Seric concentrations of copper, chromium, manganesum, nickel and selenium in aerobic, anaerobic and mixed professional sportsmen.

BACKGROUND: The aim of the present study was to determine changes in serum concentrations of trace elements Cooper (Cu), Chromiun (Cr), Manganesum (Mn), Nickel (Ni) and Selenium (Se) in high-level sportsmen. METHODS: Eighty professional athletes of different metabolic modalities, were recruited before the start of their training period. Thirty one sedentary participants of the same geographic area constituted the control group. Cu, Cr, Mn, Ni and Se analysis was performed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). RESULTS: Higher concentrations of Cr (p < 0.001), Mn (p < 0.085), and Ni (p < 0.001) were found in sportsmen in comparison to controls, inversely, Se values were lower (p < 0.001) among sportsmen. When sportsmen were classified by metabolic modalities, it was found that aerobic-anaerobic group had higher (p < 0.01) Cu concentrations than controls and the other sportsmen. The highest Cr values were found in aerobic participants. For Mn, the major levels were found in aerobic and aerobic-anaerobic groups as well (p < 0.001). The lowest Se levels were found among anaerobic sportsmen (p < 0.001). CONCLUSION: This research showed that daily, continuum physical training induced alterations in serum essential minerals concentrations, as well as that these changes can be dependent of the exercise modality practiced.

Subchronic, Low-Level Intraperitoneal Injections of Manganese (IV) Oxide and Manganese (II) Chloride Affect Rat Brain Neurochemistry.

Manganese (Mn) is neurotoxic and can induce manganism, a Parkinson-like disease categorized as being a serious central nervous system irreversible neurodegenerative disease. An increased risk of developing symptoms of Parkinson disease has been linked to work-related exposure, for example, for workers in agriculture, horticulture, and people living near areas with frequent use of Mn-containing pesticides. In this study, the focus was placed on neurochemical effects of Mn. Rats were dosed intraperitoneally with 0.9% NaCl (control), 1.22 mg Mn (as MnO2)/kg bodyweight (bw)/day, or 2.5 mg Mn (as MnCl2)/kg bw/day for 7 d/wk for 8 or 12 weeks. This dosing regimen adds relevant new knowledge about Mn neurotoxicity as a consequence of low-dose subchronic Mn dosing. Manganese concentrations increased in the striatum, the rest of the brain, and in plasma, and regional brain neurotransmitter concentrations, including noradrenaline, dopamine (DA), 5-hydroxytrytamine, glutamate, taurine, and γ-amino butyric acid, and the activity of acetylcholinesterase changed. Importantly, a target parameter for Parkinson disease and manganism, the striatal DA concentration, was reduced after 12 weeks of dosing with MnCl2. Plasma prolactin concentration was not significantly affected due to a potentially reduced dopaminergic inhibition of the prolactin release from the anterior hypophysis. No effects on the striatal α-synuclein and synaptophysin protein levels were detected.

A two-generation inhalation reproductive toxicity study upon the exposure to manganese chloride.

A number of published studies have suggested that high levels of exposure to manganese, especially those found in occupational settings, can adversely affect the reproductive system. The objective of this study was therefore to investigate if these findings can be replicated using the Sprague Dawley rat and, if so, to identify those parts of the reproductive system are more susceptible. Male and female rats were exposed to manganese dichloride (MnCl2) via inhalation at concentrations of 0 (air-control); 5, 10 and 20µg/L air over 10 weeks (F0) and over 11 weeks (F1) prior to mating, and then throughout mating, gestation and lactation until termination after the F1 and F2 generation had reached Day 21 of lactation respectively. Animals were monitored for clinical signs of toxicity and for effects on body weight, food consumption, effects on the entire reproductive system including maternal care. The offspring were monitored for survival and growth up to weaning. Blood samples were taken from all adult animals for bioanalytical of manganese analysis prior to dosing, prior to mating and prior to weaning/necropsy. There were no deaths related to treatment, though respiratory tract effects were observed in F0 animals in the mid and high dose animals. Body weight and food consumption were affected at high dose in both generation. There were no treatment-related effects on the oestrous cycles, mating performance, sexual maturity, fertility or duration of gestation or litter size, the sperm motility, count of morphology (sperm) or the ovary follicle scoring in either generation. The No Observed Effect Level (NOEL) for reproductive performance was considered to be the target dose level of 20µg/L. Based on these findings, manganese chloride could not be considered a reprotoxicant under these conditions of exposure. Therefore, soluble and insoluble forms of inorganic manganese compounds by extrapolation cannot be considered as reprotoxicants.

