Showing papers in "Biological Trace Element Research in 2015"
TL;DR: The hypothesis that selenium helps to combat oxidative stress produced by accumulation of AlCl3 in the brain and helps in prophylaxis of Alzheimer’s diseases is strengthened.
Abstract: In present study, selenium was selected for evaluating effect of selenium on aluminum chloride (AlCl3)-induced Alzheimer’s disease in rats. Thirty Wistar rats were divided into five groups of six in each. Group I (control) received distilled water, group II—AlCl3 (100 mg/kg, p.o.), group III—selenium (1 mg/kg, p.o.), group IV—AlCl3 + vitamin E (100 mg/kg, p.o. + 100 mg/kg, p.o.), and group V—AlCl3 + selenium (100 mg/kg, p.o. + 1 mg/kg, p.o.) for 21 days. At end of experiment, various behavioral, biochemical, and histopathological assessments were carried out. The animals showed increase in time to reach platform in Morris water maze and decreased step-down latencies in passive avoidance test indicating learning and memory impairment in aluminum chloride-treated group, but administration of selenium decreased time to reach platform in Morris water maze, increased step-down latencies, and strengthened its memory action in drug-treated animals. There was decrease in muscle strength measured by rotarod test indicating motor incoordination and decrease in locomotor activity assessed by actophotometer test in AlCl3 control group, whereas in selenium–AlCl3 group, there was improvement in muscle strength and locomotion. Biochemical analysis of the brain revealed that chronic administration of AlCl3 significantly increased lipid peroxidation and decreased levels of acetyl cholinesterase, catalase, reduced glutathione and glutathione reductase, an index of oxidative stress process. Administration of selenium attenuated lipid peroxidation and ameliorated the biochemical changes. There were marked changes at subcellular level observed by histopathology studies in AlCl3 group, and better improvement in these changes was observed in selenium + AlCl3group. Therefore, this study strengthens the hypothesis that selenium helps to combat oxidative stress produced by accumulation of AlCl3 in the brain and helps in prophylaxis of Alzheimer’s diseases.
93 citations
TL;DR: The improved starch metabolism, greater membrane stability, and increased activity of antioxidants were considered as possible mechanisms responsible for such improvements in emergence and seedling vigor of rice mediated by selenium priming.
Abstract: The present study was undertaken to appraise the role of selenium priming for improving emergence and seedling growth of basmati rice. Seeds of two fine rice cultivars (Super and Shaheen Basmati) were primed with concentrations of 15, 30, 45, 60, 75, 90, and 105 μmol L −1 selenium. Untreated dry- and hydro- primed seeds were maintained as the control and posi- tive control, respectively. Selenium priming resulted in early commencement of emergence, triggered seedling growth irrespective of rice cultivar over untreated con- trol, and was more effective than hydro-priming except at higher concentrations. Lower electrical conductivity of seed leachates, reduced lipid peroxidation, greater α-amylase activity, higher soluble sugars, and enhanced activities of enzymatic antioxidants (superoxide dismut- ase (SOD), peroxidase (POX), catalase (CAT), and glu- tathione peroxidase (GPX)) were observed in seeds primed with selenium. Rice seedlings derived from selenium-primed seeds exhibited more chlorophyll con- tents, while total phenolics were comparable with those of the control seedlings. The improved starch metabo- lism, greater membrane stability, and increased activity of antioxidants were considered as possible mechanisms responsible for such improvements in emergence and seedling vigor of rice mediated by selenium priming. Priming with selenium (15-60 μmol L −1 ) favored rice emer- gence and seedling growth. Nevertheless, soaking seeds in relatively concentrated (90 and 105 μmol L −1 )s elenium solu- tion had overall detrimental effects.
91 citations
TL;DR: The present results imply that as doping increases, thus subsequently increasing the Ce3+/Ce4+ ratio, antioxidant potential decreases, suggesting that differences in reactivity of CeO2 are due to the ability of Ce to transition between the two valence states and the presence of increased oxygen vacancies, rather than dependent on a specific valence state.
Abstract: Cerium oxide (CeO2) nanoparticles, which are used in a variety of products including solar cells, gas sensors, and catalysts, are expected to increase in industrial use. This will subsequently lead to additional occupational exposures, making toxicology screenings crucial. Previous toxicology studies have presented conflicting results as to the extent of CeO2 toxicity, which is hypothesized to be due to the ability of Ce to exist in both a +3 and +4 valence state. Thus, to study whether valence state and oxygen vacancy concentration are important in CeO2 toxicity, CeO2 nanoparticles were doped with gadolinium to adjust the cation (Ce, Gd) and anion (O) defect states. The hypothesis that doping would increase toxicity and decrease antioxidant abilities as a result of increased oxygen vacancies and inhibition of +3 to +4 transition was tested. Differences in toxicity and reactivity based on valence state were determined in RLE-6TN rat alveolar epithelial and NR8383 rat alveolar macrophage cells using enhanced dark field microscopy, electron paramagnetic resonance (EPR), and annexin V/propidium iodide cell viability stain. Results from EPR indicated that as doping increased, antioxidant potential decreased. Alternatively, doping had no effect on toxicity at 24 h. The present results imply that as doping increases, thus subsequently increasing the Ce3+/Ce4+ ratio, antioxidant potential decreases, suggesting that differences in reactivity of CeO2 are due to the ability of Ce to transition between the two valence states and the presence of increased oxygen vacancies, rather than dependent on a specific valence state.
Electronic supplementary material
The online version of this article (doi:10.1007/s12011-015-0297-4) contains supplementary material, which is available to authorized users.
85 citations
TL;DR: It is indicated that hesperidin and silibinin exert neuroprotective effects against AlCl3-induced cognitive impairment and neurochemical changes, and may be attributed to the impediment of oxido-nitrosative stress and inflammation in the hippocampus.
