Serum Cp Research Articles

Molybdenum Fertilization Improved Antioxidant Capacity of Grazing Nanjiang Brown Goat on Copper-Contaminated Pasture.

Copper (Cu) is an essential trace element, but excessive Cu intake can induce poor performance and Cu poisoning and result in various health problems. Cu and molybdenum (Mo) antagonize each other in vivo. Therefore, Mo can reduce the absorption and utilization of Cu. The aims of this study were to investigate the impacts of Mo fertilization on antioxidant capacity of grazing Nanjiang brown goat on Cu-polluted meadow and explore the control methods of Cu pollution in natural pasture. Fertilization and grazing experiments were carried out in Liangshan Yi Nationality Prefecture of the Western Sichuan Plateau, Sichuan Province, Southwest China. Cu-polluted meadows of 12 hm2 were fenced, and randomly divided into two groups (3 replications/group, 2 hm2/replication), control group and treatment group, fed with basic diets supplemented with 0 and 3 kg Mo/hm2 [ammonium molybdate tetrahydrate, (NH4)6Mo7O24·4H2O], respectively. In the current study, 36 healthy Nanjiang brown goats (1 year old, 32.8 ± 1.1 kg) were randomly divided into two groups (3 replications/group, 6 goats/replication) and assigned to the experimental pastures. The grazing experiment lasted for 60 days. The results showed that the concentration of Mo in soil in treatment group was 96.28 mg/kg, far exceeding the normal levels. At days 30 and 60, the levels of Hb, RBC, and PCV in blood in treatment group and the activities of serum SOD, GSH-Px, T-AOC, CAT, and Cp were higher than those in control group (P < 0.01). The MDA content in treatment group was lower than that in control group (P < 0.01). The contents of Cu in blood and liver in treatment goats were lower than those in control animals (P < 0.01). The contents of Zn and Mo in blood and liver in treatment goats were higher than those in control animals (P < 0.01). The Mn content in liver in treatment group was higher than that in control animals (P < 0.01). These results indicated that fertilization of (NH4)6Mo7O24 not only markedly influenced the mineral contents in blood and liver, but also extremely improved antioxidant capacity of grazing Nanjiang brown goat from fertilized pastures and relieved the damage caused by Cu pollution.

The Combinations of Sulfur and Molybdenum Fertilization Improved Antioxidant Capacity in Grazing Nanjiang Brown Goat.

To assess the impacts of sulfur (S) and molybdenum (Mo) fertilization on antioxidant capacity of grazing Nanjiang brown goat in copper (Cu)-polluted meadow, and explore the control methods of Cu pollution in natural pasture, fertilizer treatments and grazing experiments were carried out in Garzê Tibetan Autonomous Prefecture of the Western Sichuan Plateau, Sichuan Province, Southwest China. 24 hm2 Cu-polluted meadows were fenced and randomly divided into four groups (3 replications/group, 2 hm2/replication): (1) control group, no fertilizer; (2) treatment groups, applied 1 kg Mo+40 kg S, 2 kg Mo+80 kg S, and 3 kg Mo+120 kg S per hectare for group I, group II, and group III, respectively. Seventy-two healthy Nanjiang brown goats (1 year old, 30.9 ± 1.1 kg) were randomly divided into 4 groups (3 replications/group, 6 goats/replication) and assigned to the tested pastures. The grazing experiment lasted for 60 days. The results showed that the contents of N, S, Mn, Zn, and Mo in herbage in fertilized pastures were higher than those in control group (P < 0.01). The contents of Cu and Se in herbage in fertilized pastures were lower than those in control group (P < 0.01). There were no differences among the fertilized pastures (P > 0.05). The contents of Mn, Zn, Mo, and S in serum and liver in the treatment goats were higher than those in control animals (P < 0.01). The contents of Cu and Se in serum and liver in the treatment goats were lower than those in control animals (P < 0.01). There was no difference in Fe and Co contents in herbage, serum, and liver among the four groups (P > 0.05). The levels of Hb, RBC, and PCV in blood in the treatment goats and the activities of SOD, GSH-Px, T-AOC, CAT, and Cp in serum were higher than those in control goats (P < 0.01). The contents of MDA in the treatment goats were lower than those in control animals (P < 0.01). The contents of serum Cu and Mo, and liver Cu in group III were lower than those in group I and group II (P < 0.01). Taken together, the combinations of S and Mo fertilization did not influence the mineral contents in herbage, serum, and liver, but reduced the toxicity of Cu in Cu-polluted grassland and improved antioxidant capacity in grazing Nanjiang brown goat from fertilized pastures.

