Search Results (269)

Elevated levels of circulating β₂-microglobulin (β₂M) are linked to an increased risk of hypertension and mortality from diabetes. The present study tests the hypothesis that the environmental pollutants, cadmium (Cd) and lead (Pb), by increasing plasma β₂M levels, promote the development of hypertension and progression of diabetic kidney disease. Herein, we analyzed data from a Thai cohort of 72 individuals with diabetes and 65 controls without diabetes who were chronically exposed to low levels of Cd and Pb. In all subjects, serum concentrations of β₂M inversely correlated with the estimated glomerular filtration rate (eGFR) (r = −0.265) and directly with age (r = 0.200), fasting plasma glucose (r = 0.210), and systolic blood pressure (r = 0.229). The prevalence odds ratio (POR) for hyperglycemia increased 7.7% for every 1-year increase in age and increased 3.9-fold, 3.1-fold, and 3.7-fold in those with serum β₂M levels ≥ 5 mg/L, Cd/Pb exposure categories 2 and 3, respectively. The POR for hypertension increased 2.9-fold, 3-fold, and 4-fold by hyperglycemia (p = 0.011), Cd/Pb exposure categories 2 and 3. The POR for albuminuria increased 3.5-fold by hyperglycemia. In conclusion, kidney damage, evident from albuminuria, was particularly pronounced in participants with diabetes who had a serum β₂M above 5 mg/L plus chronic exposure to low-dose Cd and Pb. For the first time, through a mediation analysis, we provide evidence that links Cd exposure to the SH2B3-β₂M pathway of blood pressure homeostasis in people with and without diabetes. Full article

Cadmium exposure has been associated with shortened telomeres, alterations in DNA methylation patterns, and increased mortality. However, the role of DNA methylation in mediating the relationship between cadmium and telomere dynamics is still unclear. Additionally, it is unknow how telomere dynamics and DNA methylation alterations may affect the association between cadmium exposure and mortality outcomes. We utilized data from 8716 National Health and Nutrition Examination Survey (NHANES) participants aged 18 and above, collected between 1999 and 2002, and linked these to mortality outcomes from the National Center for Health Statistics (NCHS) through 2019. In the final model, ln-blood cadmium was significantly and inversely associated with ln-T/S ratio (β = −0.043, 95% CI: −0.059 to −0.027, p < 0.001), while ln-Horvath DNAmTL was strongly and positively associated with ln-T/S ratio (β = 1.782, 95% CI: 1.467 to 2.097, p < 0.001). Moreover, ln-blood cadmium also showed a significant inverse association with ln-Horvath DNAmTL (β = −0.010, 95% CI: −0.014 to −0.006, p < 0.001). Structural equation modeling showed that the association between cadmium and T/S ratio was mediated by Horvath DNAmTL, with a total effect of −0.044, a direct effect of −0.027, and an indirect effect of −0.017. Furthermore, stratified analyses revealed that a 1-unit increase in ln-blood cadmium was associated with higher all-cause mortality, with hazard ratios (HR) of 1.47 for participants with T/S ratio below the median and 1.41 for those above. Similar patterns were observed for cardiovascular (HR = 1.68 vs. 1.30) and cancer mortality (HR = 1.75 vs. 1.42). For Horvath DNAmTL, the association was significant only for all-cause mortality (HR = 1.36 vs. 1.31). However, no significant interactions were detected. In conclusion, our findings suggest that Horvath DNAmTL is associated with the relationship between cadmium and telomere length, suggesting a potential DNA methylation pathway that warrants further longitudinal investigation. Individuals with lower T/S ratios or Horvath DNAmTL appear to be more susceptible to cadmium-related mortality. Further research is necessary to confirm these results. Full article

Maternal health during pregnancy can be influenced by exposure to essential trace and toxic elements, notably cadmium, lead, chromium, and arsenic. Using inductively coupled plasma optical emission spectrometry, this study determined blood concentrations of toxic elements together with zinc, copper, and iron, which are nutritionally essential, in 200 pregnant women who attended the antenatal care at Thasala Hospital, Nakhon Si Thammarat, between January and July 2023. Associations of maternal clinical outcomes with the measured blood elemental composition were evaluated by Spearman’s rank correlation analysis. Iron showed the highest concentration among trace elements (75,178 ± 12,045 µg/dL), followed by zinc (1189.20 ± 211.38 µg/dL) and copper (294.72 ± 67.19 µg/dL). Among the toxic elements, lead had the highest concentration (5.59 ± 1.61 µg/dL), followed by chromium (2.80 ± 1.47 µg/dL), with arsenic and cadmium having the lowest concentrations. Synergistic associations were observed among lead, zinc, and iron. Blood lead concentration correlated inversely with hematocrit, while blood arsenic and blood cadmium both showed inverse association with urine glucose. Plasma glucose concentration varied directly with zinc and iron. These findings indicate effects and interactions of essential versus toxic elements on the health of pregnant women. They underscore the need to continue research into the strategies to minimize the impact of toxic elements and to further improve the nutritional status of zinc and iron during pregnancy. Full article

