Toxics

Editorial

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5 pages, 216 KiB

Open AccessEditorial

Editorial to Special Issue Toxic Metals, Chronic Diseases and Related Cancers

by Soisungwan Satarug

Toxics 2022, 10(3), 125; https://doi.org/10.3390/toxics10030125 - 5 Mar 2022

Cited by 1 | Viewed by 2510

Abstract

In this Special Issue, entitled “Toxic Metals, Chronic Diseases and Related Cancers”, there are 19 published manuscripts, including reports of environmental exposure monitoring [...] Full article

(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)

Research

Jump to: Editorial, Review

12 pages, 292 KiB

Open AccessArticle

Associations between Maternal Cadmium Exposure with Risk of Preterm Birth and Low Birth Weight: Effect of Mediterranean Diet Adherence on Affected Prenatal Outcomes

by Sarah Gonzalez-Nahm, Kiran Nihlani, John S. House, Rachel L. Maguire, Harlyn G. Skinner and Cathrine Hoyo

Toxics 2020, 8(4), 90; https://doi.org/10.3390/toxics8040090 - 20 Oct 2020

Cited by 16 | Viewed by 3030

Abstract

Prenatal cadmium exposure at non-occupational levels has been associated with poor birth outcomes. The intake of essential metals, such as iron and selenium, may mitigate cadmium exposure effects. However, at high levels, these metals can be toxic. The role of dietary patterns rich [...] Read more.

Prenatal cadmium exposure at non-occupational levels has been associated with poor birth outcomes. The intake of essential metals, such as iron and selenium, may mitigate cadmium exposure effects. However, at high levels, these metals can be toxic. The role of dietary patterns rich in these metals is less studied. We used a linear and logistic regression in a cohort of 185 mother–infant pairs to assess if a Mediterranean diet pattern during pregnancy modified the associations between prenatal cadmium exposure and (1) birth weight and (2) preterm birth. We found that increased cadmium exposure during pregnancy was associated with lower birth weight (β = −210.4; 95% CI: −332.0, −88.8; p = 0.008) and preterm birth (OR = 0.11; 95% CI: 0.01, 0.72; p = 0.04); however, these associations were comparable in offspring born to women reporting high adherence to a Mediterranean diet (β = −274.95; 95% CI: −701.17, 151.26; p = 0.20) and those with low adherence (β = −64.76; 95% CI: −359.90, 230.37; p = 0.66). While the small sample size limits inference, our findings suggest that adherence to a Mediterranean dietary pattern may not mitigate cadmium exposure effects. Given the multiple organs targeted by cadmium and its slow excretion rate, larger studies are required to clarify these findings. Full article

(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)

11 pages, 519 KiB

Open AccessArticle

Early-Life Dietary Cadmium Exposure and Kidney Function in 9-Year-Old Children from the PROGRESS Cohort

by Edna Rodríguez-López, Marcela Tamayo-Ortiz, Ana Carolina Ariza, Eduardo Ortiz-Panozo, Andrea L. Deierlein, Ivan Pantic, Mari Cruz Tolentino, Guadalupe Estrada-Gutiérrez, Sandra Parra-Hernández, Aurora Espejel-Núñez, Martha María Téllez-Rojo, Robert O. Wright and Alison P. Sanders

Toxics 2020, 8(4), 83; https://doi.org/10.3390/toxics8040083 - 7 Oct 2020

Cited by 17 | Viewed by 3148

Abstract

Cadmium (Cd) is a toxic metal associated with adverse health effects, including kidney injury or disease. The aims of this study were to estimate dietary Cd exposure during childhood, and to evaluate the association of early-life dietary Cd with biomarkers of glomerular kidney [...] Read more.

Cadmium (Cd) is a toxic metal associated with adverse health effects, including kidney injury or disease. The aims of this study were to estimate dietary Cd exposure during childhood, and to evaluate the association of early-life dietary Cd with biomarkers of glomerular kidney function in 9-year-old Mexican children. Our study included 601 children from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort with up to five follow-up food frequency questionnaires from 1 to 9 years of age; and 480 children with measures of serum creatinine, cystatin C, and blood nitrogen urea (BUN), as well as 9-year-old estimated glomerular filtration rate. Dietary Cd was estimated through food composition tables. Multiple linear regression models were used to analyze the association between 1 and 9 years, cumulative dietary Cd, and each kidney parameter. Dietary Cd exposure increased with age and exceeded the tolerable weekly intake (TWI = 2.5 µg/kg body weight) by 16–64% at all ages. Early-life dietary Cd exposure was above the TWI and we observed inverse associations between dietary Cd exposure and kidney function parameters. Additional studies are needed to assess kidney function trajectories through adolescence. Identifying preventable risk factors including environmental exposures in early life can contribute to decreasing the incidence of adult kidney disease. Full article

(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)

