Serum Mn Research Articles

Elevated thyroid manganese reduces thyroid iodine to induce hypothyroidism in mice, but not rats, lacking SLC30A10 transporter.

Elevated manganese (Mn) accumulates in the brain and induces neurotoxicity. SLC30A10 is an Mn efflux transporter that controls body Mn levels. We previously reported that full-body Slc30a10 knockout mice (1) recapitulate the body Mn retention phenotype of humans with loss-of-function SLC30A10 mutations and (2) unexpectedly develop hypothyroidism induced by Mn accumulation in the thyroid, which reduces intra-thyroid thyroxine. Subsequent analyses of National Health and Nutrition Examination Survey data identified an association between serum Mn and subclinical thyroid changes. The emergence of thyroid deficits as a feature of Mn toxicity suggests that changes in thyroid function may be an underappreciated, but critical, modulator of Mn-induced disease. To better understand the relationship between thyroid function and Mn toxicity, here we further defined the mechanism of Mn-induced hypothyroidism using mouse and rat models. Slc30a10 knockout mice exhibited a profound deficit in thyroid iodine levels that occurred contemporaneously with increases in thyroid Mn levels and preceded the onset of overt hypothyroidism. Wild-type Mn-exposed mice also exhibited increased thyroid Mn levels, an inverse correlation between thyroid Mn and iodine levels, and subclinical hypothyroidism. In contrast, thyroid iodine levels were unaltered in newly generated Slc30a10 knockout rats despite an increase in thyroid Mn levels, and the knockout rats were euthyroid. Thus, Mn-induced thyroid dysfunction in genetic or Mn exposure-induced mouse models occurs due to a reduction in thyroid iodine subsequent to an increase in thyroid Mn levels. Moreover, rat and mouse thyroids have differential sensitivities to Mn, which may impact the manifestations of Mn-induced disease in these routinely used animal models.

Influence of subchronic exposure to manganese carried by female rats during pregnancy on the behavioral and cognitive abilities of their offspring at later stages of postnatal development

The study evaluated the effects of prenatal exposure to manganese (Mn) on the functional state of offspring at later stages of postnatal development (PND). Female rats were treated with MnSO4·5H2O in the diet at a dose of 1433 mg/kg starting 28 days prior to breeding and through gestation. The pregnancy proceeded normally, no physical abnormalities were observed. There was a lag in physical development of the offspring, which was characterized by a later opening of the eyes, the formation of a coat and the eruption of incisors, the weight gain was attenuated from PND 0-84. Offspring had hyperactive behavior and deterioration in spatial learning and memory. The level of Mn in the blood serum and cerebral cortex was higher than the control values by 11 % and 53 % respectively. The acetylcholinesterase level in the serum was higher by 47 %. These findings highlight the risk of prenatal exposure to subchronic doses of Mn.

Concentrations of Bioelements (Zn, Cu, Fe, Cr, Mg, Mn) in Serum and Bone Tissue of Aging Men Undergoing Hip Arthroplasty: Implications for Erectile Dysfunction.

Background: Erectile dysfunction (ED) stands out as one of the most prevalent sexual disorders in men, with its incidence progressively escalating with age. As delineated by the International Consultation Committee for Sexual Medicine on Definitions/Epidemiology/Risk Factors for Sexual Dysfunction, the prevalence of ED among men under 40 years is estimated to be within the range of 1-10%. The aim of this study was to determine the relationship between the concentration of bioelements (Zn, Cu, Fe, Cr, Mg, and Mn) in the serum and bone tissue and the concentration of selected hormones in men with and without erectile dysfunction. Materials and methods: The retrospective cohort study included 152 men who underwent total hip arthroplasty for hip osteoarthritis at the Department of Orthopaedic Traumatology and Musculoskeletal Oncology at the Pomeranian Medical University in Szczecin. Certain exclusion criteria were applied to ensure the integrity of the study. These included individuals with diabetes, a history of cancer, alcohol abuse, liver or kidney failure, New York Heart Association (NYHA) class III or IV heart failure, and those taking medications that affect bone metabolism, such as mineral supplements, neuroleptics, chemotherapeutic agents, immunosuppressants, corticosteroids, or antidepressants. Patients with hypogonadism or infertility were excluded from the study. Results: The study showed an association between bioT concentrations and Cu concentrations in both patients with and without erectile dysfunction. A correlation between bioactive testosterone and Cr concentrations was also observed in both groups. Patients with erectile dysfunction showed a relationship between bioT concentration and Zn concentration, TT concentration and Mn concentration, FT concentration and Zn concentration, and E2 concentration and Cr concentration. An analysis of elemental concentrations in bone tissue showed an association between FT and Mg and Mn concentrations, but only in patients with erectile dysfunction. In patients without erectile dysfunction, a correlation was observed between FT and Cu concentrations. A correlation was also observed between bioT concentrations and Mg, Mn, and Zn concentrations, but only in patients with erectile dysfunction. In patients without erectile dysfunction, a correlation was observed between bioT and Cu concentrations. Conclusions: Studying the relationship between the concentration of bioelements (Zn, Cu, Fe, Cr, Mg, and Mn) in the serum and bone tissue and the concentration of selected hormones in men may be important in explaining the etiology of the problem. The study of the concentration of Zn and Cu in bone tissue and serum showed that these two elements, regardless of the place of accumulation, may be related to the concentration of androgens in men.

