Trace Mineral Metabolism Research Articles

56 Metabolic status of respiratory disease challenged beef steers altered by intranasal Zn and vitamin A treatments

Abstract Bovine respiratory disease (BRD) is a major cause of morbidity and mortality in the cattle industry. Increasing the ability of a calf to respond to disease is of interest due to the loss of production during disease. Zinc and vitamin A (VA) are key micronutrients involved in many immunologic processes such as cell signaling and mucosal immunity. Angus crossbred steers [n = 48; body weight (BW) = 333 ± 4.2 kg] were utilized in this 14-d BRD challenge investigating intranasal (IN) treatments of Zn and VA. Steers were split into two groups (n = 24) with identical disease challenge and sample collection schedules. Before disease challenge, steers were housed at the Iowa State University Beef Nutrition farm (BNF). Steers were weighed on d -2 and -1 of viral challenge and trucked for 6 h before delivery to the Iowa State University Animal Resource Station. On d 0, steers were challenged with an aerosol inoculation with 104 TCID50 BRSV followed by 5x108 CFU of Mannheimia haemolytica on d 5. On d 4, steers received IN treatments of Zn (ZN; ZnO nanoparticles), VA (VA), Zn and VA (VA+ZN), or control with no IN treatment (CON). For trace mineral and VA analysis, liver biopsies were collected on d -9 and 20 and plasma collected on d 0, 4 (trace mineral only), 5, 7 and 14. Steers were tested for viral shedding on d 0, 4, 5, 7, 10 and 14. RNA was isolated from bronchioalveolar lavage (BAL) cells (d 0 and 7) for gene expression related to inflammation, VA and trace mineral metabolism. Statistical analysis was completed using the GLIMMIX and MIXED procedures in SAS 9.4. Throughout the study, viral shedding was not affected by intranasal treatment (P ≥ 0.59). There were no group × TRT × day effects for plasma trace minerals (Cu, Zn, Fe) or VA concentrations (P ≥ 0.18). Intranasal VA prevented a decrease in plasma VA on d 5, after which all treatments were similar (P < 0.01). There were no TRT × day effects for plasma Zn and Cu (P ≥ 0.50). Post challenge, liver VA was increased in VA treated steers compared with steers not treated with VA (P = 0.04). Liver Mn tended to be increased post challenge in IN ZN treated steers (P = 0.08). IN Zn treated steers tended to have lesser expression of IL-10 in BAL cells on d 7 post infection (P = 0.07). Local IN supplementation of Zn and VA can have systemic and local affects on respiratory disease challenged steers and may support increased response to disease.

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Trace Element Interactions, Inflammatory Signaling, and Male Sex Implicated in Reduced Growth Following Excess Oral Iron Supplementation in Pre-Weanling Rats.

Iron supplements are frequently provided to infants in high-income countries despite low incidence of iron deficiency. There is growing concern regarding adverse health and development outcomes of excess iron provision in early life. Excess iron may directly damage developing organs through the formation of reactive oxygen species, alter systemic inflammatory signaling, and/or dysregulate trace mineral metabolism. To better characterize the in vivo effects of excess iron on development, we utilized a pre-weanling rat pup model. Lewis rat litters were culled to eight pups (four males and four females) and randomly assigned to daily supplementation groups receiving either vehicle control (CON; 10% w/v sucrose solution) or ferrous sulfate (FS) iron at one of the following doses: 10, 30, or 90 mg iron/kg body weight—FS-10, FS-30, and FS-90, respectively—from postnatal day (PD) 2 through 9. FS-90 litters, but not FS-30 or FS-10, failed to thrive compared to CON litters and had smaller brains on PD 10. Among the groups, FS-90 liver iron levels were highest, as were white blood cell counts. Compared to CON, circulating MCP-1 and liver zinc were increased in FS-90 pups, whereas liver copper was decreased. Growth defects due to excess FS provision in pre-weanling rats may be related to liver injury, inflammation, and altered trace mineral metabolism.