Association between body levels of trace metals and glaucoma prevalence.

IMPORTANCE: Abnormal body levels of essential elements and exposure to toxic trace metals have been postulated to contribute to the pathogenesis of diseases affecting many organ systems, including the eye. OBJECTIVE: To investigate associations between body levels of trace metals and the prevalence of glaucoma in a cross-sectional population-based study. DESIGN, SETTING, AND PARTICIPANTS: Blood or urine metallic element levels and information pertaining to ocular disease were available for 2680 individuals 19 years and older participating in the fourth Korea National Health and Nutrition Examination Survey between January 1, 2008, and December 31, 2009, the second and the third years of the survey (2007-2009). Glaucoma diagnosis was based on criteria established by the International Society of Geographic and Epidemiologic Ophthalmology. Demographic, comorbidity, and health-related behavior information was obtained via interview. Multivariable logistic regression analyses were performed to determine associations between blood and urine trace element levels and the odds of glaucoma diagnosis. All analyses were performed between September 2014 and December 2014. MAIN OUTCOME AND MEASURE: The presence or absence of glaucoma. RESULTS: After adjustment for potential confounders, blood manganese level was negatively associated with the odds of glaucoma diagnosis (odds ratio [OR], 0.44; 95% CI, 0.21-0.92). Blood mercury level was positively associated with glaucoma prevalence (OR, 1.01; 95% CI, 1.00-1.03). No definitive association was identified between blood cadmium or lead levels or urine arsenic level and a diagnosis of glaucoma. CONCLUSIONS AND RELEVANCE: These findings in a cross-sectional study of the South Korean population suggest that a lower blood manganese level and a higher blood mercury level are associated with greater odds of glaucoma. For more confidence that trace metals may have a role in the pathogenesis of glaucoma, prospective studies would need to confirm that the presence of such trace metals increases the chance of developing glaucoma.

Neurohepatic toxicity of subacute manganese chloride exposure and potential chemoprotective effects of lycopene.

Excess manganese (Mn) is potentially toxic resulting in a permanent neurodegenerative disorder, clinically known as "manganism" that is distinctive for hepaticencephalopathy. The present study was designed to explore the toxic impacts of subacute Mn exposure on brain and liver tissues, and the relative abilities of lycopene in averting such neurohepatic damage. Rats were daily injected with MnCl(2) (0 or 6mg/kg, i.p.) 20 days after lycopene administration (0 or 10mg/kg, p.o.), and killed 4 weeks after MnCl(2) exposure. MnCl(2)-induced lipid peroxidation and perturbation in antioxidant system, increase of acetylcholinesterase, aminotransferases, and decrease alkaline phosphatase, and lactate dehydrogenase activities with hyperglycemia as demonstrated by Alzheimer type II astrocytosis, and periportal hepatic necrosis and apoptosis were prevented by lycopene. However, lycopene did not prevent the increased body burden of Mn and the altered Fe and Cu homeostasis induced by MnCl(2). Glutathione S-transferase and catalase activities, and glutathione content were reduced in MnCl(2)-challenged rats, and sustained by lycopene. Our results indicate that although lycopene failed to reduce Mn concentration or retain disturbed elemental status; it appears to be a highly effective in alleviating its neurohepatic deleterious effects by preventing lipid peroxidation, hyperglycemia and changes in the activity of acetylcholinesterase and hepatobiliary enzymes, and antioxidant pathways.

Ingestion of Mn and Pb by rats during and after pregnancy alters iron metabolism and behavior in offspring.

