Effects of Fluoride on Synaptic Membrane Fluidity and PSD-95 Expression Level in Rat Hippocampus

The objective of this study is to investigate the neurotoxicity of drinking water fluorosis on rat hippocampus. Just weaning male Sprague–Dawley rats were randomly divided into four groups and given 15, 30, and 60 mg/L NaF solution and distilled water, respectively, for 9 months. The fluidity of brain synaptic membrane and expression level of postsynaptic density 95 (PSD-95) were tested. Results showed that the fluidity of brain synaptic membrane decreased gradually with increasing of fluoride concentration, and it was significantly decreased (P < 0.05) in moderate-fluoride group compared with control group, and expression level of PSD-95 was significantly decreased (P < 0.01) in moderate-fluoride group when compared with that of control group. These results indicate that decrease of synaptic membrane fluidity and PSD-95 expression level may be the molecular basis of central nervous system damage caused by fluoride intoxication; PSD-95 in CA3 region of hippocampus is probably a target molecule for fluoride.     

The MMP-9/TIMP-1 System is Involved in Fluoride-Induced Reproductive Dysfunctions in Female Mice

A total of 84 healthy female mice were kept with various concentrations of sodium fluoride (F) (0, 50, 100, 150 mg F^?/L in drinking water for 90 days) and were then mated with healthy male mice for 1 week to study the effect of excessive fluoride on female reproductive function, particularly in embryo implantation. The rate of pregnancy, litter size, and the birth weight of female mice were evaluated. Ultrastructural changes of uteri tissues were observed by transmission electron microscopy (TEM). The mRNA expression levels of MMP-9 and TIMP-1 were determined by quantitative real-time PCR. The protein expression levels of MMP-9 and TIMP-1 were analyzed by western blotting. Results showed a significant decrease of litter size in mice exposed to fluoride. TEM images of uteri tissue of mice that underwent a 150 mg/L F^? treatment for 90 days showed a vague nucleus, reduced microvilli, increased lysosomes, a dilated endoplasmic reticulum, and a vacuolization mitochondrion when compared with the control group. Following the damage of the structure, the expression levels of MMP-9 and TIMP-1 in uteri tissues were significantly unregulated in the F 150 group. These results show that MMP-9/TIMP-1 system disturbance and changes of histological structure in uteri tissue are involved in fluoride-induced reproductive dysfunctions.     

Influence of Different Amounts and Sources of Selenium Supplementation on Performance, Some Blood Parameters, and Nutrient Digestibility in Lambs

Two trials were conducted in a 2?×?2?+?1 factorial arrangement based on a completely randomized design to evaluate the effects of different sources of selenium (Se) on performance, blood metabolites, and nutrient digestibility in male lambs on a barley-based diet. The first trial lasted for 70 days and consisted of 30 lambs (35.6?±?2.6 kg mean body weight, about 4–5 months of age) which were randomly allotted to five treatments including: (1) basal diet (containing 0.06 mg Se/kg DM; control) without supplementary Se, (2) basal diet?+?0.20 mg/kg Se as sodium selenite (SeS 0.20), (3) basal diet?+?0.40 mg/kg Se as sodium selenite (SeS 0.40), (4) basal diet?+?0.20 mg/kg Se as selenium yeast (SeY 0.20), and (5) basal diet?+?0.40 mg/kg Se as selenium yeast (SeY 0.40). For the second trial, four lambs from each group of experiment 1 were randomly allocated to individual metabolic cages for 14 days to measure the effects of dietary Se on nutrient digestibility. The results revealed that there were no significant differences for average daily gain, average daily feed intake, feed/gain ratio, hematological parameters (packed cell volume, red blood cell, white blood cell, and hemoglobin values), serum total protein, albumin, globulin, aspartate amino transferase, alkaline phosphatase, and creatine phosphokinase due to supplementation of different amounts and sources of Se in lambs. Dietary Se supplementation significantly improved (P?<?0.001) glutathione peroxidase activity in blood. Furthermore, at the end of the trial, serum tri-iodothyronine (T3) amount also increased (P?<?0.05), while serum thyroxine (T4) amount decreased (P?<?0.05). Digestibility of dry matter, organic matter, crude protein, neutral detergent fiber, and acid detergent fiber increased (P?<?0.05) by Se yeast supplementation. It may be concluded that supplementation of Se in lambs had no significant effect on performance and blood hematology, but increased blood glutathione peroxidase activity and serum T3 amount and decreased serum T4 amount as compared to non-supplemented control lambs. Furthermore, Se yeast improved nutrient digestibility in lambs.     