The prepubertal period represents a critical stage of development, where the reproductive system is susceptible to toxicants such as cadmium (Cd). Cd induces oxidative stress, causes alterations in the antioxidant enzymes and testosterone concentration, and affects reproductive organs. (–)-Epigallocatechin-3-gallate (EGCG), a polyphenol with antioxidant properties, has been studied for its protective effects. We evaluated the effects of EGCG on antioxidant activity and improvement of testicular and epididymal histology in Cd-exposed prepubertal rats. Twenty-eight male Wistar rats, on postnatal day (PND) 21, were distributed into four groups: Ctrl (saline), Cd (1 mg/kg CdCl₂), EGCG (10 mg/kg), and Cd+EGCG (1 mg/kg CdCl₂ + 10 mg/kg EGCG). Treatments were administered intraperitoneally from PND 21 to 49. After euthanasia, blood, testes, and epididymides were collected for Cd content, testosterone concentration, antioxidant activity, and histological evaluation. Cd exposure increased blood Cd, reduced testosterone, impaired antioxidant activity, and caused epithelial disorganization in both organs. In contrast, co-administration of EGCG significantly lowered Cd accumulation, restored testosterone concentration and antioxidant enzymes, and preserved histological integrity of testes and epididymides. These findings demonstrate that EGCG exerts protective effects against Cd-induced reproductive damage during the prepubertal period, suggesting its potential therapeutic use to counteract Cd toxicity in reproductive development. Full article

In the Japanese Multi-Centered Environmental Toxicant Study (JMETS) conducted in five areas across Japan, we demonstrated that bone mineral density (BMD) in female farmers without renal tubular dysfunction was not adversely affected by exposure to low to moderate levels of cadmium (Cd). We then expanded JMETS to the most Cd-polluted area in northern Japan, Akita prefecture, with area A as the control and areas B and C as Cd-polluted areas (Cd exposure levels: B < C), which also covered more female farmers with a wider age range (20–82 years) and Cd exposure sufficient to induce renal tubular dysfunction. We selected 1267 eligible subjects in the three areas and classified them by age and menstrual status. The distribution of blood and urinary Cd levels over the areas was A < B < C (blood Cd: 2.10, 3.78, and 3.39 µg/L, and urinary Cd: 3.02, 4.29, and 6.15 µg/g cr., respectively; p < 0.05), with the steepest age-dependent increase in area C, particularly in older postmenopausal subjects with a urinary Cd level around the threshold for renal tubular dysfunction. Urinary α1-microglobulin (α1MG) and ß2-microglobulin (ß2MG) levels in the three areas also showed age-dependent increases, with higher levels being observed in areas B and C than in area A. Furthermore, ß2MG levels in older postmenopausal subjects were significantly higher in area C than in area A (273 and 157 μg/g cr., respectively, p < 0.05). Age-dependent decreases in BMD were noted in all areas, with rapid reductions from peri- to postmenopausal subjects; however, marked differences in each age class were not observed among the three areas. In multiple regression models of BMD in all subjects using age, body weight, grip, urinary creatinine, urinary α1MG or ß2MG, and blood or urinary Cd as independent variables, urinary α1MG and ß2MG levels correlated with BMD, whereas blood and urinary Cd levels did not. Moreover, age and body weight correlated more strongly with BMD than blood and urinary Cd levels. Therefore, Cd, not only at a low level but also at a level that was sufficient to deteriorate renal tubular function, did not affect bones. These results provide further support for Cd exposure itself not directly affecting bones. Full article

