Zn-deficient Group Research Articles

Effect of Maternal Marginal Zinc Deficiency on Development, Redox Status, and Gene Expression Related to Oxidation and Apoptosis in an Avian Embryo Model.

Maternal severe zinc (Zn) deficiency resulted in growth retardation and high mortality during embryonic development in human. Therefore, this study is aimed at evaluating the effect of maternal marginal Zn deficiency on the development and redox status to avoid severe Zn deficiency using an avian model. A total of 324 laying duck breeders at 214 days old were randomly allotted into 3 dietary Zn levels with 6 replicates of 18 ducks per replicate. The birds were fed experimental diets including 3 dietary supplemental Zn levels of 0 mg/kg (maternal Zn-deficient group, 29.2 mg Zn/kg diet), 60 mg/kg (maternal Zn-adequate group), and 120 mg/kg (maternal Zn-high group) for 6 weeks. Dietary Zn levels had on effect on egg production and fertility (P > 0.05), whereas dietary Zn deficiency decreased breeder plasma Zn concentration and erythrocytic alkaline phosphatase activity at week 6 and inhibited erythrocytic 5′-nucleotidase (5′-NT) activity at weeks 2, 4, and 6 (P < 0.05), indicating that marginal Zn-deficient status occurred after Zn depletion. Maternal marginal Zn deficiency increased embryonic mortality and contents of superoxide anion radical, MDA, and PPC and reduced MT content and CuZnSOD activity in duck embryonic livers on E29. The MDA content was positively correlated with embryonic mortality. Maternal marginal Zn deficiency increased BCL2-associated X protein and Caspase-9 mRNA expressions as well as decreased B-cell lymphoma-2 and MT1 mRNA and signal AKT1 and ERK1 protein expressions (P < 0.05). Breeder plasma Zn concentration and erythrocytic 5′-NT activities at week 6 were positively correlated with GSH-Px activity and GPx, MT1, and BCL2 mRNA expressions in embryonic livers on E29. In conclusion, erythrocytic 5′-NT activity could be more rapid and reliable to monitor marginal Zn-deficient status. Marginal Zn deficiency impaired hatchability and antioxidant defense system and then induced oxidative damage and apoptosis in the embryonic liver, contributing to the greater loss of duck embryonic death.

The status of zinc in type 2 diabetic patients and its association with glycemic control.

BACKGROUND:Zinc (Zn) is a trace element that carries antioxidant properties. Deficiency of Zn increases oxidative stress, especially in diabetes. The objective of this study was to assess the relationship between the level of Zn and glycemic control in type 2 diabetes.MATERIALS AND METHODS:A cross-sectional study was carried out in the Department of Medicine at King Abdullah bin Abdulaziz University Hospital, Riyadh, Saudi Arabia, from March 2018 to September 2018. A total of 440 participants were included in the study; 252 of these had type 2 diabetes and 188 were controls. All participants had laboratory investigations including fasting blood sugar (FBS), glycosylated hemoglobin, and lipid profile and Zn levels. These two groups (diabetics and controls) were further divided into Zn deficient group and normal Zn group according to their Zn levels. Data were analyzed by using SPSS software.RESULTS:The mean Zn level was 11.7 + 1.5 in the control group, whereas it was significantly low (9.3 + 1.6) in the diabetic group (P < 0.001). Zn deficiency in the control group was only 6.4%, while in the diabetic group, it was 67.9%, (P ≤ 0.001). The mean ages for the low Zn group and normal Zn group were 40.9 + 12.5 and 37.5 + 10.1, respectively, and the Zn deficient group was higher in age (P = 0.003). There was no significant statistical difference between genders regarding Zn deficiency. Obesity was associated with significantly low Zn levels (P = 0.016). The serum Zn level was significantly negatively associated with FBS and glycated hemoglobin in diabetic participants (P < 0.001).CONCLUSION:Diabetic patients have Zn deficiency compared to normal individuals and poor glycemic control is associated with low Zn levels.