Abstract: Mounting evidence suggests that long-term aluminum exposure results in severe toxic effects, including neurobehavioral and neurochemical anomalies. The present study was performed to examine the neuroprotective potential of hesperidin and silibinin against aluminum chloride (AlCl3)-induced neurotoxicity in mice. AlCl3 (100 mg/kg/day) was injected daily through oral gavage for 42 days. Concomitantly, hesperidin (50 and 100 mg/kg/day, p.o.) and silibinin (100 and 200 mg/kg/day, p.o.) was administered for 42 days in different groups. The extent of cognitive impairment was assessed by Morris water maze and novel object recognition test on the 43rd day. Neurotoxicity was assessed by measuring oxido-nitrosative stress and proinflammatory cytokines in the hippocampus of mice. Six weeks treatment with AlCl3 caused cognitive impairment as indicated by an increase in the retention latency time and reduction in the percentage of recognition index. AlCl3-treated group showed oxido-nitrosative stress as indicated by increase in the level of lipid peroxidation, nitrite and depleted reduced glutathione, catalase activity in the hippocampus. Moreover, the chronic AlCl3 administration raised the proinflammatory cytokines (interleukin-1β and tumor necrosis factor-α) level and increased acetylcholinesterase activity and reduced the BDNF content in the hippocampus of AlCl3-treated animals. However, chronic treatment with hesperidin and silibinin at higher doses significantly ameliorated the AlCl3-induced cognitive impairment and hippocampal biochemical anomalies. The present study clearly indicated that hesperidin and silibinin exert neuroprotective effects against AlCl3-induced cognitive impairment and neurochemical changes. Amelioration of cognitive impairment may be attributed to the impediment of oxido-nitrosative stress and inflammation in the hippocampus.
82 citations
TL;DR: It is suggested that Cd exposure caused renal injury and that Se ameliorated Cd-induced nephrotoxicity in chickens.
Abstract: The harmful influences of dietary cadmium (Cd) on the chicken kidney and the protective role of selenium (Se) against Cd-induced nephrotoxicity in the chicken are relatively unexplored subjects. The aim of this study was to investigate the ameliorative role of Se on the effects of Cd-induced oxidative stress, endoplasmic reticulum stress, and apoptosis in chicken kidneys. For this study, 100-day-old chickens received Se (as 10 mg Na2SeO3/kg dry weight of diet), Cd (as 150 mg CdCl2/kg dry weight of diet), or Cd + Se in their diets for 60 days. Then, the histopathological changes, Cd and Se contents, levels of oxidative stress, inducible nitric oxide synthase-nitric oxide (iNOS-NO) system activity, levels of endoplasmic reticulum (ER) stress, results of the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay of apoptosis, and expression levels of Bcl-2 and caspase 3 in the kidney were examined. The results showed that Cd exposure caused histopathological and ultrastructural damage and apoptosis of the kidneys. Cd administration significantly increased the accumulation of Cd, the malondialdehyde (MDA) content, NO production, iNOS activity, iNOS expression levels, expression levels of ER stress-related genes (GRP78, GRP94, ATF4, ATF6, and IRE) and the pro-apoptosis gene caspase 3, and the rate of apoptosis. Cd administration markedly decreased the Se content, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, and anti-apoptosis gene Bcl-2 expression levels. Co-treatment with Se and Cd obviously reduced the accumulation of Cd, Cd-induced histopathological and ultrastructural changes, oxidative stress, iNOS-NO system activity, ER stress, caspase 3 expression levels, and the rate of apoptosis in the kidneys. These results suggested that Cd exposure caused renal injury and that Se ameliorated Cd-induced nephrotoxicity in chickens.
78 citations
TL;DR: An optimum response with supplementation of selenium in diet has been found to improve feed intake, body weight gain, feed efficiency, egg production and quality, and antioxidant status in heat-stressed poultry.
Abstract: Heat stress is associated with compromised performance and productivity in poultry due to declines in feed intake, nutrient utilization, growth rate, egg production and quality, and feed efficiency. Emerging evidences have shown that acute heat exposure results in increased production of free radicals and causes oxidative damage to lipids, proteins, and DNA. Additionally, heat stress can influence immune response by changing the expression of cytokines and by making the immune cells more susceptible to oxidative stress. Selenium, as a part of specific selenoproteins, can help to maintain antioxidant defenses, thereby preventing damages to tissues. An optimum response with supplementation of selenium in diet has been found to improve feed intake, body weight gain, feed efficiency, egg production and quality, and antioxidant status in heat-stressed poultry. Selenium compounds are also known to improve immune responses by altering the production of certain cytokines secreted by cells of the immune system and by enhancing the resistance of the immune cells to oxidative stress. It was reported that selenium supplementation had inhibitory effects on tumor necrosis factor alpha levels in heat-stressed broiler chicks, but the details are not completely elucidated. In the present review, the effect of selenium on production performance, nutrient utilization, antioxidative status, and immune responses of heat-stressed poultry is summarized.
76 citations
TL;DR: Serum zinc, magnesium, and selenium levels were significantly decreased with advancement of liver disease as compared to early stage of liver cirrhosis and showed a significant negative correlation with Child-Pugh Score, suggesting that liver dysfunction may alter the metabolism of trace elements.
Abstract: The objectives of this study are to evaluate trace elements in patients with liver cirrhosis and to assess their association with severity of the disease. One hundred fifty cirrhotic subjects of either sex ranging in age from 20-70 years were included in the study, and the results were compared with 50 age- and sex-matched healthy control subjects. All cirrhotic subjects were assessed for severity of disease as mild (Child A), moderate (Child B), and severe (Child C) as per Child-Pugh classification. Routine investigations were done and trace elements (Cu, Zn, Se, and Mg) were analyzed on atomic absorption spectrophotometer. Serum level of copper was found significantly increased in patients with liver cirrhosis as compared to control group. Whereas serum zinc, selenium, and magnesium levels were significantly decreased in cirrhotic subjects as compared to controls. Trace elements were compared with severity of liver cirrhosis. Serum copper concentration was slightly increased in patients with more severe clinical state of liver cirrhosis; however, mean level difference of copper among the Child-Pugh groups were statistically not significant. Moreover, there was no significant correlation between copper and Child-Pugh Score. However, copper showed a significant negative correlation with zinc. Serum zinc, magnesium, and selenium levels were significantly decreased with advancement of liver disease as compared to early stage of liver cirrhosis and showed a significant negative correlation with Child-Pugh Score. Trace element abnormalities may reflect the condition of liver dysfunction. These results suggest that liver dysfunction may alter the metabolism of trace elements. Our study shows that micronutrients status in liver cirrhosis correlates well with severity of liver cirrhosis. Micronutrients supplementation in liver cirrhotic patients may prevent progression of disease and development of complications; however, further research needs to be done.