Low serum manganese as a noninvasive marker predicting the presence of myosteatosis among hospitalized patients with cirrhosis

Emerging evidence expands on a close connection between trace elements and muscular abnormalities, mostly focusing on sarcopenia. We hypothesized an association between concentrations of serum trace elements and myosteatosis, given that myosteatosis has a more pronounced clinical implication relative to sarcopenia, but there is a paucity of data in patients with cirrhosis. Consecutive patients were hospitalized for cirrhosis-associated complications. Serum trace elements (zinc, copper, manganese [Mn], magnesium, calcium, and iron) were measured by inductively coupled plasma mass spectrometry. The presence of myosteatosis was defined according to computed tomography–demarcated intramuscular adipose tissue content. In total, the 295 patients with cirrhosis analyzed had a median age of 63 years and 53.6% were male. Among them, 42 patients presented with myosteatosis (14.2%) and concomitant higher Model for End-stage Liver Disease-Sodium and triglyceride concentrations and lower neutrophil counts and serum Mn concentrations (all P < .05). No differences were found regarding other 5 trace elements in patients with versus without myosteatosis. The median serum Mn concentrations were 1.16 µg/L, and this population was categorized into high-Mn and low-Mn groups. The proportion of myosteatosis was significantly lower in high-Mn group than that in low-Mn group (8.1% vs 20.4%, P < .001). Univariable binary logistic regression indicated that low Mn was associated with myosteatosis (odds ratio, 2.906; 95% confidence interval, 1.424–5.932; P = .003) in the context of cirrhosis. This result was validated according to multivariable analysis by adjusting for confounding factors. In conclusion, low serum Mn can be predictive of myosteatosis, a novel muscular abnormality representing more clinical relevance and close relation to inferior outcomes among cirrhosis.

Association between blood heavy metal exposure levels and risk of metabolic dysfunction associated fatty liver disease in adults: 2015-2020 NHANES large cross-sectional study.

The relationships between heavy metals and fatty liver, especially the threshold values, have not been fully elucidated. The objective of this research was to further investigate the correlation between blood heavy metal exposures and the risk of Metabolic dysfunction Associated Fatty Liver Disease (MAFLD) in adults. Laboratory data on blood metal exposure levels were obtained from National Health and Nutrition Examination Survey (NHANES) data for the period 2015 to 2020 for a cross-sectional study in adults. Associations between blood levels of common heavy metals and the risk of MAFLD in adults were analyzed using multifactorial logistic regression and ranked for heavy metal importance using a random forest model. Finally, thresholds for important heavy metals were calculated using piecewise linear regression model. In a multifactorial logistic regression model, we found that elevated levels of selenium (Se) and manganese (Mn) blood exposure were strongly associated with the risk of MAFLD in adults. The random forest model importance ranking also found that Se and Mn blood exposure levels were in the top two positions of importance for the risk of disease in adults. The restricted cubic spline suggested a non-linear relationship between Se and Mn blood exposure and adult risk of disease. The OR (95% CI) for MAFLD prevalence was 3.936 (2.631-5.887) for every 1 unit increase in Log Mn until serum Mn levels rose to the turning point (Log Mn = 1.10, Mn = 12.61 μg/L). This correlation was not significant (p > 0.05) after serum Mn levels rose to the turning point. A similar phenomenon was observed for serum Se levels, with a turning point of (Log Se = 2.30, Se = 199.55 μg/L). Blood heavy metals, especially Se and Mn, are significantly associated with MAFLD in adults. They have a non-linear relationship with a clear threshold.

