Search Results (175)

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

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

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

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

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

Background: Heavy metal interactions within aquatic ecosystems significantly affect fish physiology. This study evaluated the protective role of selenium against cadmium-induced hematological, biochemical, and electrophoretic alterations in goldfish. Methods: A total of 120 goldfish individuals were divided into four groups: control, cadmium chloride-treated (2.8 mg/L), sodium selenite-treated (2 mg/L), and a combined cadmium and selenium-treated group. After 14 days, blood samples were collected and analyzed for hematological parameters, biochemical markers, and serum protein electrophoresis. Results: Cadmium exposure led to significant reductions in red blood cell (RBC) and white blood cell (WBC) counts, hemoglobin (Hb), and hematocrit (HCT) (p < 0.001). Selenium supplementation alleviated these declines and improved overall hematological function. Additionally, cadmium exposure decreased albumin and total protein levels while elevating aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, indicating liver damage. Selenium co-treatment reduced cadmium accumulation and mitigated liver toxicity. Elevated urea and creatinine levels in cadmium-exposed fish were also significantly lowered in the combined treatment group (p < 0.0001). Furthermore, selenium supplementation enhanced antioxidant defense mechanisms by increasing catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activity while reducing malondialdehyde (MDA) levels, effectively counteracting cadmium-induced oxidative stress. Conclusion: Sodium selenite at a dose of 2 mg/L effectively mitigated the toxic effects of cadmium chloride on hematological, biochemical, and oxidative stress markers in goldfish, demonstrating its protective potential against heavy metal toxicity. Full article

While cigarette smoking has declined, e-cigarette use among young adults has increased in the USA. This cross-sectional study compared complete blood counts, C-reactive protein, and select blood metals (lead, cadmium, mercury, selenium, manganese) among exclusive combustible tobacco users, exclusive e-cigarette users, and non-users using NHANES data from 2013–2023 in the USA. The goal of this study was to compare biomarker data from e-cigarette users and combustible tobacco users to that of non-users. Among 756 participants aged 18–30, 229 reported no tobacco use, 74 used only e-cigarettes, and 453 smoked only combustible tobacco. Survey-weighted analyses adjusted for age, sex, race/ethnicity, and body mass index revealed that exclusive combustible use was associated with significantly elevated white blood cell counts, hemoglobin, hematocrit, mean corpuscular volume, lymphocytes, monocytes, neutrophils, and higher blood lead and cadmium. E-cigarette-only use showed fewer deviations overall but included higher mean corpuscular hemoglobin concentration and lower cadmium, selenium, and methyl mercury relative to non-users. Neither group differed significantly in red blood cell count or C-reactive protein, and inorganic/ethyl mercury and manganese levels were largely unchanged. These findings underscore pronounced hematologic and metal-related alterations in combustible tobacco users and fewer, but not negligible, changes among e-cigarette users. Further research is needed to determine the long-term health implications of exclusive e-cigarette use, including potential impacts on antioxidant micronutrient levels. Full article

Background: Folate is critical for many physiological processes, and low folate levels have been associated with a wide range of health outcomes, including chronic diseases and developmental outcomes. Many environmental chemicals are suspected to contribute to the etiology of health outcomes related to folate deficiency. However, little is known about how these pollutants influence folate levels as potential mechanistic pathways. Objective: To investigate the individual and joint associations between a mixture of 39 pollutants and red blood cell (RBC) folate concentrations in the U.S. population. Methods: We used available data on 27,938 participants, aged 18–80 from the U.S. National Health and Nutrition Examination survey (2007–2016), with available RBC folate concentrations and 39 environmental pollutants’ concentrations. We estimated covariate-adjusted independent and joint associations between environmental pollutants and RBC folate, and compared evidence from two complimentary mixture approaches: exposome-wide association study (ExWAS) and quantile-based g computation (Q-gcomp). Results: In the ExWAS analysis, 12 environmental chemicals, including metals (cadmium, arsenic, lead, and mercury), perfluoroalkyl substances, phthalates, phenols and parabens, and polycyclic aromatic hydrocarbons, were inversely associated with RBC folate, whereas four environmental pollutants, including metals (manganese and selenium) and two phthalate metabolites, were positively associated with RBC folate. Q-gcomp showed convergent results with the ExWAS analysis; a quartile increase in the metal and PFAS mixtures was significantly associated with a decrease of −38.4 ng/mL (95%CI: −52.3, −24.4) and −48.9 ng/mL (95%CI: −57.6, −39.6) in RBC folate concentrations, respectively. Conclusion: The present study shows that higher exposure to PFASs, metals, and PAHs are associated with lower RBC folate concentrations. However, given the cross-sectional design, we cannot make inferences about the directionality of the observed associations. Full article

