Effects of cadmium and copper on zinc transport kinetics by isolated renal proximal cells

Zinc, cadmium, and copper are known to interact in many transport processes, but the mechanism of inhibition is widely debated, being either competitive or noncompetitive according to the experimental model employed. We investigated the mechanisms of inhibition of zinc transport by cadmium and copper using renal proximal cells isolated from rabbit kidney. Initial rates of⁶⁵Zn uptake were assessed after 0.5 min of incubation. The kinetics parameters of zinc uptake obtained at 20°C were a J_max of 208.0±8.4 pmol· min⁻¹·(mg protein)⁻¹, aK _m of 15.0±1.5 μM and an unsaturable constant of 0.259±0.104 (n=8). Cadmium at 15 μM competitively inhibited zinc uptake. In the presence of 50 μM cadmium, or copper at both 15 and 50 μM, there was evidence of noncompetitive inhibition. These data suggest that zinc and cadmium enter renal proximal cells via a common, saturable, carrier-mediated process. The mechanisms of the noncompetitive inhibition observed at higher concentrations of cadmium or with copper require further investigation, but may involve a toxic effect on the cytoskeleton.     

Effects of diabetes type and treatment on zinc status in diabetes mellitus

Zinc status was assessed in 53 diabetic patients: 18 insulin-dependent diabetic patients (IDDM), 22 noninsulin-dependent diabetic patients (NIDDM) treated with oral antidiabetic agents, and 13 insulin-treated, noninsulin-dependent diabetic patients (IRDM). Plasma zinc concentrations were in the usual range for healthy subjects in these three groups (15.3±0.9 μmol/L). Urinary zinc excretions were elevated in the IDDM group (18.3±4.1 μmol/24 h;p<0.01 vs normal) and in the NIDDM group (17.5±3.5 μmol/24 h;p<0.01 vs normal), but normal in the IRDM group (11.3±2.4 μmol/24 h). In 14 NIDDM patients treated with transient continuous sc insulin injections, urinary zinc decreased from 16.5±2.2 μmol/24 h before insulin treatment to 11.5±0.3 μmol/24 h after insulin treatment without any modification in plasma zinc concentrations.     

The relationship between zinc and copper status and lipid levels in African-Americans

Studies examining the role of zinc and copper nutriture as risk factors for cardiovascular disease in European Americans have produced conflicting results. This study assessed the associations between zinc and copper status and serum lipid levels in an adult African-American community. A cross-sectional study was conducted on 600 individuals (233 males, 367 females) from 25 to 65 yr of age using a random sampling design in a small city in Alabama. Anthropometric, dietary, and serum zinc, copper, and lipid measurements were made. The mean serum zinc and copper levels and dietary zinc intake were similar to that reported previously for European Americans. There were no significant associations between serum zinc, copper, or zinc/copper ratio and total serum cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), or triglyceride levels. For males, there was a small but significant association between dietary zinc and the total cholesterol/HDL-C ratio (r=−0.17, p=0.03). Similarly, females taking either zinc supplements or a multivitamin including zinc had higher HDL-C values than nonsupplementing females. Further prospective studies of the relationship between zinc status and lipid levels in African Americans are needed to verify these results.     

Longitudinal study of serum zinc and copper levels in hemodialysis patients and their relation to biochemical markers

