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Morphological changes in spleen after dietary zinc deficiency and supplementation in Wistar rats

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Background: Study was conducted to determine the effect of dietary zinc deficiency and supplementation on the spleen morphology. Methods: Pre-pubertal Wistar rats (40-50 g) were divided into two groups with 6 sub-groups each viz. zinc control (ZC, 100 μg/g zinc diet), pair fed (PF, 100 μg/g zinc diet), zinc deficient (ZD, <1 μg/g zinc diet, zinc supplementation control (ZCS), zinc supplementation pair-fed (PFS) and zinc supplementation deficient (ZDS, 100 μg/g zinc control diet). Experiments were set for 2- and 4-weeks followed by 4 weeks of zinc supplementation. Results: In the present study body weight and BMI decreased significantly along with incidence of splenomegaly as typified by the increased splenic index in deficient groups compared with that of respective control groups. Histopathological changes such as disorganization of red pulp, several infiltered lymphocytes, vacuolization, loss of cellularity, karyolysis, dissolution of matrix, indistinct differentiation between red and white pulp were evident in spleen of 2ZD and 4ZD group animals. Degeneration was more severe after 4 weeks of zinc deficiency as giant cells formation and hypertrophy were also evident. Conclusion: The findings revealed that zinc deficiency causes growth retardation and splenomegaly. Degenerative and atrophic changes in rat spleen suggest reduced cellular defense potential which will have a direct effect on immunity. Zinc supplementation may prove to be beneficial as there were varying degrees of cellular recovery after cessation of zinc deficiency.

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... We could recently show that a suboptimal supply of Fe, Zn, Cu, I, and Se in mice results in splenomegaly indicating that the spleen is sensitive towards the systemic trace element status [30]. Similar effects have also been described for Zn deficiency in rats [31]. However, in this study, mice received a standard chow diet with high levels of Cu (1.5-fold the requirement) and Zn (3-fold the requirement) which were only very moderately reduced by NAC treatment. ...
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The present study investigates the effect of dietary zinc deficiency on testes of Wistar rats. Pre-pubertal rats (40-50g) were divided into three groups of 10 each viz. zinc control (ZC) and pair fed (PF) [100ppm zinc diet] and zinc deficient (ZD) [1ppm zinc diet]. Experiments were set for 2- and 4-weeks. Pre-pubertal rats fed zinc deficient diet for 2- and 4-weeks exhibited significant (P<0.05) decrease in diet consumption when compared with their respective control groups. Parallel to the reduced diet consumption, a significant (P<0.05) decrease in body and testicular weight of ZD animals was also observed. These observations indicate that the zinc deficiency reduces diet consumption and growth of the animals. Histological studies revealed degeneration in testes of ZD rats as evident by decreased seminiferous tubular diameter and Leydig cell nuclear diameter. Decreased Leydig cell nuclear diameter is responsible for disruption of the biochemical function of Leydig cell. Testicular atrophy (viz. wavy tunica propria, karyolysis, pyknosis, karyorhexis, apoptotic bodies, multinucleated giant cells, few sperms in the lumen, atrophied Leydig cells and accumulation of oedematous fluid in the interstitium) accompanied by significant loss of germ/somatic cells (viz. Type A and Type B spermatogonia, leptotene, zygotene, pachytene spermatocytes, Golgi, cap and acrosome spermatids, Sertoli and Leydig cell) was evident in ZD groups. The degeneration was severe after 4-weeks of zinc deficiency. These observations provide evidence that the functional and morphological changes in testes are probably due to zinc deficiency. Further, the increased oedematous fluid in the interstitial region is due to the cellular death. Impairment of spermatogenesis can be attributed to the direct action of zinc on testes or indirectly from Leydig cell degeneration indicating that zinc is a critical component for maintenance of both mitotic and meiotic stages of spermatogenesis.
