High Dietary Mn Research Articles

Long-term relatively high dietary manganese intake could decrease the risk of hyperuricemia: Twelve-year distinct dietary manganese consumption trajectories and the China Health and Nutrition Survey

Background and aimCurrently, the relationship between dynamic changes in dietary manganese (Mn) intake and risk of hyperuricemia (HU) is still unclear. This study aimed to identify dietary Mn consumption trajectories in the Chinese adults and assess their relation with the risk of HU. Methods and resultsCohort data from the China Health and Nutrition Survey (CHNS) 1997–2009 were employed in this study. Overall, 6886 adult participants were included. Participants were designated into subgroups based on the trajectories of dietary Mn consumption by sex. Cox proportional hazard models were used to explore the associations between different trajectories and the risk of HU. For men, compared with low stable trajectory group, moderate to high trajectory group was significantly related to reduced risk of HU (HR = 0.61, 95% CI: 0.38 to 0.98) with adjustment for covariates. TC, HDL-C, ApoB, and TG exerted partial regulation function between trajectories and HU. For women, compared with low stable trajectory group, high stable trajectory group was significantly related to reduced risk of HU (HR = 0.76, 95% CI: 0.60 to 0.95) with adjustment for covariates. Similarly, TC, HDL-C, ApoB, and ApoA exerted partial regulation function between trajectories and HU. ConclusionsLong-term relatively high dietary Mn consumption may have a protective effect against HU in Chinese adults. The differences in HU-related factors among different dietary Mn intake trajectories partially regulated the association between these trajectories and HU.

Manganese-Induced Oxidative Stress Contributes to Intestinal Lipid Deposition via the Deacetylation of PPARγ at K339 by SIRT1.

Aims: Excessive manganese (Mn) exposure is toxic, and induces lipid deposition, but the underlying mechanisms remain elusive. Herein, we explored how dietary Mn supplementation affects lipid deposition and metabolism in the intestine of vertebrates using the yellow catfish Pelteobagrus fulvidraco as the model. Results: High-Mn (H-Mn) diet increased intestinal Mn content, promoted lipid accumulation and lipogenesis, and inhibited lipolysis. In addition, it induced oxidative stress, upregulated metal-response element-binding transcription factor-1 (MTF-1), and peroxisome proliferator-activated receptor gamma (PPARγ) protein expression in the nucleus, induced PPARγ acetylation, and the interaction between PPARγ and retinoid X receptor alpha (RXRα), while it downregulated sirtuin 1 (SIRT1) expression and activity. Mechanistically, Mn activated the MTF-1/divalent metal transporter 1 (DMT1) pathway, increased Mn accumulation in the mitochondria, and induced oxidative stress. This in turn promoted lipid deposition via deacetylation of PPARγ at K339 by SIRT1. Subsequently, PPARγ mediated Mn-induced lipid accumulation through transcriptionally activating fatty acid translocase, stearoyl-CoA desaturase 1, and perilipin 2 promoters. Innovation: These studies uncover a previously unknown mechanism by which Mn induces lipid deposition in the intestine via the oxidative stress-SIRT1-PPARγ pathway. Conclusion: High dietary Mn intake activates MTF-1/DMT1 and oxidative stress pathways. Oxidative stress-mediated PPARγ deacetylation at K339 site contributes to increased lipid accumulation. Our results provided a direct link between Mn and lipid metabolism via the oxidative stress-SIRT1-PPARγ axis. Antioxid. Redox Signal. 37, 417-436.

Increased Dietary Manganese Impairs Neutrophil Extracellular Trap Formation Rendering Neutrophils Ineffective at Combating Staphylococcus aureus.