Zinc Deficiency Promoted Fibrosis via ROS and TIMP/MMPs in the Myocardium of Mice.

Zinc (Zn) is an important trace element in the body that has antioxidant effects. It has been proven that Zn deficiency can cause oxidative stress. The purpose of the present study was to clarify the effect and mechanism of Zn deficiency on myocardial fibrosis. Mice were fed with different Zn levels dietary for 9 weeks: Zn-normal group (ZnN, 34 mg Zn/kg), Zn-deficient group (ZnD, 2 mg Zn/kg), and Zn-adequate group (ZnA, 100 mg Zn/kg). We found that the Zn-deficient diet reduced the Zn concentration in myocardial tissue. Moreover, the TUNEL results demonstrated that cardiomyocytes in the ZnD group died in large numbers. Furthermore, ROS levels were significantly increased, and metallothionein (MT) expression levels decreased in the ZnD group. The results of Sirius Red staining indicated an increase in collagen in the ZnD group. Moreover, the ELISA results showed that collagen I, III, and IV and fibronectin (FN) were increased. In addition, the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) was detected by RT-qPCR. The results showed that the expression of TIMP-1 in the ZnD group was increased, while MMPs were decreased. Immunohistochemical results showed an increase in the content of α-smooth muscle actin (α-SMA), while H&E staining showed an increase in interstitial width and a decrease in the number of cardiac cells. All data suggest that Zn deficiency enhances the oxidative stress response of myocardial tissue and eventually triggers myocardial fibrosis.

Zinc Deficiency Induces Oxidative Damage and Causes Spleen Fibrosis.

Zinc (Zn) is an essential trace element for animals. Zn controls the action of more than 300 enzymes and plays an important role in the regulation of gene expression. Evidence has shown that Zn has an antioxidant function, and oxidative damage can occur with Zn deficiency. To assess the effect of Zn deficiency-induced spleen fibrosis, Zn-deficient mice, normal mice, and high-Zn mice were generated and assessed. The Zn content of the spleen in each group was determined, and histopathological examination of the spleens of each group was performed. In the film, we found that the spleens of the Zn-deficient group had high levels of proteinaceous material exudation, interstitial broadening, and lymphocyte reduction, with increased collagen, α-SMA expression, antioxidants, and oxygen free radicals. Zn deficiency inhibited the expression of antioxidants in mice, and the activity of oxygen free radicals in Zn-deficient mice was increased. The detection of α-SMA, collagen 1, and TGF-β by fluorescence quantitative PCR revealed that the expression index increased in Zn-deficient mice. In addition, to verify the effect of Zn deficiency on the extracellular matrix (ECM) regulatory system, MMPs were determined by real-time PCR, and the expression in the Zn deficiency group was lower than that in the normal group and high-Zn group. The MMP-2 and MMP-13 analyses showed that the expression of the high-Zn group was significantly higher than that of the normal group, indicating that Zn plays an important role in its expression. The above experimental analysis showed that Zn deficiency induces oxygen free radical damage, which further leads to spleen fibrosis.

Increased Iron Deficiency and Iron Deficiency Anemia in Children with Zinc Deficiency.