Taurine Ameliorates Renal Oxidative Damage and Thyroid Dysfunction in Rats Chronically Exposed to Fluoride

Excessive exposure to fluoride poses several detrimental effects to human health particularly the kidney which is a major organ involved in its elimination from the body. The influence of taurine on fluoride-induced renal toxicity was investigated in a co-exposure paradigm for 45 days using five groups of eight rats each. Group I rats received normal drinking water alone, group II rats were exposed to sodium fluoride (NaF) in drinking water at 15 mg/L alone, group III received taurine alone at a dose of 200 mg/kg group IV rats were co-administered with NaF and taurine (100 mg/kg), while group V rats were co-administered with NaF and taurine (200 mg/kg). Administration of taurine significantly reversed the fluoride-mediated decrease in absolute weight and organo-somatic index of the kidney in the exposed rats. Taurine significantly prevented fluoride-induced elevation in plasma urea and creatinine levels in the exposed rats. Moreover, taurine restored fluoride-mediated decrease in the circulatory concentrations of triiodothyronine, thyroxine, and the ratio of triiodothyronine to thyroxine. Taurine ameliorated fluoride-mediated decrease in renal antioxidant status by significantly enhancing the antioxidant enzyme activities as well as glutathione level in the exposed rats. Additionally, taurine inhibited fluoride-induced renal oxidative damage by markedly decreasing the hydrogen peroxide and malondialdehyde levels as well as improved the kidney architecture in the treated rats. Collectively, taurine protected against fluoride-induced renal toxicity via enhancement of thyroid gland function, renal antioxidant status, and histology in rats.     

Intervention of Selenium on Chronic Fluorosis-Induced Injury of Blood Antioxidant Capacity in Rats

This study was conducted to further explore the effects of selenium on the blood antioxidant capacity in rats exposed to fluoride to find out the optimal dosage level of selenium. Animals were divided into prevention sequence (Selenium?→?NaF, water?→?NaF) and treatment sequence (NaF?→?Selenium, NaF?→?water) (sodium fluoride 50?mg/L; sodium selenite 0.375, 0.75, 1.5?mg/L). The exposure time was 12?months. Then, the fluidity of erythrocyte membrane by electron spin resonance was analyzed, and the blood was collected for GSH-Px and SOD activity, total antioxidant capacity (T-AOC) and uric acid assay, sialic acid and MDA content. The results showed that, compared with control group, GSH-Px activity and T-AOC level increased significantly (P??0.05). The fluidity of erythrocyte membrane showed significant increase (P?相似文献   

Selenium (Na<Subscript>2</Subscript>SeO<Subscript>3</Subscript>) Upregulates Expression of Immune Genes and Blood–Testis Barrier Constituent Proteins of Bovine Sertoli Cell In Vitro

Sertoli cells were isolated from newborn calves and cultured in a medium supplemented with 0, 0.25, 0.50, 0.75, and 1.00 mg/L of sodium selenite to study their immune stimulatory effect, influence on cell’s viability, and expression of blood–testis barrier proteins (occludin, connexin-43, zonula occluden, E-cadherin) using quantitative PCR and western blot analyses. Results showed that medium supplemented with 0.50 mg/L of selenium significantly (P?<?0.05) promoted cell viability, upregulated toll-like receptor gene (TLR4), anti-inflammatory cytokines (IL-4, IL-10, TGFβ1), and expressions of blood–testis barrier proteins, and modulated expressions of pro-inflammatory cytokines (TNF-α, IL-1β, IFN-γ). Sertoli cells grown in culture medium supplemented with 0.25 mg/L of selenium significantly upregulated TLR4, IL-4, IL-10, TGFβ1, and blood–testis barrier proteins compared to the control group. Sodium selenite supplementation at 0.75 and 1.00 mg/L levels was cytotoxic and temporarily downregulated the expression of blood–testis barrier protein within 24 h after culture; however, commencing from 72 h post culture, increased cell viability and upregulation of expression of blood–testis barrier proteins were observed. In conclusion, the results of this study showed that selenium supplementation in the culture medium up to 0.50 mg/L concentration upregulates immune genes and blood–testis barrier constituent proteins of bovine Sertoli cells.     