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9 pages, 587 KiB

Open AccessArticle

Lifetime Cadmium Exposure and Mortality for Renal Diseases in Residents of the Cadmium-Polluted Kakehashi River Basin in Japan

by Muneko Nishijo, Kazuhiro Nogawa, Yasushi Suwazono, Teruhiko Kido, Masaru Sakurai and Hideaki Nakagawa

Toxics 2020, 8(4), 81; https://doi.org/10.3390/toxics8040081 - 1 Oct 2020

Cited by 17 | Viewed by 2428

Abstract

Very few studies have investigated the dose–response relationship between external cadmium (Cd) exposure and mortality. We aim to investigate the relationship between lifetime Cd intake (LCd) and mortality in the Cd-polluted Kakehashi River basin in Japan. Mortality risk ratios for a unit of [...] Read more.

Very few studies have investigated the dose–response relationship between external cadmium (Cd) exposure and mortality. We aim to investigate the relationship between lifetime Cd intake (LCd) and mortality in the Cd-polluted Kakehashi River basin in Japan. Mortality risk ratios for a unit of increase of LCd and urinary Cd were analyzed using Cox’s proportional model. LCd was estimated based on residency and Cd in rice produced in their living areas. In men, mortality for all causes was significantly increased for a 10-μg/g Cr increase in urinary Cd, but not for a 1-g increase in LCd. In women, mortality risks for all causes and renal diseases, particularly renal failure, were significantly increased for a 10-μg/g Cr increase in urinary Cd. Similarly, mortality risks for renal diseases and renal failure were significantly increased for a 1-g increase of LCd in women. Comparing the contribution of two exposure markers to increased mortality in women, LCd was more effective for increasing mortality risks for renal diseases and renal failure, while urinary Cd contributed more to increased mortality risk for all causes. LCd may show a better dose–response relationship with mortality risk for renal diseases in women. Full article

(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)

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14 pages, 848 KiB

Open AccessArticle

Association between Heavy Metals and Rare Earth Elements with Acute Ischemic Stroke: A Case-Control Study Conducted in the Canary Islands (Spain)

by Florián Medina-Estévez, Manuel Zumbado, Octavio P. Luzardo, Ángel Rodríguez-Hernández, Luis D. Boada, Fernando Fernández-Fuertes, María Elvira Santandreu-Jimenez and Luis Alberto Henríquez-Hernández

Toxics 2020, 8(3), 66; https://doi.org/10.3390/toxics8030066 - 2 Sep 2020

Cited by 17 | Viewed by 3156

Abstract

The role of inorganic elements as risk factors for stroke has been suggested. We designed a case-control study to explore the role of 45 inorganic elements as factors associated with stroke in 92 patients and 83 controls. Nineteen elements were detected in >80% [...] Read more.

The role of inorganic elements as risk factors for stroke has been suggested. We designed a case-control study to explore the role of 45 inorganic elements as factors associated with stroke in 92 patients and 83 controls. Nineteen elements were detected in >80% of patients and 21 were detected in >80% of controls. Blood level of lead was significantly higher among patients (11.2 vs. 9.03 ng/mL) while gold and cerium were significantly higher among controls (0.013 vs. 0.007 ng/mL; and 18.0 vs. 15.0 ng/mL). Lead was associated with stroke in univariate and multivariate analysis (OR = 1.65 (95% CI, 1.09–2.50) and OR = 1.91 (95% CI, 1.20–3.04), respectively). Gold and cerium showed an inverse association with stroke in multivariate analysis (OR = 0.81 (95% CI, 0.69–0.95) and OR = 0.50 (95% CI, 0.31–0.78)). Future studies are needed to elucidate the potential sources of exposure and disclose the mechanisms of action. Full article

(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)

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12 pages, 1567 KiB

Open AccessArticle

The Immunotoxicity of Chronic Exposure to High Levels of Lead: An Ex Vivo Investigation

by Kawinsaya Pukanha, Supabhorn Yimthiang and Wiyada Kwanhian

Toxics 2020, 8(3), 56; https://doi.org/10.3390/toxics8030056 - 13 Aug 2020

Cited by 8 | Viewed by 4400

Abstract

Lead (Pb) is a toxic metal known for its wide-ranging adverse health effects. However, a compound of Pb is still used in the caulking process to repair wooden fishing boats. The present study aimed to measure Pb exposure and its immunologic effects in [...] Read more.