Article
Research advances defining how zinc is transported into and out of cells and organelles have increased exponentially within the past five years. Research has progressed through application of molecular techniques including genomic analysis, cell transfection, RNA interference, kinetic analysis of ion transport, and application of cell and animal models including knockout mice. The knowledge base has increased for most of 10 members of the ZnT family and 14 members of the Zrt-, Irt-like protein (ZIP) family. Relative to the handling of dietary zinc is the involvement of ZnT1, ZIP4, and ZIP5 in intestinal zinc transport, involvement of ZIP10 and ZnT1 in renal zinc reabsorption, and the roles of ZIP5, ZnT2, and ZnT1 in pancreatic release of endogenous zinc. These events are major factors in regulation of zinc homeostasis. Other salient findings are the involvement of ZnT2 in lactation, ZIP14 in the hypozincemia of inflammation, ZIP6, ZIP7, and ZIP10 in metastatic breast cancer, and ZnT8 in insulin processing and as an autoantigen in diabetes.
Article
This study was performed to investigate the serum zinc (Zn), plasma ghrelin, leptin levels and nutritional status, and to evaluate the potential association between malnutrition and these investigated parameters in malnourished hemodialysis (HD) patients. Fifteen malnourished HD patients, aged 42.9 +/- 2.11 years, who underwent the HD for 46.44 +/- 7.1 months and 15 healthy volunteers, aged 41.0 +/- 2.17 years, were included in this study. The nutritional status of the subjects was determined by the subjective global assessment (SGA). Anthropometric measurements were taken by bioelectrical impedance after HD. Blood samples were collected for the analysis of zinc (Zn), ghrelin, leptin, and selected blood parameters. The HD patients consumed less energy and nutrients than controls. In HD patients, body weight, body mass index (BMI) (p < 0.001), basal metabolic rate (BMR), body fat, lean body mass (LBM), serum Zn, copper (Cu) (p < 0.05), sodium (Na) (p < 0.01), glucose (p < 0.05), albumin (p < 0.01), total cholesterol (p < 0.001), and ghrelin (p < 0.05) were lower whereas body water ratio (p < 0.001), serum potassium (K) (p < 0.01), inorganic phosphorous (Pi), blood urea nitrogen, creatinine (p < 0.001), and plasma insulin (p < 0.05) levels were higher than the controls. No difference existed between HD patients and controls regarding plasma leptin levels. There were positive correlations for body weight-fasting glucose and body weight-leptin (p < 0.05), body weight-BMI and body weight-LBM (p < 0.01); body fat-leptin (p < 0.05); BMI-fasting glucose, BMI-leptin, and BMI-body fat (p < 0.05); albumin-hemoglobin and albumin-insulin (p < 0.05). Negative correlation was found for SGA score-ghrelin (p < 0.05). Malnutrition in HD patients may result from inadequate energy and nutrient intake and low Zn and ghrelin levels. Zinc supplementation to the diets of HD patients may be of value to prevent the malnutrition.
Article
Zinc is an essential nutrient that is required in humans and animals for many physiological functions, including immune and antioxidant function, growth and reproduction. Many aspects of zinc deficiency-induced anorexia have been well studied in experimental animals, most notably the laboratory rat. There is evidence that suggests zinc deficiency may be intimately involved with anorexia in humans: if not as an initiating cause, then as an accelerating or exacerbating factor that may deepen the pathology of the anorexia. The present review describes recent research investigating the relationship between zinc deficiency and the regulation of food intake, along with advances in the understanding of the food intake and body weight regulation systems. For more comprehensive reviews of zinc nutrition and zinc deficiency, readers are referred to the other reviews in this volume and the review text of Mills (1989). An excellent review focused solely on zinc status and food intake has been presented by O'Dell and Reeves (1989).
Article
A syndrome occurring in males, characterized by severe iron-deficiency anemia, hypogonadism, dwarfism, hepatosplenomegaly, and geophagia, has been observed in villagers in Iran suffering from malnutrition. Eleven such patients, studied in detail, are described. Despite ht hepatosplenomegaly, results of the liver function tests were uniformly normal except for the serum all;aline phosphatase, which was consistently elevated. The anemia was not associated with blood loss, hookworm infestation, or intestinal malabsorption, and patients responded promptly to oral iron therapy. Although the diet contained adequate amounts of iron, it is believed that the predominantly wheat diet, with its high phosphate content, interfered with absorption because of the formation of insoluble iron complexes. Correction of the anemia resulted in marked decrease in the size of the liver and spleen. Prolonged follow-up of patients receiving a well balanced diet indicates that the endocrine abnormalities of growth and sexual development are reversible. The relationship of geophagia (which occurred in nearly all patients) to this syndrome is not clear and is discussed. The possibility of zinc deficiency is considered as an explanation of hypogonadism, dwarfism, and changes in alkaline phosphatase.