Dietary metals can modify the risk to infection. Previously, we demonstrated that heightened dietary manganese (Mn) during systemic Staphylococcus aureus infection increases S. aureus virulence. However, immune cells also operate in these same environments and the effect of dietary Mn on neutrophil function in vivo has not been assessed. This study reveals that increased concentrations of Mn impairs mitochondrial respiration and superoxide production in neutrophils responding to S. aureus. As a result, high Mn accelerates primary degranulation, while impairing suicidal neutrophil extracellular trap (NET) formation, which decreases bactericidal activity. In vivo, elevated dietary Mn accumulated extracellularly in the heart, indicating that excess Mn may be more bioavailable in the heart. Coinciding with this phenotype, neutrophil function in the heart was most impacted by a high Mn diet, as neutrophils produced lower levels of mitochondrial superoxide and underwent less suicidal NET formation. Consistent with an ineffective neutrophil response when mice are on a high Mn diet, S. aureus burdens were increased in the heart and mice were more susceptible to systemic infection. Therefore, elevated dietary Mn not only affects S. aureus but also renders neutrophils less capable of restricting staphylococcal infection.

Manganese-induced hyperactivity and dopaminergic dysfunction depend on age, sex and YAC128 genotype

Manganese (Mn) is an essential micronutrient but is neurotoxic in excess. Environmental and genetic factors influence vulnerability to Mn toxicity, including sex, age, and the autosomal dominant mutation that causes Huntington disease (HD). To better understand the differential effects of Mn in wild-type (WT) versus YAC128 mice, we examined impacts of Mn exposure across different ages and sexes on disease-relevant behavioral tasks and dopamine dynamics. Young (3-week) and aged (12-month) WT and YAC128 mice received control (70 ppm) or high (2400 ppm) Mn diet for 8 weeks followed by a battery of behavioral tasks. In young female WT mice, high Mn diet induced hyperactivity across two independent behavioral tasks. Changes in the expression of tyrosine hydroxylase (TH) were consistent with the behavioral data in young females such that elevated TH in YAC128 on control diet was decreased by high Mn diet. Aged YAC128 mice showed the expected disease-relevant behavioral impairments in females and decreased TH expression, but we observed no significant effects of Mn diet in either genotype of the aged group. Fast-scan cyclic voltammetry recorded dopamine release and clearance in the nucleus accumbens of eight-month-old WT and YAC128 mice following acute Mn exposure (3×/1 week subcutaneous injections of 50 mg/kg MnCl[2]-tetrahydrate or saline). In WT mice, Mn exposure led to faster dopamine clearance that resembled saline treated YAC128 mice. Mn treatment increased dopamine release only in YAC128 mice, possibly indirectly correcting the faster dopamine clearance observed in saline treated YAC128 mice. The same exposure paradigm led to decreased dopamine and serotonin and metabolites (3-MT, HVA and 5-HIAA) in striatum and increased glutamate in YAC128 mice but not WT mice. These studies confirm an adverse effect of Mn in young, female WT animals and support a role for Mn exposure in stabilizing dopaminergic dysfunction and motivated behavior in early HD.

Regulation of the Metal Transporters ZIP14 and ZnT10 by Manganese Intake in Mice.

The metal transporters ZIP14 and ZnT10 play key physiological roles in maintaining manganese (Mn) homeostasis. However, in vivo regulation of these two transporters by Mn is not understood. Here, we examined how dietary Mn intake regulates ZIP14 and ZnT10 by feeding mice a low-Mn diet, a control diet, or a high-Mn diet for 6 weeks. Inductively coupled plasma mass spectrometry was used to measure Mn and iron (Fe) levels. ZIP14 and ZnT10 protein levels were measured by western blot analysis. While mice on the high-Mn diet exhibited significantly higher levels of Mn in the blood, liver, and brain, the low-Mn diet group did not display matching reductions, indicating that high Mn intake is more effective in disrupting Mn homeostasis in mice. Additionally, Fe levels were only slightly altered, suggesting independent transport mechanisms for Mn and Fe. In the high-Mn diet group, ZIP14 and ZnT10 were both upregulated in the liver, as well as in the small intestine, indicating a coordinated role for these transporters in Mn excretion. Unexpectedly, this upregulation only occurred in male mice, with the exception of hepatic ZIP14, providing new insight into mechanisms behind widely observed sex differences in Mn homeostasis.