Lead (Pb) is a toxic metal known for its wide-ranging adverse health effects. However, a compound of Pb is still used in the caulking process to repair wooden fishing boats. The present study aimed to measure Pb exposure and its immunologic effects in boatyard workers in Nakhon Si Thammarat province, Thailand, in comparison with an age-matched control group of farmers. The age, body mass index, and smoking history in workers (n = 14) and controls (n = 16) did not differ. The median blood Pb concentration was 8.7-fold higher in workers than controls (37.1 versus 4.3 µg/dL, p < 0.001). Workers had 8.4% lower phagocytic active cells than controls (89.9% versus 98.1%, p = 0.019). In response to a mitogen stimulation, the peripheral blood mononuclear cells (PBMCs) from workers produced 2-fold higher ratios of interleukin-4 (IL-4) to interferon-γ than the PBMCs from controls (p = 0.026). Furthermore, Pb-exposed workers had 33.9% lower cytotoxic T (Tc) cells than controls (24.3% versus 36.8%, p = 0.004). In stark contrast, the percentage of regulatory T (Treg) cells in workers was 2.7-fold higher than controls (6.1% versus 2.3%, p < 0.001). In all subjects, blood Pb showed positive correlations with the percentages of Treg cells (r = 0.843, p < 0.001) and IL-4 (r = 0.473, p = 0.041) while showing an inverse correlation with the percentages of Tc cells (r = −0.563, p = 0.015). These findings indicate that chronic high Pb exposure may cause a shift towards humoral immune response, together with a suppression of cellular immunity, thereby suggesting an elevation in cancer risk in Pb-exposed workers. Full article

(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)

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16 pages, 2588 KiB

Open AccessArticle

Increased Mitochondrial Fragmentation Mediated by Dynamin-Related Protein 1 Contributes to Hexavalent Chromium-Induced Mitochondrial Respiratory Chain Complex I-Dependent Cytotoxicity

by Yu Ma, Yujing Zhang, Yuanyuan Xiao and Fang Xiao

Toxics 2020, 8(3), 50; https://doi.org/10.3390/toxics8030050 - 29 Jul 2020

Cited by 7 | Viewed by 2616

Abstract

Hexavalent chromium (Cr(VI)) pollution is a severe public health problem in the world. Although it is believed that mitochondrial fragmentation is a common phenomenon in apoptosis, whether excessive fission is crucial for apoptosis remains controversial. We previously confirmed that Cr(VI) mainly targeted mitochondrial [...] Read more.

Hexavalent chromium (Cr(VI)) pollution is a severe public health problem in the world. Although it is believed that mitochondrial fragmentation is a common phenomenon in apoptosis, whether excessive fission is crucial for apoptosis remains controversial. We previously confirmed that Cr(VI) mainly targeted mitochondrial respiratory chain complex I (MRCC I) to induce reactive oxygen species (ROS)-mediated apoptosis, but the related mechanism was unclear. In this study, we found Cr(VI) targeted MRCC I to induce ROS accumulation and triggered mitochondria-related cytotoxicity. Cr(VI)-induced cytotoxicity was alleviated by pretreatment of Glutamate/malate (Glu/Mal; MRCC I substrates), and was aggravated by cotreatment of rotenone (ROT; MRCC I inhibitor). Cr(VI) induced excessive mitochondrial fragmentation and mitochondrial dynamin-related protein 1 (Drp1) translocation, the application of Drp1-siRNA alleviated Cr(VI)-induced apoptosis. The cytotoxicity in the Drp1-si plus Cr(VI) treatment group was alleviated by the application of Glu/Mal, and was aggravated by the application of ROT. Drp1 siRNA promoted the inhibition of Glu/Mal on Cr(VI)-induced cytotoxicity, and alleviated the aggravation of ROT on Cr(VI)-induced cytotoxicity. Taken together, Cr(VI)-induced Drp1 modulation was dependent on MRCC I inhibition-mediated ROS production, and Drp1-mediated mitochondrial fragmentation contributed to Cr(VI)-induced MRCC I-dependent cytotoxicity, which provided the experimental basis for further elucidating Cr(VI)-induced cytotoxicity. Full article

(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)

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13 pages, 1143 KiB

Open AccessArticle

Mercury Exposure and Associations with Hyperlipidemia and Elevated Liver Enzymes: A Nationwide Cross-Sectional Survey

by Seungho Lee, Sung-Ran Cho, Inchul Jeong, Jae Bum Park, Mi-Yeon Shin, Sungkyoon Kim and Jin Hee Kim

Toxics 2020, 8(3), 47; https://doi.org/10.3390/toxics8030047 - 1 Jul 2020

Cited by 23 | Viewed by 3902

Abstract

Mercury (Hg) has obesogenic properties. However, the associated health outcomes of population-level mercury exposure were unclear. This study investigated the relationships between blood mercury levels and obesity-related outcomes such as hyperlipidemia and elevated liver enzymes. Using the second cycle of the Korean National [...] Read more.