Red Blood Cell and Serum Magnesium Levels Among Children and Adolescents With Sickle Cell Anemia

This study investigated neurotoxicity of chronic fluorosis in the rat hippocampus. Newly weaning, male, Sprague-Dawley (SD) rats were administered 15, 30, and 60 mg/L sodium fluoride (NaF) solution (fluorine ion concentration 8.25, 16.50, and 33.00 mg/L, respectively), and tap water, for 18 months. The neurotoxicological mechanism was examined with a focus on intracellular calcium overload. Results showed that as the fluoride concentration increased, calcium ion concentration [Ca²⁺], the expression of calcium/calmodulin-dependent protein kinase II α (CaMKIIα), and the expression of catus proto-oncogene protein c-fos (c-fos) all tend to increase. Compared to the control group, Ca²⁺, CaMKIIα, and c-fos significantly increased (P < 0.05) in the moderate-fluoride and the high-fluoride groups. These results indicate that Ca²⁺/CaMKIIα/c-fos channel signal may be the molecular mechanism of central nervous system damage caused by chronic fluoride intoxication. Moreover, elevated Ca²⁺ concentration in the hippocampus may be the initiating factor of neuronal apoptosis induced by fluoride.     

Effects of Dietary Selenium Deficiency or Excess on Gene Expression of Selenoprotein N in Chicken Muscle Tissues

Previous studies have determined the effects of dietary selenium (Se) supplementation on selenoprotein N (SelN, SEPN1), selenophosphate synthetase-1 (SPS1), and selenocysteine-synthase (SecS) mRNA abundance in chicken skeletal and cardiac muscles. To investigate collective responses of these genes to dietary Se concentrations ranging from deficiency to moderately high level in muscle tissues of chicken, 1-day-old chickens were exposed to a diet of deficient Se and supplemented with Se (0.15 mg Se/kg and 1.50 mg Se/kg) as sodium selenite in the feed for 35 days. Muscle tissues (flight, breast, leg, and cardiac muscles) were collected and examined for Se content and mRNA levels of SelN on days 1, 15, 25, and 35 days, respectively. Moreover, SPS1 and SecS mRNA levels were analyzed. The results showed that the expression of SelN gene in cardiac muscle responded to dietary Se concentrations. SelN gene was downregulated in the Se deficiency group (L group), and upregulated in the Se excess group (H group) compared with the moderate Se group (M group) (P?<?0.05) in cardiac muscle. Se deficiency mainly unregulated SelN mRNA level in skeletal muscles compared with M group. Excess dietary Se mainly resulted in the upregulation of SelN mRNA level in skeletal muscles compared with the M group. SecS mRNA levels responded to dietary Se concentrations showed a similar change compared with SelN in cardiac muscle. SPS1 mRNA levels responded to dietary Se concentrations showed a downregulation in L group and upregulation in H group. However, SelN mRNA levels displayed a different expression pattern in different skeletal and cardiac muscles. Moreover, Se also regulated the levels of SPS1 and SecS mRNAs. In summary, Se regulated the expression of SelN gene and affected the mRNA levels of SecS and SPS1. The level of Se in the feed may regulate SelN biosynthesis by affecting the levels of SPS1 and SecS mRNA.     

Source of Selenium Supplementation Influences Testis Selenium Content and Gene Expression Profiles in Single Comb White Leghorn Roosters

Spermatogenesis is a tightly regulated, selenium-dependent process. Nutritional deficiencies, including Se, have been associated with decreased fertility. During Se depletion, testes preferentially retain Se while other tissues are depleted. This study was aimed at evaluating the effect of Se source (inorganic or organic yeast derived) on testes weight, Se content, and gene expression. At 17 weeks of age, roosters were randomly assigned to one of three treatments: basal diet (control), basal diet?+?0.3 mg organic Se/kg organic yeast-derived Se (YS; Sel-Plex®, Alltech Inc.), or basal diet?+?0.3 mg inorganic Se /kg inorganic Se as sodium selenite (SS). At 40 weeks of age, seven roosters from each treatment were euthanized and testes removed. Testes weight did not differ between treatments, but Se content was greater (P?≤?0.01) in YS than SS and control. Testicular differential gene expression profiling was accomplished using the Affymetrix Genechip® chicken genome array. Ingenuity® pathway analysis revealed that Se supplementation, regardless of source, results in the up-regulation of genes governing cell structure/morphology. The enrichment of such pathways was greater with YS than SS. These expression patterns suggest that aside from playing a role in antioxidant defense, Se, especially in the organic YS form, is useful for maintaining testicular cell structure.     