Dietary Manganese Promotes Staphylococcal Infection of the Heart

Diet, and specifically dietary metals, can modify the risk of infection. However, the mechanisms by which manganese (Mn), a common dietary supplement, alters infection remain unexplored. We report that dietary Mn levels dictate the outcome of systemic infections caused by Staphylococcus aureus, a leading cause of bacterial endocarditis. Mice fed a high Mn diet display alterations in Mn levels and localization within infected tissues, and S.aureus virulence and infection of the heart are enhanced. Although the canonical mammalian Mn-sequestering protein calprotectin surrounds staphylococcal heart abscesses, calprotectin is not released into the abscess nidus and does not limit Mn in this organ.Consequently, excess Mn is bioavailable to S.aureus in the heart. Bioavailable Mn is utilized by S.aureus to detoxify reactive oxygen species and protect against neutrophil killing, enhancing fitness within the heart. Therefore, a single dietary modification overwhelms vital host antimicrobial strategies, leading to fatal staphylococcal infection.

Manganese transporter Slc39a14 deficiency revealed its key role in maintaining manganese homeostasis in mice

SLC39A14 (also known as ZIP14), a member of the SLC39A transmembrane metal transporter family, has been reported to mediate the cellular uptake of iron and zinc. Recently, however, mutations in the SLC39A14 gene have been linked to manganese (Mn) accumulation in the brain and childhood-onset parkinsonism dystonia. It has therefore been suggested that SLC39A14 deficiency impairs hepatic Mn uptake and biliary excretion, resulting in the accumulation of Mn in the circulation and brain. To test this hypothesis, we generated and characterized global Slc39a14-knockout (Slc39a14−/−) mice and hepatocyte-specific Slc39a14-knockout (Slc39a14fl/fl;Alb-Cre+) mice. Slc39a14−/− mice develop markedly increased Mn concentrations in the brain and several extrahepatic tissues, as well as motor deficits that can be rescued by treatment with the metal chelator Na2CaEDTA. In contrast, Slc39a14fl/fl;Alb-Cre+ mice do not accumulate Mn in the brain or other extrahepatic tissues and do not develop motor deficits, indicating that the loss of Slc39a14 expression selectively in hepatocytes is not sufficient to cause Mn accumulation. Interestingly, Slc39a14fl/fl;Alb-Cre+ mice fed a high Mn diet have increased Mn levels in the serum, brain and pancreas, but not in the liver. Taken together, our results indicate that Slc39a14−/− mice develop brain Mn accumulation and motor deficits that cannot be explained by a loss of Slc39a14 expression in hepatocytes. These findings provide insight into the physiological role that SLC39A14 has in maintaining Mn homeostasis. Our tissue-specific Slc39a14-knockout mouse model can serve as a valuable tool for further dissecting the organ-specific role of SLC39A14 in regulating the body’s susceptibility to Mn toxicity.

Plasma and liver lipids of iron‐deficient rats with excessive dietary manganese

Recently, manganese (Mn) toxicity in a child with iron (Fe) deficiency was reported. Since there is a possibility that effect of Fe deficiency is augmented by excessive Mn, plasma and liver lipids in rats were analyzed. Thirty‐two 3‐week‐old male Wistar rats were randomly assigned in a 2×2 factorial design (eight rats each): FeA/MnA group fed AIN‐93G diet, FeA/MnE group fed a high Mn diet (1000 ppm), FeD/MnA group fed a low‐Fe diet (no supplemental Fe), and FeD/MnE group fed a low Fe/high Mn diet. Rats were fed ad libitum for six weeks and then fasted overnight. Plasma and liver lipids were measured enzymatically. Data were analyzed by two‐way ANOVA and P values less than 0.05 was considered significant. The low Fe diet increased plasma triglycerides, phospholipids and free fatty acids. The low Fe diet decreased plasma glucose and HDL cholesterol, and concomitant high Mn augmented their reduction. The low Fe diet increased liver triglycerides. Both the low Fe and high Mn diets increased liver phospholipids. The low Fe diet increased liver cholesterol, and concomitant high Mn attenuated its rise. These results suggest that concomitant high dietary Mn modulates changes in plasma and liver lipids induced by Fe deficiency. Partly supported by Japan Society for the Promotion of Science Grants‐in‐Aid for Scientific Research (C) (22500772).