Mercury (Hg) has obesogenic properties. However, the associated health outcomes of population-level mercury exposure were unclear. This study investigated the relationships between blood mercury levels and obesity-related outcomes such as hyperlipidemia and elevated liver enzymes. Using the second cycle of the Korean National Environmental Health Survey (n = 6454), we performed logistic regression to examine the effects of Hg on hyperlipidemia and elevated liver enzymes. The blood mercury levels were significantly higher in the hyperlipidemia group (n = 3699, male: 4.03 μg/L, female: 2.83 μg/L) compared to the non-hyperlipidemia group (n = 2755, male: 3.48 μg/L, female: 2.69 μg/L), and high blood mercury levels were associated with an 11% higher risk of hyperlipidemia. The elevated liver enzymes group had higher mean blood mercury levels (n = 1189, male: 4.38 μg/L, female: 3.25 μg/L) than the normal group (n = 5265, male: 3.64 μg/L, female: 2.70 μg/L), and elevated blood mercury was associated with a 35% higher risk of elevated liver enzymes. Moreover, the effect was constant after adjusting for personal medications. These results indicate that mercury exposure is significantly associated with hyperlipidemia and elevated liver enzymes. Full article

(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)

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16 pages, 1259 KiB

Open AccessArticle

Exposure Assessment of Cadmium in Female Farmers in Cadmium-Polluted Areas in Northern Japan

by Hyogo Horiguchi, Etsuko Oguma, Satoshi Sasaki, Kayoko Miyamoto, Yoko Hosoi, Akira Ono and Fujio Kayama

Toxics 2020, 8(2), 44; https://doi.org/10.3390/toxics8020044 - 17 Jun 2020

Cited by 10 | Viewed by 3329

Abstract

Akita prefecture is located in the northern part of Japan and has many cadmium-polluted areas. We herein performed an exposure assessment of cadmium in 712 and 432 female farmers in two adjacent cadmium-polluted areas (A and B, respectively), who underwent local health examinations [...] Read more.

Akita prefecture is located in the northern part of Japan and has many cadmium-polluted areas. We herein performed an exposure assessment of cadmium in 712 and 432 female farmers in two adjacent cadmium-polluted areas (A and B, respectively), who underwent local health examinations from 2001–2004. We measured cadmium concentrations in 100 food items collected from local markets in 2003. We then multiplied the intake of each food item by its cadmium concentration in each subject to assess cadmium intake from food and summed cadmium intake from all food items to obtain the total cadmium intake. Median cadmium intake levels in areas A and B were 55.7 and 47.8 µg/day, respectively, which were both higher than that of the general population and were attributed to local agricultural products, particularly rice. We also calculated weekly cadmium intake per body weight and compared it to the previous provisional tolerable weekly intake reported by the Joint FAO (Food and Agriculture Organization)/WHO (World Health Organization) expert committee on food additives or current tolerable weekly intake in Japan of 7 µg/kg BW/week. Medians in areas A and B were 7.2 and 6.0 µg/kg BW/week, respectively. Similar estimated values were also obtained by the Monte Carlo simulation. These results demonstrated that the cadmium exposure levels among the farmers were high enough to be approximately the tolerable weekly intake. Full article

(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)

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14 pages, 1269 KiB

Open AccessArticle

Genotoxic Effects of Aluminum Chloride and Their Relationship with N-Nitroso-N-Methylurea (NMU)-Induced Breast Cancer in Sprague Dawley Rats

by Alejandro Monserrat García-Alegría, Agustín Gómez-Álvarez, Iván Anduro-Corona, Armando Burgos-Hernández, Eduardo Ruíz-Bustos, Rafael Canett-Romero, Humberto González-Ríos, José Guillermo López-Cervantes, Karen Lillian Rodríguez-Martínez and Humberto Astiazaran-Garcia

Toxics 2020, 8(2), 31; https://doi.org/10.3390/toxics8020031 - 20 Apr 2020

Cited by 7 | Viewed by 5411

Abstract

Recently, soluble forms of aluminum for human use or consumption have been determined to be potentially toxic due to their association with hepatic, neurological, hematological, neoplastic, and bone conditions. This study aims to assess the genotoxic effect of aluminum chloride on genomic instability [...] Read more.

Recently, soluble forms of aluminum for human use or consumption have been determined to be potentially toxic due to their association with hepatic, neurological, hematological, neoplastic, and bone conditions. This study aims to assess the genotoxic effect of aluminum chloride on genomic instability associated with the onset of N-nitroso-N-methylurea (NMU)-induced breast cancer in Sprague Dawley rats. The dietary behavior of the rats was assessed, and the concentration of aluminum in the mammary glands was determined using atomic absorption spectroscopy. Genomic instability was determined in the histological sections of mammary glands stained with hematoxylin and eosin. Moreover, micronucleus in peripheral blood and comet assays were performed. The results of dietary behavior evaluation indicated no significant differences between the experimental treatments. However, aluminum concentration in breast tissues was high in the +2000Al/−NMU treatment. This experimental treatment caused moderate intraductal cell proliferation, lymph node hyperplasia, and serous gland adenoma. Furthermore, micronucleus and comet test results revealed that +2000Al/−NMU led to a genotoxic effect after a 10-day exposure and the damage was more evident after a 15-day exposure. Therefore, in conclusion, genomic instability is present and the experimental conditions assessed are not associated with breast cancer. Full article

