Copper–zinc imbalance induces kidney tubule damage and oxidative stress in a population exposed to chronic environmental cadmium

Eom, Sang‐Yong; Yim, Dong‐Hyuk; Huang, Mingai; Park, Choong-Hee; Kim, Guen-Bae; Yu, Seung-Do; Choi, Byung-Sun; Park, Jung-Duck; Kim, Yong‐Dae; Kim, Heon

doi:10.1007/s00420-019-01490-9

Cited by 33 publications

(18 citation statements)

References 39 publications

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“…A recent Korean cross-sectional study considered the effect of exposure to Cd 80 on urinary NAG, β 2 -MG and malondialdehyde (MDA) in adults living in a Cd-polluted area near an abandoned copper refinery. In both the high and low exposure groups urinary Cd levels were positively associated with urinary NAG levels but not with the erum copper to zinc ratio (CZR).…”

Section: Heavy Metalsmentioning

confidence: 99%

Nephrotoxic Biomarkers with Specific Indications for Metallic Pollutants: Implications for Environmental Health

2022

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Environmental and occupational exposure to heavy metals and metalloids is a major global health risk. The kidney is often a site of early damage. Nephrotoxicity is both a major consequence of heavy metal exposure and potentially an early warning of greater damage. A paradigm shift occurred at the beginning of the 21st century in the field of renal medicine. The medical model of kidney failure and treatment began to give way to a social model of risk factors and prevention with important implications for environmental health. This development threw into focus the need for better biomarkers: markers of exposure to known nephrotoxins; markers of early damage for diagnosis and prevention; markers of disease development for intervention and choice of therapy. Constituents of electronic waste, e-waste or e-pollution, such as cadmium (Cd), lead (Pb), mercury (HG), arsenic (As) and silica (SiO2) are all potential nephrotoxins; they target the renal proximal tubules through distinct pathways. Different nephrotoxic biomarkers offer the possibility of identifying exposure to individual pollutants. In this review, a selection of prominent urinary markers of tubule damage is considered as potential tools for identifying environmental exposure to some key metallic pollutants.

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Section: Heavy Metalsmentioning

confidence: 99%

Nephrotoxic Biomarkers with Specific Indications for Metallic Pollutants: Implications for Environmental Health

2022

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“…In addition, Cd has a similar ionic radius to that of calcium (Ca) and electronegativity similar to that of zinc (Zn), and both Cd and Pb exhibit higher affinity than Zn for sulphur-containing ligands (Cd > Pb > Zn) [ 23 , 24 , 25 , 26 ]. Consequently, displacement of Zn and Ca and disruption of Zn and Cu homeostasis are other plausible toxic mechanisms [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. All sulphur-containing amino acids, peptides and proteins with functional thiol (-SH) groups are potential ligands (molecular targets) for Cd and Pb.…”

Section: Introductionmentioning

confidence: 99%

Cadmium and Lead Exposure, Nephrotoxicity, and Mortality

Satarug

Gobé

Vesey

et al. 2020

Toxics

148

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The present review aims to provide an update on health risks associated with the low-to-moderate levels of environmental cadmium (Cd) and lead (Pb) to which most populations are exposed. Epidemiological studies examining the adverse effects of coexposure to Cd and Pb have shown that Pb may enhance the nephrotoxicity of Cd and vice versa. Herein, the existing tolerable intake levels of Cd and Pb are discussed together with the conventional urinary Cd threshold limit of 5.24 μg/g creatinine. Dietary sources of Cd and Pb and the intake levels reported for average consumers in the U.S., Spain, Korea, Germany and China are summarized. The utility of urine, whole blood, plasma/serum, and erythrocytes to quantify exposure levels of Cd and Pb are discussed. Epidemiological studies that linked one of these measurements to risks of chronic kidney disease (CKD) and mortality from common ailments are reviewed. A Cd intake level of 23.2 μg/day, which is less than half the safe intake stated by the guidelines, may increase the risk of CKD by 73%, and urinary Cd levels one-tenth of the threshold limit, defined by excessive ß2-microglobulin excretion, were associated with increased risk of CKD, mortality from heart disease, cancer of any site and Alzheimer’s disease. These findings indicate that the current tolerable intake of Cd and the conventional urinary Cd threshold limit do not provide adequate health protection. Any excessive Cd excretion is probably indicative of tubular injury. In light of the evolving realization of the interaction between Cd and Pb, actions to minimize environmental exposure to these toxic metals are imperative.

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“…In early works, increased Cu excretion was noted in Japanese subjects with high Cd exposure [25][26][27]. A similar effect has later been observed in Australians, Thais and Koreans whose environmental exposure to Cd was markedly lower than those in Japanese studies [28][29][30]. However, the clinical relevance of the Cd-induced metal dysregulation remains unclear.…”

Section: Introductionmentioning

confidence: 63%

Gender Differences in Zinc and Copper Excretion in Response to Co-Exposure to Low Environmental Concentrations of Cadmium and Lead

et al. 2020

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Disruption of the homeostasis of zinc (Zn) and copper (Cu) has been associated with nephrotoxicity of cadmium (Cd). Herein, we report the results of a cross sectional analysis of urinary excretion of Zn, Cu, Cd and lead (Pb) in 392 Thais (mean age 33.6) living in an area of low-level environmental exposure to Cd and Pb, reflected by the respective median Cd and Pb excretion rates of 0.44 and 1.75 μg/g creatinine. Evidence for dysregulation of Zn and Cu homeostasis has emerged together with gender differentiated responses. In men, excretion rates for Zn and Cu were increased concomitantly, and their urinary Zn-to-Cu ratios were maintained. In women, only Cu excretion rose, causing a reduction in urinary Zn-to-Cu ratios. Only in women, urinary Zn-to-Cu ratios were associated with worse kidney function, assessed by estimated glomerular filtration rate (eGFR) (β = −7.76, p = 0.015). Only in men, a positive association was seen between eGFR and body iron stores, reflected by serum ferritin (β = 5.32, p = 0.030). Thus, co-exposure to Cd and Pb may disrupt the homeostasis of Zn and Cu more severely in women than men, while urinary Zn-to-Cu ratios and body iron stores can serve as predictors of an adverse effect of co-exposure to Cd and Pb.

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Copper–zinc imbalance induces kidney tubule damage and oxidative stress in a population exposed to chronic environmental cadmium

Cited by 33 publications

References 39 publications

Nephrotoxic Biomarkers with Specific Indications for Metallic Pollutants: Implications for Environmental Health

Nephrotoxic Biomarkers with Specific Indications for Metallic Pollutants: Implications for Environmental Health

Cadmium and Lead Exposure, Nephrotoxicity, and Mortality

Gender Differences in Zinc and Copper Excretion in Response to Co-Exposure to Low Environmental Concentrations of Cadmium and Lead

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