Article
Zinc deficiency is associated with multiple clinical complications, including taste disturbance, anorexia, growth retardation, skin changes, and hypogonadism. We investigated the zinc-deficiency-induced morphologic changes in the vallate taste buds of weanling and young adult male Wistar rats. A total of 24 weanling and 30 young adult rats were used. Each age group was further divided into a control group fed a zinc-adequate (50 ppm) diet, a zinc-deficient (< 1 ppm) diet group, and a zinc-adequate pair-fed group who were fed the same amount of food as that taken by the zinc-deficient group. Weanling rats were fed for 4 weeks and young adult rats were fed for 6 weeks. The morphometry and morphologic changes of vallate taste buds were analyzed using light and transmission electron microscopy. Light microscopy revealed no significant difference in papilla size and morphology among the various groups. In both weanling and young adult rats in the zinc-deficient diet and pair-fed groups, the number of taste buds per papilla (per animal) and the average profile area of the taste bud were significantly smaller than those of the corresponding controls (p < 0.05). Ultrastructural changes were seen only in the taste buds of weanling rats fed the zinc-deficient diet, with derangement of the architecture of the taste bud and widening of the intercellular space between taste bud cells. The proportion of type I taste bud cells in the taste buds of weanling rats fed the zinc-deficient diet decreased from 59% to 39%, and that of type II taste bud cells decreased from 25% to 12%. No obvious changes in the ultrastructure of type III taste bud cells were observed. The main effects of zinc deficiency in weanling and young adult rats and in adequate diet pair-fed rats were changes in the number and size of taste buds, and fine structure changes in the taste bud cells, especially during the accelerated growth stage after weaning.
Article
With advancing age there is a progressive decline in immune responses although this is not inevitable. The impairment in immunocompetence is noticeable as early as 35-40 years in many individuals. At the same time, some persons even in the 80s may show a vigorous immune system comparable with that of the young adult. Nutrient deficiencies are frequent in older populations. A variety of nutrients are affected: zinc, iron, beta-carotene, Vitamins B6, B12, C, D and E, ad folic acid. The causal interaction between nutritional deficiencies and impaired immunity has been known in children; a similar relationship has been postulated in the elderly. In the last 25 years, many studies employing different designs have examined the role of diet, nutritional status, and nutrient supplements in the immune responses of older individuals. Some nutrients, for example zinc and Vitamin E, have been shown to increase selected immune responses but have not been beneficial in terms of reduction in infectious morbidity. A growing consensus indicates that the use of a multinutrient containing optimum amounts of essential trace elements and vitamins is likely to result in enhanced immune responses and reduction in the occurrence of common infections. These findings have considerable fundamental, clinical and public health significance.
Article
The effects of zinc and/or melatonin deficiencies on cellular immunity were investigated in rats infected with Toxoplasma gondii. A total of 50 adult male Sprague-Dawley rats were divided into 5 groups of 10 rats each. In group I, the rats were infected with T. gondii and fed a zinc-deficient diet; in group II, the rats were infected and their pineal gland was surgically removed. Group III included rats that were infected, pinealectomized, and fed a zinc-deficient diet. Group IV consisted of T. gondii-infested rats that received no treatment of any kind, and group V were normal controls. After 3 wk of treatment, all rats were sacrificed and the percentages of CD3, CD4, and CD8 lymphocytes, zinc, and melatonin levels in plasma and the percentage of lymphocyte in blood smears were analyzed. The CD3 ratios of groups I-III were significantly lower than those of groups IV and V (p<0.01). The CD4 lymphocytes were significantly higher in group IV than that in all other groups (p<0.05). In group IV, the CD8 lymphocytes were higher than in groups I-III (p<0.01) and those in group V were higher than for groups I and III (p<0.01). Lymphocyte incidence in group IV was higher than in the other four groups (p<0.01). The plasma zinc and plasma melatonin levels in groups I-III were significantly lower than those in the controls (p<0.01, both cases). These results suggest that zinc and/or melatonin deficiency have a negative influence on cellular immunity in rats with toxoplasmosis.