The aim of the present study is to determine the presence of iron (Fe) deficiency and Fe deficiency anemia in children with zinc (Zn) deficiency. This retrospective study comprised 560 patients aged 6 months to 16 years in whom Zn levels in hair samples were measured concurrently with serum levels of ferritin, Fe, Fe-binding capacity, and blood count analysis. For all patients, we retrospectively assessed serum ferritin, serum Fe, Fe-binding capacity, transferrin saturation index, red blood cell count, hemoglobin levels, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and red cell distribution width (RDW). Patients were divided into two groups according to the level of the hair Zn level as Zn deficiency (hair Zn level <100 µg/g) and without Zn deficiency (hair Zn level >100 µg/g). Data were analyzed to determine whether there was a significant difference between any of these parameters and the presence of Fe deficiency and Fe deficiency anemia between patients with and without Zn deficiency. A total of 238 patients had Zn levels <100 µg/g, and 322 patients had Zn levels >100 µg/g. The median ferritin level was 16.2 (9.8-24.9) ng/mL in the Zn-deficient group and 18.7 (12-29.3) ng/mL in those without Zn deficiency group. The presence of Fe deficiency was higher in the Zn deficiency group (60.1%) than in the without Zn deficiency group (50%; p<0.05). The presence of Fe deficiency anemia was significantly higher in the Zn deficiency group (20.2%) than in the without Zn deficiency group (12.7%; p<0.05). There were very weak negative significant correlation between hair Zn and RDW level (r=-0.24; p<0.001) and weak positive correlation between hair Zn and MCV (r=0.31; p<0.001). Fe deficiency and Fe deficiency anemia increased in patients with zinc deficiency.

Increased vitamin B12 levels in children with zinc deficiency.

Additional nutritional deficiencies may accompany zinc deficiency. We determined the vitamin B12 levels in patients with zinc (Zn) deficiency. This retrospective study enrolled 256 patients age 6 months to 16 years (176 females and 80 males) in whom Zn levels in hair samples were measured concurrently with serum vitamin B12 and ferritin levels. For all patients, we retrospectively assessed the hair Zn levels, serum ferritin and vitamin B12 levels, red blood cell count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and red cell distribution levels. Data were analyzed to determine whether there was a significant difference between any of these parameters and the presence of vitamin B12 deficiency between patients with and without Zn deficiency. In all 118 patients had Zn levels < 100 μg/g and 138 patients had levels > 100 μg/g. No significant differences were observed in ferritin levels, red blood cell parameters, or presence of iron deficiency or anemia between the two groups (p > 0.05). The median vitamin B12 level was 323 (range 238-440) pg/mL in the Zn-deficient group and 276 (range 208-382) pg/mL in those with normal Zn levels. Vitamin B12 levels were significantly higher in the Zn-deficient group (p = 0.02). A significant negative correlation was detected between vitamin B12 levels and Zn levels (r = -0.17, p = 0.004). Vitamin B12 levels are higher in patients with Zn deficiency; thus, Zn may have a negative effect on vitamin B12 levels.

Changes of gene expressions in zinc deficiency and diet restriction in rats (1043.8)

We previously reported that both zinc deficiency and diet restriction affect total RNA concentration and expression of Gapdh and Actb in kidney. In this study, we have examined whether zinc deficiency and diet restriction affect Crebbp and Taf5l in kidney. Thirty 3‐week‐old male Sprague‐Dawley rats were assigned into 3 dietary treatment groups of 10 for the four‐week study: Control group (AIN‐93G), Zn‐deficient group (4.5 mg Zn/kg) and pair‐fed group (AIN‐93G). Kidney was separated into cortex and medulla for RNA isolation. Quantitative real time RT‐PCR using TaqMan proves was performed for mRNAs of Crebbp and Taf5l. Difference between groups was statistically analyzed by Fisher's PLSD. P value less than 0.05 was considered significant. Kidney cortex Crebbp per total RNA was not changed by the treatments. Kidney medulla Crebbp per total RNA was significantly increased by zinc deficiency and diet restriction, respectively. Kidney cortex Taf5l per total RNA was significantly increased by zinc deficiency and diet restriction, respectively. Kidney medulla Taf5l per gram tissue was significantly decreased by zinc deficiency and diet restriction, respectively. These results suggest that zinc deficiency and diet restriction differently affect expression of Crebbp and Taf5l in kidney cortex and medulla. This work was supported by KAKENHI grant‐in‐aid for Young Scientists (B) (23700928).