Selenium in cardiology and angiology

The effect selenium in the form of sodium selenite on central hemodynamic conditions and coronary artery flow was studied in pig hearts infarcted by a ligature of the ramus interventricularis anterior. Infusions of sodium selenite solutions at levels of 1–3 mg/kg body wt improved the survival of infarcted pigs. Both short-term and long-term protective effects of selenite could be demonstrated. It is of potential therapeutic importance that sodium selenite administration suppresses the electrical vulnerability of the cell membrane, notably the occurrence of ventricular late potentials in the ischemic border zone. Coronary blood circulation, as evidenced by an increase of heart rate and coronary artery dilatation and peripheral vasodilatation was also improved. The pulsatile coronary blood flow thus is altered, increasing total perfusion of the infarcted heart. Initial observations with human subjects suggest that selenium deficiency is a factor in the pathogenesis of ischemic and arteriosclerotic heart disease. In 54 hospitalized patients with clinical diagnosis of acute myocardial infarction, serum selenium levels were 670±266 nmol/L, as compared to 981±209 nmol/L in 93 healthy controls. In 32 patients with general arteriosclerosis, the serum Se level was 375±85 nmol/L, in 64 patients with arteriosclerotic occlusional disease in the leg region, 366±85 nmol/L, respectively. Serum selenium levels of healthy subjects were found to be age-and sex dependent. In men, the selenium concentrations reached maximum levels of 1083 nmol/L in the 41–50 y age group. In women in the same age group, the serum Se level was 1385 nmol/L. Evidence is presented to suggest that selenium is preventing oxidative damage of heart cell membranes by lipid peroxidation.     

Chronic Alcoholism-Mediated Impairment in the Medulla Oblongata: A Mechanism of Alcohol-Related Mortality in Traumatic Brain Injury?

Alcohol-related traumatic brain injury (TBI) is a common condition in medical and forensic practice, and results in high prehospital mortality. We investigated the mechanism of chronic alcoholism-related mortality by examining the effects of alcohol on the synapses of the medulla oblongata in a rat model of TBI. Seventy adult male Sprague–Dawley rats were randomly assigned to either ethanol (EtOH) group, EtOH-TBI group, or control groups (water group, water-TBI group). To establish chronic alcoholism model, rats in the EtOH group were given EtOH twice daily (4 g/kg for 2 weeks and 6 g/kg for another 2 weeks). The rats also received a minor strike on the occipital tuberosity with an iron pendulum. Histopathologic and ultrastructure changes and the numerical density of the synapses in the medulla oblongata were examined. Expression of postsynaptic density-95 (PSD-95) in the medulla oblongata was measured by ELISA. Compared with rats in the control group, rats in the chronic alcoholism group showed: (1) minor axonal degeneration; (2) a significant decrease in the numerical density of synapses (p < 0.01); and (3) compensatory increase in PSD-95 expression (p < 0.01). Rats in the EtOH-TBI group showed: (1) high mortality (50 %, p < 0.01); (2) inhibited respiration before death; (3) severe axonal injury; and (4) decrease in PSD-95 expression (p < 0.05). Chronic alcoholism induces significant synapse loss and axonal impairment in the medulla oblongata and renders the brain more susceptible to TBI. The combined effects of chronic alcoholism and TBI induce significant synapse and axon impairment and result in high mortality.     