74 citations
TL;DR: This is the first study indicating that boron containing hydrogel is able to heal burn wounds effectively, and the formulation promoted burn wound healing via complex mechanisms including stimulation of cell migration, growth factor expression, inflammatory response, and vascularization.
Abstract: Burn injuries, the most common and destructive forms of wounds, are generally accompanied with life-threatening infections, inflammation, reduced angiogenesis, inadequate extracellular matrix production, and lack of growth factor stimulation. In the current study, a new antimicrobial carbopol-based hydrogel formulated with boron and pluronic block copolymers was evaluated for its healing activity using in vitro cell culture techniques and an experimental burn model. Cell viability, gene expression, and wound healing assays showed that gel formulation increased wound healing potential. In vitro tube-like structure formation and histopathological examinations revealed that gel not only increased wound closure by fibroblastic cell activity, but also induced vascularization process. Moreover, gel formulation exerted remarkable antimicrobial effects against bacteria, yeast, and fungi. Migration, angiogenesis, and contraction-related protein expressions including collagen, α-smooth muscle actin, transforming growth factor-β1, vimentin, and vascular endothelial growth factor were considerably enhanced in gel-treated groups. Macrophage-specific antigen showed an oscillating expression at the burn wounds, indicating the role of initial macrophage migration to the wound site and reduced inflammation phase. This is the first study indicating that boron containing hydrogel is able to heal burn wounds effectively. The formulation promoted burn wound healing via complex mechanisms including stimulation of cell migration, growth factor expression, inflammatory response, and vascularization.
72 citations
TL;DR: The evidence for the pharmacological mechanism of Cr(III)’s ability to increase insulin sensitivity by acting as a second messenger is reviewed, and proposals for testing this hypothesis are described.
Abstract: Although recent studies have shown that chromium (as the trivalent ion) is not an essential trace element, it has been demonstrated to generate beneficial effects at pharmacologically relevant doses on insulin sensitivity and cholesterol levels of rodent models of insulin insensitivity, including models of type 2 diabetes. The mode of action of Cr(III) at a molecular level is still an area of active debate; however, the movement of Cr(III) in the body, particularly in response to changes in insulin concentration, suggests that Cr(III) could act as a second messenger, amplifying insulin signaling. The evidence for the pharmacological mechanism of Cr(III)’s ability to increase insulin sensitivity by acting as a second messenger is reviewed, and proposals for testing this hypothesis are described.
70 citations
TL;DR: Prior and coadministration of curcumin with LA for 7 days significantly improved the ameliorated changes in liver and kidney, immunoglobulins, and mRNA expression, and the potential of curCumin to counteract the immunosuppressive alteration in gene expression as well as hepatic and renal damage occurred after Pb2+ intoxication.
Abstract: Lead (Pb2+) toxicity is the most common form of heavy metal intoxication in humans and animals. Therefore, the current study was conducted to evaluate the potential ameliorative effects of curcumin on lead acetate (LA)-induced deleterious effects in the liver and kidney. Forty male Wistar rats were divided into four equal groups; first group was used as a control and given both corn oil orally and vehicle of lead acetate intraperitoneally (i.p). Groups from 2–4 were treated with lead acetate (LA; 50 mg/kg BW i.p), curcumin (200 mg/kg BW orally), and curcumin plus lead acetate, respectively. Curcumin was administered 3 weeks before LA injection for 7 days. Pb2+-intoxicated rats have higher Pb2+ levels compared to other treated groups. Results revealed that lead acetate significantly increased the serum levels of hepatic transaminases (GPT and GOT), urea and creatinine, while albumin was significantly decreased. In parallel, serum IgG, IgM, and IgA were significantly decreased in LA-injected rats. LA groups showed decrease in messenger RNA (mRNA) expression of catalase, SOD, GST, GPx, and alpha-1 acid glycoprotein (AGP), while the gene expression of desmin, vimentin, transforming growth factor-β1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1), and alpha-2 macroglobulin (α-2M) was increased. Prior and coadministration of curcumin with LA for 7 days significantly improved the ameliorated changes in liver and kidney, immunoglobulins, and mRNA expression. Moreover, curcumin ameliorated LA-induced congestion of hepatic and renal blood vessels and decreased fibrous tissue proliferation and necrosis of hepatocytes. In the kidney, LA-induced degeneration in tubular epithelium and intraluminal hyaline casts and prior curcumin administration restored normal renal structure with mild congestion of renal blood vessels. The results clarify the potential of curcumin to counteract the immunosuppressive alteration in gene expression as well as hepatic and renal damage occurred after Pb2+ intoxication.
69 citations
TL;DR: It is suggested that chronic exposure to fluoride causes damages to liver histopathology and leads to liver apoptosis through caspase-mediated pathways.
Abstract: Fluoride compounds are abundant and widely distributed in the environment at a variety of concentrations. Further, fluoride induces toxic effects in target organs such as the liver. In this study, we investigated liver histopathology, DNA damage, apoptosis, and the mRNA and protein expressions of caspase-3 and −9 in the rat livers by administering varying concentrations of fluoride (0, 50, 100, 200 mg/L ) for 120 days. The results showed fluoride-induced morphological changes and significantly increased apoptosis and DNA damage in rats exposed to fluoride, especially in response to higher doses. The immunohistochemical and qRT-PCR results indicated that caspase-3, caspase-9 protein positive expression and mRNA relative expression enhanced with increasing NaF concentration. In summary, our findings suggest that chronic exposure to fluoride causes damages to liver histopathology and leads to liver apoptosis through caspase-mediated pathways.
TL;DR: This work addresses putative biomarkers, which may assist in assessing the onset of neurological diseases associated with exposure to this metal mixture, and builds upon their shared mechanisms of toxicity.