A 6-mo longitudinal study of 48 hemodialysis patients (HPs) with chronic renal failure was performed. Three blood samplings were done. Samples of whole blood from each patient were collected during hemodialysis sessions after passing through the artificial kidney. Zinc and copper levels were measured by atomic absorption spectrometry. Additionally, 36 biochemical indexes were evaluated during the study. Fifty-two healthy matched controls were also considered. Mean serum zinc and copper concentrations in HPs were significantly decreased (Zn) and increased (Cu), when compared with healthy controls (p<0.01). Zinc concentrations found in the first and second blood samplings from patients were significantly lower than those measured for the third sampling (p<0.01). The etiology of chronic renal failure influenced the statistically serum Zn levels of patients (p<0.05). Serum copper levels of HPs were significantly diminished by the existence of secondary associated diseases (p<0.01). Uric acid and parathyroid hormone, and total-cholesterol and glutamic-pyruvic-transaminase levels were significantly (p<0.05) and linearly related with serum zinc and copper concentrations, respectively. From all of indexes, creatinine, direct bilirubin, magnesium, calcium, parathyroid hormone, transferrin, and albumin were statistically modified along the longitudinal study (p<0.05). Transferrin serum levels were significantly diminished in the third blood sampling, indicating the tendency toward anemia in the patients. This result is reinforced by low levels of biochemical and hematological indexes related with iron body staus.     

Selenium status,plasma zinc,copper, and magnesium in vegetarians

Plasma zinc (Zn), copper (Cu), and magnesium (Mg) concentrations, copper/zinc ratio, and selenium (Se) status were studied in 44 vegetarians (22 males and 22 females) and their age- and sex-matched nonvegetarians in the Bratislava region (Slovakia). Vegetarians had statistically significant lower levels of plasma Zn and Cu than nonvegetarians, which may be the result of lower bioavailability of Zn and Cu from this type of diet. No differences in plasma Mg levels were found between vegetarians and nonvegetarians. Se status, as expressed by plasma and erythrocyte concentrations and plasma and erythrocyte glutathione peroxidase activities (GPx), was significantly lower in vegetarians when compared to nonvegetarians. In the series as a whole, there were significantly higher correlations between plasma and erythrocyte Se concentrations and between plasma and erythrocyte GPx activities. Significant positive correlations were also found between plasma Se concentrations and erythrocyte GPx activities, and between erythrocyte Se concentrations and erythrocyte GPx activities. A vegetarian diet does not provide a sufficient supply of essential antioxidant trace elements, like Zn, Cu, and especially Se. Se supplementation should be recommended to this risk group of the population.     

Leucocyte copper, a marker of copper body status is low in coronary artery disease

To elucidate the relationship between leucocyte copper as a reliable, sensitive index of copper body status and extent of atherosclerosis in patients with Coronary Artery Disease (CAD) the present case-control study was carried out. 80 subjects were studied (23 females and 57 males), aged between 30-70, due to have a angiography. Individual angiograms were scored by combining the individual scores in all the major coronary arteries into one score of a scale 1.00 for patency to 0.00 for severe CAD. Serum and leucocyte copper and zinc were determined by GFAAS. No significant difference between patients with advanced CAD and relatively normal arteries were observed in the lipid profile and levels of plasma copper. Leucocyte copper had a significant link with the severity of atherosclerosis which was independent of sex. There was a linear relationship between the degree of decreasing leucocyte copper concentration and angiogram score. These findings give support to the hypothesis that marginal copper status, assessed by decreased leucocyte copper level, is associated with developing CAD.     

Effect of medium copper concentration on the growth,uptake and intracellular balance of copper and zinc in Menkes' and normal control cells

The precise nature of the variation in cellular copper load against medium copper concentration is defined using a comprehensive logarithmically incremented series of medium copper concentrations ranging from low levels (4.8 p.p.b.) through normal to toxic levels (40 p.p.m.) in which fibroblasts were grown followed by determination of intracellular content. Menkes' fibroblasts showed an unexpected plateau region of stable intracellular copper content against a change in medium concentration of over 100-fold, albeit only when sufficient copper was present in the medium (0.08–8.0 p.p.m.). Thus, Menkes' cells are clearly capable of balancing uptake/efflux providing copper availability allows. Simultaneous analysis of cellular copper and zinc load at various medium copper concentrations shows an indistinguishable intracellular copper:zinc ratio between the two cell lines. The nature of non-labeled copper uptake by fibroblasts over a 40 min and 7 day period is reported. During the 40 min period copper uptake (20 p.p.m.) was essentially the same in both cell lines. However, copper absorbed was superimposed upon large pre-existing copper pools in the case of Menkes' cells only. Advantages of techniques determining non-labeled copper in copper uptake/efflux experiments are discussed in the light of these results. Fibroblast growth studies showed that, compared with normal cells, Menkes' cells are significantly (P < 0.01) more growth sensitive to extended exposure to low copper concentrations. Thus, Menkes' disease appears to be not only a result of copper maldistribution but also a direct result of an inability of Menkes' cells to function normally in low copper environments.     