Effects of Fluoride on Surface Structure of Primary Culture Leydig Cells in Mouse

Fluoride (F) is known to induce reproduction toxicity, and the elucidation of its underlying mechanisms is an ongoing research. These findings aim to provide deeper insights into roles of soduim fluoride (NaF) in testis damage, which could contribute to a better understanding of fluoride-induced male reproductive toxicity. The Leydig cells were administrated by 0, 5, 10, and 20 mg/L NaF for 24 h, respectively. Scanning electron microscope was used to identify the change of surface structure in the Leydig cells. The results showed that fluoride exposure of high-dose induced bulged balloon in the membrane of the Leydig cell. We speculated that high doses of NaF inhibited cell proliferation and induced cell apoptosis in Leydig cells. This is the first time that we have reported that fluoride impaired cytomembrane and cytoskeleton of the Leydig cells in vitro treated with different doses of fluoride for 24 h by using a scanning electron microscope. Damage to the cytoskeleton and cytomembrane may be one of the reasons of male reproductive toxicity induced by fluoride.     

Dual palmitoylation of PSD-95 mediates its vesiculotubular sorting, postsynaptic targeting, and ion channel clustering

Postsynaptic density-95 (PSD-95/SAP-90) is a palmitoylated peripheral membrane protein that scaffolds ion channels at excitatory synapses. To elucidate mechanisms for postsynaptic ion channel clustering, we analyzed the cellular trafficking of PSD-95. We find that PSD-95 transiently associates with a perinuclear membranous compartment and traffics with vesiculotubular structures, which migrate in a microtubule-dependent manner. Trafficking of PSD-95 with these vesiculotubular structures requires dual palmitoylation, which is specified by five consecutive hydrophobic residues at the NH(2) terminus. Mutations that disrupt dual palmitoylation of PSD-95 block both ion channel clustering by PSD-95 and its synaptic targeting. Replacing the palmitoylated NH(2) terminus of PSD-95 with alternative palmitoylation motifs at either the NH(2) or COOH termini restores ion channel clustering also induces postsynaptic targeting, respectively. In brain, we find that PSD-95 occurs not only at PSDs but also in association with intracellular smooth tubular structures in dendrites and spines. These data imply that PSD-95 is an itinerant vesicular protein; initial targeting of PSD-95 to an intracellular membrane compartment may participate in postsynaptic ion channel clustering by PSD-95.     

Fluoride and Arsenic Exposure Impairs Learning and Memory and Decreases mGluR5 Expression in the Hippocampus and Cortex in Rats

Fluoride and arsenic are two common inorganic contaminants in drinking water that are associated with impairment in child development and retarded intelligence. The present study was conducted to explore the effects on spatial learning, memory, glutamate levels, and group I metabotropic glutamate receptors (mGluRs) expression in the hippocampus and cortex after subchronic exposure to fluoride, arsenic, and a fluoride and arsenic combination in rats. Weaned male Sprague-Dawley rats were assigned to four groups. The control rats drank tap water. Rats in the three exposure groups drank water with sodium fluoride (120 mg/L), sodium arsenite (70 mg/L), and a sodium fluoride (120 mg/L) and sodium arsenite (70 mg/L) combination for 3 months. Spatial learning and memory was measured in Morris water maze. mGluR1 and mGluR5 mRNA and protein expression in the hippocampus and cortex was detected using RT-PCR and Western blot, respectively. Compared with controls, learning and memory ability declined in rats that were exposed to fluoride and arsenic both alone and combined. Combined fluoride and arsenic exposure did not have a more pronounced effect on spatial learning and memory compared with arsenic and fluoride exposure alone. Compared with controls, glutamate levels decreased in the hippocampus and cortex of rats exposed to fluoride and combined fluoride and arsenic, and in cortex of arsenic-exposed rats. mGluR5 mRNA and protein expressions in the hippocampus and mGluR5 protein expression in the cortex decreased in rats exposed to arsenic alone. Interestingly, compared with fluoride and arsenic exposure alone, fluoride and arsenic combination decreased mGluR5 mRNA expression in the cortex and protein expression in the hippocampus, suggesting a synergistic effect of fluoride and arsenic. These data indicate that fluoride and arsenic, either alone or combined, can decrease learning and memory ability in rats. The mechanism may be associated with changes of glutamate level and mGluR5 expression in cortex and hippocampus.     

