J. Anim Sci. 2007. 85:2198-2204. doi:10.2527/jas.2006-841
© 2007 American Society of Animal Science
Plasma diamine oxidase: A biomarker of copper deficiency in the bovine1,2
L. R. Legleiter and
J. W. Spears3
Department of Animal Science and Interdepartmental Nutrition Program, North Carolina State University, Raleigh 27695
 |
Abstract
|
|---|
This study was designed to test the efficacy of plasma diamine oxidase (DAO) activity as a biomarker of Cu deficiency in the bovine. Angus steers (n = 11) and heifers (n = 17) were assigned to 1 of 3 treatments: 1) control (adequate dietary Cu), 2) Cu-deficient (–Cu), and 3) Cu-deficient plus high dietary Mn (–Cu+Mn), and fed from weaning through finishing. Molybdenum (2 mg/kg of DM) was supplemented to treatments –Cu and –Cu+Mn to induce Cu deficiency via the formation of ruminal thiomolybdates. Samples were collected on 2 sampling dates (d 160 and 190) to determine the efficacy of plasma DAO activity as a biomarker of Cu deficiency. For both sampling dates, liver Cu, plasma Cu, and plasma ceruloplasmin activity indicated that cattle receiving diets designed to induce Cu deficiency (–Cu and –Cu+Mn) were Cu-deficient, with all indices of Cu status lower (P < 0.001) than the control animals. In addition to these traditional indices of Cu status, plasma DAO activity also effectively identified Cu-deficient animals because plasma DAO levels were reduced (P < 0.001) by 2- to 3-fold compared with controls. Correlation analysis indicated that plasma DAO activity was highly correlated to all other indices of Cu status (Pearson R = 0.73 to 0.87). During the growing phase, ADG (P = 0.09) and G:F (P = 0.002) were depressed in Cu-deficient animals compared with controls, whereas cattle performed equally well across all treatments in the finishing phase. The plasma DAO activity assay was precise and reliable based on an intraassay CV of 4.4% and interassay CV of 11.1%. Due to increased variability, freezing and thawing of plasma samples resulted in significant changes in DAO activity relative to fresh plasma DAO activity values. Thus, fresh plasma DAO activity, a relatively simple assay, may serve as an effective tool to diagnose Cu deficiency in the bovine.
Key Words: cattle • copper deficiency • diamine oxidase
|
INTRODUCTION
|
|---|
Copper deficiency in the bovine, a widespread problem in many areas of North America, may result in decreased growth, anemia, weak bones, cardiac failure, depigmentation of hair, and reduced reproductive efficiency (NRC, 1996
). A Cu deficiency in ruminants can occur as a primary deficiency, where Cu intake is inadequate, or as a secondary deficiency, whereby other factors in the diet interfere with the absorption or metabolism of Cu (Gengelbach et al., 1994). Copper bioavailability in ruminant diets is particularly low when Mo and S are present in moderate to high concentrations, which results in the formation of highly antagonistic thiomolybdates (Davis and Mertz, 1987; Suttle, 1991).
Currently there are several effective ways to diagnose Cu deficiency; however, each poses unique challenges. For example, assaying liver Cu requires invasive sampling procedures, and plasma Cu and plasma ceruloplasmin activity can erroneously overpredict Cu status during stress and inflammation (Cousins, 1985; DiSilvestro, 1990). Therefore, it would be advantageous to have an effective biomarker of Cu status that is easy to acquire, simple to analyze, and free of confounding factors. Plasma diamine oxidase (DAO) is a Cu-containing enzyme responsible for the oxidative deamination of diamines (cadaverine and putrescine), their derivatives, and histamine (Wolvekamp and DeBruin, 1994). A relatively simple and sensitive colorimetric assay for plasma DAO was developed by Takagi et al. (1994) and slightly modified by Kehoe et al. (2000). Further, recent research in rodent models has indicated that plasma DAO may serve as a sensitive biomarker of Cu deficiency (Kehoe et al., 2000). Thus, the objective of this study was to determine the efficacy of plasma diamine oxidase activity as a biomarker of Cu deficiency in the bovine.