Manganese (Mn) and lead (Pb) exposures during developmental period can impair development by direct neurotoxicity or through interaction with iron metabolism. Therefore, we examined the effects of maternal ingestion of Mn or Pb in drinking water during gestation and lactation on iron metabolism as well as behavior in their offspring. Pregnant dams were given distilled water, 4.79mg/ml Mn, or 2.84mg/ml Pb in drinking water during gestation and lactation. Pups were studied at time of weaning for (59)Fe absorption from the gut, duodenal divalent metal transporter 1 (DMT1) expression, hematological parameters, and anxiety-related behavior using an Elevated Plus Maze (EPM) test. Metal-exposed pups had lower body weights and elevated blood and brain concentrations of the respective metal. Pb-exposed pups had lower hematocrits and higher blood Zn protoporphyrin levels. In contrast, Mn exposed pups had normal hematological parameters but significantly reduced Zn protoporphyrin. Pharmacokinetic studies using (59)Fe showed that intestinal absorption in metal-exposed pups was not different from controls, nor was it correlated with duodenal DMT1 expression. However, intravenously injected (59)Fe was cleared more slowly in Pb-exposed pups resulting in higher plasma levels. The overall tissue uptake of (59)Fe was lower in Mn-exposed and lower in the brain in Pb-exposed pups. The EPM test demonstrated that Mn-exposed, but not Pb-exposed, pups had lower anxiety-related behavior compared to controls. We conclude that gestational and lactational exposures to Mn or Pb differentially alter Fe metabolism and anxiety-related behavior. The data suggest that perturbation in Fe metabolism may contribute to the pathophysiologic consequences of Mn and Pb exposure during early development.

Manganese uptake and distribution in the brain after methyl bromide-induced lesions in the olfactory epithelia.

Manganese (Mn) is an essential nutrient with potential neurotoxic effects. Mn deposited in the nose is apparently transported to the brain through anterograde axonal transport, bypassing the blood-brain barrier. However, the role of the olfactory epithelial cells in Mn transport from the nasal cavity to the blood and brain is not well understood. We utilized the methyl bromide (MeBr) lesion model wherein the olfactory epithelium fully regenerates in a time-dependent and cell type-specific manner over the course of 6-8 weeks postinjury. We instilled (54)MnCl(2) intranasally at different recovery periods to study the role of specific olfactory epithelial cell types in Mn transport. (54)MnCl(2) was instilled at 2, 4, 7, 21, and 56 days post-MeBr treatment. (54)Mn concentrations in the blood were measured over the first 4-h period and in the brain and other tissues at 7 days postinstillation. Age-matched control rats were similarly studied at 2 and 56 days. Blood and tissue (54)Mn levels were reduced initially but returned to control values by day 7 post-MeBr exposure, coinciding with the reestablishment of sustentacular cells. Brain (54)Mn levels also decreased but returned to control levels only by 21 days, the period near the completion of neuronal regeneration/bulbar reinnervation. Our data show that Mn transport to the blood and brain temporally correlated with olfactory epithelial regeneration post-MeBr injury. We conclude that (1) sustentacular cells are necessary for Mn transport to the blood and (2) intact axonal projections are required for Mn transport from the nasal cavity to the olfactory bulb and brain.

Chronic exposure to manganese alters brain responses to amphetamine: a pharmacological magnetic resonance imaging study.

The parkinsonian symptoms and increased Mn accumulation in dopaminergic (DAergic) neurons of the basal ganglia implicate impaired dopamine signaling in the neurotoxic effects of chronic manganese overexposure. Using blood oxygenation level-dependent (BOLD) pharmacological magnetic resonance imaging (phMRI), we mapped brain responses to acute amphetamine (AMPH; 3 mg/kg, ip), which stimulates midbrain DAergic systems, in male Sprague-Dawley rats following 6 weeks of chronic MnCl(2) (5 mg Mn/kg, one per week, iv) or saline treatment. Plasma Mn content, measured immediately following phMRI, was elevated twofold in Mn-treated animals (p < 0.05), but the twofold increase in mean striatal Mn content did not reach significance. In saline-treated animals, AMPH stimulated robust positive BOLD responses throughout the basal ganglia and their reciprocally innervated connections. In contrast, acute AMPH stimulated a negative BOLD response in many of these structures in the Mn-treated group, resulting in significant differences between saline- and Mn-treated AMPH-evoked BOLD responses within caudate putamen, globus pallidus, substantia nigra, mediodorsal thalamic nucleus, and somatosensory cortex. These results demonstrate the utility of AMPH-evoked phMRI as readout of the DAergic signaling in vivo and confirm the vulnerability of DAergic systems to Mn.