Suppression of Mitochondrial Oxidative Phosphorylation and TCA Enzymes in Discrete Brain Regions of Mice Exposed to High Fluoride: Amelioration by Panax ginseng (Ginseng) and Lagerstroemia speciosa (Banaba) Extracts

Chronic fluoride intoxication results in pathophysiological complications pertaining to soft tissues, called non-skeletal fluorosis. This study examined whether fluoride-induced alterations in selected parameters that are indicative of mitochondrial dysfunction accompany the toxic effects of fluoride in discrete brain regions in vivo and also explored the possibility of treatment with Ginseng (GE) and Banaba (BLE) either alone or with their co-exposure which is capable of reversing parameters indicative of fluoride-induced impairments in mitochondrial function. Swiss mice, Mus musculus, were given 270 ppm fluoride (600 ppm NaF) in their drinking water for 30 days, while continuing the fluoride exposure, toxicated animals were given differential doses (50–250 mg/kg body wt) of phytoextracts through oral gavage for 2 weeks. Discrete brain regions separated from dissected animals to perform biochemical assessments. Disturbances in mitochondrial enzyme complexes (I-IV) and decrements in TCA enzymes (ICDH, SDH, and aconitase) were noted in discrete brain regions upon F exposure, suggesting mitochondrial dysfunction. In addition, a significant reduction in oxidative stress indices with increased MDA content as well as decrease in reduced glutathione content and increases in catalase and SOD enzyme activity suggests the involvement of severe oxidative stress affecting the mitochondrial function(s). Treatment with either GE or BLE reversed F-induced alterations in augmenting the suppressed complex enzymes followed by TCA enzymes and oxidative stress indices in a dose independent manner. However, the co-exposure of GE and BLE at a dose of 150 mg/kgbw appeared to restore mitochondrial functioning. These results provide in vivo evidence supporting the hypothesis that fluoride induces impairments in mitochondrial function, which can be reversed by treatment with GE and BLE as well their co-exposure at 150 mg/kgbw.     

Dietary High Fluorine Induces Apoptosis and Alters Bcl-2, Bax, and Caspase-3 Protein Expression in the Cecal Tonsil Lymphocytes of Broilers

Long-term excessive fluoride intake is known to be toxic and can lead to fluorosis and bone pathologies. However, the cellular mechanisms underlying sodium fluoride-induced cytotoxicity in the cecal tonsil lymphocytes are not well understood. The aims of this study were to investigate the effects of high dietary fluorine on apoptosis and the expression of the Bcl-2, Bax, and caspase-3 in the cecal tonsil lymphocytes of broilers. The broilers were fed on high-fluorine diets containing 0, 400, 800, and 1,200 mg/kg fluorine. As measured by flow cytometry, the percentage of apoptotic lymphocytes was significantly increased in the high-fluorine groups II and III when compared with those in the control group. Meanwhile, immunohistochemical tests showed that the Bcl-2 protein expression decreased, and the Bax and caspase-3 protein expression increased in the high-fluorine groups II and III. In conclusion, dietary fluorine in the range of 800–1,200 mg/kg increased lymphocyte apoptosis in the cecal tonsil of broilers, suggesting that the lymphocyte apoptosis in the cecal tonsil was mediated by direct effects of fluoride on the expression of Bcl-2, Bax, and caspase-3.     

Colostrum and milk selenium,antioxidative capacity and immune status of dairy cows fed sodium selenite or selenium yeast

Dietary selenium (Se) can be supplemented from organic or inorganic sources and this may affect Se metabolism and functional outcome such as antioxidative status and immune functions in dairy cows. A feeding trial was performed with 16 Holstein-Friesian dairy cows fed with a total mixed ration (0.18 mg Se/kg dry matter (DM)) either without Se supplement (Control, n = 5), or with Se from sodium selenite (Group SeS, n = 5) or Se yeast (Group SeY, n = 6). In Groups SeS and SeY, the Se supplementation amounted to an additional intake of 4 mg Se and 6 mg Se/d during gestation and lactation, respectively. The effect of both Se sources was characterised by milk Se and antioxidant levels, and the phenotyping and functional assessment of phagocytic activity of milk immune cells. Se yeast has been found to increase (p ≤ 0.001) the milk Se and antioxidant levels markedly compared to the control group. The experimental treatment did not affect the immune parameters of the cows. Lymphocyte subpopulations and phagocytosis activity of neutrophilic granulocytes were affected neither by the Se intake nor by the two different dietary supplements. It can be concluded that sodium selenite and Se yeast differ considerably in their effects on antioxidant status in dairy cows. However, the basal dietary Se concentration of 0.18 mg/kg DM seemed to be high enough for the measured immune variables.