Male renal functions are associated with serum short- and medium-chain chlorinated paraffins in residents from Jinan, China

BackgroundChlorinated paraffins (CPs) are contaminants ubiquitously detected in environmental samples, and reports addressing CPs in human samples are expanding. While CP exposure was suggested to impair kidney function by in vivo/in vitro experiments, epidemiological evidence is lacking. ObjectiveTo examine the associations between serum total short-chain CP and medium-chain CP concentrations (∑SCCPs and ∑MCCPs) with human kidney function. MethodsThe study samples were obtained from 387 participants living in Jinan, North China. We quantified ∑SCCPs and ∑MCCPs in serum samples and evaluated the kidney function of included subjects by estimated glomerular filtration rate (eGFR). The associations between serum ∑SCCPs, ∑MCCPs and eGFR were estimated using multivariable linear regression and logistic regression. The possible gender-dependent effects were studied by stratified analysis. ResultsAfter adjusting for age, education, smoking status, drinking status, body mass index (BMI), family history of chronic kidney disease (CKD), fasting serum glucose, systolic blood pressure and diastolic blood pressure, higher concentrations of serum ∑SCCPs and ∑MCCPs were associated with higher male eGFR (β = 3.13 mL/min/1.73 m2 per one ln-unit increase of serum ∑SCCPs, 95%CI: 1.72, 4.54, p = 0.016; β = 3.52 mL/min/1.73 m2 per one ln-unit increase of serum ∑MCCPs, 95%CI: 1.89, 5.17, p = 0.011). Associations between serum ∑SCCPs, ∑MCCPs and female eGFR were null. Comparing higher (above the median serum CP levels) vs. lower exposure groups, serum ∑SCCPs and ∑MCCPs were associated with an elevated risk of glomerular hyperfiltration (GH, eGFR ≥ 135 mL/min/1.73 m2), which was associated with glomerular damage and represented as an early stage of chronic kidney disease (OR = 2.98; 95% CI: 1.24, 4.71 for SCCPs; OR = 3.25; 95% CI: 1.20, 5.29 for MCCPs). ConclusionsOur study suggests that male serum ∑SCCPs and ∑MCCPs are associated with an increased risk of GH, indicating early-stage kidney impairment.

The effects of water deprivation-induced dehydration on serum acute phase protein concentrations in sheep

The effects of dehydration on serum acute phase proteins (APPs) concentrations are unknown in sheep. In this study, it was aimed to reveal the effect of dehydration on the blood concentrations of serum amyloid a (SAA), haptoglobin (Hp), ceruloplasmin (Cp) and fibrinogen (Fb) in Kivircik cross-breeds sheep. The animal materials of the study consisted of 20 healthy sheep. They were divided into 4 equal groups: systemic inflammation group (SIG), a single dose of 5 ml Freund’s complete adjuvant (FCA) was administered intramuscularly, drinking water were provided as ad libitum; dehydration group (DEH), a single dose of 5 ml placebo 0.9% NaCl was administered intramuscularly and water was deprived for consecutive 5 days; systemic inflammation+dehydrationgroup (SIG+DEH), a single dose of 5 ml FCA was administered intramuscularly and water was deprived for consecutive 5 days; and the control group (CON), a single dose of 5 ml placebo 0.9% NaCl was administered intramuscularly and drinking water was provided as ad libitum. Also, feed was offered ad libitum throughout the experimental period in all study groups. Blood samples were collected on days 0 (baseline values), 1, 3, 5, and 7 while clinical examinations were performed daily during the study. Significant increases were found in serum Hp, SAA, Cp and plasma Fb concentrations in SIG and SIG+DEH groups. There was a significant increase only in serum Hp concentration over time in the DEH group. In conclusion, this study exhibited that Hp concentration increased as part of an acute phase reaction in water deprivation-induced dehydration in Kivircik cross-breeds sheep.