|
MATERIALS AND METHODS
|
|---|
Animals and Experimental Design
All animal care, handling, and sampling procedures were approved by the North Carolina State University Animal Care and Use Committee prior to the initiation of the study. Angus steers (n = 11) and heifers (n = 17) were used to determine the efficacy of plasma diamine oxidase activity as a biomarker of Cu deficiency in the bovine. The steers and heifers were born to dams assigned to one of the following treatments: 1) control, 2) Cu-deficient (–Cu), and 3) Cu-deficient plus high dietary Mn (–Cu+Mn; Table 1). Copper deficiency alone or in combination with high Mn was induced by addition of 2 mg of Mo/kg of DM and omission of supplemental Cu from the diet. These animals were on a concurrent study evaluating the relationships between Cu, Mn, and brain prion proteins (Legleiter, 2006), explaining the need for the –Cu+Mn treatment.
After weaning (7 mo of age) calves were maintained on the same treatments (Table 1
) through 15 mo of age and were individually fed via Calan gates (American Calan, Northwood, NH). Cattle were allowed ad libitum access to a corn silage-based diet (7.0 mg Cu/kg of DM) during the growing phase (85 d) and a corn-based diet (5.4 mg Cu/kg of DM) during the finishing phase (110 d). Diets (Table 2) were formulated to meet or exceed all nutrient requirements, with the exception of Cu, for growing and finishing beef cattle (NRC, 1996). Cattle were housed in covered, slotted-floor pens (3 x 4 m) with ad libitum access to water.
Samples were collected from all animals on 2 sampling dates (160 and 190 d postweaning; sample dates 1 and 2, respectively) to assess Cu status and the effectiveness of plasma DAO as a biomarker of Cu deficiency. Blood samples were collected for the determination of plasma Cu, plasma ceruloplasmin activity, and plasma DAO activity. Blood samples were collected via jugular venipuncture into heparinized tubes specifically designed for trace mineral analysis (Vacutainer 9735, Becton Dickinson, Franklin Lakes, NJ). Blood samples were transported to the laboratory on ice and centrifuged at 1,200 x g for 20 min. The plasma not used for fresh analysis was stored in acid-washed storage tubes and frozen (–20°C) for later analysis. Liver biopsies were collected on the first sampling date to determine liver Cu stores. Liver biopsies were obtained using the true-cut technique (Pearson and Craig, 1980) as described by Engle and Spears (2000).
Analytical Procedures
Plasma and Liver Copper Analysis.
Frozen plasma was thawed at room temperature, diluted 1:3 (vol/vol) in 5% trace mineral grade nitric acid (Fisher Scientific, Fair Lawn, NJ) and centrifuged at 1,200 x g for 20 min. The supernatant was analyzed as described below. Liver samples were dried at 55°C and were subsequently prepared using a microwave digestion (Mars 5, CEM Corp., Matthews, NC) procedure described by Gengelbach et al. (1994).
Liver and plasma Cu concentrations were determined by analyzing the digested liver samples and plasma supernatant using acetylene flame atomic absorption spectroscopy (AA-6701F, Shimadzu Scientific Instruments, Kyoto, Japan). Standard curves were prepared from certified Cu reference solutions (Fisher Scientific) in a matrix similar to that of the liver and plasma samples so as to minimize any matrix effect. Further, sample Cu concentrations were determined using a minimum of duplicate measurements with an intraassay CV of 
10%. Corrections were made for baseline drift (e.g., a slight change in baseline absorbance) every 10 samples.
Ceruloplasmin Assay.
Ceruloplasmin activity of fresh plasma was determined as described by Houchin (1958). Briefly, 0.1 mL of fresh plasma (heated to 37°C) was added to 1 mL of freshly prepared 0.1% paraphenylenediamine (Sigma Chemical, St. Louis, MO) and incubated at 37°C for 30 min. The reaction was stopped by the addition of 5 mL of cold 0.02% sodium azide (Sigma). Samples and blanks were vortexed and read on a spectrophotometer (Spectronic 1001, Bausch and Lomb, Rochester, NY) at 525 nm. Ceruloplasmin activity was expressed as milligrams per deciliter via the following equation: Y1 = a + bx, where Y1 = ceruloplasmin concentration (mg/dL), a = –1.7, b = 150, and x = Cu oxidase activity in optical density units (Scheinberg et al., 1957).
Diamine Oxidase Assay.