Association between serum trace element, mineral, and amino acid levels with non-alcoholic fatty liver disease (NAFLD) in adult women

The objective of the present study is assessment of serum trace element and amino acid levels in non-alcoholic fatty liver disease (NAFLD) patients with subsequent evaluation of its independent associations with markers of liver injury and metabolic risk. Materials and methods140 women aged 20–90 years old with diagnosed NAFLD and 140 healthy women with a respective age range were enrolled in the current study. Analysis of serum and hair levels of trace elements and minerals was performed with inductively-coupled plasma mass-spectrometry (ICP-MS). Serum amino acid concentrations were evaluated by high-pressure liquid chromatography (HPLC) with UV-detection. In addition, routine biochemical parameters including liver damage markers, alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT), were assessed spectrophotometrically. ResultsThe findings demonstrated that patients with NAFLD were characterized by higher ALT, GGT, lactate dehydrogenase (LDH) and cholinesterase (CE) activity, as well as increased levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, and uric acid. NAFLD patients were characterized by reduced serum and hair Co, Se, and Zn levels, as well as hair Cu content and serum Mn concentrations in comparison to controls. Circulating Ala, Cit, Glu, Gly, Ile, Leu, Phe, and Tyr levels in NAFLD patients exceeded those in the control group. Multiple linear regression demonstrated that serum and hair trace element levels were significantly associated with circulating amino acid levels after adjustment for age, BMI, and metabolic parameters including liver damage markers. ConclusionIt is proposed that altered trace element handling may contribute to NAFLD pathogenesis through modulation of amino acid metabolism.

Association between serum heavy metal levels and diabetic retinopathy in NHANES 2011–2020

The present study utilized the National Health and Nutrition Examination Survey (NHANES) database to examine the relationship between serum levels of heavy metals and Diabetic retinopathy (DR) in individuals aged over 30 years with type 2 diabetes mellitus (T2DM) in the United States. A cross-sectional analysis was conducted on 1583 individuals with T2DM from the NHANES 2011–2020, including 331 individuals in the DR group and 1252 individuals in the non-DR group. We collected data on serum levels of heavy metals, DR, and serum albumin for descriptive statistics, linear regression, and logistical regression analysis. After adjusting for age, gender, race and other factors, there was no statistically significant association between blood cadmium, selenium, mercury, or lead and DR. However, serum manganese (Mn) and DR had a significant negative association (β = − 0.2045, 95% CI = − 0.3484, − 0.0606). Serum albumin partially modulated the indirect influence of serum Mn on the incidence of DR, accounting for 12.80% of the association between serum Mn and DR. There was a negative association between serum Mn levels and the prevalence of DR in people with T2DM. Mn intake at least in this study has a little influence on the onset and development of DR.

Effects of a manganese complex with lysine and glutamic acid on growth performance, manganese deposition, and emission, antioxidant capacity and metacarpal strength in weaned piglets.

The present study sought to assess the effects of manganese complexes with lysine and glutamic acid (Mn-LG) as manganese (Mn) sources on growth performance, trace element deposition, antioxidant capacity, and metacarpal strength in weaned piglets. The study involved 288 healthy Duroc × Landrace × Yorkshire piglets that were weaned at 25 to 28 d of age and weighed 8.66 ± 0.96kg. These piglets were randomly divided into six groups: a control group (Mn-LG-0, receiving a basal diet without Mn supplementation), a Mn sulfate group (basal diet supplemented with 40 mg·kg-1 diet of Mn, Mn-S-40 group), and four Mn-LG groups (Mn-LG-20, Mn-LG-40, Mn-LG-60, Mn-LG-80, supplemented with 20, 40, 60, and 80 mg·kg-1 Mn from Mn-LG in the basal diet). Grouping began at weaning on the 0th day of the experiment. The corn-soybean-based basal diet during the early (days 0 to 14) and late (days 15 to 42) phases of the experiment contained 20.88 and 30.12 mg·kg-1 Mn, respectively. Blood samples were collected on days 14 and 42, and pigs were sacrificed for sample collection on day 42. The results indicated no significant differences in average daily gain, average daily feed intake, or feed-to-gain ratio among the groups (P > 0.05). The diarrhea rates of all Mn-LG groups and the Mn-S-40 group were significantly lower in the 0 to 14 d and during the entire experimental period than in the Mn-LG-0 group (P < 0.001). The Mn-LG-40 group exhibited a significant increase in liver Mn concentration and serum Mn superoxide dismutase (Mn-SOD) activity on day 42 (P < 0.01), as well as a significant decrease in fecal Mn concentration (P < 0.05), compared to those of the Mn-S-40 group. Significant differences (P < 0.05) were detected in the serum, liver, and fecal Mn concentrations, as well as in the serum and liver Mn-SOD activity, across the different Mn-LG groups. The serum and fecal Mn concentrations and serum Mn-SOD activity increased linearly or quadratically (P < 0.01) with increasing Mn-LG supplementation. No significant differences (P > 0.05) were found in kidney, heart, or metacarpal bone Mn concentrations or in bone strength indices. In summary, compared with the Mn-LG-0 diet, dietary supplementation with Mn-LG enhanced serum Mn deposition and Mn-SOD activity and decreased the incidence of diarrhea. Additionally, the fecal Mn concentration was lower in the Mn-LG group than in the inorganic group at equivalent dosages.