Selenium status indices,laboratory data,and selected biochemical parameters in end-stage renal disease patients

We investigated the relations between selenium status (SeS) parameters, indexes of nutrition, erythropoiesis, and uremic toxemia, serum electrolytes, and other biochemical markers in end-stage renal disease (ESRD) patients, as no multivariate statistical analysis concerning all of these parameters was performed so far. SeS was evaluated by plasma Se concentration (plSe) and glutathione peroxidase (plGSHPx) activity in 69 uremic patients treated with hemodialysis (HD) and 40 healthy controls. The hierarchical multivariate partial least squares model (PLS2) was employed to establish data structure and correlations between parameters investigated. plSe and plGSHPx activity were significantly lower in patients when compared with controls (p=0.000). plSe was positively associated with indexes of erythropoiesis and nutritional status, as well as serum electrolytes and parameters of uremic toxemia. plGSHPx was inversely dependent on the pair of parameters: intact parathyroid hormone (iPTH) and aluminum plasma concentration (Al). We conclude that (1) ESRD strongly decreases selenium status and (2) the PLS2 approach revealed the existence of significant interactions among plSe, plGSHPx, and selected biochemical parameters or groups of such parameters; some of these associations need further studies to be clarified.     

Superoxide dismutase activity and zinc and copper concentrations in growth retardation

The aim of this study was to determine the effects of oral zinc treatment on red cell copper/zinc-superoxide dismutase (Cu/Zn-SOD) activity and zinc and copper concentrations in growth retardation. Thirty-five patients, average age of 11 yr, were selected. The control group consisted of 10 healthy children whose average age was 10 yr. Superoxide dismutase activity was determined by spectrophotometer. Copper and zinc concentrations were measured by an atomic absorption spectrophotometer. The activity of Cu/Zn-SOD before zinc treatment was higher than the controls (p<0.001). There was a decrease in Cu/Zn-SOD activity after zinc treatment (p<0.001) and the values after treatment were still higher than the controls (p<0.001). Plasma zinc concentrations before zinc treatment were lower than controls (p<0.01). After treatment, there was an increase in plasma zinc concentrations compared to controls and the patients' values before zinc treatment, respectively (p<0.001, p<0.001). After zinc treatment, plasma copper concentrations were decreased significantly (p<0.01). An increase in red cell zinc concentration (p<0.01) and a decrease in copper concentration (p<0.001), which were statistically significant, were seen after zinc treatment. The results suggested that there were significant alterations in Cu/Zn-SOD activity and zinc and copper concentrations during growth retardation. With zinc treatment, these parameters appeared to approach normal values.     

Effect of sulfite exposure on zinc, iron, and copper levels in rat liver and kidney tissues

Sulfite is a potentially toxic molecule that might enter the body via ingestion, inhalation, or injection. For cellular detoxification, mammalians rely on sulfite oxidase to convert sulfite to sulfate. The purpose of this research was to determine the effect of sulfite on zinc, iron, and copper levels in rat liver and kidney tissues. Forty normal and sulfite oxidase-deficient male albino rats were divided into four groups that included untreated controls (group C), a sulfite-supplemented group that received 70 mg sodium metabisulfite per kilogram per day (group S), a sulfite oxidase-deficient group (group D), and a sulfite oxidase-deficient group that was also given 70 mg sodium metabisulfite per kilogram per day (group DS). The iron and zinc levels in the liver and kidney in groups S and DS were not affected by sulfite treatment compared to their respective controls (groups C and D). Sulfite exposure led to an increase of kidney copper content in the S group when compared to untreated controls. The kidney copper levels were significantly increased in the unexposed deficient rats, but it was not different than that of the deficient rats that were given oral sulfite treatment. These results suggest that kidney copper levels might be affected by exogenous or endogenous sulfite. An erratum to this article is available at .     