The addition of high manganese to a copper-deficient diet further depresses copper status and growth of cattle

A study was conducted evaluating the effect of long-term Cu deficiency, with or without high Mn, on growth, gene expression and Cu status of beef cattle. Twenty-one Angus calves were born to cows receiving one of the following treatments: (1) 10 mg supplemental Cu/kg DM (+Cu); (2) no supplemental Cu and 2 mg Mo/kg DM ( - Cu); (3) - Cu diet plus 500 mg supplemental Mn/kg DM ( - Cu+Mn). Calves were weaned at approximately 183 d of age and individually fed throughout the growing and finishing phases. Plasma Cu was lower (P < 0.01) in - Cu calves compared with +Cu calves while high dietary Mn further depressed (P < 0.01) plasma Cu in - Cu+Mn calves v. - Cu calves. Liver Cu concentrations in +Cu calves were greater (P < 0.01) than in - Cu calves, with no differences between - Cu and - Cu+Mn calves. The daily body-weight gain of +Cu calves was greater (P < 0.01) than - Cu calves during the period from birth to weaning, but did not differ during the growing phase. - Cu+Mn calves gained less (P < 0.05) than - Cu calves during the growing phase. DM intake was lower (P < 0.01) in - Cu+Mn calves v. - Cu calves, and did not differ among +Cu and - Cu calves. The relative gene expression of cytochrome c oxidase in the liver was lower (P < 0.05) in - Cu calves compared with +Cu or - Cu+Mn calves. In conclusion, feeding a Cu - deficient diet in combination with high Mn negatively affected the growth and Cu status of beef cattle.

Copper deficiency in the young bovine results in dramatic decreases in brain copper concentration but does not alter brain prion protein biology1,2

An Mn for Cu substitution on cellular prion proteins (PrP(c)) in the brain that results in biochemical changes to PrP(c) has been implicated in the pathogenesis of transmissible spongiform encephalopathies. Recent research in the mature bovine does not support this theory. The present study tested this hypothesis by using progeny from gestating cows receiving Cu-deficient diets or Cu-deficient diets coupled with high dietary Mn. Copper-adequate cows (n = 39) were assigned randomly to 1 of 3 treatments: 1) control (adequate in Cu and Mn), 2) Cu deficient (-Cu), or 3) Cu deficient plus high dietary Mn (-Cu+Mn). Cows assigned to treatments -Cu and -Cu+Mn received no supplemental Cu and were supplemented with Mo to further induce Cu deficiency. The -Cu+Mn treatment also received 500 mg of supplemental Mn/kg of dietary DM. Calves were weaned at 180 d and maintained on the same treatments as their respective dams for 260 d. Copper-deficient calves (-Cu and -Cu+Mn) had decreased (P = 0.001) brain (obex) Cu and tended to have increased (P = 0.09) obex Mn relative to control calves. Obex Mn:Cu ratios were substantially increased (P < 0.001) in calves receiving -Cu and -Cu+Mn treatments compared with control calves and were greater (P < 0.001) in -Cu+Mn calves than in -Cu calves. Obex prion protein characteristics, including proteinase K degradability, superoxide dismutase (SOD)-like activity, and glycoform distributions, were largely unaffected. Obex tissue antioxidant capacity was not compromised by perturbations in brain metals, but Cu-deficient calves tended to have decreased (P = 0.06) Cu:Zn SOD activity and increased (P = 0.06) Mn SOD activity. Although obex Cu was decreased because of Cu deficiency and Mn increased because of exposure to high dietary Mn, the obex metal imbalance had minimal effects on PrP(c) functional characteristics in the calves.

