Tissue Mn Content Research Articles

Effects of dietary manganese supplementation on the growth performance, tissue manganese content and antioxidant capacity of coho salmon (Oncorhynchus kisutch) post-smolts

A 10-week growth trial was carried out to study the impact of dietary manganese (Mn) level on growth, tissue Mn content and anti-oxidative capacity of coho salmon (Oncorhynchus kisutch) post-smolts (186.51 ± 1.43 g). Six iso-nitrogenous (42.40% Protein) and iso-lipidic (10.27% Lipid) purified diets based on casein-gelatin were formulated to contain varied graded (MnSO4·H2O as a Mn source) levels of 0.40, 9.50, 16.80, 25.80, 33.40 and 41.20 Mn mg/kg. Fish were reared in a freshwater flow-through rearing system and fed to apparent satiation 3 times daily. No significant effects were found on the survival rate, morphological indices, whole-body proximate composition (p > .05) among the groups. However, higher dietary Mn supplementation level than 25.80 mg/kg improved the growth performance, increased the deposition of Mn in whole-body and vertebral, improved hepatic digestive enzyme activity, enhanced anti-oxidative enzyme activities, and decreased the malondialdehyde content in liver and serum (p < .05). Hepatic and serum total antioxidant capacity, glutathione peroxidase, glutathione reductase, total superoxide dismutase, Mn-superoxide dismutase and catalase activities were enhanced with increasing level of dietary Mn, and then stabilized when dietary Mn level up to 25.80 mg/kg. Using the cubic analysis (based on specific growth rate and feed conversion ratio), the optimal dietary Mn levels were 33.25 and 29.55 mg/kg, respectively. Using the broken-line analysis (based on the deposition of Mn, Mn-superoxide dismutase in liver and serum), the dietary Mn requirements of coho salmon post-smolts were estimated to be 24.52, 26.34, 24.74 and 26.05 mg/kg, respectively.

Manganese triggers phosphorylation-mediated endocytosis of the Arabidopsis metal transporter NRAMP1.

The NATURAL RESISTANCE-ASSOCIATED MACROPHAGE PROTEIN1 (NRAMP1) transporter guarantees plant survival of manganese (Mn) deficiency by mediating Mn entry into root cells. Unlike other high-affinity metal transporters, NRAMP1 is only slightly regulated at the transcriptional level. We show here that adequate Mn content in tissues is safeguarded through a tight control of the quantity of NRAMP1 present at the surface of root cells. Depending on Mn availability, an NRAMP1-GFP fusion protein cycles dynamically between the plasma membrane (PM) and endosomal compartments. This involves a clathrin-mediated endocytosis pathway, as disrupting this pathway in auxilin-overexpressor lines prevents NRAMP1 internalization. Mutation of the phosphorylated serine residues 20, 22 and 24 in the cytosol-exposed N terminus of NRAMP1 alters its membrane distribution. Indeed, a phospho-dead mutation stabilizes NRAMP1 at the PM, regardless of the Mn regime, and dramatically reduces plant tolerance to Mn toxicity. Conversely a phosphomimetic mutant is constitutively internalized into endosomes. Together, these data establish that phosphorylation of NRAMP1 is the trigger for its Mn-induced endocytosis and represents the main level of regulation of this transporter. Furthermore, the extent of Mn toxicity observed when interrupting NRAMP1 membrane cycling undermines the dogma that Mn is only marginally toxic to plants.

Unprecedented Kinetic Inertness for a Mn2+ -Bispidine Chelate: A Novel Structural Entry for Mn2+ -Based Imaging Agents.

The search for more biocompatible alternatives to Gd3+ -based MRI agents, and the interest in 52 Mn for PET imaging call for ligands that form inert Mn2+ chelates. Given the labile nature of Mn2+ , high inertness is challenging to achieve. The strongly preorganized structure of the 2,4-pyridyl-disubstituted bispidol ligand L1 endows its Mn2+ complex with exceptional kinetic inertness. Indeed, MnL1 did not show any dissociation for 140 days in the presence of 50 equiv. of Zn2+ (37 °C, pH 6), while recently reported potential MRI agents MnPyC3A and MnPC2A-EA have dissociation half-lives of 0.285 h and 54.4 h under similar conditions. In addition, the relaxivity of MnL1 (4.28 mm-1 s-1 at 25 °C, 20 MHz) is remarkable for a monohydrated, small Mn2+ chelate. In vivo MRI experiments in mice and determination of the tissue Mn content evidence rapid renal clearance of MnL1 . Additionally, L1 could be radiolabeled with 52 Mn and the complex revealed good stability in biological media.