The DAO assay was based on methods described by Takagi et al. (1994) and Kehoe et al. (2000). The DAO assay was conducted at 37°C in 96-well plates. Thirty microliters of plasma or standard were added to 20 uL of PIPES dilution buffer (Sigma) and incubated with 130 uL of cadaverine (Sigma) substrate solution (30 mM cadaverine in 25 mM PIPES buffer containing 0.5% Triton X-100, Fisher, Atlanta, GA, pH 7.2) for 30 min. After the 30-min incubation, 150 uL of color solution containing chromagen DA-67 (Wako Chemical, Osaka, Japan), ascorbate oxidase (Sigma), and peroxidase type X (Sigma) was added. Methylene blue was allowed to develop for 15 min at which point the absorbance was read at 668 nm using a microplate spectrophotometer (Synergy HT, BioTek Instruments Inc., Winooski, VT). Diamine oxidase activity (U/mL) was quantified using a standard curve prepared from porcine kidney diamine oxidase (Sigma Chemical). All samples were run in duplicate, and all reported DAO values are means based on duplicate assays with inter- and intraassay CV reported.
In addition to testing the efficacy of plasma DAO as a biomarker of Cu deficiency, the plasma DAO enzyme was tested for its stability after plasma samples were exposed to freezing and thawing. For both collection dates, plasma DAO activity was first measured on fresh plasma within a few hours of being collected. To test the effects of 1 freeze-thaw cycle, samples were frozen for 7 d at –20°C then allowed to thaw at room temperature and immediately assayed for DAO activity. This freezing and thawing cycle (7 d) was repeated on the same plasma samples to test the effect of 2 freeze-thaw cycles on DAO activity.
Statistical Analysis
Liver Cu, plasma Cu, plasma ceruloplasmin activity, and plasma DAO activity were analyzed for both sampling dates using ANOVA with PROC MIXED (SAS Inst. Inc., Cary, NC) to determine the effectiveness of each assay to diagnose Cu deficiency. Animal performance data from the growing and finishing phases were also analyzed using the MIXED procedure of SAS, with the fixed effects of treatment, sex, and treatment x sex included in the model. The following orthogonal, single df contrasts were used to separate the means: 1) control vs. –Cu and –Cu+Mn; and 2) –Cu vs. –Cu+Mn. To test the stability of the DAO enzyme after freezing and thawing, the DAO activities after 0, 1, and 2 freeze-thaw cycles were analyzed using ANOVA with the MIXED procedure of SAS. The DAO activities for each treatment were analyzed across the 3 freeze-thaw cycles. Two, single df contrasts were used to separate the means: 1) 0 (fresh) vs. 1 freeze-thaw cycle, and 2) 0 (fresh) vs. 2 freeze-thaw cycles. Pearson correlation analysis was conducted on the 4 indices of Cu status using PROC CORR of SAS. Effects were considered significant at P < 0.05.
|
RESULTS AND DISCUSSION
|
|---|
Using supplemental Mo and S to induce Cu deficiency was successful as indicated by all indices of Cu status (Table 3). Liver Cu, measured via liver biopsies taken on the first sample date, was significantly decreased (P < 0.001) in cattle receiving –Cu and –Cu+Mn relative to controls (Table 3) and averaged less than 20 mg/kg of DM, which is indicative of Cu deficiency (Underwood, 1981). Likewise, plasma Cu was decreased (P < 0.001), for both sampling dates, in cattle receiving –Cu and –Cu+Mn treatments compared with controls and averaged less than 0.5 ug/mL, which is indicative of Cu deficiency in the bovine (Underwood, 1981). On both sampling dates ceruloplasmin activity was reduced (P < 0.001) in Cu-deficient cattle (–Cu and –Cu+Mn) compared with the controls. Ceruloplasmin activities below 15 mg/dL are indicative of Cu deficiency in the bovine. These decreases in biomarkers of Cu status were expected and in agreement with others that have induced Cu deficiency in growing cattle using the antagonists Mo and S (Gengelbach et al., 1994; Arthington et al., 1996; Ward and Spears, 1997).