Cytoprotective mechanisms in rats lung parenchyma with zinc deprivation

Suboptimal intake of Zinc (Zn) is one of the most common worldwide nutritional problems. The aim of this study is to provide new evidence on the relation between moderate Zn restriction, and cytoprotective functions in airway epithelium. We analyzed the effect of moderate Zn deficiency (ZD) on the expression of several pro and anti-apoptotic proteins and cytoprotective factors (Hsp27 and Hsp 70i), as well as the effect of restoring Zn during the refeeding period. Adult male rats were divided into three groups: Zn-adequate control group, Zn-deficient group and Zn-refed group. Our previous findings showed an important oxidative and nitrosative stress during ZD, this situation is accompanied by inflammation and alterations in the expression of matrix extracellular proteins. We observed a strong immunopositive area of anti and pro-apoptotics proteins in ZD groups. The mRNA levels of Nrf-2, Bax and Bad were increased in ZD, while in ZD refed group its levels were similar to the control values. The increased expression of Nrf-2 is likely to be critical for protection of lung under inflammatory process triggered during ZD. Hsp27 and Hsp 70i showed an increase of immunostaining area but they were not significant. During the supplementation period, heat-shock proteins increased significantly. In conclusion, our results provide further evidence of the pathways involved in cytoprotection and apoptosis caused by ZD. Additional studies are required in order to investigate whether Hsp27 and Hsp70 are consistently associated with cellular stress and inflammation in lung. There may be a beneficial role for improved Zn nutrition or Zn supplements early in lung pathology.

A possible role of plasma aldosterone in hypotension secondary to iron-deficiency anaemia combined with zinc deficiency in rats

Patients with Fe-deficiency anaemia are often afflicted by hypotension. However, the mechanism of secondary hypotension in Fe-deficiency anaemia is unknown. To investigate the pathogenesis of secondary hypotension in Fe-deficiency anaemia, we examined the effects of Fe deprivation on plasma aldosterone concentration and blood pressure in rats. A total of forty 4-week-old male Sprague-Dawley rats were assigned into four treatment groups of ten each for the 4-week study: Fe-deficient group (FD), Zn-deficient group (ZD), Fe/Zn-deficient group (FZD) and control group (CON). At days 26 and 27, blood pressure was measured by the tail-cuff method. Plasma aldosterone concentration was determined by ELISA. The data were analysed by Tukey's multiple comparison test. Rats in the FZD had significantly lower mean blood pressure (P<0·01) and diastolic blood pressures (P<0·05) and plasma aldosterone concentration (P<0·01) compared to the CON. These results suggest that blood pressure is decreased in Fe-deficiency anaemia combined with Zn deficiency partly due to decreased circulating aldosterone concentrations in addition to decreased haematocrit.

Changes of erythropoietin concentrations in plasma and kidney induced by zinc deficiency in rats

Some researchers reported that oral zinc (Zn) effectively cured iron refractory anemia. We reported before that Zn deficiency depressed plasma erythropoietin (EPO) concentration in rats. We propose a hypothesis that Zn deficiency depresses EPO production in kidney. To test the hypothesis, thirty 3‐week‐old male SD rats were assigned into 3 groups of 10 for the 4‐week study receiving AIN‐93G‐based EDTA‐treated casein diet: ad libitum fed control group (AIN‐93G), moderate Zn‐deficient group (4.5 mg Zn/kg diet) and pair‐fed group (AIN‐93G). Plasma and kidney (medulla and cortex) EPO concentrations were measured using ELISA kit. Difference between groups was statistically analyzed by Fisher's PLSD. P value less than 0.05 was considered significant. Plasma EPO concentration of Zn‐deficient group was significantly decreased compared with control group, and pair‐fed group was marginally decreased compared with control group (P=0.056). Kidney medulla EPO concentration was decreased in Zn‐deficient group compared with pair‐fed group. Kidney medulla EPO concentration in pair‐fed group was higher than that of control group but the difference was not significant. No significant difference was observed in kidney cortex EPO concentration. These results support the hypothesis that Zn deficiency impairs EPO production in kidney.This work was supported by Japan Society for the Promotion of Science Young Scientists (Start‐up) (21800073).