Treatment of copper deficiency in Texel-crossbred sheep by the feeding of a concentrate formulated for dairy cows

Six Texel-crossbred sheep, from a flock with a history of a dull appearance and mild diarrhea, were presented to the faculty of veterinary medicine (University of Utrecht) . The clinical signs were found to be related to Copper (Cu) deficiency as indicated by low hepatic Cu values. It was decided to treat the animals by feeding them concentrates specifically formulated for dairy cows because such concentrates have a rather high Cu content compared to concentrates designed for sheep. Sheep Cu status was monitored by measuring liver Cu concentrations. Current results indicate the potential of feeding cow concentrate as a practical method to treat Cu deficiency in Texel-crossbred sheep. In contrast to hepatic Cu concentrations, serum Ceruloplasmin concentration (Cp) values did not respond to the treatment thereby indicating that serum Cp is inferior to evaluate Cu status in sheep compared to liver Cu measurements.

Reverse regulation of hepatic ceruloplasmin production in rat model of myocardial ischemia

BackgroundCeruloplasmin (Cp) is a major copper-binding protein produced in the liver and delivers copper to extrahepatic organs. Patients with myocardial infarction are often featured by an elevation of serum copper concentrations due to copper efflux from ischemic hearts. The present study was undertaken to test the hypothesis that serum copper elevation leads to up-regulation of hepatic Cp in myocardial infarction. MethodsAdult male Sprague-Dawley rats were subjected to left anterior descending (LAD) coronary artery ligation to induce myocardial infarction. Serum copper and Cp levels, as well as changes in hepatic Cp and copper-transporting P-type ATPase (Atp7b), were determined from blood and liver samples collected on day 1, 4, or 7 after the operation. ResultsSerum copper concentrations were significantly increased on day 4 after LAD ligation, accompanied by an increase in serum Cp levels and activities. Concomitantly, the protein levels of Cp and copper exporter, Atp7b, were also significantly increased in the liver. Furthermore, inhibiting the increase of serum copper by a copper chelator, triethylenetetramine (TETA), effectively abolished the elevated Cp activity after LAD ligation. ConclusionThese results indicate that serum Cp elevation in response to myocardial ischemia most likely resulted from the increased hepatic Cp production, which in turn was more responsive to serum copper elevation than inflammatory response following myocardial ischemia.

Effects of dose and duration of dietary copper administration on hepatic lipid peroxidation and ultrastructure alteration in piglets’ model

Background: Copper is an essential microelement for animals and has been used at pharmacological doses in weaned piglets to improve growth performance. However, it also induces systemic oxidative stress after short-term feeding. The aim of this study was to investigate the effects of dose and duration of dietary copper on lipid peroxidation and oxidative stress status in model of weaned piglets. Methods: A total of 48 crossbred piglets (weaned at 21d, weight ∼8.2 kg) were randomly assigned into 4 groups of 12 in each. The control group and 3 treatment groups fed with basal diet supplemented with 20, 100 and 200 mg/kg copper as copper sulfate for 3 and 6 weeks, respectively. Results: Dietary copper supplementation significantly affected the activities of ALP, LDH, LIPC and the levels of Ca and TG in serum as well as the copper and zinc deposition in liver. Increased MDA concentrations, and decreased GPX, CP and CAT concentrations in serum were found in 0, 100 and 200 mg Cu/kg diet groups at 3 weeks post weaning. Hepatic lipid peroxidation was also induced in these groups indicated from hepatic SOD1, GPX1, CAT, CP, MT1A and MT2A transcriptional levels. Those adverse symptoms were alleviative at 6 weeks post weaning. The hepatic Cu and Zn concentrations, serum MDA concentrations, and serum CAT and GPX activities were significantly correlated with Actinobacillus, Lactobacillus, Sarcina, Helicobacter, Campylobacterales, which could affect the intestinal health further. Conclusion: These results indicated that copper deficiency or over supplementation would affect the systemic lipid peroxidation. These adverse changes were not observed when the dietary copper concentration at 20 mg Cu/kg diet. The results suggested the appropriate dietary copper concentration is around 20 mg Cu/kg diet, and its range might be much stricter than we thought.