Unprecedented Kinetic Inertness for a Mn2+‐Bispidine Chelate: A Novel Structural Entry for Mn2+‐Based Imaging Agents

AbstractThe search for more biocompatible alternatives to Gd3+‐based MRI agents, and the interest in 52Mn for PET imaging call for ligands that form inert Mn2+ chelates. Given the labile nature of Mn2+, high inertness is challenging to achieve. The strongly preorganized structure of the 2,4‐pyridyl‐disubstituted bispidol ligand L1 endows its Mn2+ complex with exceptional kinetic inertness. Indeed, MnL1 did not show any dissociation for 140 days in the presence of 50 equiv. of Zn2+ (37 °C, pH 6), while recently reported potential MRI agents MnPyC3A and MnPC2A‐EA have dissociation half‐lives of 0.285 h and 54.4 h under similar conditions. In addition, the relaxivity of MnL1 (4.28 mm−1 s−1 at 25 °C, 20 MHz) is remarkable for a monohydrated, small Mn2+ chelate. In vivo MRI experiments in mice and determination of the tissue Mn content evidence rapid renal clearance of MnL1. Additionally, L1 could be radiolabeled with 52Mn and the complex revealed good stability in biological media.

Effects of dietary manganese source and supplemental levels on growth performance, antioxidant enzymes activities, tissue Mn concentrations and cytosolic manganese superoxide dismutase (cMnSOD) mRNA expression level of juvenile Litopenaeus vannamei

This experiment was conducted to study the effects of different forms and levels of manganese (Mn) on the growth performance, antioxidant activities, tissue Mn content and cytosolic manganese superoxide dismutase (cMnSOD) gene expression of Litopenaeus vannamei. Treatments consisted of 0, 10, 20, 30, 40 and 60 mg Mn kg−1 from manganese sulphate (Mn-S) and manganese methionine (Mn-Met), providing the actual dietary value of 5.17, 15.62, 25.55, 34.22, 44.48 and 67.90 mg Mn kg−1 Mn-S, and 5.17, 15.71, 25.36, 35.86, 45.16 and 65.06 mg Mn kg−1 Mn-Met, respectively. Each diet was fed to triplicate groups of L. vannamei (initial body weight: 1.925 ± 0.002 g) in a recirculated fresh water rearing system for 8 weeks. Weight gain rate (WGR) increased in prawns provided with from 25.55 to 44.48 mg Mn kg−1 Mn-S and 15.71 to 45.16 mg Mn kg−1 Mn-Met and then declined above these levels. The lowest protein efficiency ratio (PER) and the highest feed conversion rate (FCR) were observed in prawns fed the control diet (P 0.05). Survival rate (SR) was not affected by the dietary treatments (P > 0.05). Total SOD and Mn-SOD activities were higher in the hepatopancreas of prawns fed with Mn-supplemented diets from 15.71 to 44.48 mg Mn kg−1 (P < 0.05). On the contrary, malondialdehyde (MDA) content was lower in the hepatopancreas of prawns fed the basal diet (P < 0.05). Mn concentrations in the hepatopancreas and muscles increased with increasing levels of dietary Mn supplementation. Moreover, Mn accumulation was lower in the muscle than in the hepatopancreas of the prawns. The mRNA expression of cMnSOD gene in the hepatopancreas of prawns was upregulated with increasing dietary Mn levels of Mn-S from 25.55 to 44.48 mg Mn kg−1, Mn-Met from 15.71 to 45.16 mg Mn kg−1 and then plateaued above these levels. Broken-line regression analysis of WGR indicated that the optimal dietary Mn requirements for juvenile L. vannamei were 32.26 mg Mn kg−1 Mn-S and 23.90 mg Mn kg−1 Mn-Met, respectively.

Effect of dietary manganese on antioxidant status and expression levels of heat-shock proteins and factors in tissues of laying broiler breeders under normal and high environmental temperatures.