Exposure to low dietary copper or low copper coupled with high dietary manganese for one year does not alter brain prion protein characteristics in the mature cow1,2

It is now widely accepted that abnormal prion proteins are the likely causative agent in bovine spongiform encephalopathy. Cellular prion proteins (PrP(c)) bind Cu, which appears to be required to maintain functional characteristics of the protein. The replacement of Cu on PrP(c) with Mn has resulted in loss of function and increased protease resistance. Twelve mature cows were used to determine the effects of Cu deficiency, alone and coupled with high dietary Mn, on brain Cu and Mn concentrations and on PrP(c) functional characteristics. Copper-adequate cows were randomly assigned to treatments: 1) control (adequate in Cu and Mn), 2) Cu-deficient (-Cu), and 3) Cu-deficient plus high dietary Mn (-Cu+Mn). Cows assigned to treatments -Cu and -Cu+Mn received no supplemental Cu and were supplemented with Mo to further induce Cu deficiency. After 360 d, Cu-deficient cows (-Cu and -Cu+Mn) tended to have lesser concentrations of Cu (P = 0.09) in the obex region of the brain stem. Brain Mn tended (P = 0.09) to be greater in -Cu+Mn cattle compared with -Cu cattle. Western blots revealed that PrP(c) relative optical densities, proteinase K degradability, elution profiles, molecular weights, and glycoform distributions were not different among treatments. The concentration of PrP(c), as determined by ELISA, was similar across treatment groups. Brain tissue (obex) Mn superoxide dismutase activity was greatest (P = 0.04) in cattle receiving -Cu+Mn, whereas immunopurified PrP(c) had similar superoxide dismutase-like activities among treatments. Immunopurified PrP(c) had similar Cu concentrations across treatments, whereas Mn was undetectable. We concluded that Cu deficiency, coupled with excessive Mn intake, in the bovine may decrease brain Cu and increase brain Mn. Copper deficiency, alone or coupled with high dietary Mn, did not cause detectable alterations in PrP(c) functional characteristics.

Plasma diamine oxidase: A biomarker of copper deficiency in the bovine1,2

This study was designed to test the efficacy of plasma diamine oxidase (DAO) activity as a biomarker of Cu deficiency in the bovine. Angus steers (n = 11) and heifers (n = 17) were assigned to 1 of 3 treatments: 1) control (adequate dietary Cu), 2) Cu-deficient (-Cu), and 3) Cu-deficient plus high dietary Mn (-Cu+Mn), and fed from weaning through finishing. Molybdenum (2 mg/kg of DM) was supplemented to treatments -Cu and -Cu+Mn to induce Cu deficiency via the formation of ruminal thiomolybdates. Samples were collected on 2 sampling dates (d 160 and 190) to determine the efficacy of plasma DAO activity as a biomarker of Cu deficiency. For both sampling dates, liver Cu, plasma Cu, and plasma ceruloplasmin activity indicated that cattle receiving diets designed to induce Cu deficiency (-Cu and -Cu+Mn) were Cu-deficient, with all indices of Cu status lower (P < 0.001) than the control animals. In addition to these traditional indices of Cu status, plasma DAO activity also effectively identified Cu-deficient animals because plasma DAO levels were reduced (P < 0.001) by 2- to 3-fold compared with controls. Correlation analysis indicated that plasma DAO activity was highly correlated to all other indices of Cu status (Pearson R = 0.73 to 0.87). During the growing phase, ADG (P = 0.09) and G:F (P = 0.002) were depressed in Cu-deficient animals compared with controls, whereas cattle performed equally well across all treatments in the finishing phase. The plasma DAO activity assay was precise and reliable based on an intraassay CV of 4.4% and interassay CV of 11.1%. Due to increased variability, freezing and thawing of plasma samples resulted in significant changes in DAO activity relative to fresh plasma DAO activity values. Thus, fresh plasma DAO activity, a relatively simple assay, may serve as an effective tool to diagnose Cu deficiency in the bovine.