Article
The present study aims to examine how zinc and testosterone supplementation, in combination and separately, affect plasma LH, FSH and leptin levels in castrated rats. Eighty experimental animals used in the study were allocated to 8 groups, each containing an equal number of rats. Group 1, control group; Group 2, castration group; Group 3, testosterone group (5 mg/kg/day); Group 4, zinc-supplemented group (3 mg/kg/day); Group 5, testosterone and zinc-supplemented group; Group 6, zinc-supplemented castration group; Group 7, testosterone and castration group; and Group 8, zinc-supplemented, testosterone and castration group. Plasma zinc, leptin, LH, FSH and free and total testosterone levels were determined in the blood samples collected from the animals by decapitation. Group 2 had the highest leptin levels and together with group 6, it also showed the highest LH and FSH levels (p<0.01). The lowest leptin levels were observed in groups 3 and 7 (p<0.01). Leptin levels in groups 4 and 6 were higher than those in groups 1, 5 and 8 (p<0.01). LH levels in group 4 were lower than those in groups 2 and 6 and higher than those in all other groups (p<0.01). Free and total testosterone levels in groups 7 and 8 were lower than those in groups 3 and 5, but higher than those in all other groups (p<0.01). Plasma LH levels may be more effective than testosterone on plasma leptin and zinc may be an important mediator of the effect LH has on leptin.
Article
The spleen contains hematopoietic and lymphoid elements, is a primary site of extramedullary hematopoiesis, and removes degenerate and aged red blood cells as well as particulate materials and circulating bacteria from the blood supply. Lesions of this important component of the immune system may center on the red pulp, the white pulp or involve both compartments The spleen is the site of direct and indirect toxicity, a target for some carcinogens, and also a site for metastatic neoplasia. Many systemic or generalized diseases have splenic involvement. This paper documents spontaneous background and treatment-induced lesions seen in rodent toxicity and carcinogenicity studies.
Article
Zinc deficiency in humans decreases the activity of serum thymulin (a thymic hormone), which is required for maturation of T-helper cells. T-helper 1 (Th(1)) cytokines are decreased but T-helper 2 (Th(2)) cytokines are not affected by zinc deficiency in humans. This shift of Th(1) to Th(2) function results in cell-mediated immune dysfunction. Because IL-2 production (Th(1) cytokine) is decreased, this leads to decreased activities of natural-killer cell and T cytolytic cells, which are involved in killing viruses, bacteria, and tumor cells. In humans, zinc deficiency may decrease the generation of new CD4+ T cells from the thymus. In cell culture studies (HUT-78, a Th(0) human malignant lymphoblastoid cell line), as a result of zinc deficiency, nuclear factor-kappaB (NF-kappaB) activation, phosphorylation of IkappaB, and binding of NF-kappaB to DNA are decreased and this results in decreased Th(1) cytokine production. In another study, zinc supplementation to humans decreased the gene expression and production of pro-inflammatory cytokines and decreased oxidative stress markers. In HL-60 cells (a human pro-myelocytic leukemia cell line), zinc deficiency increased the levels of TNF-alpha, IL-1beta, and IL-8 cytokines and mRNA. In these cells, zinc induced A20, a zinc finger protein that inhibited NF-kappaB activation via tumor necrosis factor receptor associated factor pathway, and this decreased gene expression of pro-inflammatory cytokines and oxidative stress markers. We conclude that zinc has an important role in cell-mediated immune functions and also functions as antiinflammatory and antioxidant agent.
Morphology and osmotic fragility in Wistar rat erythrocytes after zinc deficiency and supplementation
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Plasma leptin levels and body mass index in north Indian subjects: correlation with insulin resistance
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Effect of zinc deficient diet on oral tissues and periodontal indices in rats
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