Interestingly, high dietary Mn (–Cu+Mn) further depressed plasma Cu compared with the –Cu diet alone on the first (P < 0.001) and second (P = 0.05) sampling dates (Table 3). It is well known that Mo in combination with S acts as a strong Cu antagonist through the formation of thiomolybdates (Allen and Gawthorne, 1987) and may lead to Cu deficiency in the bovine (Humphries et al., 1983; Phillippo et al., 1987; Gengelbach et al., 1994); however, this study suggests that high levels of Mn may further decrease Cu bioavailability when present in conjunction with Mo. Liver Cu concentrations and plasma ceruloplasmin did not differ among the –Cu and –Cu+Mn treatments.
Plasma DAO activity effectively separated Cu-deficient and Cu-adequate animals as the enzyme activity was decreased (P < 0.001) in Cu-deficient cattle compared with controls (Table 3). These data indicate that plasma DAO activity may be an effective biomarker of Cu deficiency in the bovine. Similar to plasma Cu, fresh plasma DAO activity from the second sampling date indicated that cattle receiving high dietary Mn in addition to Mo (–Cu+Mn) had a further reduced (P = 0.04) activity compared with cattle only receiving Mo (–Cu; Table 3). This may indicate that plasma Cu and plasma DAO were more sensitive than liver Cu and plasma ceruloplasmin activity in detecting differences in Cu status among cattle deficient in Cu. However, plasma DAO did not differ (P = 0.20) among cattle fed the –Cu and –Cu+Mn diets on the first sampling date, although numerically DAO tended to be lower in –Cu+Mn cattle.
The liver is the primary storage site for Cu (Underwood, 1981); thus, it is commonly sampled for determination of Cu status. Although liver Cu appears to be an accurate predictor of Cu stores, the liver biopsy technique required for sample collection poses challenges because it is an invasive procedure that requires special training. Thus, simpler and less invasive methods of determining Cu status are often used based on practicality.
The enzymatic activity assay used to measure plasma ceruloplasmin activity is relatively simple, but ceruloplasmin is an acute phase protein that is increased during inflammation and may therefore erroneously overpredict Cu status during various stresses and disease-related processes (Cousins, 1985; DiSilvestro, 1990). Rodent studies have demonstrated that the combination of moderate Cu deficiency plus inflammatory stress results in normal to above normal plasma ceruloplasmin activities (DiSilvestro, 1990; DiSilvestro and Marten, 1990).
Although plasma Cu responds nicely to Cu deficiency and is simpler and less invasive than determining liver Cu, it is influenced by factors other than Cu status. Because ceruloplasmin represents 90 to 95% of the plasma Cu content (Cousins, 1985), plasma Cu and ceruloplasmin activity are highly correlated (Underwood, 1981). Thus, any inflammatory stress causing an increase in ceruloplasmin would effectively increase plasma Cu concentrations as documented by Arthington et al. (1996). Also, in marginal Cu deficiencies, plasma Cu often does not reflect liver Cu stores (Xin et al., 1991; Arthington et al., 1996). Further, total plasma Cu may not be indicative of available Cu because some plasma Cu can be tightly bound to albumin, particularly in the presence of high dietary Mo (Smith and Wright, 1975). Therefore, it would be advantageous to have an indicator of Cu status in the bovine that is easy to acquire and simple to analyze with few confounding factors or limitations. Plasma DAO may effectively serve this purpose because this Cu-metalloenzyme has proven to be a sensitive biomarker of Cu status in humans and rodents and is relatively simple to assay (DiSilvestro et al., 1997; Jones et al., 1997; Kehoe et al., 2000). Further, DAO activity as a biomarker of Cu status may prove to be free of the confounding factors that currently limit the effectiveness of presently utilized Cu biomarkers.
Although our study indicates that DAO is adequately effective in separating Cu-deficient and Cu-adequate cattle, depending on the severity of the induced Cu deficiency, this study may not fully test the sensitivity of the DAO assay in the bovine. The disparity in the Cu status between the Cu-adequate and Cu-deficient animals, as determined by liver Cu stores, plasma Cu concentrations, and plasma ceruloplasmin activity, was large enough that it would not require an extraordinarily sensitive test to separate the 2 Cu states. Based on liver Cu and ceruloplasmin activities, the cattle receiving treatments –Cu and –Cu+Mn would be classified as severely Cu-deficient, whereas plasma Cu concentrations were indicative of moderate to severe deficiencies. In fact, in our laboratory, only one other time has an induced Cu deficiency resulted in cattle averaging less than 5 mg Cu/kg of liver DM (Legleiter et al., 2006a), and liver Cu levels rarely dropped below 7 mg/kg of DM (Stabel et al., 1993; Ward and Spears, 1997, Legleiter et al., 2006b). These extremely low levels of Cu stores and plasma Cu indices would indicate a severe Cu deficiency was achieved.