Alteration in the expression of inflammatory parameters as a result of oxidative stress produced by moderate zinc deficiency in rat lung

ABSTRACTSuboptimal intake of dietary zinc (Zn) is one of the most common nutritional problems worldwide. Previously, the authors have shown that zinc deficiency (ZD) produces oxidative and nitrosative stress in lung of male rats. The goal of this study is to test the effect of moderate ZD on insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-5, NADH oxidase (NOX)-2, tumor necrosis factor alpha (TNFα), as well as the effect of restoring zinc during the refeeding period. Adult male rats were divided into 3 groups: Zn-adequate control group, Zn-deficient group, and Zn-refeeding group. eNOS, metallothionein (MT) II, and NOX-2 was increased in ZD group. The authors observed an increased gene transcription of superoxide dismutase (SOD)-2 and gluthathione peroxidase (GPx)-1 in ZD group, as well as in ZD-refeeding group, but catalase (CAT) transcription did not change in the treated groups. Proinflammatory factors, such as TNFα and vascular cell adhesion molecular (VCAM)-1 increased in ZD, whereas it decreased in ZD refeeding. However, peroxisome proliferator-activated receptor gamma (PPARγ) and IGF-1 gene transcription decreased in ZD, whereas IGFBP-5 decreased in the ZD group. These parameters are associated to alterations in the lung histoarchitecture. The zinc supplementation period is brief (only 10 days), but it is enough to inhibit some proinflammatory factors. Perhaps, zinc deficiency implications must be taken into account in health interventions because inflammation and prooxidant environment are associated with ZD in lung.

Evaluating the role of zinc in the occurrence of fibrosis of the skin: A preclinical study

To investigate the possible role of Zn as a trigger for NSF we were using a previously established preclinical model. The depletion of endogenous Zinc ions (Zn) caused by the administration of gadolinium-based contrast agents (GBCAs) has been suggested as a possible pathomechanism for nephrogenic systemic fibrosis (NSF). In the Zn supplementation study, rats were injected with Gadodiamide, Omniscan, and Magnevist with or without Zn supplementation. In the Zn depletion study, animals were kept on a Zn-deficient diet or a special control diet and received injections of Omniscan, OptiMARK, Magnevist, Gadovist, and Gd-EDTA. Gd, Zn, and Cu concentrations in tissue were measured and histology of the skin was performed. As seen in earlier studies, a difference in Gd concentration in the skin was observed following treatment with the different GBCAs. High Gd concentration in the skin correlated with the occurrence of NSF-like skin lesions. We observed no differences in the occurrence of skin lesions between the Zn supplementation and the Zn-deficient groups compared to their respective control groups. We found no significant effect of Zn on the initiation of NSF-like skin lesions. The results further support data from previous studies highlighting the importance of complex stability of the investigated GBCAs.

Effects of iron and/or zinc deficiency on blood biochemical parameters in rats

To investigate the effects of iron (Fe) and zinc (Zn) deficiency on blood biochemical parameters (plasma lipids, protein, plasma AST, ALT and ACE activities), forty 4‐week‐old male Sprague‐Dawley rats were assigned into 4 dietary treatment groups of 10 for the 4‐week study: severely Fe‐deficient group (FD), moderately Zn‐deficient group (ZD), severely Fe‐deficient/moderately Zn‐deficient group (FZD), and control group (Control). After 4 weeks on dietary regimen, rats were fasted overnight and anesthetized with diethylether. Blood was collected from the abdominal aorta with heparin. Statistical analysis was conducted using Tukey's simultaneous multiple comparison test. Plasma TG, T‐Cho and FFA concentrations were not significantly different among all treatment groups. Plasma PL concentration of FD and FZD was significantly higher than that of ZD. Compared with Control, plasma total protein and globulin concentrations of FD were significantly higher, and those of ZD tended to decrease. However, the Fe deficiency‐associated alterations were suppressed in the combined deficiency of Fe and Zn. Plasma albumin concentration was not significantly different among all treatment groups. The A/G ratio of FZD was significantly higher than FD. Plasma AST activity of FD was significantly higher than that of Control. Plasma ACE activity of FD, ZD and FZD were significantly higher than that of Control. These data indicate an interaction between Fe and Zn metabolism.