Effect of supplemental magnesium on the kidney levels of cadmium, zinc, and copper of mice exposed to toxic levels of cadmium

In this report, we present the results of our investigations on the effect of Mg pretreatment on Cd and bioelements (Cu and Zn) contents in kidney of mice exposed to acute and subacute Cd intoxication. Acute intoxication was performed on male Swiss mice given a single oral dose of 20 mg Cd/kg body weight and mice given the same dose of Cd but pretreated with 40 mg Mg/kg body weight. For subacute intoxication one group of mice was given 10 mg Cd/kg body weight every day, for 2 wk, and the other one received the same dose of Cd after oral Mg intake of 20 mg/kg body weight. Cd, Cu, and Zn content was determined in kidney by atomic absorption spectrophotometry. In acute Cd intoxication, Mg pretreatment resulted in significant decrease of Cd in kidney after 4 and 6 h, compared with animals given only Cd. Under the condition of subacute Cd intoxication, Mg supplementation reduced Cd kidney content after 2 wk for about 30%, compared with animals treated with Cd only. The effect of Mg on Cu and Zn kidney content was also beneficial.     

Serum zinc and copper levels in southeastern Turkish children with giardiasis or amebiasis

Alterations of serum zinc (Zn) and copper (Cu) concentrations are commonly found in patients suffering from gastrointestinal infections and with hepatic, renal, cardiovascular, and malignant diseases. In this study, the serum Zn and Cu levels in 20 children with giardiasis and in 40 children with amebiasis were evaluated. The serum Zn levels showed a significant decrease when compared to controls (p<0.001). After metronidazole therapy, a significant increase in Zn levels was observed (p<0.001). There was no significant difference in serum Cu levels between patients and controls before therapy. Before therapy, the serum Cu/Zn ratio in children with either giardiasis or amebiasis was significantly higher than that of the control group. After therapy, the Cu/Zn ratio was found to be back to normal. There were no significant differences in serum Zn levels and Cu/Zn ratios between children with and without diarrhea and there was no significant difference in children with or without failure to thrive. We concluded that Zn deficiency and elevated Cu/Zn ratio could be acute-phase responses to parasitic infections in children with giardiasis or amebiasis and that a successful treatment of the primary disorder will lead to complete recovery. Further studies are in progress to confirm the benefit of Zn supplementation during the acute phase of the disease, particularly in zinc-deficient regions of the world, such as in the case of Turkey.     

维持性血液透析终末期肾病患者肠道优势菌群多样性变化研究

目的探讨维持性血液透析终末期肾病患者肠道优势菌群多样性及其与炎症因子的相关性。方法采集维持性血液透析的稳定终末期肾病患者和健康对照受试者的血液和粪便样本,采用荧光实时定量PCR(real-time quantitative PCR,QPCR)检测肠道优势菌群的变化情况,应用酶联免疫吸附技术(enzymelinked immunosorbent assay,ELISA)检测患者血液中的白介素1β(interleukin 1β,IL-1β)、白介素6(interleukin 6,IL-6)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)和内毒素(lipoposaccharide,LPS)。结果维持性血液透析终末期肾病患者肠道菌群总菌量差异无统计学意义,但肠道内有益菌群如双歧杆菌属细菌、乳酸杆菌属细菌和粪杆菌属细菌显著降低,而肠道内有害菌如肠杆菌科细菌和肠球菌属细菌均显著升高(P0.05)。维持性血液透析终末期肾病患者血液中IL-6、TNF-α和LPS显著升高,均与双歧杆菌属细菌有显著负相关,与肠杆菌科细菌有显著正相关。肠道内乳酸杆菌属细菌和粪杆菌属细菌与IL-6呈显著负相关,肠球菌属细菌与其呈显著正相关。此外,乳杆菌属细菌与TNF-α呈显著负相关,肠球菌属细菌和LPS呈显著正相关。结论维持性血液透析终末期肾病患者肠道优势菌群多样性发生了显著变化,且与患者炎症因子有密切的相关性。     

