Zinc and Copper Levels in Bladder Cancer: A Systematic Review and Meta-Analysis

It is well documented that oxidative stress is involved in the pathogenesis of bladder cancer. Zinc (Zn) and copper (Cu) are important components of antioxidants. However, the association between Zn or Cu levels and bladder cancer remains elusive. The present study was designed to investigate the alteration of serum and urinary levels of Zn or Cu in bladder cancer patients compared with controls by performing a systematic review. We searched the PubMed, Embase, and Cochrane databases from January 1990 to March 2013 to identify studies that met our predefined criteria. Six studies were included. Bladder cancer patients demonstrated significantly lower levels of serum Zn (three studies, random effects standard mean deviation (SMD): ?1.072, 95 % CI: ?1.489 to ?0.656, P <0.0001), markedly higher levels of serum Cu (three studies, random effects SMD: 1.069, 95 % CI: 0.302 to 1.836, P?=?0.006) and urinary Zn (three studies, random effects SMD: 2.114, 95 % CI: 0.328 to 3.899, P?=?0.02) compared with controls. No obvious difference was observed in urinary Cu levels between bladder cancer patients and controls (two studies, random effects SMD: 0.153, 95 % CI: ?0.244 to 0.55, P?=?0.449). No evidence of publication bias was observed. In conclusion, the disorder of Zn and Cu is closely associated with bladder cancer. Frequent monitoring and early intervention should be recommended.     

Partial suppression of cell mediated immunity in chromoblastomycosis

The cellular immune response of 8 patients from the Brazilian Amazon region with chromoblastomycosis was analyzed. Primary immunological responses of patients were tested by contact sensitization to 2,4-dinitro-chlorobenzene (DNCB), or rejection of first set skin allografts. 2 of 8 patients were reactive to DNCB after sensitization, and skin allograft rejection occured in an average of 14 days. Capacity of patients to mount recall immunological responses was measured by skin testing with two fungal antigens and three bacterial antigens. Delayed skin reaction to trichophytin and Candida antigens was negative in the majority of the patients. However, reactivity to mycobacterial (tuberculin), and bacterial (staphylococcal, streptococcal) antigen was high, or only slightly diminished respectively. The data suggest that patients with chromoblastomycosis have suppressed nonspecific, cell mediated immunity for some antigens (skin allografts, DNCB, fungal antigens), while reactivity to bacterial and mycobacterial antigens is not impaired.     

Study of the oxidative metabolic function and chemotaxis of neutrophils from patients with cancer influenced by Selenium Yeast

The effects of Selenium Yeast (SY) given orally to patients with cancer on the oxidative metabolic function and chemotaxis of neutrophils were studied by Lumino-dependent Chemiluminescence (CL) assay and agarose plates assay, respectively. The results showed that the background CL and the peak value CL of neutrophils from patients with cancer 14 d after taking SY were, on the average, 4 and 1.2 times higher than those before taking SY. The chemotactic index (CI) and chemotactic differential (CD) increased in response to SY supplementation; the differences are statistically significant (p less than 0.01), and no corresponding differences could be seen in the control group (taking yeast).     

Immune competence in breast cancer — Relationship of pretreatment immunologic tests to diagnosis and tumor stage

Summary The immune competence of a group of 276 patients with suspected breast cancer has been assessed using a spectrum of tests: the peripheral lymphocyte count, serum immunoglobulin levels, lymphocyte response to phytohemagglutinin (PHA), Mantoux test, and dinitrochlorobenzene (DNCB) skin test. All tests were completed prior to any form of treatment as the initial part of an ongoing, long-term assessment which will ultimately relate immune competence to prognosis. 225 patients with breast cancer were allocated into stages based on their TNM status. The remaining 51 patients proved to have benign breast disease and made up the control group. In analysis, control patients were compared with early breast cancer patients, while the effect of advancing disease was assessed by betweenstage comparisons in the cancer group.There were no significant differences between early breast cancer and control patients or between cancer stages in peripheral lymphocyte count, serum immunoglobulin levels, lymphocyte response to PHA, or Mantoux responses. Age was found to have a crucial effect on some of these parameters and some apparent differences between the various groups lost significance after appropriate allowances were made for age.Important differences seen with the DNCB test persisted after allowing for age effects. Responses to DNCB were significantly depressed in patients with early breast cancer compared to controls. Patients with disseminated cancer showed greater depression than early breast cancer patients, but surprisingly, patients with locally advanced tumors had good responses to DNCB. Possible reasons for the paradoxical preservation of DNCB reactivity in patients with locally advanced cancer are discussed.The DNCB test is the most discriminating of the five tests of immune function studied.     