Chronic kidney disease (CKD) has now reached epidemic proportions in many parts of the world, primarily due to the high incidence of diabetes and hypertension. By 2040, CKD is predicted to be the fifth-leading cause of years of life lost. Developing strategies to prevent CKD and to reduce its progression to kidney failure is thus of great public health significance. Hypertension is known to be both a cause and a consequence of kidney damage and an eminently modifiable risk factor. An increased risk of hypertension, especially among women, has been linked to chronic exposure to the ubiquitous food contaminant cadmium (Cd). The mechanism is unclear but is likely to involve its action on the proximal tubular cells (PTCs) of the kidney, where Cd accumulates. Here, it leads to chronic tubular injury and a sustained drop in the estimated glomerular filtration rate (eGFR), a common sequela of ischemic acute tubular necrosis and acute and chronic tubulointerstitial inflammation, all of which hinder glomerular filtration. The present review discusses exposure levels of Cd that have been associated with an increased risk of hypertension, albuminuria, and eGFR ≤ 60 mL/min/1.73 m² (low eGFR) in environmentally exposed people. It highlights the potential role of 20-hydroxyeicosatetraenoic acid (20-HETE), the second messenger produced in the kidneys, as the contributing factor to gender-differentiated effects of Cd-induced hypertension. Use of GFR loss and albumin excretion in toxicological risk calculation, and derivation of Cd exposure limits, instead of β₂-microglobulin (β₂M) excretion at a rate of 300 µg/g creatinine, are recommended. Full article

Background: Electronic waste (e-waste) recycling in informal settings like Agbogbloshie in Accra, Ghana, releases toxic metals into the environment, posing serious health risks to nearby residents, particularly children. This study assessed the body burdens of lead (Pb), manganese (Mn), cadmium (Cd), chromium (Cr), nickel (Ni), and arsenic (As) and their association with cognitive function in schoolchildren living within 1 km of the Agbogbloshie site. Method: A cross-sectional study involving 56 pupils collected demographic data and blood and urine samples and administered the Wechsler Intelligence Scale for Children—Fourth Edition (WISC-IV). Blood was tested for Pb and Mn and urine for Cd, Cr, Ni, and As. Associations between metal levels and cognitive outcomes were examined using regression analyses, adjusting for confounders. Result: Children showed elevated metal levels, with mean blood Pb of 60.43 µg/L and urinary s of 21.50 µg/L. Symptoms of cognitive dysfunction were common: 75% reported confusion, 67.9% poor memory, and 66% poor concentration. Urinary Cr levels were significantly associated with lower Full-Scale IQ (β = −18.42, p < 0.05) and increased difficulty in decision-making (OR = 0.1, p < 0.05). Conclusion: These findings underscore the neurodevelopmental risks of heavy metal exposure from e-waste in low- and middle-income countries and call for urgent public health interventions and policy actions. Full article

Environmental exposures to heavy metals, polychlorinated biphenyls (PCBs), dioxins, and furans have been associated with adverse cardiovascular outcomes, yet their combined effects remain underexplored. This study examined the joint influence of these contaminants on cardiovascular risk indicators in a representative sample of U.S. adults from the 2003–2004 National Health and Nutrition Examination Survey (NHANES). Biomarkers of exposure included lead, cadmium, mercury, twelve PCB congeners, seven dioxins, and ten furans. Cardiovascular outcomes were assessed using blood pressure, Framingham Risk Score (FRS), and lipid profiles. Associations were analyzed using multivariable linear regression and Bayesian Kernel Machine Regression (BKMR), adjusting for age, sex, ethnicity, body mass index, smoking, alcohol consumption, and income. The results demonstrated that metals, particularly mercury, were strongly associated with increased blood pressure and altered HDL cholesterol. PCBs were predominantly linked to elevated systolic blood pressure and FRS, with PCB156 and PCB126 identified as principal contributors. Furans exhibited the strongest associations with dyslipidemia, including elevated LDL cholesterol, total cholesterol, and triglycerides. Combined exposure analysis revealed a complex pattern, with increasing pollutant burdens associated with rising blood pressure and risk scores but declining lipid levels. These findings underscore the outcome-specific effects of pollutant mixtures and suggest that chronic low-level exposure to multiple environmental contaminants may contribute to cardiovascular dysfunction in the general population. Further longitudinal research is needed to confirm these associations and guide risk reduction strategies. Full article