Abstract: The increasing exposure of human populations to excessive levels of metals continues to represent a matter of public health concern. Several biomarkers have been studied and proposed for the detection of adverse health effects induced by lead (Pb), arsenic (As), and manganese (Mn); however, these studies have relied on exposures to each single metal, which fails to replicate real-life exposure scenarios. These three metals are commonly detected in different environmental, occupational, and food contexts and they share common neurotoxic effects, which are progressive and once clinically apparent may be irreversible. Thus, chronic exposure to low levels of a mixture of these metals may represent an additive risk of toxicity. Building upon their shared mechanisms of toxicity, such as oxidative stress, interference with neurotransmitters, and effects on the hematopoietic system, we address putative biomarkers, which may assist in assessing the onset of neurological diseases associated with exposure to this metal mixture.
TL;DR: The results of the association between metal levels and hormone levels indicated that Ni, Cu, and Zn may play a role in the pathogenesis of PCOS related with reproductive hormone levels.
Abstract: To investigate the serum concentrations of 11 heavy metals and trace elements in patients with polycystic ovary syndrome (PCOS). A total of 369 women (including 96 patients with PCOS) were studied. No differences with statistical significance in the median barium, cadmium, lead, arsenic, chromium, gallium, strontium, and vanadium concentrations were observed between the patients with PCOS and the control group. Serum nickel (Ni) (P = 0.000) and copper (Cu) (P = 0.000) levels were significantly higher, but zinc (Zn) levels (P = 0.009) were significantly lower in patients with PCOS compared with the control group. The results of the association between metal levels and hormone levels indicated that Ni, Cu, and Zn may play a role in the pathogenesis of PCOS related with reproductive hormone levels. The findings in the present study should be investigated with further trials in order to obtain new insights into PCOS.
TL;DR: It appears that this combination of CeO2 and/or Y2O3 nanoparticles may potentially be beneficial for protection against lead-caused acute toxicity in the brain through improving the oxidative stress-mediated programmed cell death pathway.
Abstract: Due to numerous industrial applications, lead has caused widespread pollution in the environment; it seems that the central nervous system (CNS) is the main target for lead in the human body. Oxidative stress and programmed cell death in the CNS have been assumed as two mechanisms related to neurotoxicity of lead. Cerium oxide (CeO2) and yttrium oxide (Y2O3) nanoparticles have recently shown antioxidant effects, particularly when used together, through scavenging the amount of reactive oxygen species (ROS) required for cell apoptosis. We looked into the neuroprotective effects of the combinations of these nanoparticles against acute lead-induced neurotoxicity in rat hippocampus. We used five groups in this study: control, lead, CeO2 nanoparticles + lead, Y2O3 nanoparticles + lead, and CeO2 and Y2O3 nanoparticles + lead. Nanoparticles of CeO2 (1000 mg/kg) and Y2O3 (230 mg/kg) were administered intraperitoneally during 2 days prior to intraperitoneal injection of the lead (25 mg/kg for 3 days). At the end of the treatments, oxidative stress markers, antioxidant enzymes activity, and apoptosis indexes were investigated. The results demonstrated that pretreatments with CeO2 and/or Y2O3 nanoparticles recovered lead-caused oxidative stress markers (ROS, lipid peroxidation, and total thiol molecules) and apoptosis indexes (Bax/Bcl-2 and caspase-3 protein expression). Besides, these nanoparticles reduced the activities of lead-induced superoxide dismutase and catalase as well as the ADP/ATP ratio. Interestingly, the best recovery resulted from the compound of these nanoparticles. Based on these outcomes, it appears that this combination may potentially be beneficial for protection against lead-caused acute toxicity in the brain through improving the oxidative stress-mediated programmed cell death pathway.
TL;DR: The results of present study indicate that arsenic- induced disturbed mitochondrial metabolism, decreased removal of ROS, decrease in protein synthesis, and altered membrane lipid polarity and fluidity may be responsible for the mitochondrial oxidative damage in rat brain that may further be implicated as contributing factor in arsenic-induced neurodegeneration.
Abstract: Oxidative stress is associated with the generation of reactive oxygen species (ROS), which is supposed to be one of the mechanisms of arsenic-induced neurodegeneration. Mitochondria, being the major source of ROS generation may present an important target of arsenic-mediated neurotoxicity. Hence, we planned the study to elucidate the possible biochemical and molecular alterations induced by arsenic exposure in rat brain mitochondria. Chronic sodium arsenite treatment (25 ppm for 12 weeks) resulted in decreased activity of mitochondrial complexes I, II, and IV followed by increased ROS generation. There was decrease in mitochondrial superoxide dismutase (MnSOD) activity in arsenic-treated rat brain further showing increased superoxide radical generation in mitochondria. The decrease in MnSOD activity might be responsible for the increased protein and lipid oxidation as observed in our study. Protein and messenger RNA (mRNA) levels of MnSOD and mitochondrial uncoupling protein 2 (UCP-2) were downregulated suggesting decreased removal of ROS in rat brain. Fourier transform infrared (FTIR) spectroscopy analysis revealed significant decrease in amide A, amide I, amide II, and Olefinic = CH stretching band area suggesting molecular alteration in proteins and lipids after arsenic treatment. The results of present study indicate that arsenic-induced disturbed mitochondrial metabolism, decreased removal of ROS, decrease in protein synthesis, and altered membrane lipid polarity and fluidity may be responsible for the mitochondrial oxidative damage in rat brain that may further be implicated as contributing factor in arsenic-induced neurodegeneration.
TL;DR: The aim of the present study was to determine the levels of metals in blood as well as the specific porphyrin levels in the urine of patients with autism spectrum disorder (ASD) compared with patients with other neurological disorders.