(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)

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16 pages, 883 KiB

Open AccessArticle

Theoretical Modeling of Oral Glucose Tolerance Tests Guides the Interpretation of the Impact of Perinatal Cadmium Exposure on the Offspring’s Glucose Homeostasis

by Alexandre Rocca, Eric Fanchon and Jean-Marc Moulis

Toxics 2020, 8(2), 30; https://doi.org/10.3390/toxics8020030 - 15 Apr 2020

Cited by 5 | Viewed by 3332

Abstract

Oral glucose tolerance tests, in which the concentration of glucose is monitored in the circulation over 2 h after ingesting a bolus, probe diabetic or pre-diabetic conditions. The resulting glucose curves inform about glucose turnover, insulin production and sensitivity, and other parameters. However, [...] Read more.

Oral glucose tolerance tests, in which the concentration of glucose is monitored in the circulation over 2 h after ingesting a bolus, probe diabetic or pre-diabetic conditions. The resulting glucose curves inform about glucose turnover, insulin production and sensitivity, and other parameters. However, extracting the relevant parameters from a single complex curve is not straightforward. We propose a simple modeling method recapitulating the most salient features of the role of insulin-secreting pancreatic

β

-cells and insulin sensitive tissues. This method implements four ordinary differential equations with ten parameters describing the time-dependence of glucose concentration, its removal rate, and the circulating and stored insulin concentrations. From the initial parameter set adjusted to a reference condition, fitting is done by minimizing a weighted least-square residual. In doing so, the sensitivity of

β

-cells to glucose was identified as the most likely impacted function at weaning for the progeny of rats that were lightly exposed to cadmium in the perigestational period. Later in life, after young rats received non-contaminated carbohydrate enriched food, differences are more subtle, but modeling agrees with long-lasting perturbation of glucose homeostasis. Full article

(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)

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12 pages, 2176 KiB

Open AccessArticle

In Vitro Evaluation of the Effects of Cadmium on Endocytic Uptakes of Proteins into Cultured Proximal Tubule Epithelial Cells

by Hitomi Fujishiro, Hazuki Yamamoto, Nobuki Otera, Nanae Oka, Mei Jinno and Seiichiro Himeno

Toxics 2020, 8(2), 24; https://doi.org/10.3390/toxics8020024 - 1 Apr 2020

Cited by 9 | Viewed by 3731

Abstract

Cadmium (Cd) is an environmental pollutant known to cause dysfunctions of the tubular reabsorption of biomolecules in the kidney. Elevated levels of urinary excretion of low-molecular-weight proteins such as β₂-microglobulin (β₂-MG) have been used as an indicator of Cd-induced [...] Read more.

Cadmium (Cd) is an environmental pollutant known to cause dysfunctions of the tubular reabsorption of biomolecules in the kidney. Elevated levels of urinary excretion of low-molecular-weight proteins such as β₂-microglobulin (β₂-MG) have been used as an indicator of Cd-induced renal tubular dysfunctions. However, very few studies have examined the direct effects of Cd on the reabsorption efficiency of proteins using cultured renal cells. Here, we developed an in vitro assay system for quantifying the endocytic uptakes of fluorescent-labeled proteins by flow cytometry in S1 and S2 cells derived from mouse kidney proximal tubules. Endocytic uptakes of fluorescent-labeled albumin, transferrin, β₂-MG, and metallothionein into S1 cells were confirmed by fluorescence imaging and flow cytometry. The exposure of S1 and S2 cells to Cd at 1 and 3 µM for 3 days resulted in significant decreases in the uptakes of β₂-MG and metallothionein but not in those of albumin or transferrin. These results suggest that Cd affects the tubular reabsorption of low-molecular-weight proteins even at nonlethal concentrations. The in vitro assay system developed in this study to evaluate the endocytic uptakes of proteins may serve as a useful tool for detecting toxicants that cause renal tubular dysfunctions. Full article

(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)

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14 pages, 530 KiB

Open AccessArticle

A Comparison of the Nephrotoxicity of Low Doses of Cadmium and Lead

by Soisungwan Satarug, Glenda C. Gobe, Pailin Ujjin and David A. Vesey

Toxics 2020, 8(1), 18; https://doi.org/10.3390/toxics8010018 - 2 Mar 2020

Cited by 28 | Viewed by 4703

Abstract

Environmental exposure to moderate-to-high levels of cadmium (Cd) and lead (Pb) is associated with nephrotoxicity. In comparison, the health impacts of chronic low-level exposure to Cd and Pb remain controversial. The aim of this study was to therefore evaluate kidney dysfunction associated with [...] Read more.