MINERAL STATUS OF LACTATING EWES IN THE ARID AND SEMI-ARID ZONES OF NORTH-CENTRAL MEXICO

Profitable sheep production depends greatly on the mineral content of range forages, as adequate nutrition is a prerequisite for reaching the animal’s optimum performance. The objective was to determine the contents of calcium (Ca), phosphorus (P), copper (Cu), zinc (Zn), and manganese (Mn) in range forages and blood serum of grazing, lactating ewes in the arid and semi-arid zones of North-Central Mexico. Samples of forages and blood of lactating ewes were collected in two seasons (spring and winter) from four randomly selected sheep farms located in the state of Aguascalientes. The P content was analyzed using the colorimetrical method, while levels of Ca, Cu, Zn, and Mn were determined by spectrophotometry. Forage mineral content averaged 0.20% P, 0.34% Ca, 8 ppm Cu, 483 ppm Mn, and 29 ppm Zn. In blood serum, mineral content reached 20 ppm P, 147 ppm Ca, 0.52 ppm Cu, 2.9 ppm Mn, and 0.80 ppm Zn in winter, and values of 20.5 ppm P, 177 ppm Ca, 0.57 ppm Cu, 3.13 ppm Mn, and 0.89 ppm Zn in spring. Overall, in both spring and winter seasons, 58-100% of sampled forages showed Ca, P, Cu, and Zn deficiencies, but all of them fitted the optimal content of Mn. Blood samples showed similar patterns in winter and spring seasons, Ca was not deficient (145-180 ppm vs. optimal range: 90-120 ppm), but P, Cu, and Zn were deficient (P: 9-21 ppm vs. optimal range: 50-65 ppm; Cu: 0.51-0.58 vs. optimal range: 0.60-1.5 ppm; and Zn: 0.71-0.92 ppm vs. optimal range: 0.50-1.2 ppm); Mn was slightly over the optimal range (2.89-3.2 μg/L vs. optimal range: 2 to 40 μg/L). In some cases, forage mineral content might not be related to blood serum contents. However, it should be desirable to understand all the uncontrolled factors in addition to the mineral interactions that could interfere with further studies.

Serum and salivary Cu/Zn ratio as a diagnostic biomarker for oral submucosal fibrosis: an analysis of trace metals and LOX gene variants.

This study aimed to analyze the serum and salivary levels of copper (Cu), zinc (Zn), iron (Fe), chromium (Cr), manganese (Mn) and the Cu/Zn ratio and investigate the association between LOX gene variants (rs18800449 and rs2288393) and oral submucosal fibrosis (OSMF). A total of 250 subjects were included in the study: OSMF patients (n = 50), areca nut chewers without OSMF (n = 100) and controls (n = 100). Trace metals were measured using an atomic absorption spectrophotometer, while LOX gene variants were genotyped using the tetra primer amplification refractory mutation system (tetra ARMS) polymerase chain reaction (PCR) method. The results showed significant variations in serum and salivary Cu, Zn, Fe and Cr levels and serum Mn concentrations among the three groups (p < 0.0001). Serum Cu levels were significantly higher in OSMF patients, while serum Zn levels were significantly lower. Both serum and salivary Cu/Zn ratios demonstrated a statistically significant difference (p < 0.0001) and diagnostic potential to differentiate OSMF from chewers and controls. However, LOX gene variants did not show an association between OSMF and chewers, except for rs1800449 genotypes, which showed a significant and increased risk with the AA genotype in OSMF patients compared to controls (OR = 7.58; 95%CI 2.30-24.97). The study suggests that trace elements and genetic variants may impact the etiology of OSMF. The findings may aid in early diagnosis, suitable treatment, and as a prognostic indicator for disease progression.