Abstract: The aim of the present study was to determine the levels of metals in blood (zinc (Zn), copper (Cu), aluminium (Al), lead (Pb) and mercury (Hg)), as well as the specific porphyrin levels in the urine of patients with autism spectrum disorder (ASD) compared with patients with other neurological disorders. The study was performed in a group of children with ASD (N = 52, average age = 6.2 years) and a control group of children with other neurological disorders (N = 22, average age = 6.6 years), matched in terms of intellectual abilities (Mann-Whitney U = 565.0, p = 0.595). Measurement of metals in blood was performed by atomic absorption spectrometry, while the HPLC method via a fluorescence detector was used to test urinary porphyrin levels. Results were compared across groups using a multivariate analysis of covariance (MANCOVA). In addition, a generalized linear model was used to establish the impact of group membership on the blood Cu/Zn ratio. In terms of blood levels of metals, no significant difference between the groups was found. However, compared to the control group, ASD group had significantly elevated blood Cu/Zn ratio (Wald χ
2 = 6.6, df = 1, p = 0.010). Additionally, no significant difference between the groups was found in terms of uroporphyrin I, heptacarboxyporphyrin I, hexacarboxyporphyrin and pentacarboxyporphyrin I. However, the levels of coproporphyrin I and coproporphyrin III were lower in the ASD group compared to the controls. Due to observed higher Cu/Zn ratio, it is suggested to test blood levels of Zn and Cu in all autistic children and give them a Zn supplement if needed.
TL;DR: This meta-analysis supports a significant association between serum levels of Se, Cu, and Mg with thyroid cancer, however, the subgroup analysis found that there was significant effect modification ofSe, Cu levels by ethnic, like China and Poland.
Abstract: There are conflicting reports on the correlation between serum levels of selenium (Se), copper (Cu), and magnesium (Mg) with thyroid cancer. The purpose of the present study is to clarify the association between Se, Cu, and Mg levels with thyroid cancer using a meta-analysis approach. We searched articles indexed in PubMed published as of January 2015 that met our predefined criteria. Eight eligible articles involving 1291 subjects were identified. Overall, pooled analysis indicated that subjects with thyroid cancer had lower serum levels of Se and Mg, but higher levels of Cu than the healthy controls [Se: standardized mean difference (SMD) = −0.485, 95% confidence interval (95%CI) = (−0.878, −0.092), p = 0.016; Cu: SMD = 2.372, 95%CI = (0.945, 3.799), p = 0.001; Mg: SMD = −0.795, 95%CI = (−1.092, −0.498), p < 0.001]. Further subgroup analysis found lower serum levels of Se in thyroid cancer in Norway [SMD = −0.410, 95%CI = (−0.758, −0.062), p = 0.021] and Austria [SMD = −0.549, 95%CI = (−0.743, −0.355), p < 0.001], but not in Poland (SMD = −0.417, 95%CI = (−1.724, 0.891), p = 0.532]. Further subgroup analysis also found that patients with thyroid cancer had higher serum levels of Cu in China [SMD = 1.571, 95%CI = (1.121, 2.020), p < 0.001] and Turkey [SMD = 0.977, 95%CI = (0.521, 1.432), p < 0.001], but not in Poland [SMD = 3.471, 95%CI = (−0.056, 6.997], p = 0.054]. In conclusion, this meta-analysis supports a significant association between serum levels of Se, Cu, and Mg with thyroid cancer. However, the subgroup analysis found that there was significant effect modification of Se, Cu levels by ethnic, like China and Poland. Thus, this finding needs further confirmation by a trans-regional multicenter study to obtain better understanding of causal relationship between Se, Cu, and Mg with thyroid cancer of different human races or regions.
TL;DR: It is demonstrated that dietary supplementation of an organic Mn, Zn, Cu, and Cr mixture increases the bioavailability of Mn and Zn compared with inorganic sources and that a lower level of trace mineral supplementation results in lower mineral excretion, particularly in an organic form.
Abstract: In the present study, the effects of dietary supplementation of organic and inorganic Mn, Zn, Cu, and Cr mixtures using two different levels (80, 60, 5, and 0.15 mg/kg and 40, 30, 2.5, and 0.07 mg/kg, respectively) on the bioavailability of these trace minerals and Ca in late-phase laying hens were evaluated. Three hundred and sixty laying hens (Barred Rock) at 50 weeks of age were used, and the duration of study was 16 weeks. Each of the four dietary regimes was randomly assigned to six replicates, which included 15 hens each. Organic trace minerals were provided as methionine chelates; inorganic Mn, Zn, and Cr were provided as oxides; and Cu was provided as sulfate. The organic form significantly increased the concentrations of serum Mn, Zn, Cu, and Ca; egg Mn, Zn, Cu, and Cr; and eggshell Zn and Cr compared with the inorganic form. However, the form of trace minerals did not affect the concentrations of serum Cr and eggshell Mn, Cu, and Ca. High-level addition of trace minerals significantly increased serum Mn and Zn; egg Mn, Zn, Cu, and Cr; and eggshell Mn, Zn, and Cu concentrations compared with low-level addition but did not affect serum Cu, Cr, and Ca or eggshell Cr and Ca concentrations. While the organic form reduced the excretion of Mn, Zn, Cu, Cr, and Ca, the high-level supplement increased Mn, Zn, and Cu excretion. The addition level did not affect Cr and Ca excretion. These results demonstrate that dietary supplementation of an organic Mn, Zn, Cu, and Cr mixture increases the bioavailability of Mn, Zn, Cu, Cr, and Ca compared with inorganic sources and that a lower level of trace mineral supplementation results in lower mineral excretion, particularly in an organic form.
TL;DR: The results indicated that Se deficiency induced oxidative damage in the intestinal tracts of chickens and that low levels of GSH-Px and high contents of NO may exert a major role in the injury of the intestinal tract induced by Se deficiency.