To investigate the effect of Mn on antioxidant status and expression levels of heat-shock proteins/factors in tissues of laying broiler breeders subjected to heat challenge, we used a completely randomised design (n 6) with a factorial arrangement of 2 environmental temperatures (normal, 21 (sem 1)°C and high, 32 (sem 1)°C)×3 dietary Mn treatments (an Mn-unsupplemented basal diet (CON), or a basal diet supplemented with 120 mg Mn/kg diet as inorganic Mn sulphate (iMn) or organic Mn proteinate (oMn)). There were no interactions (P>0·10) between environmental temperature and dietary Mn in all of the measured indices. High temperature decreased (P<0·003) Mn content, and also tended (P=0·07) to decrease copper zinc superoxide dismutase (CuZnSOD) activity in the liver and heart. However, an increased manganese superoxide dismutase (MnSOD) activity (P<0·05) and a slight increase of malondialdehyde level (P=0·06) were detected in breast muscle. Up-regulated (P<0·05) expression levels of heat-shock factor 1 (HSF1) and HSF3 mRNA and heat-shock protein 70 (HSP70) mRNA and protein were found in all three tissues. Broiler breeders fed either iMn or oMn had higher tissue Mn content (P<0·0001), heart MnSOD and CuZnSOD activities (P<0·01) and breast muscle MnSOD protein levels (P<0·05), and lower (P<0·05) breast muscle HSP70 mRNA and protein levels than those fed CON. Broiler breeders fed oMn had higher (P<0·03) bone Mn content than those fed iMn. These results indicate that high temperature decreases Mn retention and increases HSP70 and HSF1, HSF3 expression levels in tissues of laying broiler breeders. Furthermore, dietary supplementation with Mn in either source may enhance heart antioxidant ability and inhibit the expression of HSP70 in breast muscle. Finally, the organic Mn appears to be more available than inorganic Mn for bone in laying broiler breeders regardless of environmental temperatures.

Manganese uptake and accumulation in a woody hyperaccumulator, Schima superba

A wide-spread subtropical tree species, &lt;I&gt;Schima superba (Theaceae)&lt;/I&gt;, occurring in a Mn mine wasteland, was found to contain unusually high Mn content in the leaf tissues. A pot growth experiment with different Mn treatments was conducted to further illustrate its Mn tolerance, accumulation and relocation capacity. &lt;I&gt;Schima&lt;/I&gt; saplings grew well and showed no symptoms of Mn toxicity with Mn supply below 60 mmol/l. Total plant biomass decreased with the increase of Mn supply, but Mn contents in tissues increased significantly, and peaked (62 412.3 mg/kg) in stem at 150 mmol/l treatment. Under all treatments, Mn concentrations in the aboveground tissues were constantly greater than those in roots. When the external Mn supply was over 40 mmol/l, the Mn levels in the leaves and stems all exceeded 10 000 mg/kg, the suggested value for Mn hyperaccumulation. Most of the Mn taken from the substrates were transported to the aboveground tissues, e.g. over 86% accumulated in the aboveground parts at 150 mmol/l treatment. These findings confirmed that Schima superba is a Mn hyperaccumulator.

Manganese???Calcium Interactions With Contrast Media for Cardiac Magnetic Resonance Imaging

Manganese ions (Mn) enter cardiomyocytes via calcium (Ca) channels and enhance relaxation intracellularly. To prevent negative inotropy, new Mn-releasing contrast agents have been supplemented with high Ca. The study aim was to investigate how this affects cardiac function and magnetic resonance efficacy. MnCl2 based contrast agents, manganese and manganese-calcium (Ca:Mn 10:1), were infused during 4 repeated washin-washout sequences in perfused guinea pig hearts. [Mn] were 10, 50, 100 and 500 microM. During washin, manganese depressed left ventricular developed pressure (LVDP) by 4, 9, 17, and 53% whereas manganese-calcium increased LVDP by 13, 18, 25, and 56%. After experiments, tissue Mn contents (nmol/g dry wt) were control <40, manganese 3720, and manganese-calcium 1620. T1 was reduced by 85-92% in Mn-enriched hearts. High Ca supplements to Mn-releasing contrast agents may be counterproductive by inducing a strong positive inotropic response and by reducing the magnetic resonance efficacy.