Environmental exposure to moderate-to-high levels of cadmium (Cd) and lead (Pb) is associated with nephrotoxicity. In comparison, the health impacts of chronic low-level exposure to Cd and Pb remain controversial. The aim of this study was to therefore evaluate kidney dysfunction associated with chronic low-level exposure to Cd and Pb in a population of residents in Bangkok, Thailand. The mean age and the estimated glomerular filtration rate (eGFR) for 392 participants (195 men and 197 women) were 34.9 years and 104 mL/min/1.73 m², respectively, while the geometric mean concentrations of urinary Cd and Pb were 0.25 μg/L (0.45 μg/g of creatinine) and 0.89 μg/L (1.52 μg/g of creatinine), respectively. In a multivariable regression analysis, the eGFR varied inversely with blood urea nitrogen in both men (β = −0.125, p = 0.044) and women (β = −0.170, p = 0.008), while inverse associations of the eGFR with urinary Cd (β = −0.132, p = 0.043) and urinary Pb (β = −0.130, p = 0.044) were seen only in women. An increased urinary level of Cd to the median level of 0.38 μg/L (0.44 μg/g of creatinine) was associated with a decrease in the eGFR by 4.94 mL/min/1.73 m² (p = 0.011). The prevalence odds of a reduced eGFR rose 2.5-, 2.9- and 2.3-fold in the urinary Cd quartile 3 (p = 0.013), the urinary Cd quartile 4 (p = 0.008), and the urinary Pb quartile 4 (p = 0.039), respectively. This study suggests that chronic exposure to low-level Cd is associated with a decline in kidney function and that women may be more susceptible than men to nephrotoxicity due to an elevated intake of Cd and Pb. Full article

(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)

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10 pages, 571 KiB

Open AccessArticle

Biomonitoring of Trace Elements in Subjects Living Near a Hazardous Waste Incinerator: Concentrations in Autopsy Tissues

by Francisco García, Montse Marquès, Eneko Barbería, Pilar Torralba, Inés Landin, Carlos Laguna, José L. Domingo and Martí Nadal

Toxics 2020, 8(1), 11; https://doi.org/10.3390/toxics8010011 - 11 Feb 2020

Cited by 10 | Viewed by 2958

Abstract

The only hazardous waste incinerator (HWI) in Spain started to operate in 1999. Twenty years later, the levels of 11 trace elements (As, Be, Cd, Cr, Hg, Mn, Ni, Pb, Sn, Tl and V) were analyzed in five different autopsy tissues (kidney, liver, [...] Read more.

The only hazardous waste incinerator (HWI) in Spain started to operate in 1999. Twenty years later, the levels of 11 trace elements (As, Be, Cd, Cr, Hg, Mn, Ni, Pb, Sn, Tl and V) were analyzed in five different autopsy tissues (kidney, liver, brain, bone and lung) from 20 individuals who had been living near the facility. In 2019, As, Be, Tl and V were not detected in any of the analyzed tissues, while Hg could be only quantified in very few samples. The highest levels of Cd and Pb were found in kidney and bone, respectively, while those of Mn were observed in liver and kidney. In turn, the mean concentrations of Cr and Sn were very similar in all tissues. A consistent temporal trend (1998–2019) was only found for Cr and Pb. On the one hand, the mean Cr concentrations in kidney and bone have increased progressively since 1998. In contrast, the mean levels of Pb decreased significantly over time, probably due to ban of Pb as gasoline additive. The data global analysis indicates that the emissions of trace elements by the HWI have not increased the exposure and/or accumulation of these elements in individuals living near the facility. Full article

(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)

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15 pages, 3878 KiB

Open AccessArticle

The Source and Pathophysiologic Significance of Excreted Cadmium

by Soisungwan Satarug, David A. Vesey, Werawan Ruangyuttikarn, Muneko Nishijo, Glenda C. Gobe and Kenneth R. Phelps

Toxics 2019, 7(4), 55; https://doi.org/10.3390/toxics7040055 - 18 Oct 2019

Cited by 24 | Viewed by 4492

Abstract

In theory, the identification of the source of excreted cadmium (Cd) might elucidate the pathogenesis of Cd-induced chronic kidney disease (CKD). With that possibility in mind, we studied Thai subjects with low, moderate, and high Cd exposure. We measured urine concentrations of Cd, [...] Read more.