The role of intracellular zinc in chromium(VI)-induced oxidative stress, DNA damage and apoptosis

Several studies have demonstrated that zinc is required for the optimal functioning of the skin. Changes in intracellular zinc concentrations have been associated with both improved protection of skin cells against various noxious factors as well as with increased susceptibility to external stress. Still, little is known about the role of intracellular zinc in hexavalent chromium (Cr(VI))-induced skin injury. To address this question, the effects of zinc deficiency or supplementation on Cr(VI)-induced cytotoxicity, oxidative stress, DNA injury and cell death were investigated in human diploid dermal fibroblasts during 48 h. Zinc levels in fibroblasts were manipulated by pretreatment of cells with 100 microM ZnSO4 and 4 or 25 microM zinc chelator TPEN. Cr(VI) (50, 10 and 1 microM) was found to produce time- and dose-dependent cytotoxicity resulting in oxidative stress, suppression of antioxidant systems and activation of p53-dependent apoptosis which is reported for the first time in this model in relation to environmental Cr(VI). Increased intracellular zinc partially attenuated Cr(VI)-induced cytotoxicity, oxidative stress and apoptosis by enhancing cellular antioxidant systems while inhibiting Cr(VI)-dependent apoptosis by preventing the activation of caspase-3. Decreased intracellular zinc enhanced cytotoxic effects of all the tested Cr(VI) concentrations, leading to rapid loss of cell membrane integrity and nuclear dispersion--hallmarks of necrosis. These new findings suggest that Cr(VI) as a model environmental toxin may damage in deeper regions residing skin fibroblasts whose susceptibility to such toxin depends among others on their intracellular Zn levels. Further investigation of the impact of Zn status on skin cells as well as any other cell populations exposed to Cr(VI) or other heavy metals is warranted.     

Changes in zinc levels and superoxide dismutase activities in the skin of acute, ultraviolet-B-irradiated mice after treatment with ginkgo biloba extract

Acute ultraviolet-B (UV-B) irradiation is known to act as an initiator in the formation of reactive oxygen species. These oxygen products are highly reactive and they are able to cause irreversible damage to cellular components. Oxygen free radicals are normally neutralized by very efficient systems in the body. These include antioxidant enzymes like superoxide dismutase (SOD). In a healthy subject, there is a balance between free radicals and the levels of antioxidants. In some pathological conditions such as oxidative stress, the level of antioxidants is significantly reduced. The skin contains relatively high levels of zinc (Zn), an essential element known to be a cofactor in some metabolic pathways. Zinc has also been reported to have antioxidant properties. In the present study, we investigated the effect of ginkgo biloba extract (Gbe), a potent free-radical scavenger, on UV-B-irradiated skin by measuring SOD activity and Zn levels in the skin, before and after treatment. The SOD activity was decreased after UV-B exposure, in comparison with the control group (p<0.05). After Gbe treatment, the SOD activity increased (p<0.05) as compared with the untreated UV-B irradiated group. The Zn levels changed in the same pattern as the SOD activity values.     

Zinc and the Diabetic Heart

Zinc (Zn) is an essential mineral that is required for various cellular functions. Its abnormal metabolism is related to certain disorders such as diabetic complications. Oxidative stress has been considered as the major causative factor for diabetic cardiomyopathy. Zn has a critical antioxidant action in protecting the heart from various oxidative stresses. Zn deficiency was found to be a risk factor for cardiac oxidative damage and supplementation with Zn provides a significant prevention of oxidative damage to the heart. Diabetes causes a significant systemic oxidative stress and also often is accompanied by Zn deficiency that increases the susceptibility of the heart to oxidative damage. Therefore, there is a strong rationale to consider the strategy of Zn supplementation to prevent or delay diabetic cardiomyopathy. This short article collects the preliminary evidence, based on our own studies and those by others, for a preventive effect of Zn supplementation on diabetes-induced injury to the heart in animals and under in vitro conditions. Possible mechanisms by which Zn supplementation prevents diabetic heart disease are discussed. They include an antioxidant action of Zn, insulin function and metallothionein induction. In the final section, the future of Zn supplementation for diabetic patients is also briefly discussed. Although Zn supplementation has not been clinically used to prevent diabetic complications, because several issues need to be addressed, the fact that Zn supplementation is being used clinically for other disorders encourages us to explore its direct clinical application for the prevention of diabetic cardiomyopathy.     