A Manganese-Enhanced Diet Alters Brain Metals and Transporters in the Developing Rat

Manganese (Mn) neurotoxicity in adults can result in psychological and neurological disturbances similar to Parkinson's disease, including extrapyramidal motor system defects and altered behaviors. However, virtually nothing is known regarding excess Mn accumulation during central nervous system development. Developing rats were exposed to a diet high in Mn via maternal milk during lactation (PN4-21). The high Mn diet resulted in changes in hematological parameters similar to those seen with iron (Fe) deficiency in dams (decreased plasma Fe; increased plasma transferrin [Tf]) and pups (decreased hemoglobin [Hb] and plasma Fe; increased plasma Tf and total iron binding capacity). Mn-exposed pups showed an increase in brain Mn, chromium, and zinc concurrent with a decrease in brain Fe. In conjunction with the altered transport and distribution of essential metals within the brain, there was enhanced protein expression of the divalent metal transporter-1 (DMT-1) and transferrin receptor (TfR) overall in the brain; there was a general increase in each region analyzed (cerebellum, cortex, hippocampus, midbrain, and striatum). Neurochemical changes were observed as an increase in gamma-aminobutyric acid (GABA) and the ratio of GABA to glutamate, indicating enhanced inhibitory transmission in the brain. The results of this study demonstrate that developing rats undergo alterations in the transport and distribution of essential metals translating to neurochemical perturbations after maternal exposure to a diet supplemented with excess levels of Mn.

Manganese depresses rat heart muscle respiration

It has previously been reported that moderately high dietary manganese (Mn) in combination with marginal magnesium (Mg) resulted in ultrastructural damage to heart mitochondria. Manganese may replace Mg in biological functions, including the role of enzyme cofactor. Manganese may accumulate and substitute for Mg during the condition of Mg-deficiency. The objective of the current study was to determine whether high Mn alters heart muscle respiration and Mg-enzyme activity as well as whole body Mn retention under marginal Mg. An additional objective was to determine whether high Mn results in increased oxidative stress. In experiment 1: forty-eight rats were fed a 2 x 3 factorial arrangement of Mn (10, 100, or 1000 mg/kg) and Mg (200 or 500 mg/kg). In experiment 2: thirty-two rats were fed one of four diets in a 2 x 2 factorial arrangement of Mn (10 or 250 mg/kg) and Mg (200 or 500 mg/kg). In experiment 3: thirty-two rats were fed one of four diets in a 2 x 2 factorial arrangement of Mn (10 or 650 mg/kg) and Mg (200 or 500 mg/kg). In experiment 2, high Mn and marginal Mg reduced (P<0.05) oxygen consumption of left ventricle muscle. Marginal Mg, but not Mn, reduced (P<0.05) activity of sarcoplasmic reticulum calcium-ATPase enzyme. Dietary Mg had no affect on (54)Mn kinetics, but high dietary Mn decreased (P<0.01) absorption, retention, and rate of excretion of (54)Mn. Neither cellular stress, measured by Comet assay, nor antioxidant activities were increased by high Mn. A strong interaction (P<0.001) between increasing Mn and adequate Mg on hematology was observed. These results confirm previous research in swine that high Mn alters myocardial integrity as well as function, but not as a result of altered calcium transport or oxidative stress.

Manganese alters mitochodrial integrity in the hearts of swine marginally deficient in magnesium.

