Original ResearchAssociation Between Low Serum Zinc Concentration and Hypogammaglobulinemia in Foals of Different Age Categories
Introduction
Zinc (Zn) is an essential trace element, which is crucial for the development and growth of organisms. The importance of Zn in organisms was described by Bertrand et al. in the early 20th century [1], and Todd et al. in 1934 described the importance of Zn in a nutritional rat model [2].
It has been demonstrated that the suboptimal Zn status has important impact on many aspects of the immune system. Zn deficiency causes immune disorders such as lymphopenia and thymic atrophy [3], [4], [5], which are due to high losses of T and B cells precursors in the bone marrow, producing a rapid decrease of antibody and cell-mediated responses [6]. Zn has been demonstrated to be a cofactor for thymulin, a hormone that induces T cell differentiation in thymus [7], and it may be critical for the activity and binding of protein kinase C in lymphocyte membranes and for the activation/inactivation of immunoregulatory genes [8]. In addition, Haase et al. (2008) [9] described that signaling pathways for the activation of monocytes and dendritic cells in response to bacterial lipopolysaccharide require optimal Zn levels.
Moreover, monocytes, natural killer cells, and neutrophil granulocytes show decreased function after Zn depletion [10], [11], with the activity of natural killer cells and interleukin-2 production markedly decreased in Zn deficiency [12]. The production of T helper1 cell (TH1) cytokines and interferon-α by leukocytes is also decreased in Zn deficiency [13]. Zn deprivation also causes important failures in the humoral immune response. A decrease of up to 70% of B prolymphocytes has been observed owing to mitogenesis disfunction, leading to low serum concentration of immunoglobulins [14], [15] and a reduced level of antibody response to T-dependent antigens [16]. Multiple functions of the immune system and therefore the defense against pathogens are affected by Zn deficiency.
Zn deficiency also affects animal production; for example, Damir et al. (1988) [17] described that cattle with low Zn input showed general weakness, stunted growth, infertility, parakeratosis, and achromotrichia. Mills et al. (1967) [18] found that calves and lambs with Zn deficiency have a diminished weight gain. A reduction in plasma alkaline phosphatase activity was observed in sheep and lambs fed on a low Zn diet [19], [20]. Goats fed on a Zn-deficient diet developed alopecy [21]. The beneficial effects of Zn on the reproductive performance of livestock species have been extensively described, that is, pigs fed on diets supplemented with Zn oxide proved to have an increased food consumption and greater body weight gain [22], [23].
Zn deficiency is also known to cause growth disorders in foals, with reduction in plasma alkaline phosphatase activity [24]. Other signs of Zn deficiency in foals include hair loss and decreased growth rate [25]. Low level of Zn means a concentration in serum between 80 and 100 μg/dL, whereas deficiency is defined as a Zn concentration below 80 μg/dL [24]. The average Zn serum concentration has been reported to be 126 ± 26 μg/dL in race horses of Argentina, and no significant differences were reported for different foal age categories [24]; similar values were described by Cymbaluk et al. in Canada [26] and by Stubley in the United Kingdom [27]. However, literature data concerning the relationship between Zn low levels and immune system disorders in foals are scarce.
In previous works, we have found that many samples belonging to foals that had low Zn serum levels had an increased albumin/globulin ratio and a decreased γ-globulin fraction in the electrophoretic profile of proteins. Surprisingly, the foals studied in this work had total protein concentrations that were within the normal range (5.9 ± 0.55 g/dL; mean ± standard deviation [SD]) and albumin absolute values were within the normal range 3.4 ± 0.45 g/dL. The reference normal values, in percentage, for each protein fraction in adult horses are as follows: albumin, 38.405 ± 5.72; α-globulin, 19.62 ± 5.61; β-globulin, 25.56 ± 4.38; and γ-globulin, 23.98 ± 4.61. These values are similar to those described by De Vega et al [28]. The normal range for the albumin/globulin ratio previously determined in our laboratory is 1.2 ± 0.3.
The objective of this work was to evaluate Zn levels and serum protein profile in foals of different age categories. We hypothesized that serum Zn levels are associated with the level of each protein fraction in the different age-groups of foals studied. To corroborate our hypothesis, Zn, albumin, total proteins, and the albumin/globulin ratio were measured in the sera of 304 foals of different age categories. The percentage (%) of each fraction was also determined by an electrophoretic proteinogram.
Section snippets
Animals and Samples
Blood samples were collected without anticoagulant by jugular vein puncture from race horses aged between 7 and 24 months (n = 304) raised in different stud farms in the Provinces of Buenos Aires and La Pampa, Argentina. Sera were separated and stored at −20°C until used. The stud farms had controlled conditions of health and nutrition management. In all cases, the animals were fed ad libitum by grazing on natural pastures and supplemented with commercial balanced feed according to the age and
Determination of Serum Zn in Foals
We initially analyzed serum Zn concentration in foals of different age-groups, dividing the animals into two ranges, that is, normal Zn (100-160 μg/dL, 173/304) and low Zn (<100 μg/dL, 131/304; Table 1 and Fig. 1) [24], [26]. The normal mean value of serum Zn in adult horses and foals previously determined in our laboratory is 126 μg/dL, SD = 26 (normal range: 100-160 μg/dL).
In normal Zn group, the serum Zn value (μg/dL) was 137.43 ± 30.406 (mean ± SD), and in the low Zn group this value was
Discussion
Taking into account the results obtained in this study, we concluded that more than 40% of race foals produced in the best geographic areas of Argentina proved to have Zn deficiency, and this percentage varied between the different stages of foals' growth. In all cases, foals were fed on balanced diets supplemented with minerals and vitamins according to those recommended for each category. This result would indicate that either mineral supplementations currently used do not provide sufficient
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