Altered ex vivo cytokine production in zinc-deficient, pair-fed and marginally zinc-deficient growing rats is independent of serum corticosterone concentrations

The objective of the present study was to examine the effects of dietary Zn deficiency on the ex vivo cytokine production (IL-2, interferon-gamma (IFN-gamma), IL-6 and IL-10) of isolated thymocytes and splenocytes after mitogenic stimulation with concavalin A and to explore the role of corticosterone in this regulation. Weanling rats were assigned to one of four dietary treatments for 3 weeks: Zn-deficient (< 1mg Zn/kg diet, ad libitum), pair-fed (30 mg Zn/kg diet, limited to amount of feed as consumed by the Zn-deficient group), marginally Zn-deficient (10 mg Zn/kg diet, ad libitum) and control (30 mg Zn/kg diet, ad libitum). Thymocytes and splenocytes were isolated for cytokine stimulation and determination of T-cell phenotypes. Serum corticosterone concentrations were determined by ELISA. The Zn-deficient and pair-fed groups had 14-fold higher serum corticosterone concentrations compared with the marginally Zn-deficient and control groups (P<0.0001). The proportions of thymocyte subsets were not altered in the Zn-deficient, pair-fed or marginally Zn-deficient groups; however, thymocyte IL-2 and IL-6 production in these groups was 33-54% lower compared with the control group (P<0.05). The Zn-deficient group had an 18-28% lower proportion of new T-cells (TCRalphabeta+CD90+), but no difference in the proportion of new T-cells that were cytotoxic or helper. The Zn-deficient group had a 49-62% lower production of Th1 cytokines (IL-2), but no difference in the production of Th2 cytokines (IL-6, IL-10) by stimulated splenocytes compared with the pair-fed, marginally Zn-deficient and control groups (P<0.01). These results indicate that Zn status is associated with altered cytokine production, while in vivo corticosterone concentrations are not associated with ex vivo cytokine production.

Increased Oxidant Stress and Decreased Antioxidant Status in Erythrocytes of Rats Fed with Zinc-deficient Diet

The aim of this study was to evaluate the lipid peroxidation, nitric oxide (NO), and free radical scavenging enzyme activities in erythrocytes of zinc (Zn)-deficient rats and to investigate the relationship among these parameters in either group. Sixteen male rats with a weight of 40-50 g were used for the experiment. The rats were divided into control (n = 8) and Zn-deficient groups. At the end of the experiment, the animals were anesthetized with ketamine-HCl (Ketalar, 20 mg/kg(-1), i.p.), and the blood was collected by cardiac puncture after thoracotomy. Blood samples were collected in vacutainer tubes without and with K(3)-EDTA as anticoagulant. Erythrocyte catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GRD), glutathione-S-transferase (GST), superoxide dismutase (SOD) activities, total (enzymatic plus nonenzymatic) superoxide scavenger activity (TSSA), nonenzymatic superoxide scavenger activity (NSSA), antioxidant potential (AOP), and serum zinc (Zn) values in the Zn-deficient group were significantly lower than those of the control group, whereas NO and malondialdehyde (MDA) levels were significantly higher than those of the control group. The results show that Zn deficiency causes a decrease in antioxidant defense system and an increase in oxidative stress in erythrocyte of rats.