The assessment of serum trace element levels as the diagnostic biomarkers of functional state of broiler chickens.

Elemental analysis is a useful technique for predicting metabolic disorders in broiler chickens. Elemental imbalances are also important for the development of new methods to diagnose the health status of birds that can be implemented on a farm-wide scale. This study aimed to identify elemental markers related to pre-nosological diagnoses of metabolic disorders in broiler chickens. We compared birds given high-protein, high-carbohydrate, and high-fat diets. A control group received the standard diet recommended by the All-Russian Research and Technological Institute of Poultry, while experimental Group I received a diet with high-protein content, Group II received a diet with high-carbohydrate content, and Group III received a diet with high-fat content. At the end of the experiment, blood samples were taken for biochemical and elemental analysis. Biochemical analysis was carried out using an automated biochemical analyzer, and the levels of trace elements in the serum were assessed using inductively coupled plasma spectrometry. We found that the high-protein diet was accompanied by a decrease in chicken body weight, cholesterol, and several elements (i.e., P, Cr, Cu, Zn, and B) as well as an increase in the levels of Ca, Co, and Si. The high-carbohydrate diet led to a significant increase in glucose levels as well as a decrease in the levels of albumin, triglycerides, and Cr, Mn, Se, I, and Cu. Finally, the high-fat diet led to an increase in body weight, glucose, cholesterol, triglycerides, and the elements Cu, Zn, and Si as well as a decrease in the levels of Mg, Cr, and Fe. The determination of the levels of trace elements such as Co, Cr, Mn, Fe, and Cu in chicken blood serum may be an important indicator of the state of protein, carbohydrate, and lipid metabolism of poultry stock.

Oligoelements in serum and intestinal tissue of pediatric IBD patients

IntroductionInflammatory bowel disease (IBD) develops through complex interplay of genetic, microbial, immune, and environmental factors. Trace elements alterations are commonly present in IBD and may have influence on IBD development. Heavy metal pollution is one of the major environmental issues nowadays and IBD incidence is rising in countries where industry starts to develop. Metals are implicated in processes that are connected to IBD pathogenesis. AimThe aim of this study was to investigate toxic and trace element levels in pediatric population of IBD patients both in serum and intestinal mucosa. Materials and methodsThis prospective study enrolled children newly diagnosed with IBD in University children’s hospital in Belgrade. Concentrations of thirteen elements: Al, As, Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Na, Se and Zn in serum and intestinal mucosa of 17 newly diagnosed children with IBD (10 Crohn’s disease (CD) and 7ulcerative colitis (UC)) and 10 controls were assessed using inductively coupled plasma mass spectrometry (ICP-MS). Intestinal mucosa samples were taken from terminal ileum and six different colon segments (cecum, ascending colon, colon transversum, descending and sigmoid colon and rectum). ResultsThe results demonstrated significant alterations in serum and intestinal mucosa concentrations of investigated elements. Serum iron was significantly decreased in IBD and CD group, compared to controls while serum Cu significantly differed between three investigated groups with highest concentration observed in CD children. Serum manganese was the highest in the UC subgroup. Terminal ileums of IBD patients contained significantly lower amount of Cu, Mg, Mn and Zn with Mn being significantly decreased also in CD patients compared to control. IBD patients’ caecum contained significantly less Mg and Cu while colon transversum tissue samples from IBD and Crohn’s patients contained significantly more chromium than controls. Moreover, sigmoid colon of IBD patients were poorer in Mg than controls (p < 0.05). Colon Al, As and Cd were significantly reduced in IBD, and UC children compared to control. Correlations of investigated elements in CD and UC groups were different from controls. Biochemical and clinical parameters showed correlation with element concentrations in intestines. ConclusionSera of CD, UC and control children significantly differ in Fe, Cu and Mn levels. Serum manganese was the highest in the UC subgroup creating the most prominent and only significant difference between UC and CD subgroups. Terminal ileum of IBD patients contained significantly lower amount of majority of investigated essential trace elements and toxic elements were significantly reduced in colon of IBD and UC patients. Investigation of macro- and microelement alterations in children and adults has potential to further elucidate IBD pathogenesis.