Effects of trace minerals supply from rumen sustained release boluses on milk yields and components, rumen fermentation and the rumen bacteria in lactating yaks (Bos grunniens)

The experiment was conducted to evaluate trace mineral supplies of iron (Fe), copper (Cu), manganese (Mn), zinc (Zn), cobalt (Co), iodine (I) and selenium (Se) using rumen sustained release boluses on milk yield and milk components, rumen fermentation and the rumen bacteria in lactating yaks. Sixteen multiparous lactating yaks, blocked by parity, liveweight, and milk yield, were randomly assigned to two groups: CON (control group), a high forage diet with no supplemental iron Fe, Cu, Mn, Zn, Co, I and Se; MIN (dietary supplementation of inorganic trace minerals), the CON diet was fed and one rumen sustained release boluses providing inorganic Fe, Cu, Mn, Zn, Co, I and Se were given. The milk yield and lactoferrin concentration were greater (P < 0.01) in the MIN group than those in the CON group. The MIN group had a higher yield of milk protein (P = 0.02) and lactose (P < 0.01) and a lower milk fat content (P = 0.04) than those in the CON group. Relative to the CON group, MIN group had higher (P < 0.05) milk content of Ca, P, Mg, Cu, Mn and Fe. The rumen ammonia nitrogen (NH3-N) concentration (P = 0.02) and valerate proportion (P = 0.01) were higher and acetate proportion were lower (P = 0.03) in the MIN group than those in the CON group. The relative abundances of Planctomycetes tended to be higher and the Lentisphaerae, Candidatus_Melainabacteria Erysipelotrichaceae_UCG-004 and Tenericutes_bacterium tended to be lower in MIN group. Operational taxonomic units (OTU) unique to the CON and MIN belonged mainly to the phylum Bacteroidetes and Firmicutes, respectively. The relative abundance of Candidatus_Saccharimonas, Erysipelotrichaceae_UCG-004, Ruminococcaceae_UCG-014 and Ruminococcaceae_NK4A214_group correlated positively with concentration of milk fat and acetate. Relative abundance of Succiniclasticum and Acinetobacter positively correlated with concentration of lactoferrin, milk yield, milk protein yield and milk lactose yield. Overall, these results suggest that trace mineral supply from rumen sustained release boluses has influenced milk yield, milk components and rumen microbiota of lactating yaks, which provides new insights in understanding the trace mineral metabolism, and shed lights on the trace mineral application of yaks and other ruminants lived at Qinghai-Tibetan Plateau.

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186 Hormone content of anabolic implants differentially affects plasma and liver trace mineral concentrations

Abstract Forty-eight commercial Angus steers (327 ± 25 kg) were utilized to determine effects of varying implant hormone composition on liver and plasma trace mineral concentrations. Implant (IMP) treatments (n = 12/treatment) included: no implant (CON), estradiol (E2; Compudose; 25.7 mg estradiol; Elanco Animal Health; Greenfield, IN), trenbolone acetate (TBA; Finaplix H; 200 mg trenbolone acetate; Merck Animal Health; Madison, NJ), and a combination of estradiol and trenbolone acetate (ETBA Revalor-S; 24 mg estradiol + 120 mg trenbolone acetate; Merck Animal Health). Cattle were fed forage-based step up rations throughout the sampling period. Plasma samples were collected on d 0, 2, 10 and 30, with liver biopsies collected on d 2 and 10. Data were analyzed with ProcMixed of SAS with fixed effect of IMP. Contrast statements for each treatment vs CON were developed. Plasma trace mineral analysis utilized repeated measures (repeated effect = day). No IMP × Day effects (P ≥ 0.18) on plasma trace mineral were observed. Day 2 liver Zn and Cu and d 10 liver Mn were lesser (P ≤ 0.04) for TBA implanted steers than CON and d 2 liver Mn tended to be lesser (P = 0.06). The Mn response may reflect changes in protein metabolism due to TBA. However, E2 and ETBA tended to have greater (P ≤ 0.07) d 10 liver Fe concentrations than CON while plasma Fe was unaffected (P ≥ 0.75) by E2, TBA, or ETBA. Both d 2 liver and plasma Zn were lesser for ETBA than CON (P ≤ 0.04) likely driven by the TBA in the implant. Implant contrasts did not affect (P ≥ 0.13) other plasma or liver trace mineral concentrations. These data indicate implant strategies, and thus hormones differentially influence trace mineral metabolism in feedlot steers, which may have implications for diet formulation.

