Zinc dyshomeostasis in azoxymethane induced colonic precancerous and cancerous lesions in Fisher rats

Metallomics ◽  
2020 ◽  
Author(s):  
Kavitha Velagapudi ◽  
J Naveena Lavanya Latha ◽  
Vijaya Lakshmi Bodiga

Abstract Zinc is an essential micronutrient involved in various biological processes, including growth, maintenance, proliferation and immune functions. It is also argued that tumors need zinc for maintenance and proliferation, although excess zinc may induce tumor cell apoptosis. Thus, the role of zinc merits attention in the carcinogenic process. Scanty literature is available on the mechanisms underlying the alterations in tissue zinc in colon cancer and how the altered zinc levels contribute to the preneoplastic lesions and progression to cancer. Zinc homeostasis is regulated by the gastrointestinal tract and involves interplay of host, dietary, environmental and social factors such as alcohol consumption. The DNA alkylation agent azoxymethane (AOM), which is primarily activated in the liver, induces a high incidence of initiation and promotion steps of precancerous lesions in the colon of rats. The altered expression of hepatic zinc transporters by AOM may lead to zinc dyshomeostasis in liver. Earlier reports showed that ZIP14 was located on the inner lane of plasma membrane of hepatocytes, and increased level of ZIP14 could sequester zinc from plasma into liver under infection or in response to cancer. Decreased serum zinc concentration, despite increased liver zinc also indicates altered liver zinc mobilization and failure to regulate zinc homeostasis. During the transformation from normal colonic mucosa to colonic epithelial hyperplasia and aberrant crypt formation, a reduction in zinc concentration is observed. It will be interesting to study further if the same trend continues throughout tumor progression towards adenocarcinomas. Lowered local zinc concentrations in the colon epithelium may not just reflect a bystander effect, but may induce cell proliferation and compromise DNA integrity due to impairment of zinc-containing proteins. In congruence with the tissue zinc concentrations, metallothionein levels were found to be less induced in AOM—administered colon compared to normal healthy colon, indicating less accumulation and sequestration of zinc. Lowered tissue zinc levels in small and large intestine were also associated with increased expression of mRNA and protein ZnT1, known to transport cytosolic zinc to extracellular space. In this regard, the mode of zinc responsiveness to ZnT1 mimics that of metallothionein, albeit at a lower level for ZnT1.

1981 ◽  
Vol 61 (4) ◽  
pp. 445-449 ◽  
Author(s):  
Susan Boobis ◽  
Rose E. Hartley

1. The effect of bacterial pyrogens on plasma zinc concentration in mice was studied as a method of bioassay for these substances. 2. A dose-related depression of plasma zinc concentrations was observed 4 h after intravenous injection of doses of 0.05-500 ng of purified endotoxins of Salmonella abortus equi, Shigella dysenteriae and Escherichia coli. Responses were dose-dependent and reproducible for each endotoxin in five strains of mice. 3. Tolerance to endotoxin could be induced in mice by injection of doses of 500 ng but was not seen with doses of <5 ng, even after repeated treatment. 4. Dinitrophenol, a metabolic inhibitor, and amphetamine, a metabolic enhancer, did not affect plasma zinc levels, indicating that changes in basal metabolic rate do not affect the outcome of this assay. The effects of pyrogenic materials other than endotoxin on plasma zinc levels were also tested and the results suggest that measurement of hypozincaemia in mice provides the basis for a simple, practical and inexpensive test for endotoxins and other pyrogens.


2014 ◽  
Vol 306 (5) ◽  
pp. C450-C459 ◽  
Author(s):  
Colin J. Mitchell ◽  
Ali Shawki ◽  
Tomas Ganz ◽  
Elizabeta Nemeth ◽  
Bryan Mackenzie