Performance characteristics were measured to determine the effects of Cu deficiency on DMI, ADG, and G:F, as well as to further characterize the severity of the Cu deficiency. Other than heifers being more efficient (P = 0.04) than steers during the finishing phase there were no effects of sex or sex x treatment; thus, only the main effects of treatment are discussed below. During the growing phase, Cu-deficient animals (–Cu and –Cu+Mn) tended (P = 0.09) to have depressed ADG compared with controls (Table 4). Further, cattle receiving the –Cu+Mn treatment had lower (P = 0.04) ADG compared with cattle receiving the –Cu diet. Copper-deficient cattle had a lower (P = 0.002) G:F in the growing phase than Cu-adequate animals. The –Cu+Mn treatment also further depressed (P = 0.02) feed efficiency within the Cu-deficient animals (Table 4). However, the depression in performance induced by Cu deficiency during the growing phase was not evident during the finishing phase where the performance characteristics were similar between Cu-deficient and Cu-adequate cattle (Table 4).
Ward et al. (1993) reported little negative effects on growth of Cu deficiency induced by Mo and S; however, their study only lasted 98 d and the Cu deficiency appears to have been less severe than in our study. Alternatively, Gengelbach et al. (1994) experimentally induced Cu deficiency, via Mo supplementation, in young growing calves, which resulted in depressed growth over a 140-d period compared with Cu-supplemented calves and to calves with experimental Cu deficiencies induced via Fe supplementation and low Cu diets. Likewise, Phillippo et al. (1987) found that beef heifers fed a low Cu diet and supplemented with 5 mg of Mo/kg of DM had depressed growth associated with a reduction in DMI and G:F. Numerous studies have described variable results with regard to cattle performance during induced Cu deficiency, which indicates that there are unknown factors that determine when and whether Cu and Mo alter performance of ruminants (Ward and Spears, 1997).
Interestingly, although the cattle in our study were severely Cu-deficient based on all indices of Cu status, no visible signs of Cu deficiency, such as depigmented hair, rough hair coats, diarrhea, or leg abnormalities (Suttle and Angus, 1976) were noted in the Cu-deficient steers and heifers. On one hand the traditional indices of Cu status and the performance depression during the growing phase indicated that cattle receiving –Cu and –Cu+Mn were severely Cu-deficient, whereas finishing phase performance was similar across all treatments and phenotypic characteristics of bovine Cu deficiency were not observed.
Pearson correlation analysis indicated that all indices of Cu status used in this study were highly correlated, with Pearson correlation coefficients ranging from 0.73 to 0.95 in sample 1 (Table 5) and 0.74 to 0.92 in sample 2 (Table 6). From the first sampling date, liver Cu and ceruloplasmin activity were most highly correlated, whereas DAO activity and ceruloplasmin activity had the lowest Pearson correlation coefficient (Table 5). Because liver biopsies were not collected on the second sampling date, plasma Cu and ceruloplasmin activity were most highly correlated, whereas DAO activity and ceruloplasmin activity again had the lowest Pearson correlation coefficient (Table 6). Although highly correlated (Pearson correlation coefficients 
0.73), relative to the other indices of Cu status, DAO activity consistently ranked the lowest in the Pearson correlation analysis for both sampling dates.