It was previously reported that pigs marginally deficient in magnesium (Mg) and fed diets high in manganese (Mn) died suddenly with signs of sudden cardiac death. Manganese, which has properties similar to Mg, may exacerbate Mg-deficiency and be accumulated by mitochondria resulting in ultrastructural damage. The objective of this study was to determine whether deaths of the type previously observed were mediated by adverse interactions of Mn and Mg resulting in ultrastructural damage to the myocardium, alterations in electrocardiographic recordings and tissue retention of Mn, Mg and calcium (Ca). Forty-eight pigs were fed one of six diets in a 2 X 3 factorial arrangement of Mg (100 or 1000 mg Mg/kg) and Mn (5, 50 or 500 mg Mn/kg) for 8 weeks. Left ventricle muscle samples were collected for examination by transmission electron microscopy. No differences in heart muscle ultrastructure were observed between pigs fed low and adequate dietary Mg. However, marked myocardial necrosis and mitochondrial swelling were observed in pigs fed high dietary Mn when combined with low Mg. Feeding low dietary Mg elevated minimum (P < 0.01), maximum (P < 0.05) and average (P < 0.001) heart rates. Low dietary Mg resulted in a 55% probability of a ventricular beat being recorded (P = 0.05) and lower Mg (P < 0.02) and Ca (P < 0.04) contents in heart atria and ventricles. These results suggest that high Mn, when fed in combination with low Mg, disrupts mitochondrial ultrastructure and is associated with the sudden deaths previously reported.

High Dietary Manganese Lowers Heart Magnesium in Pigs Fed a Low-Magnesium Diet

Young pigs were fed a diet moderately high or low in manganese (Mn) (0.95 +/- 0.10 mmol Mn/kg, n = 8 or 0.040 +/- 0.003 mmol Mn/kg, n = 6) and deficient in magnesium (Mg) (4.1 mmol Mg/kg) for 5 wk. All eight pigs consuming the high Mn diet died following convulsive seizures, whereas only two of six died in the group fed low Mn. In an attempt to determine the cause of death, a subsequent study examined the interactive effect of deficient dietary Mg and Mn on the tissue distribution of Mg and Mn. Pigs were individually fed, for 5 wk, diets that contained: 4.1 mmol Mg/kg and 36.0 micromol Mn/kg, 4.1 mmol Mg/kg and 0.91 mmol Mn/kg, 4.1 mmol Mg/kg and 0.91 mmol Mn/kg with added ultratrace minerals, or 41.1 mmol Mg/kg and 0. 91 mmol Mn/kg, and ultratrace minerals. Liver and skeletal muscle Mn concentrations were significantly elevated by increased dietary Mn. Increased dietary Mn did not affect heart Mn, but heart Mg concentrations were significantly depressed by high, as compared to low, dietary Mn (38.7 +/- 3.3 vs. 32.7 +/- 2.6 mmol Mg/kg). These data suggest high dietary Mn may exacerbate Mg deficiency in heart muscle and thus may be a complicating factor in the deaths observed in Mg-deficient pigs.

INFLUENCE OF DIETARY MANGANESE ON TISSUE TRACE MINERAL ACCUMULATION AND DEPLETION IN SHEEP

An experiment was conducted to investigate tissue trace mineral accumulation and depletion in sheep fed high dietary Mn in the form of reagent grade MnO. During the pre-trial phase, 32 wethers, 56 kg initially, were group-fed the basal corn-soybean meal diet (36 mg/kg Mn) for 8 days at which time eight sheep were slaughtered and tissues were taken to represent controls. For the remaining sheep, the experiment was divided into two phases of 6 wk and 12 wk; during the first phase (accumulation), the diet contained 8000 mg/kg supplemental Mn and during the second phase (depletion) the diet was the unsupplemented basal. Sheep were slaughtered at various intervals during both phases and tissue samples were taken. Manganese increased in all tissues measured during accumulation but decreased rapidly during the depletion phase. In general, liver and kidney Zn and Cu increased during the accumulation phase but tissue Fe decreased during this phase. MnO appeared to be a relatively safe supplemental source of Mn for sheep. Key words: Manganese, trace minerals, tissue minerals, sheep

Effect of Dietary Manganese and Age on Tissue Trace Mineral Composition of Broiler-Type Chicks as a Bioassay of Manganese Sources