Intracellular manganese ions provide strong T1 relaxation in rat myocardium.

The efficacy of manganese ions (Mn2+) as intracellular (ic) contrast agents was assessed in rat myocardium. T1 and T2 and Mn content were measured in ventricular tissue excised from isolated perfused hearts in which a 5-min wash-in with 0, 30, 100, 300, or 1000 microM of Mn dipyridoxyl diphosphate (MnDPDP) was followed by a 15-min wash-out to remove extracellular (ec) Mn2+. An inversion recovery (IR) analysis at 20 MHz revealed two T1 components: an ic and short T1-1 (650-251 ms), and an ec and longer T1-2 (2712-1042 ms). Intensities were about 68% and 32%, respectively. Tissue Mn content correlated particularly well with ic R1-1. A two-site water-exchange analysis of T1 data documented slow water exchange with ic and ec lifetimes of 11.3 s and 7.5 s, respectively, and no differences between apparent and intrinsic relaxation parameters. Ic relaxivity induced by Mn2+ ions in ic water was as high as 56 (s mM)(-1), about 8 times and 36 times higher than with Mn2+ aqua ions and MnDPDP, respectively, in vitro. This value is as high as any reported to date for any synthetic protein-bound metal chelate. The increased rotational correlation time (tauR) between proton and electron (Mn2+) spins, and maintained inner-sphere water access, might make ic Mn2+ ions and Mn2+ -ion-releasing contrast media surprisingly effective for T1-weighted imaging.

Differential tolerance of high manganese among rapeseed genotypes

Cultivation of crop cultivars resistant to high soil manganese (Mn) may reduce the negative effects of Mn toxicity on crop yield. Three studies were carried out to select Brassica genotypes (B. napus and B. rapa) resistant to high Mn concentration and to characterise the nature of any Mn resistance found. In Experiment 1, 33 B. napus and nine B. rapa genotypes were screened in a sub-irrigated nutrient solution system. Based on visual symptoms and plant size, single plants were identified with resistance to high Mn from within cultivars of four B. napus and one B. rapa. Resistance was also identified in one B. napus doubled haploid genotype. In Experiment 2, a genotype resistant to high Mn and two genotypes (progenies from Experiment 1) sensitive to high Mn were exposed to eight Mn concentrations (9–500 μM) for 2 weeks in nutrient solution. The relative shoot weight (RSW) and the relative root weight (RRW) of the genotype resistant to Mn were significantly greater at ≥100 μM Mn than both genotypes sensitive to high Mn; the sensitive genotypes reacted similarly. The three genotypes had similar tissue Mn contents and the elevated Mn tissue contents did not induce deficiencies of Mg or Fe. In Experiment 3, 12 genotypes (progenies from Experiment 1) were screened in nutrient solution at 9 μM Mn and with an additional 125 μM Mn. The RRW and RSW of the genotypes ranged from 35 to 114 and 39 to 94%, respectively. All the selections sensitive to high Mn had a RSW 70% and thus were confirmed as Mn resistant. This evidence confirmed the availability of rapeseed germplasm resistant to Mn toxicity with an ability to withstand high content of Mn through internal tissue tolerance. Also, the observed Mn tolerance in this material is genetically controlled and not an artifact of our screening assays.

ASSESSMENT OF BIOACCUMULATION AND NEUROTOXICITY IN RATS WITH PORTACAVAL ANASTOMOSIS AND EXPOSED TO MANGANESE PHOSPHATE: A PILOT STUDY