Metabolomic analyses of body fluids after subchronic manganese inhalation in rhesus monkeys.

Neurotoxicity is linked with high-dose manganese inhalation. There are few biomarkers that correlate with manganese exposure. Blood manganese concentrations depend upon the magnitude and duration of the manganese exposure and inconsistently reflect manganese exposure concentrations. The objective of this study was to search for novel biomarkers of manganese exposure in the urine and blood obtained from rhesus monkeys following subchronic manganese sulfate (MnSO(4)) inhalation. Liquid chromatography-mass spectrometry was used to identify putative biomarkers. Juvenile rhesus monkeys were exposed 5 days/week to airborne MnSO(4) at 0, 0.06, 0.3, or 1.5 mg Mn/m(3) for 65 exposure days or 1.5 mg Mn/m(3) for 15 or 33 days. Monkeys exposed to MnSO(4) at >or= 0.06 mg Mn/m(3) developed increased brain manganese concentrations. A total of 1097 parent peaks were identified in whole blood and 2462 peaks in urine. Principal component analysis was performed on a subset of 113 peaks that were found to be significantly changed following subchronic manganese exposure. Using the Nearest Centroid analysis, the subset of 113 significantly perturbed components predicted globus pallidus manganese concentrations with 72.9% accuracy for all subchronically exposed monkeys. Using the five confirmed components, the prediction rate for high brain manganese levels remained > 70%. Three of the five identified components, guanosine, disaccharides, and phenylpyruvate, were significantly correlated with brain manganese levels. In all, 27 metabolites with statistically significant expression differences were structurally confirmed by MS-MS methods. Biochemical changes identified in manganese-exposed monkeys included endpoints relate to oxidative stress (e.g., oxidized glutathione) and neurotransmission (aminobutyrate, glutamine, phenylalanine).

Brain manganese accumulation is inversely related to gamma-amino butyric acid uptake in male and female rats.

Iron (Fe) is an essential trace metal involved in numerous cellular processes. Iron deficiency (ID) is reported as the most prevalent nutritional problem worldwide. Increasing evidence suggests that ID is associated with altered neurotransmitter metabolism and a risk factor for manganese (Mn) neurotoxicity. Though recent studies have established differences in which the female brain responds to ID-related neurochemical alterations versus the male brain, little is known about the interactions of dietary ID, Mn exposure, and sex on gamma-amino butyric acid (GABA). Male and female Sprague-Dawley rats were randomly divided into four dietary treatment groups: control (CN), control/Mn supplemented, ID, and ID/Mn supplemented. After 6 weeks of treatment, both ID diets caused a highly significant decrease in Fe concentrations across all brain regions compared to CN in both sexes. Both ID and Mn supplementation led to significant accumulation of Mn across all brain regions in both sexes. There was no main effect of sex on Fe or Mn accumulation. Striatal synaptosomes were utilized to examine the effect of dietary intervention on (3)H-GABA uptake. At 4 weeks, there was a significant correlation between Fe concentration and (3)H-GABA uptake in male rats (p < 0.05). At 6 weeks, there was a significant inverse correlation between Mn concentration and (3)H-GABA uptake in male and female rats and a postitive correlation between Fe concentration and (3)H-GABA uptake in female rats (p < 0.05). In conclusion, ID-associated Mn accumulation is similar in both sexes, with Mn levels affecting GABA uptake in both sexes in a comparable fashion.

Postnatal manganese exposure attenuates cocaine-induced locomotor activity and reduces dopamine transporters in adult male rats.