Abstract: Nitric oxide (NO) is an essential messenger molecule and is associated with inflammation and oxidative stress. Although NO has important biological functions in mammals, its role in the mechanism that occurs after intestinal injuries in chickens remains unknown. The objective of the present study was to investigate the real role of NO and oxidative stress in the intestinal injuries of chickens induced by selenium (Se) deficiency. A total 150 chickens were randomly divided into the following two groups: a low-Se group (L group, fed a Se-deficient diet containing 0.020 mg/kg Se) and a control group (C group, fed a commercial diet containing 0.2 mg/kg Se). The activities and mRNA levels of glutathione peroxidase (GSH-Px), the production of glutathione (GSH) and NO, and the protein and mRNA levels of inducible nitric oxide synthase (iNOS) were examined in the intestinal tissues (duodenum, jejunum, and rectum) at 15, 25, 35, 45, and 55 days. Methane dicarboxylic aldehyde (MDA) levels were also detected by assay kits. Then, the morphologies of the tissues were observed under the microscope after hematoxylin and eosin staining (H&E staining). The results showed that Se deficiency induced higher inflammatory damage and MDA levels (P < 0.05), which were accompanied by higher levels of iNOS and NO but lower levels of GSH and GSH-Px (P < 0.05). Our results indicated that Se deficiency induced oxidative damage in the intestinal tracts of chickens and that low levels of GSH-Px and high contents of NO may exert a major role in the injury of the intestinal tract induced by Se deficiency.
TL;DR: It is suggested that increased serum level of Cu and decreased serumlevel of Zn are generally present in RA patients, and ethnicity had influence on the serum level in RA and healthy controls.
Abstract: Many publications with conflicting results have evaluated serum levels of copper (Cu) and zinc (Zn) in patients with rheumatoid arthritis (RA). To derive a more precise estimation of the relationship, a meta-analysis was conducted. Relevant published data were retrieved through PubMed, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical Database (CBM) before September 20, 2014. Weighted mean difference (WMD) with a 95 % confidence interval (95 % CI) was calculated using STATA 11.0. A total of 26 studies, including 1444 RA cases and 1241 healthy controls, were collected in this meta-analysis. Pooled analysis found that patients with RA had a higher serum level of Cu and a lower serum Zn level than the healthy controls (Cu (μg/dl), WMD = 31.824, 95 % CI = 20.334, 43.314; Zn (μg/dl), WMD = −12.683, 95 % CI = −19.783, −5.584). Subgroup analysis showed that ethnicity had influence on the serum level of Cu (μg/dl) (Caucasian, WMD = 43.907, 95 % CI = 35.090, 52.723, P < 0.001; Asian, WMD = 14.545, 95 % CI = −12.365, 41.455, P = 0.289) and Zn (μg/dl) (Caucasian, WMD = −11.038, 95 % CI = −23.420, 1.344, P = 0.081; Asian, WMD = −14.179, 95 % CI = −18.963, −9.394, P < 0.001) in RA and healthy controls. No evidence of publication bias was observed. This meta-analysis suggests that increased serum level of Cu and decreased serum level of Zn are generally present in RA patients.
TL;DR: Oral exposure to Ag-NPs produced changes in blood chemistry and hepatotoxicity as indicated by increased serum activity levels of both AST and ALT and histological damages to the liver with no significant changes between male and female mice.
Abstract: This research was carried out to evaluate toxic effects of nanosilver (Ag-NPs) on liver function and some blood parameters of male and female mice Mus musculus. A group of 54 BALB/c mice was randomly divided into three groups (each with two replications): Ag-NP (2) and control (1), each with nine mice. The experiment lasted for 14 days. In the treatment groups, two different doses of 20 and 50 ppm of Ag-NP solution were administered orally, while in the untreated (control) group, no Ag-NP solution but distilled water was used. At the end of the experiment, the serum was obtained by centrifugation of the whole blood at 3000 rpm for 15 min. The biochemical levels including alanine aminotransferase (ALT), aspartate amino transferase (AST), and blood cells were assayed by an automatic biochemical analyzer. Also, liver biopsy was performed and samples were stained using hematoxylin and eosin (H&E) staining. The values of red blood cells (RBC), hemoglobin (Hb), and hematocrit (Hct) did not vary significantly in the control and Ag-NP-treated animals. There were significant changes in the treatment and control groups in the levels of liver enzymes so that at both doses, there were significantly elevated levels of ALT and AST in mice treated with Ag-NPs compared with the control (p < 0.05). Sexuality was not significantly involved in the results. Oral exposure to Ag-NPs produced changes in blood chemistry and hepatotoxicity as indicated by increased serum activity levels of both AST and ALT and histological damages to the liver with no significant changes between male and female mice.
TL;DR: Curc appeared to be a promising agent for protection against Pb2+-induced toxicity and marked histo-cytological alterations in the renal cortex.
Abstract: This study aims to evaluate the protective role of curcumin (Curc) against hematological and biochemical changes, as well as renal pathologies induced by lead acetate [Pb (CH3COO)2·3H2O] treatment. Male albino rats were intraperitoneally treated with Pb2+ (25 mg of lead acetate/kg b.w., once a day) alone or in combination with Curc (30 mg of Curc/kg b.w., twice a day) for 7 days. Exposure of rats to Pb2+ caused significant decreases in hemoglobin (Hb) content, hematocrit (Ht) value, and platelet (Plt) count, while Pb2+-related leukocytosis was accompanied by absolute neutrophilia, monocytosis, lymphopenia, and eosinopenia. A significant rise in lipid peroxidation (LPO) and a marked drop of total antioxidant capacity (TAC) were evident in the kidney, liver, and serum of Pb2+ group compared to that of control. Furthermore, significantly high levels of total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C), and a sharp drop in serum high-density lipoprotein (HDL-C) level were also seen in blood after injection of Pb2+. Additionally, hepatorenal function tests were enhanced. Meanwhile, Pb2+ produced marked histo-cytological alterations in the renal cortex. Co-administration of Curc to the Pb2+-treated animals restored most of the parameters mentioned above to near-normal levels/features. In conclusion, Curc appeared to be a promising agent for protection against Pb2+-induced toxicity.
TL;DR: Se deficiency results in significant changes in the expression of selenoproteins, which may cause oxidative stress in the chicken thymus tissue, and immunological changes and immune stress may occur because of Se deficiency in theChicken Thymus.
