways in zinc chloride- and lead acetate-induced avoidance memory alterations.

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Silicon Reverses Lipid Peroxidation but not Acetylcholinesterase Activity Induced by Long-Term Exposure to Low Aluminum Levels in Rat Brain Regions

Abstract

Aluminum (Al) is the most widely distributed metal in the environment and is extensively used in daily life leading to easy exposure to human beings. Besides not having a recognized physiological role, Al may produce adverse effects through the interaction with the cholinergic system contributing to oxidative stress. The present study evaluated, in similar conditions of parenteral nutrition, whether the reaction of silicon (SiO₂) with Al³⁺ to form hydroxyaluminosilicates (HAS) reduces its bioavailability and toxicity through intraperitoneal administrations of 0.5 mg Al/kg/day and/or 2 mg Si/kg/day in Wistar rats. Al and Si concentrations were determined in rat brain tissue and serum. Acetylcholinesterase (AChE) activity and lipid peroxidation (LPO) were analyzed in the cerebellum, cortex, hippocampus, striatum, hypothalamus, and blood. An increase in the Al concentration was verified in the Al + Si group in the brain. All the groups demonstrated enhanced Si compared to the control animals. Al³⁺ increased LPO measured by thiobarbituric acid reactive substances (TBARS) in cerebellum and hippocampus, whereas SiO₂ reduced it when compared with the control group. An increase of AChE activity was observed in the Al-treated group in the cerebellum whereas a decrease of this enzyme activity was observed in the cortex and hippocampus in the Al and Al + Si groups. Al and Si concentrations increased in rat serum; however, no effect was observed in blood TBARS levels and AChE activity. SiO₂ showed a protective effect in the hippocampus and cerebellum against cellular damage caused by Al³⁺-induced lipid peroxidation. Thus, SiO₂ may be considered an important protector in LPO induced by Al³⁺.

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