Additionally, for both sampling dates combined, the average liver Cu concentration, plasma Cu concentration, and ceruloplasmin activity of the Cu-deficient animals (–Cu and –Cu+Mn) were all lower percents of their control values than was DAO activity. Liver Cu concentrations were reduced approximately 98% in Cu-deficient animals compared with the controls. The average plasma Cu and plasma ceruloplasmin activity for Cu-deficient animals were 80 and 86% lower than in Cu-adequate animals, whereas plasma DAO activity was reduced 67% relative to Cu-adequate animals. As in the human study conducted by DiSilvestro et al. (1997), this would imply that plasma DAO may not be as sensitive as the other indices of Cu status. Similarly, Feillet-Coudray et al. (2000) found plasma Cu and ceruloplasmin activity to react more rapidly than DAO to low Cu intakes in rats and thus concluded they were more sensitive than DAO. Alternatively, Kehoe et al. (2000) found that hepatic Cu and plasma DAO activities were the only biomarkers that distinguished between rats fed Cu-adequate and Cu-marginal diets, whereas all tested indices of Cu status were able to distinguish between rats fed Cu-adequate and Cu-deficient diets. The increased sensitivity of plasma DAO in their study allowed marginal Cu deficiencies in the rats to be diagnosed earlier. As for the bovine, initial results indicate that plasma DAO is an effective biomarker of Cu status, but further testing needs to be conducted to determine the sensitivity of plasma DAO and its effectiveness in accurately and consistently identify marginally Cu-deficient animals in a production setting.
Diamine Oxidase Assay Performance
The calculated intraassay CV for the DAO assay across both sampling dates was 4.42%. The calculated interassay CV for the DAO assay, based on duplicate assays for each sampling date, was 11.1%. The standard curves created using purified DAO and used for the quantification of plasma DAO activity were highly linear as indicated by an average R2 of 0.9987.
The effects of freezing and thawing plasma samples on plasma DAO activity was tested for both sampling dates. For the first sampling date, DAO activity in plasma from control animals increased (P < 0.001) after 2 freeze-thaw cycles, but results were similar between freshly assayed plasma and that exposed to 1 freeze-thaw cycle (Figure 1). Plasma DAO activities for –Cu and –Cu+Mn were not affected by freezing and thawing.
View larger version (15K):
[in this window]
[in a new window]
|
Figure 1. The effects of freezing and thawing (freeze-thaw cycle) on sample 1 diamine oxidase (DAO) activities. Plasma samples were analyzed for DAO activity in fresh plasma (0 freeze-thaw cycles) and after 1 or 2 freeze-thaw cycles. Each freeze-thaw cycle consisted of freezing (–20°C) for 7 d followed by thawing at room temperature. The freeze-thaw cycles were analyzed using single df contrasts for each treatment. *0 (fresh) vs. 2 freeze-thaw cycles (P < 0.001). Error bars represent SEM.
|
|
For the second sampling date, plasma DAO activity of control animals was decreased (P = 0.04) after 1 freeze-thaw cycle, whereas plasma DAO activity from –Cu+Mn animals was increased (P = 0.01) after 2 freeze-thaw cycles (Figure 2). Although there appears to be no consistent change in DAO activity due to freezing and thawing, the results of this freezing and thawing test would indicate that the process of freezing and thawing plasma samples increases the variation associated with the assay for DAO activity. Thus, it would appear that running the assay on fresh plasma would be most accurate. However, even with increased variation after freezing and thawing, the plasma DAO activity assay was still able to distinguish between Cu-adequate and Cu-deficient animals.
View larger version (14K):
[in this window]
[in a new window]
|
Figure 2. The effects of freezing and thawing (freeze-thaw cycle) on sample 2 diamine oxidase (DAO) activities. Plasma samples were analyzed for DAO activity in fresh plasma (0 freeze-thaw cycles) and after 1 and 2 freeze-thaw cycles. Each freeze-thaw cycle consisted of freezing (–20°C) for 7 d followed by thawing at room temperature. The freeze-thaw cycles were analyzed using single df contrasts for each treatment. *0 (fresh) vs. 1 freeze-thaw cycle (P = 0.04); **0 (fresh) vs. 2 freeze-thaw cycles (P = 0.01). Error bars represent SEM.
|
|
Although plasma DAO may have some advantages over established biomarkers of Cu status, there are a few unique situations where plasma DAO activity may be ineffective as a biomarker of Cu deficiency in the bovine, although none have been verified in the bovine. First, because intestine and kidney are the most concentrated sources of DAO, animals with renal disease or intestinal injury may have relatively high levels of plasma DAO regardless of Cu status, as these conditions cause the release of DAO into the plasma pool (Wolvekamp and DeBruin, 1994; DiSilvestro et al., 1997). Additionally, high plasma DAO activities were observed in pregnant women and women with gestational diseases (Kusche et al., 1974).