Determination of some trace elements and heavy metal levels (Cu, Mn, Mg, Fe, Zn, Co, Pb, and Cd) in blood serum of patients with lip and oral cavity cancers

Determination of some trace elements and heavy metal levels (Cu, Mn, Mg, Fe, Zn, Co, Pb, and Cd) in blood serum of patients with lip and oral cavity cancers

Manganese and thyroid function in the national health and nutrition examination survey, 2011–2012

ContextManganese (Mn) exposure is prevalent, as it is found naturally as ionized trace elements and released into the environment as a byproduct of manufacturing and waste disposal. Animal and human studies have suggested variable effects on thyroid function, but the association of Mn exposure with thyroid function has not been evaluated in a national sample. ObjectiveTo investigate the associations between serum and urinary Mn levels and serum thyroid hormone concentrations in a nationally representative sample. Design, Setting, Participants, and InterventionThis was a cross-sectional analysis of data from the 2011–2012 National Health and Nutrition Examination Survey among 1360 participants. Main outcome measuresSerum thyroid stimulating hormone (TSH), total triiodothyronine (T3), total thyroxine (T4), free T3, and free T4. ResultsSerum Mn levels were positively associated with increasing total T4, free T3, and total T3 in the whole cohort (p < 0.01). Urinary Mn levels were not associated with thyroid hormone levels. When subgroup analyses were performed by gender, only males had total T4 associated with serum Mn [β = 0.01, p < 0.01, confidence interval (CI): 0.004–0.018]. In individuals under 22 years old, serum Mn was significantly associated with total T4 (β = 0.02, p = 0.002, CI: 0.008–0.029). Serum Mn was positively associated with Free T3 in both genders (β = 0.07, p < 0.001). ConclusionWhile our findings do not suggest clinical thyroid dysfunction, there is an association between serum Mn and subclinical changes in thyroid function that warrant further studies. Regulatory action should be considered as Mn-based organometallic compounds are being considered as replacements for lead in gasoline and may pose future risks to human health.

Manganese and the cGAS-STING Pathway in Infectious Mononucleosis Caused by Epstein-Barr Virus Infection.

To study the clinical significance of manganese (Mn) in the serum of children with infectious mononucleosis (IM) caused by Epstein-Barr virus (EBV) infection, we analyzed the correlation between Mn and the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway and explored the immune pathogenesis of EBV infection. Children diagnosed with IM comprised the IM group, and healthy children during the same period were selected as the normal control group. Real-time reverse transcription-polymerase chain reaction was used to detect the mRNA expression levels of cGAS, STING, Tank-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), and related inflammatory factors, and Mn in serum was detected by inductively coupled plasma mass spectrometry. Interferon (IFN)-α and IFN-β expression levels in serum were detected by enzyme-linked immunosorbent assay, and the correlation between Mn levels and clinical manifestations and laboratory tests was analyzed. Mn levels and the expression levels of cGAS, STING, and related inflammatory factors were significantly higher in children with IM than in healthy children. Furthermore, Mn levels in children with IM were positively correlated with the expression levels of cGAS and related inflammatory factors. Thus, Mn, cGAS, STING, and inflammatory cytokines may be involved in the immune mechanism of IM caused by EBV infection.

Neutrophil function and antibody production during the transition period: Effect of form of supplementary trace minerals and associations with postpartum clinical disease and blood metabolites.

Our objectives were to evaluate the effect of the form of supplementary trace minerals-inorganic salts (STM: Co, Cu, Mn, and Zn sulfates and Na selenite) or organic (OTM: Co, Cu, Mn, Zn proteinates, and selenized yeast)-fed at 100% of recommended levels in both pre- and postpartum diets on in vitro phagocytic activity of neutrophils, and in vivo IgG responses to an ovalbumin challenge during the transition period. In addition, we investigated the associations of these immunological responses with incidence of postpartum clinical diseases and the dynamic changes of metabolic markers during the transition period. Pregnant heifers and cows (n = 273) were enrolled at 45 ± 3 d before expected calving, blocked by parity and body condition score, and allocated randomly to STM or OTM supplementation. Cows in both treatments were fed the same diet, except for the form of supplementary trace minerals. Automatic feeding gates were used to assign treatments to individual cows. Blood was collected on d -7 ± 3 and 7 ± 3 relative to calving in a subgroup of cows (n = 131 and 133, respectively) to measure phagocytic activity of neutrophils in vitro using flow cytometry. Subcutaneous immunization with 0.5 mg of chicken egg ovalbumin was performed in a subgroup of cows (n = 181) on d -45, -21, and 3 relative to calving. Concentration of anti-ovalbumin IgG in serum was measured by ELISA on d -45, -21, 3, 7, and 21. Trace mineral concentrations in blood were measured by inductively coupled plasma mass spectrometry on d -45, -21, -7, 0, 7, and 21 relative to calving. Selected metabolites were measured on d -21, -10, -3, 0, 3, 7, 10, 14, and 21 relative to calving. Treatment did not affect the percentage of neutrophils performing phagocytosis on d -7 or 7 but the median fluorescence intensity of phagocytosis on d 7 was greater for OTM than STM. We found no differences between treatments in the level of anti-ovalbumin IgG in serum on any of the sampling days. Changes in neutrophil function from prepartum to postpartum were associated with incidence of postpartum clinical disease, postpartum feed intake and milk production, concentrations of Ca, K, Se, Mn, Co, and total protein in serum. Immunoglobulin G responses to ovalbumin injections were not associated with incidence of postpartum clinical disease but were associated with body weight, feed intake, energy balance, and concentrations of nonesterified fatty acids, aspartate aminotransferase, gamma-glutamyl transpeptidase, albumin, Na, P, and Cu in serum. In conclusion, replacement of STM by OTM improved one measure of phagocytic capacity of neutrophils in vitro, which was also greater in cows that did not develop postpartum clinical disease. The associations of innate and acquired immune responses with feed intake, energy balance, and circulating concentrations of key macro and micronutrients reinforce the importance of nutritional management for the health of dairy cows during the transition period.