Mineral imbalances in sheep can have significant health and economic consequences, yet regional assessments of trace mineral and toxic element status are limited. Oregon is an endemically selenium (Se)-deficient region, but a statewide evaluation has not been conducted. This study assessed whole blood concentrations of 18 elements in 370 clinically normal ewes from 56 farms across Oregon to determine the prevalence of deficiencies and potential toxic exposures. A deficiency threshold of <120 ng Se/mL whole blood was used. We found that 28% of animals were Se-deficient, and 27% of farms had an average whole blood Se below this threshold. No animals reportedly showed overt clinical signs of deficiency or toxicity, and no excessive exposure to toxic elements such as arsenic, lead, or cadmium was found. We also compared mineral concentrations in blood collected using standard EDTA tubes versus mineral-free EDTA tubes, and in whole blood versus plasma, to assess alternative sampling strategies. Strong correlations (r > 0.9) for Se, cobalt (Co), and molybdenum (Mo) between plasma and whole blood allowed for the derivation of conversion equations. These findings provide updated insights into the mineral status of Oregon sheep, contribute to whole blood reference data, and support practical alternatives to improve trace mineral testing in field conditions. Full article

Most studies have focused on the levels of pollutants in drinking water and the health risks they pose. However, no studies have reported the effects of drinking water intake on pollutant levels in the human body. Therefore, this study collected data from National Health and Nutrition Examination Survey database to provide statistical evidence for the relationship between water intake and human pollutant levels. We analyzed 95 pollutants in human urine, blood, and serum. The study found that 82% (65/79) of urine pollutants unadjusted for creatinine showed a stable negative correlation with water intake, primarily due to the urine dilution effect caused by increased water consumption. Water intake was negatively correlated with cadmium, m-/p-xylene, and toluene in blood, but positively correlated with blood total mercury and methyl mercury. In summary, the habit of drinking more water may be beneficial to reduce levels of most pollutants in human urine (unadjusted for creatinine) and a small part in blood. Only a few pollutants, including total mercury and methyl mercury in blood, as well as benzophenone-3 in urine (both creatinine-adjusted and unadjusted), are positively related to water intake. The underlying mechanisms by which water intake influences pollutant levels in the human body require further investigation. Full article

Background: This study investigates the combined effects of PFAS metals (PFOA and PFOS), heavy metals (lead, cadmium, and mercury), behavioral factors (smoking and alcohol consumption), and social factors (income and education) on depressive symptoms. Methods: Using cross-sectional data from the National Health and Nutrition Examination Survey (NHANES 2017–2018), blood samples were analyzed to determine the exposure levels of PFOA, PFOS, lead, cadmium, and mercury, and self-reported behavioral and social factors were evaluated in relation to PHQ-9 scores among 181 adults. Results: Education was associated with lower odds of depressive symptoms (OR = 0.68, 95% CI: 0.43–1.07). Although the result was not statistically significant, the estimate suggested a potential protective effect that warranted further investigation. Bayesian Kernel Machine Regression demonstrated that heavy metals collectively had the strongest evidence for influencing depression (group PIP = 0.6508), followed by socioeconomic factors (group PIP = 0.642). Bivariate exposure–response analyses revealed complex interaction patterns whereby exposure effects varied substantially depending on co-exposure contexts. Conclusions: These findings highlight that depressive symptoms are shaped by complex interplays between environmental contaminants, behavior, and social determinants, underscoring the importance of mixture-based approaches in environmental mental health research and the need for integrated interventions addressing both environmental and social factors. Full article

Background: Cardiovascular disease (CVD) is a major global health burden influenced by genetic, behavioral, and environmental factors. Among these, exposure to per- and poly-fluoroalkyl substances (PFASs) and toxic metals has been increasingly implicated in adverse cardiovascular outcomes. However, the mediating role of dietary inflammation in these associations remains unclear. Objective: This study investigates the relationship between PFAS and metal exposures and CVD risk, focusing on the potential mediating role of diet, operationalized through the Dietary Inflammatory Index (DII). Additionally, this study examines age as an effect modifier in these associations. Methods: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018 cycle (n = 660), we assessed environmental exposures (lead, cadmium, mercury, perfluorooctanoic acid-PFOA, perfluorooctane sulfonate-PFOS), dietary inflammatory potential (DII), and cardiovascular markers (blood pressure, lipid profile, C-reactive protein). Statistical analyses included linear regression and Bayesian Kernel Machine Regression-Causal Mediation Analysis (BKMR-CMA) to estimate the direct, indirect (through DII), and total effects of exposure on CVD risk biomarkers. Results: Linear regression revealed significant associations between mercury and reduced systolic blood pressure (SBP) (p = 0.017) and cadmium with increased C-reactive protein (CRP) (p = 0.006). Mediation analysis suggested dietary inflammation may play a role, though estimates were imprecise. Conclusions: PFAS and metals may influence CVD risk through inflammatory pathways, with potential age-related differences. Future longitudinal studies are needed to clarify these complex interactions, reduce measurement error, and guide age-specific exposure regulations. Full article