益生菌对维持性血液透析慢性肾脏病患者肠道菌群失调的影响

目的 探究益生菌对维持性血液透析慢性肾脏病患者肠道菌群失调的影响,为此类患者的治疗提供参考。 方法 选取2017年4月到2019年4月我院收治的78例维持性血液透析慢性肾病患者,按照随机数字法分为观察组和对照组各39例。对照组患者给予常规治疗,观察组患者给予常规治疗联合益生菌。检测两组患者肠道菌群变化,同时检测血清炎性因子(IL6、TNFα、CRP)、肠道屏障功能(D乳酸、内毒素)及肾功能指标[肌酐(serum creatinine,Scr)、尿素氮(blood urea nitrogen,BUN)]水平。 结果 治疗后两组患者Scr、BUN水平均下降(均P0.05)。治疗后两组患者肠道双歧杆菌、乳杆菌数量均增加,大肠埃希菌、肠球菌数量均下降,且观察组患者改善情况优于对照组,差异有统计学意义(t=4.226、9.634、6.157、2.739,P结论 益生菌对维持性血液透析慢性肾脏病患者肠道菌群失衡、肠道屏障功能和微炎症状态均具有改善作用,可为该类患者临床治疗提供一定参考。     

The changes of metabolism balance of zinc and copper in gastric juice with widely varying dietary zinc intake

The concentrations of zinc and copper in gastric juice of humans who had widely varying dietary zinc intake were evaluated. In order to compare this with zinc and copper levels of normal dietary individuals, we also determined the zinc and copper levels in healthy individuals' plasma and in cancer patient's natural tissue, all of whom had normal diets. The correlation coefficients between zinc and copper were 0.71, 0.45, and 0.55, respectively, in gastric juice, plasma, and tissue of normal dietary subjects. Such correlation changed and was destroyed when there was a high zinc level in gastric juice. When gastric juice zinc level changed from mean value 16.8 μmol/L to 262.5 μmol/L, the correlation coefficient varied from 0.71 to −0.04, and the copper level also varied from mean value 8.96 μmol/L to 4.89 μmol/L. These findings probably give the evidence to suggest that a high zinc level will restrain the copper level and break the balance of the human body's zinc and copper metabolism.     

Nanomedicines in the treatment of anemia in renal disease: focus on CERA (Continuous Erythropoietin Receptor Activator)

Anemia is a common complication of chronic kidney disease (CKD), with erythropoietin deficiency being the major contributing factor. The availability of erythropoiesis-stimulating agents (ESAs) has been a seminal advance in the treatment of anemia related to chronic kidney disease. Over the course of the last decade and a half, newer generations of ESAs have become available. The first-generation ESAs or epoetins have a relatively shorter half-life and have traditionally been administered up to 3 times per week intravenously or subcutaneously to maintain adequate hemoglobin (Hb) levels. At the turn of the century, darbepoetin alfa, a hyperglycosylated form, became available for clinical use. It conferred greater metabolic stability in vivo owing to two additional N-linked carbohydrate chains attached to the protein backbone and has a half-life 3 times longer than that of epoetin. Recently developed and undergoing phase III clinical trials is the third-generation ESA, Continuous Erythropoiesis Receptor Activator (CERA), which has a methoxy-polyethylene glycol polymer chain integrated and has a longer elimination half-life than the first- and second-generation ESAs. Its receptor binding characteristics also differ from those of previous ESAs. Its major advantage is that extended dosing intervals are possible in the management of anemia related to erythropoietin deficiency.     