Speciation analysis of manganese against the background of its different content in the blood serum of dairy cows.

Studies in the field of microelement speciation in the body of farm animals, in particular dairy cattle, are almost completely absent. The average concentration of Mn in the blood serum of all the studied animals (n = 80) was 2.5 μg/L, which corresponds to normal values. Of the total number of animals, 21% were the cows with the low normal values (serum Mn concentration ≤ 2 µg/L, i.e. less than Q25 of the total sample) and 25% were the animals with the high normal values (serum Mn concentration ≥ 2.72 µg/L, i.e. more than Q75 of the total sample). The data obtained in the course of the study indicate that the change in the Mn level, even in the range of normal values, is accompanied by the redistribution of this element over various protein fractions. The six found Mn blood serum forms are presumably represented by α2-macroglobulin (tetramer, dimer, and monomer), transferrin/albumine, manganese citrates, and "free" metal ions. The analyzed fractions of Mn found in the blood serum of cows had the following hierarchy of concentrations: in the group with low-normal values of Mn ("free" Mn >> tetrameric form of α2-macroglobulin >> transferrin/albumine >> dimeric form of α2-macroglobulin >> monomeric form of α2-macroglobulin >> citrate), in the group with high normal manganese values ("free" Mn >> monomeric form of α2-macroglobulin >> transferring/albumine >> citrate >> tetrameric form of α2-macroglobulin >> dimeric form of α2-macroglobulin). In the group with high normal Mn values relative to the group with low normal values, there was a percentage decrease in the tetrameric fraction of a2-macroglobulin from 17.2 to 4.4%, dimeric fraction of a2-macroglobulin from 6.9 to 2.2%, "free" Mn from 54.3 to 44.4% and an increase in monomeric fraction of a2-macroglobulin from 6.7 to 23.1%, transferrin/albumine from 10.1 to 17.7%, citrate from 4.8 to 8.2%. Our data demonstrate the features of Mn redistribution of dairy cows, which can be used for an extended assessment of the microelement status of animals.

3 Impacts of Vitamin and Mineral Supplementation to Beef Heifers During Gestation on Performance Measures of the Neonatal Calf, Trace Mineral Status, and Organ Weights at 30 Hours After Birth