Background: Emerging evidence suggests a potential link between heavy metals and Alzheimer’s disease and related dementias (AD/ADRD). This study compiled epidemiological evidence from research published over the past 11 years on the impact of metals on AD/ADRD in women. Women have unique risk factors for late onset of AD/ADRD, in addition to genetic factors, apolipoprotein E allele (APOE4), and longer life expectancy. Furthermore, women are twice likely as men to experience depression, which increases their risk of developing AD/ADRD. Our narrative review underscored the necessity of a sex-specific approach to address women’s vulnerability to AD/ADRD. Methods: Electronic databases, including PubMed, Google Scholar, NIOSH Toxline, and Scopus, were thoroughly searched to identify primary epidemiological studies on older women exposed to metals and published between 2014 to 2024. Results: We identified 34 epidemiological studies that met the inclusion criteria. The findings revealed a complex interplay between environmental metals such as lead (Pb), cadmium (Cd), arsenic (As), manganese (Mn), selenium (Se), iron (Fe), zinc (Zn), copper (Cu), magnesium (Mg), and calcium (Ca) and the risk of AD/ADRD in women. Significant adverse effects were reported for Cu, Cd, As, Pb, and Mn while significant protective effects were found between Se, Fe, and Zn in blood and AD/ADRD among older women. However, some studies also reported no correlations. Conclusions: Overall, our review identified contrasting results regarding the effects of metals on AD/ADRD in women. Future studies should collect additional evidence to understanding the effects of heavy metals on AD/ADRD in women for developing preventive measures. Full article

Background: Recent advances in single-photon emission computed tomography (SPECT) technology, particularly cadmium–zinc–telluride (CZT) detectors, have improved spatial resolution and contrast in cerebral blood flow imaging. This study aimed to investigate whether these improvements translate to enhanced diagnostic accuracy for Alzheimer’s disease (AD). Methods: We compared conventional SPECT (eCAM) with CZT SPECT in 29 patients (mean age 60.9 ± 17.6 years, 69% female) with suspected neurodegenerative diseases. Results: Gray matter/white matter contrast was significantly higher in CZT SPECT compared to eCAM (1.615 ± 0.096 vs. 1.458 ± 0.068, p < 0.001). However, diagnostic accuracy for AD did not improve with CZT SPECT. For the participating psychiatrist, sensitivity decreased from 0.750 (eCAM) to 0.625 (CZT), while for the radiologist, specificity dropped from 0.571 (eCAM) to 0.429 (CZT). Overall accuracy slightly decreased for both readers. Conclusions: These findings suggest that while CZT SPECT offers superior image quality, it may not immediately translate to improved diagnostic accuracy for AD. The study highlights the importance of specialized training for clinicians in interpreting higher-resolution CZT SPECT images to fully leverage their potential in neurodegenerative disease diagnosis. Future research should focus on developing standardized training protocols and larger, multi-center studies to validate these findings. Full article

Sperm maturation involves changes in plasma membrane glycosylation for fertilization. Cadmium (Cd) exerts a negative effect by disrupting testicular and epididymal function, altering antioxidant activity. Zinc (Zn) is an essential element known for its antioxidant properties, role in testosterone synthesis, and support of spermatogenesis. However, its effect on sperm membrane glycosylation, as well as endocrine and antioxidant activity, after exposure to Cd has remained unexplored. This study evaluated the impact of Zn on epididymal sperm glycosylation, endocrine activity, and antioxidant activity in Cd-exposed rats. Four groups of male Wistar rats were analyzed: control, Cd-exposed, Zn-supplemented, and Zn + Cd groups. On postnatal day 90, tissues and blood were collected for Zn and Cd quantification, testosterone levels, antioxidant activity, histological analysis, and sperm quality. The results showed that Cd concentration increased significantly, reduced testosterone levels, modified antioxidant activity, and caused structural damage in the epididymis. The Cd-exposed group showed disrupted glycosylation and distribution patterns and reduced sperm quality. The Zn + Cd group showed lower Cd accumulation, preserved testosterone levels, restored antioxidant activity, and preserved glycosylation patterns and sperm quality. This study highlights the protective role of Zn in mitigating Cd-induced reproductive toxicity, probably through the competitive inhibition of Cd uptake and antioxidant support, thereby preserving fertility. Full article