An experiment was conducted with 144 Cobb broiler-type chicks in a 4 × 3 factorial arrangement of treatments to investigate the effects of dietary manganese (Mn) and age on trace mineral composition in tissues. Day-old chicks were fed a basal corn-soybean meal diet (112 ppm Mn) supplemented with 0, 1000, 2000, or 3000 ppm Mn as manganese sulfate monohydrate (MnSO4 · H2O) for 1, 2, or 3 weeks. There were two pen replications per treatment combination and six chicks per pen. Liver, kidney, pancreas, skeletal muscle, and bone were excised from 4 chicks per replication. Plasma was pooled from the remaining 2 chicks, and all samples were frozen for subsequent mineral analysis. There was a reduction in average daily feed intake (P<.05) at the 3000 ppm dietary level accompanied by a nonsignificant decrease in average daily gain and an increase in feed per unit gain. Tissue Mn increased (P<.001) for all tissues as dietary Mn increased. Tissue Mn concentration was reduced with age in kidney, pancreas, muscle (P<.001), and plasma (P<.05). Manganese in bone was lowest (P<.01) at 1 week of age. Of those ages tested, the optimum for bioassay based on λ criterion values appeared to be 3 weeks. The highest λ criterion values were obtained at 3 weeks of age in kidney followed by bone at 2 weeks. High dietary Mn increased copper (Cu) concentration in liver (P<.05) and plasma (P<.05) and reduced iron (Fe) in pancreas (P<.001). Liver Fe was lower (P<.001) at 3000 ppm than at 1000 or 2000 ppm dietary Mn. Plasma zinc (Zn) was higher (P<.05) at all supplemental Mn levels than the unsupplemented control, and kidney Zn increased (P<.001) at 3000 ppm dietary Mn.

Effect of high dietary Mn levels on the growth rate and the level of mineral elements in the plasma and soft tissues of sheep

Abstract Sixty grazing Romney Marsh sheep (30 ewes and 30 wethers) were randomly placed in three groups and supplemented with 0, 250, and 500 mg Mn per day to study the effect of high dietary levels of Mn on growth rate and levels of mineral elements in various soft tissues. Increasing the dietary level of Mn significantly depressed the growth rate of the sheep. There was little effect on the mineral element composition of plasma, heart, kidney, and liver, except in the first experiment, where the heart and plasma Fe levels were decreased while the liver Cu and Mn levels and plasma Mn levels were increased.

Manganese in the nutrition and metabolism of the pullet

1. The first two experiments were similar; pullets were given either a low-manganese diet, 6–7 μg/g, or a high-Mn diet containing an additional 50 μgMn/g; shell thickness as measured by weight per unit area was obtained for the first four and the last four eggs produced during a short laying period and the Mn contents of the first two and last two eggs were determined.2. Shell thickness was significantly reduced by the low-Mn diet in Expt 1, but not in Expt 2. In both experiments there was an increase in thickness from the first four to the last four shells produced.3. The Mn content of eggs from birds given the low-Mn diet was significantly lower in both experiments than that from birds given the high-Mn diet. In Expt 1 there was an increase in Mn content from the first to the last eggs laid, but no corresponding change occurred in Expt 2.4. The differences between the results of the two experiments are discussed; they were probably due to differences in the time for which the experimental diets were given before laying began.5. In Expt 3 pullets were given the high-Mn or low-Mn diet from about 4 weeks before laying began or the high-Mn diet to the point-of-lay and then the low-Mn diet. Shell thickness was determined in batches of six eggs from each bird at intervals during a 6- to 7-month laying period.6. Shell thickness was depressed by the low-Mn diet in birds given this diet 4 weeks before laying but not in those given the low-Mn diet from the point-of-lay.7. In Expt 4 shell thickness was determined on the first thirty eggs laid by four pullets given the high-Mn diet and four given the low-Mn diet from about 4 weeks before starting to lay. The difference between shells from birds given the high-Mn and low-Mn diets just failed to reach significance and there was no significant increase or decrease in the series of thirty shells from each bird, studied in successive groups of six shells.