Trace mineral metabolism and nutrient digestibility in lambs supplemented with zinc sulfate during an adrenocorticotropic hormone challenge

The objective was to evaluate the effects of Zn supplementation and adrenocorticotropic hormone (ACTH) injections on nutrient digestibility, trace mineral metabolism and status. It was hypothesized that ACTH would decrease nutrient digestibility and Zn retention, but Zn supplementation would improve Zn retention, regardless of ACTH administration. Twenty-two Polypay cross weathers previously enrolled in a trial, consumed a moderately Zn deplete diet (22 mg Zn/kg DM) for 52 d, followed by being housed in metabolism crates for 15 d while receiving one of two diets: CON (Zn deplete diet) or ZINC (CON plus 40 mg Zn/d from ZnSO4). Lambs rested for one day outside of crates then returned to crates for this 5 d study. Lambs continued to receive dietary Zn treatments and were randomly assigned to receive injectable treatments, once daily on d 1–4 at feeding: SALINE (2 mL saline I.M.), STRESS (80 I.U. ACTH I.M.); lamb was experimental unit (n = 5–6/treatment) in a 2 × 2 factorial design. Total fecal and urine collection was conducted on d 3–5, and blood samples were collected on d 0, 1, and 4, 3 h post feeding. Day 4 plasma Zn concentrations, covariate adjusted with d 0 concentrations, displayed a diet × injection tendency (P = 0.06) where ACTH given to ZINC lambs depressed plasma Zn to values similar to CON lambs. Day 1 and 4 cortisol concentrations determined 3 h after injection administration were increased in STRESS vs. SALINE (P < 0.01). Day 4 plasma Cu concentrations, covariate adjusted with d 0 concentrations were lesser in STRESS vs. SALINE (P = 0.04). Day 4 plasma Fe concentrations were unaffected by diet or injection treatment (P ≥ 0.18). Apparent absorption of Zn was increased (P < 0.01) in CON vs. ZINC, but were similar in STRESS vs. SALINE (P = 0.13). Zinc retention, and apparent absorption of Mn and Cu was similar across treatments (P ≥ 0.19). Organic matter (OM) digestibility tended to be decreased in ZINC vs. SALINE (P = 0.07); neutral detergent fiber (NDF) and acid detergent fiber (ADF) digestibility were decreased (P ≤ 0.04) in ZINC vs. SALINE. Injection treatment had no effect on macronutrient digestibility (P ≥ 0.37). The CON lambs were marginally Zn deficient based on plasma Zn concentrations and rate of apparent absorption, while fiber digestion was impaired by Zn supplementation. Plasma cortisol concentrations indicate lambs receiving ACTH experienced physiological stress, however this had limited effects on macro or micronutrient metabolism.

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Oxidative stress and imbalance of serum trace mineral metabolism contribute to bovine respiratory disease in dairy calves

Bovine respiratory disease (BRD) is the most common infectious cause of clinical disease and death in young calves. The study was undertaken to scrutinize a relationship between tissue damage by oxidative stress, concentrations of serum trace minerals and clinical status of calves during BRD. The method of clinical scoring and thoracic auscultation were used to screen and select infected calves. In this study, comparison of lipid peroxides (LPO), antioxidant enzymes and serum trace minerals was done between BRD infected and healthy subjects (18 calves in each group). The infected group was further divided into 3 subgroups according to clinical scores (CS) (5,6,7). The blood LPO levels were significantly higher in BRD infected calves. The antioxidative activities of superoxide dismutase, reduced glutathione, catalase and serum uric acid were significantly lower in BRD infected calves. The concentrations of trace minerals (copper, zinc, selenium) were significantly reduced during BRD. All hematobiochemical parameters varied proportionately with the CS of infected calves. These findings demonstrated simultaneous occurrence of increased oxidative stress and depletion of antioxidative trace minerals during BRD in calves. A strong correlation exists between severity of oxidative stress and CS of calves.