Sarcoptes canis ile Enfekte Köpeklerde Serum Amiloid-A, Haptoglobin ve Seruloplazmin Seviyelerinin Belirlenmesi

This study was aimed to determine serum amyloid-a (SAA), haptoglobin (Hp) and ceruloplasmin (Cp) levels in dogs infected with Sarcoptes canis. The animal material of the study was consisted of 25 dogs with different age, gender and race (13 female, 12 male) which were bearing symptoms such as itching, rash and crusting and were diagnosed as Sarcoptes canis in the clinics of Internal Medicine Department of Veterinary Faculty, Kafkas University. 10 healthy dogs of different age, sex and race (4 female, 6 male) were used for the control group. Biochemical analysis revealed that the SAA and Hp values of the sick animals were statistically different than healthy animals (P<0.001). Similarly, when the serum Cp values of sick animals were compared with those of healthy animals, the difference was statistically significant (P<0.05). Obtained results showed that investigated acute phase proteins were found increased in dogs with Sarcoptes canis with local skin damage. It was concluded that acute phase proteins, SAA, Hp and Cp can be used as inflammatory indicators in sarcoptic mange in dogs.

Serum Copper Elevation Promotes Hepatic Ceruloplasmin Production and Excretion in Rat Model of Myocardial Infarction

Ceruloplasmin (Cp) is a major copper‐binding protein in blood, regulating copper homeostasis. High levels of serum copper and Cp are both risk factors for coronary artery disease, particularly in patients with acute myocardial infarction. However, the relationship between the changes in serum copper and Cp levels in response to myocardial ischemia remains unknown. It is known that myocardial ischemia causes copper efflux from the heart leading to copper elevation in the blood. The present study was undertaken to test the hypothesis that the elevation of serum copper leads to an increase in hepatic Cp production and excretion. Adult male Sprague‐Dawley rats were subjected to left anterior descending (LAD) coronary artery ligation to induce myocardial infarction. Serum copper and Cp levels, as well as changes in hepatic Cp and copper‐transporting P‐type ATPase (ATP7B), were determined from blood and liver samples harvested on day 1, 4, or 7 after the operation. Serum copper concentrations were significantly increased on day 4 after LAD ligation, accompanied by an increase in serum Cp levels and activities. Concomitantly, the protein levels of Cp and copper exporter, ATP7B, were also significantly increased in the liver. Taken together, these results indicate that the elevated serum Cp levels mostly likely result from the increase in Cp production and excretion in the liver in response to the elevated serum copper levels following myocardial ischemia.Support or Funding InformationWest China Hospital, Sichuan UniversityChanges in hepatic Cp levels. At the time of 1, 4 or 7 day after LAD ligation, the liver tissues were harvested for Western blot and mRNA analysis. (A–C) Changes in hepatic Cp protein levels. (D–E) Changes in the expression of Cp, measured by RT‐PCR. Data are presented as mean ± SD, n=5–6, *P &lt; 0.05. LAD: left anterior descending; MI: myocardial infarction.Figure 1Changes in hepatic ATP7B levels. The sample preparation was as the same as presented in Figure 3. (A–C) Western blot analysis was performed to detect the protein level at different time point. (D–E) Changes in the expression of ATP7B, measured by RT‐PCR. Data are presented as mean ± SD, n=4–6, *P &lt; 0.05. MI: myocardial infarction.Figure 2