Zinc and copper in the serum of diabetic patients

The Zn/Cu ratio was examined in the serum of three groups of persons: healthy volunteers, diabetic patients on diabetic diet (NIDDM), and diabetic patients on diabetic diet and insulin (IDDM). Zinc, copper, the Zn/Cu serum ratio, and the blood glucose level were determined during fasting and 2 h after breakfast. Zn and Cu serum levels in NIDDM and IDDM patients were decreased. The Zn/Cu ratio was higher in both groups of diabetic patients. These changes in the Zn and Cu levels as well as in the Zn/Cu ratio were not related to chronic diabetic complications.     

Stabilisation of human interferon beta synthesis in Escherichia coli by zinc ions

Human interferon beta synthesized in Escherichia coli is unstable and toxic for the bacterial cell. Zinc ions are able to stabilise interferon beta in E. coli probably by inhibiting the action of cell internal proteinase(s) which affect the half-life of this foreign protein. As a result up to one order of magnitude more active IFN-beta can be detected in Zn2+-treated E. coli cells.     

Low Serum Levels of Zinc,Copper, and Iron as Risk Factors for Osteoporosis: a Meta-analysis

Zinc (Zn), copper (Cu), and iron (Fe) are essential trace elements for the growth, development, and maintenance of healthy bones. However, there are conflicting reports as to the relationship between serum level of Zn, Cu, or Fe and osteoporosis (OP). The purpose of the present study is to clarify the relationship between serum Zn, Cu, or Fe and OP using a meta-analysis approach. We searched all articles indexed in PubMed published up to May 2014 concerning the association between serum level of Zn, Cu, or Fe and OP. Eight eligible articles involving 2,188 subjects were identified. Overall, pooled analysis indicated that patients with OP had a lower serum level of Zn, Cu, or Fe than the healthy controls (Zn standardized mean difference (SMD)?=??1.396, 95 % confidence interval (CI)?=?[?2.129, ?0.663]; Cu SMD?=??0.386, 95 % CI?=?[?0.538, ?0.234]; Fe SMD?=??0.22, 95 % CI?=?[?0.30, ?0.13]). Further subgroup analysis found that geographical location and gender had an influence on the serum level of Zn in OP and healthy controls, but not on the serum level of Cu or Fe. No evidence of publication bias was observed. In conclusion, this meta-analysis suggests that low serum levels of Zn, Cu, and Fe seem to be important risk factors for OP and well-designed studies with adequate control for confounding factors are required in future investigations.     

Zinc may play a role in the regulation of thyrotropin function

We studied the in vitro and in vivo influence of physiologically relevant zinc concentrations on the thyrotropin function both at the pituitary and hypothalamic level. Zinc gluconate (Zn Glu) concentrations from 5 to 100 microM decreased basal TSH release from anterior pituitary gland in vitro, but did not affect TSH-stimulated release by TRH, cAMP or high K+ concentrations. Zn Glu altered neither the basal nor stimulated production of TRH by hypothalami in vitro. In vivo brain third ventricle injection of Zn Glu decreased serum TSH 30-60 min after injection. The ability of physiological concentrations of zinc to influence TSH secretion both in vitro and in vivo suggest that this trace element might be involved in the regulation of thyrotropin function.     

Improved viability and activity of neutrophils differentiated from HL-60 cells by co-culture with adipose tissue-derived mesenchymal stem cells

Neutropenia is a principal complication of cancer treatment. We investigated the supportive effect of adipose tissue-derived mesenchymal stem cells (AD-MSCs) on the viability and function of neutrophils. Neutrophils were derived from HL-60 cells by dimethylformamide stimulation and cultured with or without AD-MSCs under serum-starved conditions to evaluate neutrophil survival, proliferation, and function. Serum starvation resulted in the apoptosis of neutrophils and decreased cell survival. The co-culture of neutrophils and AD-MSCs resulted in cell survival and inhibited neutrophil apoptosis under serum-starved conditions. The survival rate of neutrophils was prolonged up to 72 h, and the expression levels of interferon (IFN)-α, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, and transforming growth factor (TGF)-β in AD-MSCs were increased after co-culture with neutrophils. AD-MSCs promoted the viability of neutrophils by inhibiting apoptosis as well as enhancing respiratory burst, which could potentially be mediated by the increased expression of IFN-α, G-CSF, and TGF-β. Thus, we conclude that the use of AD-MSCs may be a promising cell-based therapy for increasing immunity by accelerating neutrophil function.     