Iron homeostasis is achieved by regulating the intestinal absorption of the metal and its recycling by macrophages. Iron export from enterocytes or macrophages to blood plasma is thought to be mediated by ferroportin under the control of hepcidin. Although ferroportin was identified over a decade ago, little is understood about how it works. We expressed in Xenopus oocytes a human ferroportin-enhanced green fluorescent protein fusion protein and observed using confocal microscopy its exclusive plasma-membrane localization. As a first step in its characterization, we established an assay to detect functional expression of ferroportin by microinjecting oocytes with 55Fe and measuring efflux. Ferroportin expression increased the first-order rate constants describing 55Fe efflux up to 300-fold over control. Ferroportin-mediated 55Fe efflux was saturable, temperature-dependent (activation energy, Ea ≈ 17 kcal/mol), maximal at extracellular pH ≈ 7.5, and inactivated at extracellular pH < 6.0. We estimated that ferroportin reacts with iron at its intracellular aspect with apparent affinity constant < 10−7 M. Ferroportin expression also stimulated efflux of 65Zn and 57Co but not of 64Cu, 109Cd, or 54Mn. Hepcidin treatment of oocytes inhibited efflux of 55Fe, 65Zn, and 57Co. Whereas hepcidin administration in mice resulted in a marked hypoferremia within 4 h, we observed no effect on serum zinc levels in those same animals. We conclude that ferroportin is an iron-preferring cellular metal-efflux transporter with a narrow substrate profile that includes cobalt and zinc. Whereas hepcidin strongly regulated serum iron levels in the mouse, we found no evidence that ferroportin plays an important role in zinc homeostasis.


Author(s):  
Sahar ASKARI ◽  
Golaleh ASGHARI ◽  
Hossein FARHADNEJAD ◽  
Arash GHANBARIAN ◽  
Parvin MIRMIRAN ◽  
...  

Background: Zinc, an essential trace element, plays a key role in many biological human body functions. Serum zinc concentration is the most widely used indicator of zinc status for general populations. Considering the limited data available on seasonal fluctuation of serum zinc concentration, we aimed at determining seasonal variations in serum zinc concentrations of Tehranian adults. Methods: The current study was conducted within the framework of the Tehran Lipid and Glucose Study, on 4698 subjects, aged ≥20 years. Serum zinc samples of subjects were obtained from all four seasons over three years (from 2009 to 2011); samples of similar seasons over three years were placed in one group and the geometric means of serum zinc concentration of four seasons were compared to determine possible seasonal variations. Results: Participants with mean age 46.3 yr and geometric mean of serum zinc concentration 116.3 µg/dl, were studied for almost three years through four seasons. Serum zinc concentrations in spring and summer were significantly higher than those in autumn and winter (112.2 and 114.4 vs. 106.7 and 104.8 µg/dl; P<0.001, respectively). Moreover, monthly serum zinc concentration of all subjects differed, with the lowest and highest levels found in October and August (98.5 vs. 122.7; P<0.001). Conclusion: This study demonstrates the difference in serum zinc concentration in Iranian adults of both genders in different months and seasons during the year.


2010 ◽  
Vol 2010 ◽  
pp. 1-4 ◽  
Author(s):  
Archit Bhatt ◽  
Muhammad U. Farooq ◽  
Sailaja Enduri ◽  
Clement Pillainayagam ◽  
Bharath Naravetla ◽  
...  

Background. Zinc mediates several vital physiological, enzymatic and cellular functions. The association between serum zinc and stroke outcome has not been previously evaluated.Methods. This single center retrospective study was conducted on consecutive stroke () and TIA () patients. We sought to determine whether serum zinc concentrations in patients with acute ischemic strokes were associated with stroke severity and poor functional status at discharge, respectively.Results. Overall, out of the 224 patients analyzed (mean age 67 years), 35.7% patients had low zinc levels (65 mcg/dL). Patients with stroke () were more likely to have low zinc levels (, CI , ) compared to patients with TIA (). For patients with stroke (), multivariate analysis showed that low serum zinc levels (OR 2.82, CI , ) and strokes with admission severe strokes () (OR 2.68, CI , ) were independently associated with poor functional status () at discharge from the hospital.Conclusion. Low serum zinc concentrations are associated with more severe strokes on admission and poor functional status at discharge.