Zinc deficiency decreased cell viability both in endothelial EA.hy926 cells and mouse aortic culture ex vivo and its implication for anti-atherosclerosis

Zinc plays a protective role in anti-atherosclerosis but the clear mechanism has not been proposed yet. In the present study, we evaluated whether zinc modulates atherosclerotic markers, VACM-1 and ICAM-1 and cell viability both in endothelial cells in vitro and mouse aortic cell viability ex vivo. In study 1, as in vitro model, endothelial EA.hy926 cells were treated with TNFα for 5 hours for inducing oxidative stress, and then treated with Zn-adequacy (15 µM Zn) or Zn-deficiency (0 µM Zn) for 6 hours. Pro-atherosclerosis factors, VCAM-1 and ICAM-1 mRNA expression and cell viability was measured. In study 2, as ex vivo model, mouse aorta ring was used. Mourse aorta was removed and cut in ring then, cultured in a 96-well plate. Aortic ring was treated with various TNFα (0-30 mg/ml) and intracellular zinc chelator, N, N, N', N', -tetrakis (2-pyridylmethyl) ethylenediamine (TPEN, 0-30 µM) for cellular zinc depletion for 2 days and then cell viability was measured. The results showed that in in vitro study, Zn-adequate group induced more VCAM-1 & ICAM-1 mRNA expression than Zn-deficient group during 6-hour zinc treatment post-5 hour TNF-α treatment, unexpectedly. These results might be cautiously interpreted that zinc would biologically induce the early expression of anti-oxidative stress through the increased adhesion molecule expression for reducing atherosclerotic action, particularly under the present 6-hour zinc treatment. In ex vivo, mouse aortic ring cell viability was decreased as TNF-α and TPEN levels increased, which suggests that mouse aortic blood vessel cell viability was decreased, when oxidative stress increases and cellular zinc level decreases. Taken together, it can be suggested that zinc may have a protective role in anti-atherosclerosis by cell viability in endothelial cells and aorta tissue. Further study is needed to clarify how pro-atherosclerosis molecule expression is modulated by zinc.

Zinc Supplementation of Pregnant Rats with Adequate Zinc Nutriture Suppresses Immune Functions in Their Offspring

The knowledge about consequences of marginal zinc (Zn) deficiency and Zn supplementation during pregnancy on immune function in the offspring is limited. The aim of this study was to examine whether effects of mild Zn deficiency and subsequent Zn supplementation during pregnancy persist after weaning and affect immune function of the offspring. Adult female rats were fed a Zn-adequate diet (ZC, n = 8) or a Zn-deficient diet (ZD, n = 8) from preconception through lactation. Pregnant rats were supplemented with either Zn (1.5 mg Zn in water) or placebo (water) 3 times/wk throughout pregnancy. Pups were orally immunized with cholera toxin and bovine serum albumin-dinitrophenol (DNP) 3 times at weekly intervals and killed 1 wk after the last dose. Proliferation and cytokine responses in lymphocytes from Payer’s patches and spleen, and antigen specific antibodies in serum were studied. Zn supplementation of ZD dams led to enhanced lymphocyte proliferation and IFN-γ responses in pups ZDZ+. In contrast, Zn supplementation of ZC dams suppressed these responses in pups ZCZ+. Total and DNP-specific IgA responses were lower in pups of the Zn-deficient group compared with the Zn-adequate group. Relative thymus weight was greater in the pups (ZDZ−) of ZD placebo-supplemented dams compared with the other groups at 31 d of age. Prepregnancy and early in utero Zn deficiency affected IgA responses in pups that could not be restored with Zn supplementation during pregnancy. Zn supplementation of ZC dams induced immunosuppressive effects in utero that may also be mediated through milk and persist in the offspring after weaning.