In the present study, we examined whether exposing rats to manganese (Mn) during the preweanling period would affect basal or cocaine-induced locomotor activity in adulthood and reduce the number of striatal dopamine transporter binding sites. On postnatal day (PD) 1-21, rats were given oral supplements of vehicle or Mn chloride (250 or 750 microg/day). Striatal Mn and iron (Fe) accumulation as well as serum Fe levels were measured on PD 14, PD 21, and PD 90. Throughout the dosing period, rats were evaluated on standard measures of sensory and motor development. During adulthood, the basal and cocaine-induced locomotor activity of vehicle- and Mn-exposed rats was assessed using automated testing chambers. After completion of behavioral testing, striatal dopamine transporter binding sites were measured using [(3)H]GBR 12935. Results showed that early Mn exposure enhanced striatal Mn accumulation on PD 14 and PD 21, while depressing serum Fe levels on PD 21. Exposure to Mn on PD 1-21 did not affect striatal or serum Mn or Fe levels on PD 90. During the second postnatal week, Mn-exposed rat pups performed more poorly than controls on a negative geotaxis task, however basal motor activity of preweanling rat pups was not affected by Mn treatment. When tested in adulthood, basal locomotor activity of vehicle- and Mn-exposed rats also did not differ. In contrast, adult rats previously exposed to 750 microg/day Mn showed an enhanced locomotor response when challenged with 10 mg/kg cocaine. A different pattern of results occurred after treatment with a higher dose of the psychostimulant, because Mn-exposed rats showed an attenuated locomotor response when given 20 mg/kg cocaine. Importantly, Mn-exposed rats exhibited long-term reductions in striatal dopamine transporter binding sites. Considered together, these results indicate that postnatal Mn exposure has long-term behavioral and neurochemical effects that can persist into adulthood.

Effects of amino acids and its metabolites on prolidase activity against various iminodipeptides in erythrocytes from normal human and a patient with prolidase deficiency.

BACKGROUND: The characteristics of prolidase in erythrocytes from controls and patient with prolidase deficiency were investigated. METHODS: The erythrocytes were isolated from the heparinized blood of normal human and a patient with prolidase deficiency. Effects of various amino acids and their metabolites on prolidase activity against iminodipeptides in presence of 1 mmol/l MnCl(2) were investigated. RESULTS: Prolidase activity against glycylproline in erythrocytes from normal human was strongly enhanced by glycine, L-alanine, L-serine with MnCl(2), but the activity was strongly inhibited by L-valine, and L-leucine. However, the stereoisomers, D-leucine and D-valine enhanced the activity. The prolidase activity against methionylproline in erythrocytes from the patient with prolidase deficiency was also enhanced by glycine, L-alanine and L-serine. The activity was inhibited by l-leucine, but D-leucine and L-valine enhanced the activity against various iminodipeptides. CONCLUSION: Prolidase activity against glycylproline in normal human erythrocytes and against methionylproline from the prolidase-deficient patient was enhanced strongly by glycine, alanine and serine with MnCl(2). However, this activity was inhibited by L-leucine, but was enhanced by D-leucine.

Blood manganese and alcohol consumption interact on mood states among manganese alloy production workers.

Long-term exposure to manganese (Mn) can induce neurotoxic effects including neuromotor, neurocognitive and neuropsychiatric effects, but there is a great interpersonal variability in the occurrence of these effects. It has recently been suggested that blood Mn (MnB) may interact with alcohol use disorders, accentuating neuropsychiatric symptoms. The objective of the present study was to explore a possible interaction between alcohol consumption and MnB on mood states, using an existing data set on Mn exposed workers. Respirable Mn exposure in the plant averaged 0.23mg/m(3) and was correlated with MnB. All participants for whom all data on MnB concentration and mood (assessed with the Profile of Mood States (POMS)) were available and who reported currently drinking alcohol were included in the analyses (n=74). Workers were grouped according to their MnB concentration (<10 and > or =10 microg/l) and alcohol consumption (<400 and > or =400g per week). Two-way ANOVAs were performed on each POMS scale and Mann-Whitney tests were used to assess group differences. Workers in the higher alcohol consumption group had higher scores on three POMS scales: tension, anger and fatigue. There was no difference for POMS scale scores between MnB subgroups. Dividing the group with respect to alcohol consumption and MnB showed that the group with high alcohol consumption and high MnB displayed the highest scores. In the lower MnB category, those in the higher alcohol consumption group did not have higher scores than the others. The interaction term for alcohol consumption and MnB concentration was statistically significant (P<0.05) for the depression, anger, fatigue and confusion POMS scales. There was a tendency for tension (P<0.06), and it was not significant for vigor. This study shows the first evidence of an interaction between MnB and alcohol consumption on mood states among Mn exposed workers and supports the results from a previous population-based study.