2000 ◽  
Vol 12 (2) ◽  
pp. 49-53 ◽  
Author(s):  
Gabriel Nowak ◽  
Marta Kubera ◽  
Michael Maes

SUMMARYZinc is a trace element which plays a fundamental role in a wide range of biochemical processes in living organisms. Zinc is an essential component of various proteins and is an important factor for physiological function of the mammalian nervous and immune systems. In the central nervous system (CNS), zinc is found at high concentrations in hippocampal neurons. These neurons possess mechanisms for zinc uptake and storage in synaptic terminals and for the stimulation of zinc release along with neurotransmitters. In the central nervous system, zinc modulates predominantly the excitatory (glutamatergic) and inhibitory (GABAergic) amino acid neurotransmission pathways. In the immune system, zinc is necessary for the physiological activity of the thymus and T-cell-dependent responses. Zinc deficiency impairs the activities of the neuroendocrine and immune systems in mammalian organisms. This paper reviews the alterations in the blood and brain zinc concentrations in relation to the neuroimmune pathophysiology and treatment of depression. Major depression is related to lowered serum zinc concentrations, which may be caused by the acute phase and the inflammatory response in that illness. Repeated administration of antidepressants selectively increases and redistributes brain zinc in the hippocampus. Since zinc is an inhibitor of the glutama-te/NMDA receptor, these data are in accordance with the glutamate hypothesis of antidepressant action.


Author(s):  
Ria Buana ◽  
Jane Florida Kalumpiu ◽  
Yenny Djuardi ◽  
Taniawati Supali

Background<br />Soil-transmitted helminth (STH) infection can cause malnutrition and vice versa, and decrease serum zinc concentrations. No previous studies were found on the effect of STH treatment on serum zinc concentrations in elementary school children. The objective of this study was to evalaute the effect of STH treatment on serum zinc concentration in elementary school children in Jakarta. <br /><br />Methods<br />A pre-experimental study (one group pre and post) was conducted on 3rd - 5th grade students in one elementary school in North Jakarta. FLOTAC examination was used to determine infection status and STH intensity, while serum zinc concentrations were measured by atomic absorption spectrometry. All children were given albendazole 400 mg for three consecutive days. Stool and blood samples were collected before and three weeks after treatment with albendazole. A paired t test was used to analyze the data. <br /><br />Results<br />The STH prevalence was 63.4%; these were mainly Ascaris lumbricoides and Trichuris trichiura infections. Before treatment, children infected with A.lumbricoides and T.trichiura had significantly higher serum zinc concentrations (p=0.028; p=0.014). After treatment, children with A.lumbricoides had significantly lower serum zinc concentrations (p=0.039), while children with T.trichiura had slightly lower serum zinc concentrations (p=0.659) than before treatment. <br /><br />Conclusions<br />Albendazole treatment produces lower serum zinc concentration in elementary school children with A.lumbricoides infections. A profound understanding of the interaction between helminth infections and zinc may assist in guiding integrated and sustainable intervention strategies among affected children throughout the world.


2017 ◽  
Vol 24 (1) ◽  
pp. 31-39
Author(s):  
Amarabia N.E. Ibeawuchi ◽  
Alphonsus N. Onyiriuka ◽  
Philip O. Abiodun

AbstractBackground and Aims: In Nigeria, community-based epidemiological data related to the prevalence of zinc deficiency in preschool children are scarce. We assessed the prevalence of zinc deficiency and the associated socio-demographic variables in children aged between 6 and 60 months, living in a Nigerian rural community.Materials and Methods: In this cross-sectional study, the serum zinc concentrations of 252 children aged between 6 and 60 months in a rural community in Nigeria were assessed, using atomic absorption spectrophotometry. The study population was selected by multistage random sampling and at least two children were selected from every household which had children in the study age group. The socio-demographic characteristics of the subjects were obtained, using an interviewer-administered questionnaire.Results: A total of 252 children were studied, 134 (53.2%) males and 118 (46.8%) females. The mean age was 32.7±17.0 months, similar for both sexes. Overall, 220 (87.3%) had low serum zinc concentrations (less than 7.65µmol/L). According to age, the highest mean serum zinc concentration was 5.43±3.52µmol/L in children aged between 6 and 12 months. Correlation between serum zinc concentration and family size or socio-economic status (SES) showed that the smaller the family size and the higher the SES, the higher the serum zinc concentration.Conclusions: The high prevalence of low serum zinc concentration indicates that zinc deficiency is a public health problem in our rural communities, requiring public health intervention.


Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 967 ◽  
Author(s):  
Marc Pawlitzki ◽  
Julia Uebelhör ◽  
Catherine Sweeney-Reed ◽  
Heike Stephanik ◽  
Juliane Hoffmann ◽  
...  