The use of the additive methylcyclopentadienyl manganese tricarbonyl in unleaded gasoline has resulted in increased attention to the potential toxic effects of manganese (Mn). Hypothetically, people with chronic liver disease may be more sensitive to the adverse neurotoxic effects of Mn. In this work, bioaccumulation of Mn, as well as histopathology and neurobehavioral damage, in end-to-side portacaval anastomosis (PCA) rats exposed to Mn phosphate via inhalation was investigated. During the week before the PCA operation, 4 wk after the PCA operation, and at the end of exposure, the rats were subjected to a locomotor evaluation (day-night activities) using a computerized autotrack system. Then a group of 6 PCA rats (EXP) was exposed to 3050 µg m -3 (Mn phosphate) for 8 h/day, 5 days/wk for 4 consecutive weeks and compared to a control group (CON), 7 PCA rats exposed to 0.03 µg m -3. After exposure, the rats were euthanized and Mn content in tissues and organs was determined by neutron activation analysis. The manganese concentrations in blood (0.05 µg/g vs. 0.02 µg/g), lung (1.32 µg/g vs. 0.24 µg/g), cerebellum (0.85 µg/g vs. 0.64 µg/g), frontal cortex (0.87 µg/g vs. 0.61 µg/g), and globus pallidus (3.56 µg/g vs. 1.33 µg/g) were significantly higher in the exposed group compared to the control group (p < .05). No difference was observed in liver, kidney, testes, and caudate putamen between the two groups. Neuronal cell loss was assessed by neuronal cell counts. The loss of cells in globus pallidus and caudate putamen as well as in frontal cortex was significantly higher (p < .05) for the EXP group. Assessment of the locomotor activities did not reveal any significant difference. This study constitutes a first step toward our understanding of the potential adverse effects of Mn in sensitive populations.

Myocardial manganese elevation and proton relaxivity enhancement with manganese dipyridoxyl diphosphate. Ex vivo assessments in normally perfused and ischemic guinea pig hearts.

Manganese (Mn) dipyridoxyl diphosphate (MnDPDP) is the active component of a contrast medium for liver MRI. By being metabolized, MnDPDP releases Mn(2+), which is taken up and retained in hepatocytes. The study examined whether MnDPDP elevates Mn content and enhances proton relaxivity in normal myocardium, but not in ischemic myocardium with reduced coronary flow and impaired metabolism. Isolated guinea pig hearts were perfused at normal flow or low flow, inducing global subtotal ischemia. Ventricular ATP and Mn contents, T(1) and T(2) were measured. At normal flow tissue Mn content increased from the control level of 4.1 to 70.4 micromol/100g dry wt with MnDPDP (3000 microM), while low-flow perfusion with MnDPDP (3000 microM) resulted in a Mn content of 16.6 micromol/100 g dry wt. Prolonged ischemia (35 and 90 min) reduced tissue Mn down to the control level. T(1) shortening closely paralleled myocardial Mn elevations during both normal and low-flow perfusion. The use of a Mn(2+)-releasing contrast agent like MnDPDP may be a promising principle in MRI assessments of myocardial function and viability in coronary heart disease by revealing a differential pattern of changes in T(1) relative to coronary flow, cell Mn uptake and retention, ion channel function and metabolism.

Use of XAS to Determine the Chemical Speciation of Bioaccumulated Manganese in Potamogeton pectinatus

AbstractManganese (Mn) accumulation was measured in Potamogeton pectinatus L. (sago pondweed) over a growing season. Leaf tissue Mn content increased from 120 mg kg−1 in June to 4990 mg kg−1 by October. Our objective was to chemically speciate bioaccumulated Mn in P. pectinatus with x‐ray absorption spectroscopy (XAS). Differences were found in Mn valence in leaf tissue between June, October, and January when compared to model inorganic Mn compounds. Manganese in June leaf tissue was most like [Mn2+ (H2O)6]. By October, average valence of Mn in leaf and root tissues was similar to Mn3O4. However, there was little agreement in the chemical structure of Mn in these tissues and Mn3O4. Senescent leaf tissue in January differed from October because the valence had shifted back toward Mn2+. The Mn3+ fraction had leached from leaf tissue between October and January. This coincided with a decrease in total Mn concentration during this same period. Manganese bioaccumulation in this aquatic species occurs in two phases: (i) Mn2+ is bound in finite sites and coordinated by water, (ii) once filled, Mn2+ is oxidized and stored as a Mn3+ oxide within the plant that can be leached upon senescence.

Visual symptoms and tissue manganese concentrations associated with manganese toxicity in wheat

Abstract Wheat (Triticum aestivum L.) was grown in nutrient solution in the greenhouse. Mn concentrations in the nutrient solutions used ranged from 0.0025 to 50,000 mg/1. Visual symptoms associated with high tissue Mn content were stunting, general chlorosis, necrotic leaf spots, white flecking, purpling, and leaf tip burn. Mn tissue concentrations of 380 mg/kg were found to reduce dry matter production by 10%.