Assessment of Ceruloplasmin, Hemopexin, and Haptoglobin in Asthmatic Children

BACKGROUND: Ceruloplasmin (Cp), haptoglobin, and hemopexin play a role in iron homeostasis and may function to modulate the systemic inflammatory response and be involved in tissue repair. We hypothesized that these proteins could be biological markers for bronchial asthma that reflect the involvement of iron oxidative stress in asthma pathogenesis.&#x0D; AIM: Evaluation of serum levels of proteins involved in iron homeostasis (Cp, hemopexin, and haptoglobin) in asthmatic children and their correlation to pulmonary functions.&#x0D; MATERIALS AND METHODS: Sixty moderate to severe persistent asthmatic children aged 6–13 years were included (30 during attacks and 30 in-between attacks). Thirty healthy matched controls were also recruited. All children were subjected to history taking, clinical evaluation and assessment of complete blood picture, serum levels of Cp, haptoglobin, hemopexin, and total IgE. Pulmonary function tests were assessed for all patients.&#x0D; RESULTS: Serum Cp and haptoglobin were significantly elevated in asthmatic children between attacks (448.04 ± 386.79), (993.33 ± 554.56) compared to controls (168.42 ± 13.46), (473.33 ± 350.3), (p = 0.0002, p &lt; 0.0001) and to asthmatics during exacerbations (288.8 ± 219.6), (620 ± 467.86), (p = 0.014, p = 0.006). Serum hemopexin was significantly higher in asthmatics between attacks (509.33 ± 341.51) compared to controls (296.67 ± 158.38) (p &lt; 0.003) but no significant difference compared to acute exacerbations (477.33 ± 396.6). No significant correlations were found between any of the assessed protein levels and pulmonary functions. Hemoglobin concentration was significantly higher among stable asthmatics compared to acute exacerbation and control groups.&#x0D; CONCLUSION: Cp, haptoglobin, and hemopexin can be used as a panel of non-invasive biomarkers that reflect the involvement of iron oxidative stress in asthma pathogenesis.

Effects of Nano-Copper Poisoning on Immune and Antioxidant Function in the Wumeng Semi-Fine Wool Sheep.

The Wumeng semi-fine wool sheep is vital to the production system of the Wumeng mountainous area in Southwest China. To study the effect of nano-copper poisoning in the Wumeng semi-fine wool sheep, nano-copper poisoning model was established in sheep. We determined blood physiological and biochemical parameters, immune indexes, and antioxidant indicators. The results showed that Hb, RBC, and PCV levels in blood from the nano-copper group were markedly lower (P < 0.01) than those in the control group. Serum LDH, AST, ALT, CPK, and Cp from the nano-copper group were significantly higher (P < 0.01) than those in control animals. Serum SOD, GSH-Px, CAT, and T-AOC from the nano-copper group were significantly lower (P < 0.01) than those in control sheep, and MDA content in serum from the nano-copper group were markedly higher (P < 0.01) than those in control sheep. The levels of IL-2, IL-6, IL-1β, IgA, IgM, and IgG from the nano-copper group were significantly lower (P < 0.01) than those in the control group. It was concluded that nano-copper poisoning could not only affect the immune function of Wumeng semi-fine wool sheep but also reduce the antioxidant capacity.

A STUDY OF PLASMA GLUCOSE AND SERUM CERULOPLASMIN IN TYPE-2 DIABETES MELLITUS (T2DM) AT A TERTIARY CARE HOSPITAL

Introduction: Diabetes mellitus (DM) is a metabolic disorder occurring due to either defect in the secretion of insulin or defect in the action of insulin characterized by hyperglycemia. Hyperglycemia causes oxidative stress due to increased production of mitochondrial Reactive oxygen species (ROS) in T2DM. Ceruloplasmin (Cp) acts as an antioxidant through its ferroxidase activity. There is an association between the raised serum Cp levels and elevated plasma glucose levels in Type-2 Diabetes mellitus (T2DM) patients.&#x0D; Aim and objectives: The aim of this study is to evaluate the correlation between the fasting plasma glucose (FPG), 2hour plasma glucose (2hPG), and serum Cp level in T2DM patients as compared to non diabetics.&#x0D; Materials and methods: 165 cases of T2DM were recruited along with the 40 healthy age and sex matched controls. The blood samples were analyzed for serum Cp and FPG and 2hPG after 75-gram oral glucose.&#x0D; Results: The serum Cp levels of the patient group with T2DM were significantly higher than the control group (p = 0.000). There was a significant positive association between serum Cp level and 2hPG level of the patient population (r = 0.283, p = 0.000), but there was no significant correlation found between serum Cp levels and fasting plasma glucose levels in patients (r = 0.146, p =0.061). Similar findings were seen in the sub group analysis.&#x0D; Conclusion: Our study concludes a significant positive correlation between serum Cp and 2hPG levels in T2DM patients. Hence Cp levels may be considered as a part of the routine diagnostic panel to assess diabetes mellitus.&#x0D; Keywords: Serum Ceruloplasmin, Type-2 Diabetes Mellitus, Fasting plasma glucose, 2hour plasma glucose

Small ruminant lentivirus infection influences expression of acute phase proteins and cathelicidin genes in milk somatic cells and peripheral blood leukocytes of dairy goats