Objective: Diminished blood levels of zinc have been reported to be associated with T-cell-mediated autoimmunity, which has been implicated in multiple sclerosis (MS). We aimed to compare the distribution of serum zinc status in MS patients with that in healthy controls (HCs) and to investigate a potential correlation with clinical state, through analysis of serum zinc concentration in MS patients suffering from different disease subtypes. Methods: Serum zinc concentrations of 133 patients with relapsing (RMS) and 18 patients with the progressive form of MS (PMS), according to the McDonald criteria of 2010, were measured. Clinical status was quantified using the Expanded Disability Status Scale (EDSS). Zinc concentrations were also determined in the sera of 50 HCs, matched for age and sex at a group level. Results: MS patients showed significantly lower zinc concentrations (mean (SD)) than HCs (12.5 (2.1) µmol/L vs. 14.6 (2.3) µmol/L, p < 0.001). In contrast, we did not find any difference between RMS (12.4 (2.0) µmol/L) and PMS (13.0 (3.0) µmol/L) cases (p = 0.8). Patients receiving disease-modifying treatment showed lower mean (SD) serum zinc levels than untreated cases (12.3 (1.9) µmol/L vs. 13.5 (3.2) µmol/L, p < 0.03). Zinc levels were not related to disease duration, EDSS, annual relapse rate, or the median number of relapses. Conclusions: The data suggest that a diagnosis of MS is related to lower serum zinc concentrations than in HCs, and concentrations were lower still under disease-modifying therapy. However, zinc levels did not predict disease subtypes or disability status.


Author(s):  
Girija C. Bellad ◽  
Laxmi K. S.

Background: Zinc is a divalent cation first isolated in 1509 and since then its importance has been increasingly recognised in human health and nutrition. Present study has been undertaken to confirm the association between maternal plasma or serum zinc concentration and birth weight.Methods: Present study was cross-sectional study conducted in tertiary care hospital. Newborns with a birth weight of < 2.5kg and their mothers labelled as study group while newborns with a birth weight of > 2.5kg and their mothers were considered as control group. The analysis for the serum concentration of zinc was done using the Atomic Absorption Spectrophotometric method (AAS), this method analytically the most reliable for routine assessment of serum zinc levels. The results deduced from the analysis were accordingly grouped to the study group / control group. We had a sub-group analysis based on the gestational age, as Preterm and Term.Results: Maternal serum levels of zinc 67.04 μg /dl±16.66, in the study group, was less as compared to the maternal serum levels of zinc in the control group with a mean level of 75.39 μg/dl±17.89. The results show a significant association between zinc levels and birth weight. Mean Maternal serum levels of zinc 67.04 μg /dl±16.66, in the study group, was less as compared to the maternal serum levels of zinc in the control group with a mean level of 75.39 μg/dl±17.89. The results show a significant association between zinc levels and birth weight.Conclusions: Present study showed a positive correlation of maternal zinc levels with birth weight and prematurity. Hence, we recommend routine zinc supplementation could be included with other nutritional supplements during pregnancy.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jiang Zhao ◽  
Qingjian Wu ◽  
Xiaoyan Hu ◽  
Xingyou Dong ◽  
Liang Wang ◽  
...  

Abstract Many studies have investigated the relationship between serum zinc concentration and prostatic disease, but have shown inconsistent results. Hence, we performed a systematic literature review and meta-analysis to assess the correlation between serum zinc concentration and prostate disease. Systematic literature searches were conducted with PubMed, EMBASE, Science Direct/Elsevier, MEDLINE, CNKI and the Cochrane Library up to June 2015 for studies that involved the relationship between serum zinc concentration and prostate disease. Fourteen studies were identified from the databases. Our results illustrated that the serum zinc concentrations in prostate cancer patients were significantly lower than those in Benign prostatic hyperplasia (BPH) patients and normal controls (SMD (95% CI), −0.94 [−1.57, −0.32]; −1.18 [−1.90, −0.45]). However, the serum zinc concentrations in BPH patients were significantly higher than those in normal controls (SMD (95% CI) 1.77 [0.15, 3.39]). The present study showed that different levels of serum zinc concentrations are correlated with different prostatic disease. Serum zinc concentration may be used as a tool for the diagnosis and screening of prostate disease. But, further studies with well-designed larger sample studies are needed in this field to further clarify the correlation between serum zinc concentration and prostate disease.


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