Abstract: Selenoproteins and selenium (Se) play important roles in the immune system. Selenoprotein expression in the immune system of mammals is sensitive to dietary Se levels; however, little is known about the expression of selenoproteins and their immune functions in the chicken thymus. We assessed selenoprotein gene expression and cytokine content in the chicken thymus in this study. The animals were randomly assigned to two groups as follows: the Se-deficient group (L group) was fed a diet containing 0.033 mg Se/Kg, and the control group was fed the same basal diet supplemented with Se at 0.15 mg/kg (sodium selenite). Real-time qPCR was used to investigate the expression level of selenoproteins on days 15, 25, 35, 45, and 55, and ELISA was used to evaluate the cytokine content on days 15, 35, and 55. The messenger RNA (mRNA) levels of Txnrd1, Txnrd2, Txnrd3, Dio1, Dio2, Dio3, GPx1, GPx2, GPx3, Gpx4, Sepp1, Selo, Sep15, Sepx1, Sels, Seli, Selu, Selh, and SPS2 were all significantly decreased (P < 0.05) in the L group compared to the control group. A significant decrease in IL-2, IL-10, IL-17, IL-1β, IFN-α, and IFN-β was observed in the L group, and there was also a significant increase in IL-6, IL-8, IFN-γ, and TNF-α in the L group. In summary, Se deficiency results in significant changes in the expression of selenoproteins, which may cause oxidative stress in the chicken thymus tissue. Moreover, immunological changes and immune stress may occur because of Se deficiency in the chicken thymus.
TL;DR: It is suggested that NaF-induced H9c2 cell apoptosis is mediated by direct increased intracellular ROS and downregulated ΔΨm.
Abstract: Chronic excessive fluoride intake is known to be toxic, and effects of long-term fluorosis on different organ systems have been examined However, there are few studies about the effects of fluorosis on cardiovascular systems Here, we studied the fluoride-induced apoptosis in H9c2 cells and determined the underlying molecular mechanisms including the cell viability, intracellular reactive oxygen species (ROS) level, the changes of mitochondrial membrane potential (ΔΨm), and the cell apoptosis Sodium fluoride (NaF) at concentrations of 0, 2, 4, 8, and 16 mg/L was administered to cultured H9c2 cells for up to 48 h After the treatment, H9c2 cells were collected and the associated parameters were measured by flow cytometry Our study found that fluoride not only inhibited H9c2 cell proliferation but also induced cell apoptosis With the increment of NaF concentration, the apoptotic rates and ROS generation were increased, while the ΔΨm was decreased In summary, these data suggested that NaF-induced H9c2 cell apoptosis is mediated by direct increased intracellular ROS and downregulated ΔΨm
TL;DR: The overall data indicated that selenium exerts a potent protective effect against AFB1-induced hepatic mitochondrial damage, possibly through its antioxidant activity.
Abstract: Aflatoxin B1 (AFB1) is a mycotoxin that causes cytotoxicity through oxidative damage to its target organs. The liver is the first target of AFB1 damage. The aim of this study was to evaluate the protective effect of selenium on AFB1-induced hepatic mitochondrial damage in ducklings using molecular biological and histopathological techniques. Aflatoxin was administered via intragastric intubation (0.1 mg/kg body weight), daily for 21 days. The experimental group also received intragastric sodium selenite (1 mg/kg body weight), while the control group was given the same volume of dimethyl sulfoxide (DMSO). Sequence analysis of the mitochondrial DNA D-loop region showed that AFB1 induced damage. All AFB1-administrated ducklings were identified as having D-loop mitochondrial DNA mutations. Mutations were detected in two ducklings that had received both AFB1 and selenium. Mitochondrial swelling assays showed that opening of the mitochondrial permeability transition pores was increased in ducklings that had received AFB1 for 14 and 21 days (P < 0.05). Selenium significantly attenuated these adverse effects of AFB1. After AFB1 exposure, histological alterations were observed, including fat necrosis, steatosis, and formation of lymphoid nodules with infiltrated lymphocytes. These histological abnormalities were also attenuated by treatment with selenium. The overall data indicated that selenium exerts a potent protective effect against AFB1-induced hepatic mitochondrial damage, possibly through its antioxidant activity.
TL;DR: It was showed that iron deficiency is associated with increased levels of blood manganese and cadmium, but not blood lead, in Ohio residents and these metals showed different toxicokinetics in relation to age, sex, and menopausal status despite similar relationships between ferritin and metal concentrations.
Abstract: The objectives of this study were to assess ferritin-specific profiles of blood metal concentrations such as manganese, lead, and cadmium and to evaluate whether ferritin may affect the behavior of the blood metals in relation to menstruation, menopause, or sex in Ohio residents. Recruited participants included residents from Marietta, East Liverpool, and Mt. Vernon, OH, USA, who were aged 30–75 years and lived at least 10 years in their respective town. The levels of the neurotoxic metals such as manganese, cadmium, and lead were assayed in whole blood. Serum was analyzed for ferritin level [as a biomarker of iron (Fe) status]. An association between blood metal concentrations and independent variables (age, serum ferritin, manganese exposure status, and sex) by multiple regression analysis was assessed, controlling for various covariates such as BMI, educational level, smoking, and alcohol drinking status. Overall, the geometric means of blood manganese, cadmium, and lead levels of all participants (n = 276) were 9.307 μg/L, 0.393 μg/L, and 1.276 μg/dL, respectively. Log serum ferritin concentrations were inversely associated with log blood manganese concentration (β = −0.061 log ferritin and β = 0.146 categorical ferritin) and log blood cadmium concentrations (β = −0.090 log ferritin and β = 0.256 categorical ferritin). Log serum ferritin concentrations were not associated with log blood lead concentrations. Variables of age, sex, and exposure status were not associated with log manganese concentrations; however, log blood cadmium concentrations were higher in older population, women, and smokers. Log blood lead concentrations were higher in older population, men, and postmenopausal women. Our study showed that iron deficiency is associated with increased levels of blood manganese and cadmium, but not blood lead, in Ohio residents. These metals showed different toxicokinetics in relation to age, sex, and menopausal status despite similar relationships between ferritin and metal concentrations.
TL;DR: It is suggested that sodium selenite supplied in the diet could effectively inhibit AFB1-induced apoptosis and cell cycle blockage in renal cells of broiler.