The aim of the study was to analyze acute phase protein and cathelicidin gene responses to small ruminant lentivirus (SRLV) infection in goats. In uninfected goats, we found higher Cp and lower Fbγ mRNA levels in blood leucocytes (BL) than in milk somatic cells (MSC), as well as lower SAA, Hp, and CRP and higher Cp and AGP concentrations in blood serum than in milk. In SRLV-infected goats, we found higher Fbγ and MAP28 and lower Cp expression in MSC than in BL, and higher SAA, Hp, Fb, and MAP28 and lower AGP concentrations in milk than in blood serum. Higher SAA and Hp expressions in BL and Hp expression in MSC were found in SRLV-infected goats. In SRLV-infected goats, we observed a higher concentration of SAA in blood serum, while in milk, lower SAA, Cp, and MAP28 and higher MAP34 concentrations were observed. The expression profiles of the studied genes differed between BL/serum and MSC/milk. The elevated SAA concentration in blood serum was accompanied by a decreased concentration of SAA and Cp in the milk of infected goats. No differences in the expression of the other studied genes may mean that the SRLV has the ability to evade the immune system, continuing to replicate. The elevated concentration of SAA in blood serum may promote viral multiplication. This higher concentration of SAA in blood serum and simultaneous reduced concentration of SAA and Cp in milk may be additive indicators of this infection.

Rapid laboratory diagnosis of Wilson’s disease: One-step simultaneous detection of exchangeable copper and ceruloplasmin in serum based on nanotechnology

Monitoring the level of exchangeable copper (CuEXC) and ceruloplasmin (Cp) in serum is of great significance for Wilson’s disease (WD). In this work, a facile one-step competitive immunoassay for rapid and simultaneous detection of CuEXC and Cp has been developed based on antigens coated magnetic nanoparticles (immuno-MNPs) and antibodies functionalized quantum dots (QDs-Abs). Just by mixing immuno-MNPs, with diluted serum and QDs-Abs together, the antigens on immuno-MNPs compete with the target in serum and bind to QDs-Abs, thereby causing the changes in fluorescence intensity of QDs. Under selected conditions, this one-step method exhibited excellent precision and selectivity with the measured limit of detection of 0.2 nM and 7.0 μg/L for CuEXC and Cp, respectively. Most importantly, this method was successfully applied to detect CuEXC and Cp without the usual time-consuming pretreatment. The results showed no significant difference (P>0.01) from those of ICP-AES and ELISA; moreover, CuEXC significantly decreased to a normal level after the treatment of preliminarily diagnosed WD patients, while the changes of Cp level is not significant (P > 0.01). Therefore, the proposed one-step competitive immunoassay has great potential applications in the rapid laboratory diagnosis of WD with distinct advantages over the existing methods in terms of multi-target, accuracy, facile, fast and cost-effectiveness.

An electrochemical ceruloplasmin aptasensor using a glassy carbon electrode modified by diazonium-functionalized multiwalled carbon nanotubes

Fast and accurate determination of biological compounds in human fluids plays a crucial role in clinical analysis. Low levels and high levels of ceruloplasmin (Cp) in serum cause several diseases such as Wilson’s disease, therefore, its accurate determination in human fluids is important. A selective and sensitive electrochemical biosensor was developed for Cp detection using a Cp-specific recognition aptamer. The proposed aptasensor was based on a glassy carbon electrode modified with diazonium-functional multiwall carbon nanotubes. The aptamer was linked to the electrode surface using electrochemical approach, followed by chemical immobilization of aminated-aptamer. All fabrication steps were accompanied by changes to the electrochemical parameters. The binding of Cp to aptamer was monitored by cyclic voltammetry, differential pulse voltammetry, and electrochemical impedance spectroscopy. The effective parameters were optimized. The calibration curve for Cp concentration was linear at 0.02–3.0 ng mL−1 and 3.0–80.0 ng mL−1 with a detection limit (signal-to-noise ratio of 3) of 3.7 pg mL−1. The fabricated aptasensor can serve as a powerful sensor for rapid diagnosis of Cp in the human serum sample and shows a great potential for practical bioapplication.