Further research is needed to determine the efficacy and sensitivity of plasma DAO as a biomarker of Cu deficiency in field situations where cattle may have a less severe Cu deficiency than the experimental deficiency in this study. Overall, this study indicates that plasma DAO may serve as an effective tool in assessing the Cu status of and diagnosing Cu deficiency in cattle.
|
Footnotes
|
|---|
1 Use of trade names in this publication does not imply endorsement by the North Carolina Agric. Res. Serv. or criticism of similar products not mentioned. 
2 Appreciation is extended to S. Hansen, S. Fry, K. Lloyd, G. Shaeffer, J. Dickerson, and J. Woodlief for assistance in sampling and animal care.
3 Corresponding author: Jerry_Spears{at}ncsu.edu
Received for publication December 27, 2006.
Accepted for publication May 16, 2007.
|
LITERATURE CITED
|
|---|
Allen, J. D., and J. M. Gawthorne. 1987. Involvement of the solid phase of rumen digesta in the interaction between copper, molybdenum, and sulfur in sheep. Br. J. Nutr. 58:265–276.[CrossRef][Medline]
Arthington, J. D., L. R. Corah, and F. Blecha. 1996. The effect of molybdenum-induced copper deficiency on acute-phase protein concentrations, superoxide dismutase activity, leukocyte numbers, and lymphocyte proliferation in beef heifers inoculated with bovine herpesvirus-1. J. Anim. Sci. 74:211–217.[Abstract]
Cousins, R. J. 1985. Absorption, transport, and hepatic metabolism of copper and zinc: Special reference to metallothionein and ceruloplasmin. Physiol. Rev. 65:238–309.[Free Full Text]
Davis, G. K., and W. Mertz. 1987. Copper. Pages 301–364 in Trace Elements in Human and Animal Nutrition (5th ed.). W. Metz, ed. Academic Press, New York, NY.
DiSilvestro, R. A. 1990. Influence of dietary copper, copper injections and inflammation on rat serum ceruloplasmin activity levels. Nutr. Res. 10:355–358.[CrossRef]
DiSilvestro, R. A., A. A. Jones, D. Smith, and R. Wildman. 1997. Plasma diamine oxidase activities in renal dialysis patients, a human with spontaneous copper deficiency and marginally copper-deficient rats. Clin. Biochem. 30:559–563.[CrossRef][Medline]
DiSilvestro, R. A., and J. T. Marten. 1990. Effects of inflammation and copper intake on rat liver and erythrocyte Cu-Zn superoxide dismutase activity levels. J. Nutr. 120:1223–1227.[Abstract/Free Full Text]
Engle, T. E., and J. W. Spears. 2000. Effects of dietary copper concentration and source on performance and copper status of growing and finishing steers. J. Anim. Sci. 78:2446–2451.[Abstract/Free Full Text]
Feillet-Coudray, C., C. Coudray, D. Bayle, E. Rock, Y. Rayssiguier, and A. Mazur. 2000. Response of diamine oxidase and other plasma copper biomarkers to various dietary copper intakes in the rat and evaluation of copper absorption with a stable isotope. Br. J. Nutr. 83:561–568.[Medline]
Gengelbach, G. P., J. D. Ward, and J. W. Spears. 1994. Effect of dietary copper, iron, and molybdenum on growth and copper status of beef cows and calves. J. Anim. Sci. 72:2722–2727.[Abstract]
Houchin, O. B. 1958. A rapid colorimetric method for quantitative determination of copper oxidase activity (ceruloplasmin). Clin. Chem. 4:519–523.[Abstract]
Humphries, W. R., M. Phillippo, B. W. Young, and I. Bremmer. 1983. The influence of dietary iron and molybdenum on copper metabolism in calves. Br. J. Nutr. 49:77–86.[CrossRef][Medline]
Jones, A. A., R. A. DiSilvestro, M. Coleman, and T. L. Wagner. 1997. Copper supplementation of adult men: Effects on blood copper enzyme activities and indicators of cardiovascular disease risk. Metabolism 46:1380–1383.[CrossRef][Medline]
Kehoe, C. A., M. S. Faughnan, W. S. Gilmore, J. S. Coulter, A. N. Howard, and J. J. Strain. 2000. Plasma diamine oxidase activity is greater in copper-adequate than copper-marginal or copper-deficient rats. J. Nutr. 130:30–33.[Abstract/Free Full Text]
Kusche, J., U. V. Trotha, G. Muhlberger, and W. Lorenz. 1974. The clinical-chemical application of the NADPH test for the determination of diamine oxidase activity in human pregnancy. Agents Actions 4:188–189.[CrossRef][Medline]
Legleiter, L. R. 2006. The relationship between copper, manganese, and bovine brain prion proteins: Implications for trace mineral nutrition and bovine spongiform encephalopathy. PhD Diss. North Carolina State University, Raleigh.