Zebrafish in the sea of mineral (iron, zinc, and copper) metabolism

Iron, copper, zinc, and eight other minerals are classified as essential trace elements because they present in minute in vivo quantities and are essential for life. Because either excess or insufficient levels of trace elements can be detrimental to life (causing human diseases such as iron-deficiency anemia, hemochromatosis, Menkes syndrome and Wilson's disease), the endogenous levels of trace minerals must be tightly regulated. Many studies have demonstrated the existence of systems that maintain trace element homeostasis, and these systems are highly conserved in multiple species ranging from yeast to mice. As a model for studying trace mineral metabolism, the zebrafish is indispensable to researchers. Several large-scale mutagenesis screens have been performed in zebrafish, and these screens led to the identification of a series of metal transporters and the generation of several mutagenesis lines, providing an in-depth functional analysis at the system level. Moreover, because of their developmental advantages, zebrafish have also been used in mineral metabolism-related chemical screens and toxicology studies. Here, we systematically review the major findings of trace element homeostasis studies using the zebrafish model, with a focus on iron, zinc, copper, selenium, manganese, and iodine. We also provide a homology analysis of trace mineral transporters in fish, mice and humans. Finally, we discuss the evidence that zebrafish is an ideal experimental tool for uncovering novel mechanisms of trace mineral metabolism and for improving approaches to treat mineral imbalance-related diseases.

Alterations of serum antioxidant trace elements (Se, Zn and Cu) status in patients with cutaneous leishmaniasis

ObjectiveTo assess the serum antioxidant trace elements selenium (Se), zinc (Zn) and copper (Cu) in cutaneous leishmaniasis patients. MethodsIn this study, serum Se, Zn and Cu was determined by using atomic absorption spectrometry in patients with cutaneous leishmaniasis (n=95). The values were statistically compared between patients and control group (n=100) using One-way analysis of variance (ANOVA). ResultsOur results showed that there was a significant difference in the values of Se and Zn between two groups (P<0.000 1 and P<0.01, respectively). Meanwhile, no significant difference in level of Cu was observed between patients and healthy subjects (P>0.05). Se and Zn levels were found to be (4.33±1.06) and (70.23±19.12) μg/dL in cutaneous leishmaniasis cases, and these values were found statistically lower compared to the controls (11.10±2.37) and (119.61±26.18) μg/dL, respectively. ConclusionsThe observations that host products are released from stimulated leukocytes and could induce metabolic changes similar to an acute-phase response revealed an endocrine role for the immune system. Characteristic changes in trace-mineral metabolism are an integral part of the acute-phase response. The changes are usually reflected in decreased serum Se and Zn concentrations.

Trace Minerals in Patients with End‐Stage Renal Disease

The kidneys are famously responsible for maintaining external balance of prevalent minerals, such as sodium, chloride, and potassium. The kidney's role in handling trace minerals is more obscure to most nephrologists. Similarly, the impact of kidney failure on trace mineral metabolism is difficult to anticipate. The associated dietary modifications and dialysis create the potential for trace mineral deficiencies and intoxications. Indeed, there are numerous reports of dialysis-associated mishaps causing mineral intoxication, notable for the challenge of assigning causation. Equally challenging has been the recognition of mineral deficiency syndromes, amid what is often a cacophony of multiple comorbidities that vie for the attention of clinicians who care for patients with chronic kidney disease. In this paper, I review a variety of minerals, some of which are required for maintenance of normal human physiology (the U.S. Food and Drug Administration's list of essential minerals), and some that have attracted attention in the care of dialysis patients. For each mineral, I will discuss its role in normal physiology and will review reported deficiency and toxicity states. I will point out the interesting inter-relationships between several of the elements. Finally, I will address the special concerns of aluminum and magnesium as they pertain to the dialysis population.