First‐trimester blood urea nitrogen and risk of gestational diabetes mellitus

Prior studies indicated that urea increased insulin resistance and higher blood urea nitrogen (BUN) was associated with incident diabetes mellitus. However, it remains unclear whether BUN during the first trimester of pregnancy increases risk of gestational diabetes mellitus (GDM). We aimed to investigate the association between first‐trimester BUN and risk of incident GDM. We conducted a prospective, multicenter cohort study of pregnant women. A total of 13 448 eligible pregnant women with measured first‐trimester BUN levels were included in this analysis. Logistic regression analysis was used to estimate the relationship between BUN and GDM. Discrimination and reclassification for GDM by BUN were analysed. A total of 2973 (22.1%) women developed GDM. Compared with the lowest quartile of BUN, the third and fourth quartiles were associated with increased risk of GDM (adjusted odds ratios 1.21 [95% CI 1.07‐1.37] and 1.50 [95% CI 1.33‐1.69], respectively, P for trend <.001). The addition of BUN to conventional factor model improved discrimination (C statistic 0.2%, P = .003) and reclassification (net reclassification index 14.67%, P < .001; integrated discrimination improvement 0.12%, P < .001) for GDM. In conclusion, higher BUN concentrations during the first trimester of pregnancy were associated with increased risk of GDM, suggesting that BUN could be a potential predictor for GDM.     

2型糖尿病与糖尿病肾病患者微炎症及肠道微生物多样性分析

目的 分析2型糖尿病(T2DM)及糖尿病肾病(DKD)患者微炎症情况和肠道微生物多样性。 方法 将2016年4月至2019年7月在我院进行治疗的68例T2DM患者(T2DM组)和57例DKD患者(DKD组)纳入研究,选择同期于我院进行健康体检的36例志愿者作为对照组。收集3组对象一般资料、血液标本和粪便标本,测定血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDLC)、高密度脂蛋白胆固醇(HDLC)、糖化血红蛋白(HbAlc)、空腹血糖(FBG)、超敏C反应蛋白(hsCRP)、白细胞介素6(IL6)水平,并对肠道细菌进行16S rDNA序列测序。比较3组对象一般资料,血液指标,肠道菌群门水平构成情况,肠道菌群多样性,肠道菌属差异性,并对患者炎性指标与菌群种类进行相关性分析。 结果 DKD组患者糖尿病病程长于T2DM组(P结论 2型糖尿病患者普遍存在微炎症和肠道菌群失衡,微炎症程度与肾脏病变和肠道菌群数量密切相关。T2DM与DKD患者在肠道菌群结构上具有一致性和差异性,肠道菌群检测有可能成为预测T2DM患者发生肾脏病变的风险指标。     

Plasma zinc, copper, leptin, and body composition are associated in elite female judo athletes

This study evaluated levels of plasma zinc, copper, and leptin, body composition, and their relationship in nine elite female judo athletes under two different training conditions. Body composition and biochemical measurements (hematological indexes, plasma zinc, plasma copper, and plasma leptin) were analyzed 24 h after intense training and following a 5-d period without training (no-training). Plasma leptin and plasma zinc increased with no-training. Plasma zinc correlated negatively with percent fat mass (r=−0.62; r=0.05) and positively with plasma leptin (r=0.83; p=0.002) in the no-training condition Plasma copper did not change during the study and correlated positively with plasma leptin (r=0.66; p=0.05) and with percent fat mass (r=0.80; p=0.007) after training. Percent fat mass was associated negatively with plasma zinc (r=−0.62; p=0.05) in the no-training condition. Moreover percent fat mass was negatively associated with the Zn/Cu plasma ratio under both training conditions (r<−0.78, p<0.001). These results are consistent with the possible function of zinc as a lipid-mobilizing factor and of copper as a limiting factor in energy metabolism.