In theory, the identification of the source of excreted cadmium (Cd) might elucidate the pathogenesis of Cd-induced chronic kidney disease (CKD). With that possibility in mind, we studied Thai subjects with low, moderate, and high Cd exposure. We measured urine concentrations of Cd, ([Cd]_u); N-acetyl-β-d-glucosaminidase, a marker of cellular damage ([NAG]_u); and β₂-microglobulin, an indicator of reabsorptive dysfunction ([β₂MG]_u). To relate excretion rates of these substances to existing nephron mass, we normalized the rates to creatinine clearance, an approximation of the glomerular filtration rate (GFR) (E_Cd/C_cr, E_NAG/C_cr, and E_β2MG/C_cr). To link the loss of intact nephrons to Cd-induced tubular injury, we examined linear and quadratic regressions of estimated GFR (eGFR) on E_Cd/C_cr, eGFR on E_NAG/C_cr, and E_NAG/C_cr on E_Cd/C_cr. Estimated GFR varied inversely with both ratios, and E_NAG/C_cr varied directly with E_Cd/C_cr. Linear and quadratic regressions of E_β2MG/C_cr on E_Cd/C_cr and E_NAG/C_cr were significant in moderate and high Cd-exposure groups. The association of E_NAG/C_cr with E_Cd/C_cr implies that both ratios depicted cellular damage per surviving nephron. Consequently, we infer that excreted Cd emanated from injured tubular cells, and we attribute the reduction of eGFR to the injury. We suggest that E_Cd/C_cr, E_NAG/C_cr, and eGFR were associated with one another because each parameter was determined by the tubular burden of Cd. Full article

(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)

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9 pages, 1095 KiB

Open AccessArticle

Screening for Elevated Blood Lead Levels and Related Risk Factors among Thai Children Residing in a Fishing Community

by Supabhorn Yimthiang, Donrawee Waeyang and Saruda Kuraeiad

Toxics 2019, 7(4), 54; https://doi.org/10.3390/toxics7040054 - 12 Oct 2019

Cited by 7 | Viewed by 4154

Abstract

The present study explored environmental and behavioral factors associated with elevated blood lead (Pb) levels in 311 children (151 girls and 160 boys), aged 3–7 years, who lived in a coastal fishing community of the Pakpoon Municipality, Nakhon Si Thammarat, Thailand. The geometric [...] Read more.

The present study explored environmental and behavioral factors associated with elevated blood lead (Pb) levels in 311 children (151 girls and 160 boys), aged 3–7 years, who lived in a coastal fishing community of the Pakpoon Municipality, Nakhon Si Thammarat, Thailand. The geometric mean for blood Pb was 2.81 µg/dL, ranging between 0.03 and 26.40 µg/dL. The percentage of high blood Pb levels, defined as blood Pb ≥ 5 µg/dL, was 10.0% in boys and 13.9% in girls. Parental occupation in producing fishing nets with lead weights was associated with a marked increase in the prevalence odds ratio (POR) for high blood Pb (POR 17.54, 95%; CI: 7.093, 43.390; p < 0.001), while milk consumption was associated with 61% reduction in the POR for high blood Pb (POR 0.393, 95%; CI: 0.166, 0.931; p = 0.034). High blood Pb was associated with an increased risk for abnormal growth (POR 2.042, 95%; CI: 0.999, 4.174; p = 0.050). In contrast, milk consumption was associated with a 43% reduction in POR for abnormal growth (POR 0.573, 95%; CI: 0.337, 0.976; p = 0.040). After adjustment for age, the mean (standard error of mean, SE) values for blood Pb were 6.22 (0.50) μg/dL in boys and 6.72 (0.49) μg/dL in girls of parents with an occupation in making fishing nets with lead weights. These mean blood Pb values were respectively 2.3 and 2.5 times higher than similarly aged boys and girls of parents with other occupations. These data are essential for setting surveillance and programmes to prevent toxic Pb exposure, especially in children of coastal fishing communities in southern Thailand. Full article

(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)

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12 pages, 959 KiB

Open AccessFeature PaperArticle

Biomonitoring of Trace Elements in Hair of Schoolchildren Living Near a Hazardous Waste Incinerator—A 20 Years Follow-Up

by Roser Esplugas, Montse Mari, Montse Marquès, Marta Schuhmacher, José L. Domingo and Martí Nadal

Toxics 2019, 7(4), 52; https://doi.org/10.3390/toxics7040052 - 1 Oct 2019

Cited by 28 | Viewed by 4133

Abstract

Since 1998, a monitoring program is periodically performed to assess the environmental and human health impact of air chemicals potentially emitted by a hazardous waste incinerator (HWI) located in Constantí (Catalonia, Spain). In 2017, samples of hair were collected from 94 schoolchildren (aged [...] Read more.