Plasma aldosterone concentration depressed by iron deficiency in

To investigate effects of iron (Fe) and zinc (Zn) deficiency on blood pressure and plasma aldosterone concentration, forty 4-week-old male Sprague-Dawley rats were assigned into 4 dietary treatment groups of 10 for the 4-week study: Fe-deficient group (30 mg Zn/kg, no supplemental Fe; FD), Zn-deficient group (4.5 mg Zn and 35 mg Fe/kg; ZD), Fe/Zn-deficient group (no supplemental Fe, 4.5 mg Zn/kg; FZD), and control group (AIN-93G; Cont). At day 26–27, blood pressure was measured by tail cuff method. Plasma aldosterone concentration was determined by ELISA. Statistical analysis was performed by two-way ANOVA. Heart weight per body weight was increased by Fe deficiency (P<0.001) and was decreased by Zn deficiency (P<0.05). Compared to Cont, hematocrit was significantly decreased in both FD and FZD, and was significantly increased in ZD (P<0.01). Systolic, diastolic and mean blood pressures were decreased by Fe deficiency (P<0.001). Plasma aldosterone concentration was significantly decreased by Fe deficiency (P<0.001). These results suggest that Fe deficiency decreases blood pressure. Hypotension in Fe deficiency may be caused by decreased plasma aldosterone concentration in addition to the decreased blood viscosity due to the low hematocrit.

Morphological alterations produced by zinc deficiency in rat sciatic nerve: A histological, electron microscopic, and stereological study

Zinc (Zn) is an essential trace element for humans and animals. It is required for normal growth, gene expression, wound healing, protein metabolism, immune function, and membrane integrity. In this study, unbiased stereological methods have been used to quantify the effects of Zn deficiency on the sectioned surface area and the number of myelinated axons in the sciatic nerve of rats. Animals were fed a Zn-deficient or Zn-sufficient diet for a period of 4 weeks. At the end of this time, the samples of sciatic nerves were removed from the animals, processed for electron microscopy and embedded in resin. The Zn-deficient group of rats was found to have a lower body weight compared to rats in the control group ( P < 0.05). The sectioned surface area of nerve cross-section and myelinated axon number in Zn-deficient rats decreased by 20% and 29%, respectively, compared to the control group. A significant correlation between sectioned surface area and myelinated axon number was also determined. Morphological findings were as follows: on light microscopy, it was determined that certain abnormalities occur specifically in the experimental group, such as collapsed nerve fascicles, irregular profiles of and degeneration in myelin sheaths, and on electron microscopy, extensive myelin damage was seen in Zn-deficient groups compared with control groups. This study suggests that peripheral nerves require Zn for development and preservation of their structure.

Cardiac abnormalities induced by zinc deficiency are associated with alterations in the expression of genes regulated by the zinc-finger transcription factor GATA-4.

Zinc (Zn) deficiency during pregnancy results in a wide variety of developmental abnormalities. The objective of this study was to determine if expression of cardiac developmental genes regulated by Zn-finger transcription factors could be modulated during dietary Zn deficiency. Rats were fed 0.5 (low Zn) or 90 (controls) microg Zn/g diet throughout pregnancy. Fetal development was examined and RNA isolated at gestation day (GD) 13 and 20. Cardiac abnormalities were detected at GD 20 in 82% of fetuses from dams fed low Zn diets compared with only 2% in controls. Cardiac developmental gene expression regulated by the Zn-finger transcription factor, GATA-4, was measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). In GD 13 and 20 hearts, two genes critical for heart development, alpha-myosin heavy chain (alpha-MHC) and cardiac troponin I (cTnI), were down-regulated in Zn-deficient fetuses. Expression of alpha-MHC was 66 and 40% lower at GD 13 and 20, respectively, in fetuses from dams fed low Zn diets compared with fetuses from control dams (p<0.05). Fetal cardiac TnI RNA levels were reduced 40 and 45% at GD 13 and 20 in the Zn-deficient group compared with controls (p<0.05). Fetal cardiac transcript levels of GATA-4 and MHox, a gene regulated by a helix-loop-helix transcription factor, whose expressions are not Zn-dependent, were unaffected by diet. These data indicated that alterations in gene regulation might be an underlying mechanism of cardiac abnormalities. Dysfunction of other Zn-dependent transcription factors may be an integral part of the extensive teratogenesis associated with Zn deficiency.