Legleiter, L. R., H. S. Liu, and J. W. Spears. 2006a. Copper deficiency alone or in the presence of high dietary manganese does not affect brain prion protein concentration or functional characteristics in the bovine. FASEB J. 20:A1066. (Abstr.)[Free Full Text]
Legleiter, L. R., J. W. Spears, K. E. Lloyd, S. L. Hansen, and R. S. Fry. 2006b. Copper deficiency results in decreased brain copper but does not affect brain prion protein characteristics in mature Angus cows. J. Anim. Sci. 84(Suppl. 2):6. (Abstr.)
NRC. 1996. Nutrient Requirements of Beef Cattle. 7th ed. Natl. Acad. Press, Washington, DC. Pearson, E. G., and A. M. Craig. 1980. The diagnosis of liver disease in equine and food animals. Mod. Vet. Pract. 61:233–237.
Phillippo, M., W. R. Humphries, and P. H. Garthwaite. 1987. The effect of dietary molybdenum and iron on copper status and growth in cattle. J. Agric. Sci. 109:315–320.
Scheinberg, I. H., A. G. Morell, R. S. Harris, and A. Berger. 1957. Concentration of ceruloplasmin in schizophrenic patients. Science 126:925–926.[Free Full Text]
Smith, B. S. W., and H. Wright. 1975. Copper:molybdenum interaction, effect of dietary molybdenum on the binding of copper to plasma proteins in sheep. J. Comp. Pathol. 85:299–305.[CrossRef][Medline]
Stabel, J. R., J. W. Spears, and T. T. Brown, Jr. 1993. Effect of copper deficiency on tissue, blood characteristics, and immune function of calves challenged with infectious bovine rhinotracheitis virus and Pasteurella hemolytica. J. Anim. Sci. 71:1247–1255.[Abstract]
Suttle, N. F. 1991. The interactions between copper, molybdenum, and sulfur in ruminant nutrition. Annu. Rev. Nutr. 11:121–140.[Medline]
Suttle, N. F., and K. W. Angus. 1976. Experimental copper deficiency in the calf. J. Comp. Pathol. 86:595–608.[CrossRef][Medline]
Takagi, K., M. Nakao, Y. Ogura, T. Nabeshima, and A. Kunii. 1994. Sensitive colorimetric assay of serum diamine oxidase. Clin. Chim. Acta 226:67–75.[CrossRef][Medline]
Underwood, E. J. 1981. The Mineral Nutrition of Livestock (2nd ed.). Commonwealth Agric. Bureaux, Slough, UK.
Ward, J. D., and J. W. Spears. 1997. Long-term effects of consumption of low-copper diets with or without supplemental molybdenum on copper status, performance, and carcass characteristics of cattle. J. Anim. Sci. 75:3057–3065.[Abstract/Free Full Text]
Ward, J. D., J. W. Spears, and E. B. Kegley. 1993. Effect of copper level and source (copper lysine vs. copper sulfate) on copper status, performance, and immune response in growing steers fed diets with or without supplemental molybdenum and sulfur. J. Anim. Sci. 71:2748–2755.[Abstract]
Wolvekamp, M. C., and R. W. DeBruin. 1994. Diamine oxidase: An overview of historical, biochemical and functional aspects. Dig. Dis. 12:2–14.[Medline]
Xin, Z., D. F. Waterman, R. W. Hemken, and R. J. Harmon. 1991. Effects of copper status on neutrophil function, superoxide dismutase, and copper distribution in steers. J. Dairy Sci. 74:3078–3085.[Abstract]
Top
Abstract
INTRODUCTION