Intestinal DMT1 Is Essential for Optimal Assimilation of Dietary Copper in Male and Female Mice with Iron-Deficiency Anemia

Divalent metal-ion transporter 1 (DMT1) may transport copper, but studies to date on this topic have been equivocal. Previously, an ex vivo experiment showed that intestinal copper transport was impaired in Dmt1-mutant Belgrade rats. In this study, we tested the hypothesis that intestinal DMT1 transports copper in vivo. Intestine-specific Dmt1 knockout (Dmt1int/int) mice and normal (control) littermates (Dmt1fl/fl) were used. In study 1, intestinal copper absorption was assessed in 7-wk-old mice of both sexes and genotypes by oral-intragastric gavage of 64Cu under normal and iron-deficiency anemia (IDA) conditions. In study 2, both sexes and genotypes of 8-wk-old mice were fed diets with adequate iron concentrations [72 parts per million (ppm)] plus adequate (9 ppm) or excessive (183 ppm) copper concentrations for 4 wk. Iron- and copper-related physiologic variables were subsequently assessed. Study 1 showed that intestinal copper transport was enhanced in normal (∼11% increase in males, 35% in females) and anemic (∼42% increase in males, 35% in females) Dmt1int/int mice. Study 2 showed that, with adequate copper intakes, serum ceruloplasmin (Cp) activity was decreased (by ∼29% in males and 20% in females) and spleens were enlarged (by 3-fold in both sexes) in Dmt1int/int mice. Higher dietary copper increased hepatic copper concentrations (by ∼3.3-fold in males and 1.5-fold in females), restored serum Cp activity, and mitigated the noted splenomegaly in Dmt1int/int mice. Copper homeostasis was disrupted in Dmt1int/int mice, particularly during IDA, despite the noted increases in intestinal copper transport. This was exemplified by the fact that extra dietary copper was required to restore serum Cp activity (a biomarker of copper status) and reduce the severity of the noted splenomegaly (which could reflect changes in erythropoietic demand) in Dmt1int/int mice. Collectively, these observations show that intestinal DMT1 is essential for the assimilation of sufficient quantities of dietary copper to maintain systemic copper homeostasis during IDA.

Association of Serum Ceruloplasmin Level with Parkinson’s’s Disease

Background: Parkinson’s disease, though a common neurodegenerative disease, is still elusive regarding its pathobiology. Neuronal degeneration in the midbrain substantia nigra by excess oxidative stress may play a role. As ceruloplasmin (Cp), a plasma protein is important to maintain intracellular iron homeostasis and reduce cellular oxidative stress, decreased serum Cp level may be an important factor in the pathogenesis of Parkinson’s disease. Methods: This case-control study was conducted in the department of Neurology, BSMMU. Forty-five Parkinson’s disease patients and equal number of controls were selected. Serum ceruloplasmin level was measured in the department of Biochemistry and Molecular Biology, BSMMU. Results: Mean serum Cp level was significantly lower (p-value &lt;0.001) in case (27.64 mg/dl) than in control group (33.10 mg/dl). Conclusion: The association of low serum Cp level with Parkinson’s disease may indicate a possible iron homeostasis abnormality as a pathogenic factor in Parkinson’s disease. Bangladesh Journal of Neuroscience 2018; Vol. 34 (2): 63-65

A Novel Ceruloplasmin Mutation Causing Aceruloplasminemia with Diabetes in China

Background: Hereditary aceruloplasminemia is a rare adult-onset autosomal recessive disease characterized by a ceruloplasmin(CP) gene mutation and defective or absent ceruloplasmin function. The absence of ceruloplasmin leads to pathological iron overload in the liver, pancreas, retina, and central nervous system. It is clinically characterized by diabetes mellitus, anaemia, retinal degeneration and neurological abnormalities. Material and Methods: A 34-year-old Chinese woman who had had diabetes mellitus characterized by fast plasma glucose increasing for more than 3 years. She had tried all kinds of hypoglycemic medicines,the postprandial blood glucose could be well controlled, but still had a fast hyperglycemia. Here, we reported the identification, clinical characterization, and analysis of a novel mutation in the ceruloplasmin gene of this patient and her family members. Results: Laboratory findings revealed a complete undetectable serum Cp. Increased serum ferritin levels, elevated iron saturation, as well as results of iron quantification in the liver and CT scan also suggested iron overload in the liver. Imaging examination showed a pronounced hyperintensity in the bilateral putamina, caudate, thalamus and dentate nuclei suggesting the presence of iron overload. By sequencing the ceruloplasmin gene, A novel homozygous ceruloplasmin gene mutation, c.146+1G&amp;gt;T, was identified as the cause of aceruloplasminemia in this patient. Another healthy family members were heterozygous as well. Conclusion: So far, less than 60 families cases of aceruloplasminemia have been reported world-wide and mainly missense and nonsense mutations in the ceruloplasmin gene were detected. There was only one case about aceruloplasminemia has been reported in China before. We report herein a case of aceruloplasminemia accompanied by diabetes with a novel mucutation of CP gene, which suggests that increased awareness should be paid to this disorder as diabetes is an important typical symptoms of it. Disclosure Y. Xiao: None.