Abstract Objectives were to evaluate the effects of feeding a vitamin and mineral (VTM) supplement to beef heifers during gestation on calf performance, body measurements, trace mineral status, and organ weights at 30 h after birth. We hypothesized that VTM supplementation during gestation would improve mineral status in the neonatal calf but not impact calf performance parameters and body and organ weights at 30 hours after birth. Fourteen Angus-based heifers [initial body weight (BW)] = 273.7 ± 1.10 kg) were randomly assigned to receive either a basal diet (CON; n = 7) or a basal diet plus a VTM supplement (VTM; n = 7; 113 g•heifer-1•d-1, targeting gain of 0.45 kg/day) from 60 d pre-breeding through gestation. Immediately after parturition, blood samples were collected from dams and calves, then calves were separated from their dams. Calves were fed one feeding of colostrum replacer, followed by milk replacer every 12 h, then euthanized at 30 h. Body weight and measurements were recorded, then organs and viscera were removed, weighed, and sampled. Dam serum and neonatal serum, liver, and blood were analyzed for concentrations of minerals. Data were analyzed using the GLM Procedure of SAS with individual animal as the experimental unit. Dietary treatments did not impact calf weight (0 h or 30 h), calf body measurements, or body weight of the dam at calving (P ≥ 0.32). Further, neonatal organ weights were not influenced (P ≥ 0.21) by maternal VTM treatment. Concentrations of Se and Co in calf serum and Se in calf liver were increased (P ≤ 0.02) by VTM treatment; however, concentrations of Cu, Mn, Mo, and Zn in calf muscle, liver, and serum were not impacted (P ≥ 0.07) by VTM treatment. Concentrations of Co in serum of the dam was the only mineral affected by dietary treatments, being greater (P = 0.001) in VTM than CON dams. In the current experiment providing trace mineral supplementation throughout gestation did not impact calf weight or body measurements at birth. However, the implications of altered mineral status of the neonatal calves at birth, and presumably throughout gestation, may have additional postnatal effects that warrant further investigation.

Comparison between Macro and Trace Element Concentrations in Human Semen and Blood Serum in Highly Polluted Areas in Italy.

Macro and trace elements are important regulators of biological processes, including those ones linked to reproduction. Among them, Ca, Cu, Fe, K, Mg, Mn, Na, Se, and Zn ensure normal spermatic functions. Hence, the aim of this study was to evaluate the concentrations of 26 macro and trace elements (Al, As, Ba, Be, Ca, Cd, Co, Cr, Cu, Fe, Hg, K, Li, Mg, Mn, Na, Ni, Pb, Rb, Sb, Se, Sn, Sr, U, V, and Zn) in blood serum and also in semen of healthy young men, homogeneous for age, anthropometric characteristics, and lifestyle, living in three highly polluted areas in Italy. Furthermore, a comparison among three geographical areas was performed to highlight any difference in the investigated parameters and, overall, to speculate any correlations between chemical elements and semen quality. Statistically significant differences (p < 0.05) among the three areas were found for each investigated element, in both semen and serum samples, where inter-area differences were more evident in semen than in blood serum, suggesting human semen as an early environmental marker. Considering the homogeneity of three cohorts, these differences could be due more to environmental conditions in the recruiting areas, suggesting that variations in those involved in reproductive-associated pathways can have an impact on male fertility. Nevertheless, more research is needed to evaluate threshold values for sperm dysfunction and male infertility. Actually, the role of different dietary intake and environmental exposure underlying the observed differences in the recruiting areas is under further investigation for the same cohort.

Association between Serum Level of Multiple Trace Elements and Esophageal Squamous Cell Carcinoma Risk: A Case-Control Study in China.

Simple SummaryChina accounts for half of the global new cases of esophageal cancer (EC). A disorder of individual trace elements was established as increasing risk for developing esophageal cancer, but the truth was that people are exposed to multiple metals simultaneously in the real world, and research on the relationship between mixtures of accumulative hazards and EC remains scarce. In our current research, we used BKMR, an approach designed to estimate the overall effect of a mixture, to explore the possible role of different trace elements combined in esophageal squamous cell carcinoma (ESCC) risk. In addition, some interesting results were found in our study. We hope it will provide more evidence for environment-related carcinogenesis of ESCC.We investigated the associations between multiple serum trace element levels and risk for esophageal squamous cell carcinoma (ESCC). A total of 185 ESCC patients and 191 healthy individuals were recruited in our study. The concentration of 13 trace elements (Al, V, Cr, Mn, Co, Ni, Cu, Zn, As, Se, Sr, Cd and Pb) in serum was determined with inductively coupled plasma mass spectrometry (ICP-MS). Logistic regression and the Probit extension of Bayesian Kernel Machine Regression (BKMR) models was established to explore the associations and the cumulative and mixed effects of multiple trace elements on ESCC. Three elements (Zn, Se and Sr) displayed a negative trend with risk for ESCC, and a significant overall effect of the mixture of Al, V, Mn, Ni, Zn, Se and Sr on ESCC was found, with the effects of V, Ni and Sr being nonlinear. Bivariate exposure–response interactions among these trace elements indicated a synergistic effect between Zn and Se, and an impactful difference of V combined with Ni, Sr or Zn. Our results indicate that Ni, V, Al, Mn, Zn, Se and Sr are associated with ESCC risk, providing additional evidence of the complex effects of trace elements disorder during the etiology of EC development.