Since 1998, a monitoring program is periodically performed to assess the environmental and human health impact of air chemicals potentially emitted by a hazardous waste incinerator (HWI) located in Constantí (Catalonia, Spain). In 2017, samples of hair were collected from 94 schoolchildren (aged 10–13 years) living nearby and the levels of 11 trace elements (As, Be, Cd, Cr, Hg, Mn, Ni, Pb, Sn, Tl and V) were determined. The concentrations showed the following descending order: Pb > Hg > Ni > Sn > Mn > Cr. In turn, As, Be and Tl were not detected, while Cd and V were found only in a few samples. Some metal levels were significantly, positively correlated. Some significant differences were also noticed according to the gender and the specific zone of residence. Finally, the levels of trace elements showed fluctuations through time. Cr and Pb showed a significant decrease in comparison to the concentrations obtained in the baseline study (1998). According to the current results, metal emissions from the HWI are not relevant in terms of human health impact since their levels were similar and even lower than those reported in other contaminated areas. Full article

(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)

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Review

Jump to: Editorial, Research

31 pages, 367 KiB

Open AccessReview

Effects of Cadmium, Lead, and Mercury on the Structure and Function of Reproductive Organs

by Peter Massányi, Martin Massányi, Roberto Madeddu, Robert Stawarz and Norbert Lukáč

Toxics 2020, 8(4), 94; https://doi.org/10.3390/toxics8040094 - 29 Oct 2020

Cited by 122 | Viewed by 12144

Abstract

Reproductive organs are essential not only for the life of an individual but also for the survival and development of the species. The response of reproductive organs to toxic substances differs from that of other target organs, and they may serve as an [...] Read more.

Reproductive organs are essential not only for the life of an individual but also for the survival and development of the species. The response of reproductive organs to toxic substances differs from that of other target organs, and they may serve as an ideal “barometer” for the deleterious effects of environmental pollution on animal and human health. The incidence of infertility, cancers, and associated maladies has increased in the last fifty years or more, while various anthropogenic activities have released into the environment numerous toxic substances, including cadmium, lead, and mercury. Data from epidemiological studies suggested that environmental exposure to cadmium, lead, and mercury may have produced reproductive and developmental toxicity. The present review focused on experimental studies using rats, mice, avian, and rabbits to demonstrate unambiguously effects of cadmium, lead, or mercury on the structure and function of reproductive organs. In addition, relevant human studies are discussed. The experimental studies reviewed have indicated that the testis and ovary are particularly sensitive to cadmium, lead, and mercury because these organs are distinguished by an intense cellular activity, where vital processes of spermatogenesis, oogenesis, and folliculogenesis occur. In ovaries, manifestation of toxicity induced by cadmium, lead, or mercury included decreased follicular growth, occurrence of follicular atresia, degeneration of the corpus luteum, and alterations in cycle. In testes, toxic effects following exposure to cadmium, lead, or mercury included alterations of seminiferous tubules, testicular stroma, and decrease of spermatozoa count, motility and viability, and aberrant spermatozoa morphology. Full article

(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)

42 pages, 1227 KiB

Open AccessReview

Cadmium and Lead Exposure, Nephrotoxicity, and Mortality

by Soisungwan Satarug, Glenda C. Gobe, David A. Vesey and Kenneth R. Phelps

Toxics 2020, 8(4), 86; https://doi.org/10.3390/toxics8040086 - 13 Oct 2020

Cited by 122 | Viewed by 9770

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)

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16 pages, 742 KiB

Open AccessReview

Emerging Links between Cadmium Exposure and Insulin Resistance: Human, Animal, and Cell Study Data

by Aleksandra Buha, Danijela Đukić-Ćosić, Marijana Ćurčić, Zorica Bulat, Biljana Antonijević, Jean-Marc Moulis, Marina Goumenou and David Wallace

Toxics 2020, 8(3), 63; https://doi.org/10.3390/toxics8030063 - 27 Aug 2020

Cited by 52 | Viewed by 5633

Abstract

Recent research has helped clarify the role of cadmium (Cd) in various pathological states. We have demonstrated Cd involvement in pancreatic cancer, as well as the bioaccumulation of Cd in the pancreas. Bioaccumulation and increased toxicity suggest that Cd may also be involved [...] Read more.

Recent research has helped clarify the role of cadmium (Cd) in various pathological states. We have demonstrated Cd involvement in pancreatic cancer, as well as the bioaccumulation of Cd in the pancreas. Bioaccumulation and increased toxicity suggest that Cd may also be involved in other pancreas-mediated diseases, like diabetes. Cd falls into the category of “hyperglycemic” metals, i.e., metals that increase blood glucose levels, which could be due to increased gluconeogenesis, damage to β-cells leading to reduced insulin production, or insulin resistance at target tissue resulting in a lack of glucose uptake. This review addresses the current evidence for the role of Cd, leading to insulin resistance from human, animal, and in vitro studies. Available data have shown that Cd may affect normal insulin function through multiple pathways. There is evidence that Cd exposure results in the perturbation of the enzymes and modulatory proteins involved in insulin signal transduction at the target tissue and mutations of the insulin receptor. Cd, through well-described mechanisms of oxidative stress, inflammation, and mitochondrial damage, may also alter insulin production in β-cells. More work is necessary to elucidate the mechanisms associated with Cd-mediated insulin resistance. Full article

(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)

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