Effect of zinc supplementation on resistance of cultured human skin fibroblasts toward oxidant stress

In purified system zinc has been shown to have an antioxidant role. Its effects on the resistance of cultured cells towards oxidative stress in vitro were examined. Diploid human skin fibroblasts were grown for 21 d in culture media (RPMI 1640 containing 15% fetal calf serum) added with different zinc (Zn) concentrations (100, 125, and 150μM as Zinc chlorur ZnCl₂). In comparison, cell controls were grown in standard culture media (6.5μM Zn). The intracellular zinc levels of treated fibroblasts increased from 3- to 7-fold (2330±120 ng/mg protein in 150-μM Zn-treated cells versus 331±21 ng/mg protein in control cells). The intracellular copper increased 3- fold whereas the iron content slightly but not significantly decreased. The index of basal lipid peroxidation measured as thiobarbituric acid reactants (TBARs) of zinc-supplemented cells was lower than that of non zinc supplemented controls (0.89 μmol/g protein in 150μM Zn-treated cells versus 1.59 μmol/g protein in controls). At these high doses of zinc, fibroblasts expressed lower antioxidant metalloenzymes activities. Diminished TBARs in Zn treated cells tends to support that Zn acts protectively against free radical mediated damage. However when the cells were challenged with extracellular oxidant stresses mediated by hypoxanthine/xanthine oxidase or hydrogen peroxide (H₂O₂), an increased toxicity in Zn-supplemented cells was observed. When we applied an intracellular oxidative stress as UV-B or UV-A radiation, Zn-treated fibroblasts were more resistant than cells grown in normal medium. If Zn has shown antioxidant effect in some in vitro or in vivo systems our observations clearly demonstrate that this role is not mediated by antioxidant metalloenzymes.     

Associations of Zinc and Copper Levels in Serum and Hair with Sleep Duration in Adult Women

Zinc (Zn) and copper (Cu) are essential micronutrients involved in numerous metabolic reactions. They are also antagonists of the N-methyl-D-aspartate glutamate (NMDA) receptor in the central nervous system, which mediates mood, cognition, pain perception, and sleep. However, there have been few studies on the effects of Zn and Cu on sleep. A total of 126 adult women were recruited in this cross-sectional study. Zn and Cu levels in the serum and hair were measured for each subject. The participants completed the 7-day physical activity recall questionnaire and the Hospital Anxiety and Depression Scale. The mean hours of sleep were compared according to the tertiles of Zn, Cu, and Zn/Cu ratio in the serum and hair by analyses of covariance. The participants in the middle tertile of Zn and Zn/Cu ratio in the serum had significantly longer sleep duration compared to those in the lowest tertile (p?相似文献   

The effects of zinc supplementation on metabolic profile and oxidative stress in overweight/obese patients with non-alcoholic fatty liver disease: A randomized,double-blind,placebo-controlled trial

BackgroundEvidence indicates the positive effects of zinc on insulin resistance and oxidative stress in metabolic syndrome or diabetes. Non-alcoholic fatty liver disease (NAFLD) is the main hepatic manifestation of insulin resistance and metabolic syndrome. The present study is the first clinical trial that evaluated the effects of zinc supplementation on metabolic and oxidative stress status in overweight/obese patients with NAFLD undergoing calorie- restriction diet. Methods: Fifty six overweight/obese patients with confirmed mild to moderate NAFLD using ultrasonography were randomly allocated to receive 30 mg elemental zinc supplement (n = 29) or placebo (n = 27) along with weight loss diet for 12 weeks. Serum levels of zinc, homeostasis model of assessment-estimated insulin resistance (HOMA-IR), lipid profile, serum superoxide dismutas1 (SOD1) and malondialdhyde (MDA) levels were assessed.ResultsSerum levels of insulin, SOD1, MDA and HOMA-IR were improved in the treatment group (p < 0.05). Within group comparison showed significant reduction in serum FBS, HbA_1C, TC, LDL-c and TG in the treatment group. Conclusion: Zinc supplementation for three months improved insulin resistance and oxidative stress status in overweight/obese NAFLD patients with no beneficial effects on lipid profiles over weight loss diet. Registration ID in IRCT (IRCT NO: 20181005041238N1).