Trace mineral metabolism in the avian embryo

Trace mineral metabolism in the developing avian embryo begins with the formation of the egg and the trace mineral stores contained within it. Vitellogenin, the yolk precursor protein, serves as a trace mineral transporting protein that mediates the transfer of these essential nutrients from stores within the liver of the hen to the ovary and developing oocyte, and hence, to the yolk of the egg. Lipovitellin and phosvitin, derived from intraoocytic proteolytic processing of vitellogenin, are also trace mineral binding proteins that form important storage sites within the granule subfraction of yolk. The mobilization and uptake of egg trace mineral stores is mediated by the extra-embryonic membranes, principally the yolk sac membrane. The yolk sac also serves as a short-term storage site for trace minerals. Because it is an important site of plasma protein synthesis, the yolk sac has the ability to regulate the export of trace minerals to the embryo during development. Within the embryo, specific metaloproteins function in the interorgan transport cellular uptake, and intracellular storage of trace minerals. Thus, embryonic trace mineral homeostasis is established through the coordinated actions of the yolk sac, which mobilizes and exports trace minerals derived from egg stores; the vitelline circulation, which transports them to the embryo; and the liver, which accumulates trace minerals and distributes them to the rest of the tissues of the embryo via the embryonic circulation.

Cytokine control of nutrition and metabolism during critical illness

During the last two decades, major advances in technology and in our fundamental understanding of the biologic aspects of sepsis and cancer cachexia have dramatically affected the therapeutic strategies available to the surgeon to care for critically ill patients. It is clear, however, that cytokines affect whole body nutrition and metabolism and are responsible for many of the clinically observed nutritional effects of injury, infection, and cancer, including fever, hypermetabolism, anorexia, protein catabolism, cachexia, and altered fat, glucose, and trace mineral metabolism. These metabolic and nutritional effects of cytokines are influenced by the nutritional status of the host, which is generally altered during the course of the critical illness. In the future, the use of specialized diets and the use of selective cytokine blockade are likely to be important components of the overall care of the catabolic patient.

Trace minerals and the kidney: an overview.

The deviations from normal health produced by abnormalities in trace mineral metabolism in patients with renal disease and renal disorders produced by deficiencies or excesses of these trace minerals serve as the focus for this symposium on trace minerals and the kidney. Zinc, the trace mineral of most interest of the nephrologist, and aluminum, the nonessential (toxic) trace element of most interest, are treated in separate reviews. Iron, copper, selenium, and silicon (essential trace elements) and cadmium, lead, mercury, and lithium (nonessential or toxic elements) are covered in this review.

Effects of repetitive immunogen injections and fasting versus feeding on iron, zinc, and copper metabolism in chicks

Most investigations on the effect of immunogenic challenge on trace-mineral metabolism use a single immunogen injection in fasted animals. Because these investigations are not representative of realistic situations in which animals are constantly exposed to immunogens and still consume feed, the following studies were done. In Expt. 1, chicks were injected ip with sheep red blood cells (SRBC), Sephadex, SRBC+Sephadex, or saline. Chicks were then fasted or fed equal amounts of feed (equal fed) for 16 h. Immunogen injection decreased serum Fe and Zn and increased serum Cu within each feeding program. Differences in Cu, and to a lesser extent Zn, concentrations between immunogen- and saline-injected chicks were more pronounced in fasted than in equal-fed chicks. In Expt. 2, equalfed chicks were injected ip every 48 h for 6 d with SRBC+Sephadex or saline. Two days after each injection, tissues were taken. An additional group of chicks was injected once and subsequently fasted 16 h, whereupon tissues were taken. Changes in plasma Fe, Zn, Cu, and ceruloplasmin; hepatic Fe, Zn, Cu, and metallothionein; pancreatic Fe and Zn; and splenic Fe in repetitively injected chicks were different from changes observed in chicks injected once. The results indicate that the trace-mineral response to immunogenic challenge is dependent upon the number of immunogen injections and the nutritional state of the animal.

Presence of acute phase changes in zinc, iron, and copper metabolism in turkey embryos.