Abstract: The aim of the study was to investigate the competency of selenium (Se) in counteracting the adverse effects of aflatoxin B1 (AFB1) on apoptosis, cell cycle, and proliferation of nephritic cells. Two hundred forty 1-day-old healthy male avian broilers were randomly divided into four groups and fed basal diet (control group), 0.3 mg/kg AFB1 diet (AFB1 group), 0.4 mg/kg Se diet (+Se group), and 0.3 mg/kg AFB1 + 0.4 mg/kg Se diet (AFB1 + Se group), respectively. Compared to the control group, the number of apoptotic renal cells and expressions of Bax and caspase-3 messenger RNA (mRNA) were significantly increased, while the expression of Bcl-2 was significantly decreased in the AFB1 and the +Se groups (p < 0.01). A significantly decreased proliferating cell nuclear antigen (PCNA) expression and arrested G0/G1 phases of the cell cycle were also seen in the AFB1 and the +Se groups when compared with those of the control group. Moreover, these parameters were restored to the control group levels in the AFB1 + Se group. These results suggested that sodium selenite supplied in the diet could effectively inhibit AFB1-induced apoptosis and cell cycle blockage in renal cells of broiler.
TL;DR: The intraperitoneal injection of 15 mg/kg of K2Cr2O7, that is able to induce hepatotoxicity, was unable to induce histological and oxidative damage in other target organs, and curcumin was safe.
Abstract: Hexavalent chromium [Cr(VI)] compounds are extremely toxic and carcinogenic. Despite the vast quantity of reports about Cr(VI) toxicity, the information regarding its effects when it is intraperitoneally (i.p.) administered is still limited. In contrast, it has been shown that curcumin prevents hepatotoxicity induced by a single intraperitoneal injection of 15 mg/kg body weight (b.w.) of potassium dichromate (K2Cr2O7). This study aims to evaluate oxidative stress markers, the activity of antioxidant enzymes, and the potential histological injury in brain, heart, lung, kidney, spleen, pancreas, stomach, and intestine from rats treated with a hepatotoxic dose of K2Cr2O7 (15 mg/kg b.w.), and the effect of curcumin pretreatment. Rats were divided into four groups: control, curcumin, K2Cr2O7, and curcumin+K2Cr2O7. At the end of the treatment, plasma and ascites fluid were collected and target organs were dissected out for biochemical and histological analysis. K2Cr2O7 induced hepatotoxicity but failed to induce in all the other studied organs either oxidative or histological injury, since levels of malondialdehyde (MDA), glutathione (GSH), and the activity of superoxide dismutase (SOD), catalase (CAT), and related GSH enzymes were unchanged. As expected, curcumin was safe. Lack of K2Cr2O7-induced toxicity in those target organs could be due to the following: (1) route of administration, (2) absorption through the portal circulation, (3) lower dose than needed, (4) short time of exposure, or (5) repeated doses are required to produce damage. Thus, the intraperitoneal injection of 15 mg/kg of K2Cr2O7, that is able to induce hepatotoxicity, was unable to induce histological and oxidative damage in other target organs.
TL;DR: Investigating the effect of acute heat stress on the chicken immune response and the role of selenium and the polysaccharides of Atractylodes macrocephala Koidz (PAMK) in immune regulation showed that Se specifically regulated the TNF-α and IFN-γ pathways.
Abstract: The aim of the present study was to investigate the effect of acute heat stress (HS) on the chicken immune response and to examine the role of selenium (Se) and the polysaccharides of Atractylodes macrocephala Koidz (PAMK) in immune regulation in the chicken immune system. Two hundred chickens were randomly divided into two groups: the HS group and the control (Con) group. These chickens were treated with Se (0.3 mg/kg), PAMK (200 mg/kg) alone, and a combination of Se (0.3 mg/kg) and PAMK (200 mg/kg). The cytokines; antioxidative enzymes; and HSP60, HSP70, and HSP90 levels were examined in chicken immune organs. The results indicated that HS-induced immune dysfunction included increased levels of TNF-α, IFN-γ, IL-2, IL-4, HSP60, HSP70, HSP90, and malondialdehyde (MDA) as well as decreased levels of glutathione peroxidase (GPx) and superoxide dismutase (SOD) in immune organs (P < 0.05). Among the affected organs, the bursa of Fabricius was one primary target of HS. The immune dysfunction induced by HS was alleviated (P < 0.05 or not) by treatment with Se and PAMK in different immune organs. However, Se only regulated the expression of TNF-α and IFN-γ, and PAMK influenced more cytokines in immune organs. The results showed that Se specifically regulated the TNF-α and IFN-γ pathways. Therefore, Se and PAMK played different roles in improving the immune response in HS chicken.
TL;DR: The results show that ascorbic acid supplementation with F and CPF prevents or diminishes the hepatic damage in rats co-exposed to toxicants and may act as a putative protective agent against toxicant-induced liver tissue injury.
Abstract: The aim of the study was to investigate the ameliorative properties of ascorbic acid against the subchronic effect of co-exposure of fluoride (F) and chlorpyrifos (CPF) on oxidative damage markers such as lipid peroxidation (MDA) and antioxidant defense system in the liver of adult Wistar rats. The animal groups were provided with either vehicle or ascorbic acid (60 mg/kg, b.w.) or NOAEL dose of fluoride (1 ppm) or CPF (1 mg/kg, b.w.) or ten times of such doses orally alone and in combination or pre-treated with ascorbic acid along with co-exposure of F and CPF every consecutive day for 28 days. Hepatic damage marker analysis in blood revealed that aspartate and alanine aminotransferases, alkaline phosphatase, and lactate dehydrogenase were significantly (P < 0.05) increased with single or combined exposure of F or CPF at either dose levels. Significant increased oxidative damage of hepatocytes as indicated by increased MDA levels with decrease in tissue ascorbate and free radical scavenging enzymes like catalase, superoxide dismutase, and glutathione peroxidase was observed in groups treated with either F or CPF as well as in combinedly treated animals as compared to control animals. Supplementation of ascorbic acid restored the hepatic specific marker enzymes in blood following co-exposure of F and CPF at lower doses which were otherwise increased in the F and CPF co-exposed rats. The results show that ascorbic acid supplementation with F and CPF prevents or diminishes the hepatic damage in rats co-exposed to toxicants and may act as a putative protective agent against toxicant-induced liver tissue injury.