Copper supplementation reverses dietary iron overload-induced pathologies in mice

Dietary iron overload in rodents impairs growth and causes cardiac hypertrophy, serum and tissue copper depletion, depression of serum ceruloplasmin (Cp) activity and anemia. Notably, increasing dietary copper content to ~25-fold above requirements prevents the development of these physiological perturbations. Whether copper supplementation can reverse these high-iron-related abnormalities has, however, not been established. The current investigation was thus undertaken to test the hypothesis that supplemental copper will mitigate negative outcomes associated with dietary iron loading. Weanling mice were thus fed AIN-93G-based diets with high (>100-fold in excess) or adequate (~80 ppm) iron content. To establish the optimal experimental conditions, we first defined the time course of iron loading, and assessed the impact of supplemental copper (provided in drinking water) on the development of high-iron-related pathologies. Copper supplementation (20 mg/L) for the last 3 weeks of a 7-week high-iron feeding period reversed the anemia, normalized serum copper levels and Cp activity, and restored tissue copper concentrations. Growth rates, cardiac copper concentrations and heart size, however, were only partially normalized by copper supplementation. Furthermore, high dietary iron intake reduced intestinal 64Cu absorption (~60%) from a transport solution provided to mice by oral, intragastric gavage. Copper supplementation of iron-loaded mice enhanced intestinal 64Cu transport, thus allowing sufficient assimilation of dietary copper to correct many of the noted high-iron-related physiological perturbations. We therefore conclude that high- iron intake increases the requirement for dietary copper (to overcome the inhibition of intestinal copper absorption).

Copper supplementation in drinking water reverses dietary iron overload‐induced anemia and cardiac hypertrophy in mice

Our previous studies showed that high‐iron (0.88% carbonyl iron) diet feeding of mice and rats lead to impaired growth, severe anemia, tissue copper depletion and cardiac hypertrophy.1,2 Interestingly, these pathophysiological perturbations were prevented by addition of extra copper to the high Fe diet, indicating the role of copper deficiency in the pathogenesis. The current study was undertaken to test the hypothesis that dietary copper supplementation to Fe overload mice could restore systemic copper status, and reverse the anemia and cardiac hypertrophy. Weanling, male C57BL/6 mice were fed AIN‐93G‐based diets containing adequate (~8 ppm) Cu in combination with adequate (~80 ppm) or high (~8000 ppm) Fe for 4 weeks. Then, the mice were given 20 mg/L Cu (as Cu sulfate) in drinking water for another 3 weeks. Subsequently, the iron and copper‐related phenotype of the mice was assessed. High‐Fe diet fed mice showed a significant growth impairment and systemic Cu deficiency, accompanied by severe anemia, decreased serum ceruloplamine (Cp) activity and cardiac hypertrophy. Cu replenishment via drinking water corrected the deficits in hemoglobin (Hb), hematocrit (HCT) and serum Cp levels, restored tissue Cu status, and reversed cardiac hypertrophy. It was further found that high‐Fe feeding significantly impaired intestinal Cu absorption, and disturbed Cu tissue distribution. This study demonstrates that high Fe consumption blocks intestinal Cu absorption, leading to a systemic Cu deficiency which resulted in a severe anemia and cardiac hypertrophy in mice. Cu supplementation corrects these physiologic perturbations. These observations provided further evidence of physiologically‐relevant iron‐copper interactions in mammals.Support or Funding InformationSupported by NIH grant 1R01 DK074867 (to J.F.C.).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.