Acute phase changes in trace mineral metabolism were examined in turkey embryos. An endotoxin injection resulted in increased concentrations of serum copper and liver zinc and decreased concentrations of serum zinc in embryos incubated either in ovo or ex ovo. Changes in zinc and copper metabolism occurred when endotoxin either was injected intramuscularly, into the amnionic fluid, or administered onto the chorioallantoic membrane. Unlike poults, embryos did not respond to an inflammatory challenge with decreased serum iron concentrations. Acute phase changes in embryo serum zinc and copper as well as liver zinc concentrations were similar to those in poults. Increased liver zinc concentrations were associated with increased zinc in metallothionein (MT). An injection of a crude interleukin 1 preparation into embryos resulted in similar increases in hepatic zinc and MT concentrations as an endotoxin injection, suggesting a role for this cytokine in mediating the acute phase changes in embryonic zinc metabolism.

Effect of inflammatory agents and interleukin 1 on iron and zinc metabolism.

Injection of either sheep red blood cells (SRBC), Escherichia coli, endotoxin, starch, or Sephadex into chicks significantly decreased plasma iron and zinc concentrations. After injection of E. coli or SRBC, plasma zinc was decreased maximally by 52% at 12 h and 15.7% at 48 h, respectively. A second exposure to SRBC or E. coli did not further decrease plasma iron or zinc. Injection of a crude preparation of interleukin 1 isolated from endotoxin-stimulated peritoneal monocytes induced hypozincemia, hypoferremia, increased the concentration of liver metallothionein, and increased liver-zinc concentrations. It is proposed that interleukin 1 mediates the changes in trace mineral metabolism that occur during inflammation and that loss of zinc from plasma is due in part to a sequestration of zinc by liver.

Altered vitamin D, cyclic nucleotide and trace mineral metabolism in the X-linked hypophosphatemic mouse.

Hyp mice have a defective control system for the synthesis of 1,25-(OH)2-vitamin D that does not respond to a low phosphate stimulus. While the plasma levels of 25-OH-vitamin D are reduced somewhat, this seems to be not a serious defect since plasma 1,25-(OH)2-vitamin D levels are normal. Hyp kidneys synthesize and excrete elevated levels of cyclic AMP and cyclic GMP. The elevated tissue levels of trace minerals suggests increased food intake with normal intestinal absorption of the minerals. In addition there is the reduced renal tubular reabsorption of phosphate caused by a change in the brush border transport of phosphate. This leads to hypophosphatemia, osteomalacic bone disease and altered Mg metabolism. There is intestinal resistance to 1,25-(OH)2-vitamin D stimulation. Many of these defects seem unrelated to the reduced renal tubular reabsorption of phosphate. Yet all are derived from one mutation in the Hyp gene. The underlying explanation must account for all abnormalities by a single mutation in a single gene product. The near normal phosphate levels in soft tissues and the multiple defects argue against a genetic change in the phosphate pump as an ultimate explanation. Still to be explored are possible changes in a phosphate recognition site on a cell membrane or a change in an as yet unknown phosphate regulating system.

Alaskan malamute chondrodysplasia—VII. Isolation and characterization of copper, zinc and iron binding proteins in Canis familiaris

1. 1. Three low molecular weight (12,000, 10,000 and 7,000) metal binding proteins have been isolated from the livers of normal and chondrodysplastic Alaskan Malamutes. 2. 2. Comparison studies between kennel (mixed breed) dogs and both adult and immature Alaskan Malamutes suggested that the disturbance in trace mineral metabolism found in the Malamutes is almost entirely reflected in the 12,000 mol. wt species. 3. 3. The major copper-inducible protein (10,000 mol. wt) observed in kennel dogs was not found to be inducible in Malamutes and contained constant ratios of both copper and zinc to protein in metal binding proteins isolated from the livers of both normal and dwarf Malamutes. 4. 4. The copper and zinc found in the UM2 concentrates ( mol. wt > 2000 ) of immature Malamutes showed very little affinity to the proteins and these metals were found chiefly in a peptide fraction which apparently serves as a reservoir from which the storage proteins obtain the metals that they bind. 5. 5. Regression analysis indicated a statistically significant correlation between both copper and zinc concentrations and the carbohydrate concentration in the proteins investigated.