Although exposure to metals remains a public health concern, few studies have examined exposure to combinations of metals. This study characterized prevalent combinations of cadmium (Cd), mercury (Hg), and lead (Pb) in women (n = 10,152; aged 20–44 years) who participated in the U.S. National Health and Nutrition Examination Survey (NHANES) 1999–2018. To explore relative metal exposures within this population, Cd, Hg, and Pb blood levels were dichotomized as “high” and “low” categories using median values to represent the center of the metal concentrations in the study population, not thresholds for adverse health effects. The prevalence of the three metal combinations at “high” levels (singular, binary, tertiary combinations) was calculated. Multinomial logistic regression was used to calculate odds ratios for each combination relative to none of these combinations after adjusting for potential confounders. Among the pregnant women (n = 1297), singular Hg was most prevalent (19.2% [95% CI 15.0–23.3]), followed by singular Cd (14.7% [95% CI 11.2–18.2]), tertiary combination Cd/Hg/Pb (11.0% [95% CI 8.7–13.2]), binary combinations Cd/Pb (9.8% [95% CI 7.4–12.2]), Hg/Pb (9.2% [95% CI 6.5–11.8]), Cd/Hg (7.8% [95% CI 6.0–9.6]), and singular Pb (5.5% [95% CI 4.1–6.9]). We found significantly lower odds of having Cd/Hg/Pb (adjusted odds ratio (adjOR) = 0.49: p < 0.001) and Cd/Pb (adjOR = 0.68: p < 0.0364) combinations among pregnant women compared to non-pregnant women. The odds of having higher levels of singular Pb were significantly lower (adjOR = 0.31: p < 0.0001) in women pregnant in their first and second trimesters (n = 563) than in non-pregnant women (n = 6412), whereas, though nonsignificant, the odds were higher for women pregnant in their third trimester (n = 366) (adjOR = 1.25: p = 0.4715). These results indicate the possibility that the fetus might be exposed to higher levels of the metal mixtures due to placental transfer, particularly to Pb, during the early stages of pregnancy. Further research is warranted to understand the relationship between metal combination exposures during pregnancy and maternal and infant health. Full article

Introduction/Objectives: Type 2 diabetes (T2D) continues to pose a substantial global public health challenge. Current evidence has linked an increase in the risk of T2D to chronic exposure to the heavy metals cadmium (Cd) and lead (Pb). The present study aimed to examine whether the reported links existed in an area of southern Thailand with known Pb contamination. Materials and Methods: A case–control study design was used to recruit 88 diagnosed T2D cases and 90 age-, gender- and locality-matched non-diabetic controls. Blood levels of Cd and Pb were used as exposure indicators. Exposure-related risk factors and socio-demographic data were collected through questionnaires. Results: A significant association was found between blood Pb and T2D diagnosis, but the association between blood Cd and T2D was not statistically significant. Factors related to high Pb exposure were education, occupation, income, smoking habits, alcohol consumption, and dietary patterns, particularly the consumption of sweet and fatty foods. Participants with higher blood Pb levels had poorer glycemic control, thereby suggesting potential interference of Pb with oral hypoglycemic agents. Conclusions: This study confirms the connection between Pb exposure and increased risk of having T2D. Additionally, it identified socio-demographic factors, and consumption habits that contributed to such an enhanced T2D risk. The role of Cd exposure requires further studies, using urinary Cd excretion, which reflects long-term exposure conditions. These findings suggest the need to incorporate environmental and occupational exposure in diabetes care strategies. From the clinical and public health perspectives, targeted interventions should focus on reducing heavy metal exposure, improving risk awareness, and strengthening occupational safety measures to prevent disease progression. Full article

Cadmium (Cd) is an important environmental pollutant that can enter the body and inflict kidney damage. Quercetin (Que) is a natural flavonoid compound that can alleviate kidney damage in Cd-treated rats, but the specific mechanism is unclear. Herein, 24 male Sprague–Dawley rats were divided into four groups, namely the control, Cd, Cd + Que, and Que groups. Four weeks later, the rats were anesthetized with ether and were euthanized; then, their blood was collected and their kidneys were removed. Renal function markers were measured. Kidney tissue structure was observed by HE staining, cell apoptosis was detected by the TUNEL method, and mRNA and protein expression levels in the IRE1α-XBP1 apoptosis signaling pathway were analyzed by RT-PCR and Western blotting. Results showed that the Cd treatment group exhibited decreased renal dysfunction and pathologic injury. Cd-induced tissue damage and cell apoptosis and significantly increased the mRNA and protein expression levels (p < 0.01) related to the IRE1α-XBP1 signaling pathway. Compared with the Cd group, the Cd + Que group exhibited increased renal dysfunction. Conversely, kidney tissue damage and renal cell apoptosis decreased, and the mRNA and protein expression levels of IRE1α and XBP1 significantly decreased (p < 0.01). Cd treatment inflicted renal damage. Therefore, Que can restore the kidney tissue damage and alleviate the cell apoptosis caused by Cd through the inhibition of the IRE1α-XBP1 signaling pathway. Full article

Background: Environmental exposures to heavy metals/metalloids such as arsenic, cadmium, and mercury have been implicated in adverse cardiovascular health outcomes. Using data from the All of Us research program, we investigated the associations between these metals/metalloids and six cardiovascular-related biomarkers: systolic blood pressure (SBP), HDL cholesterol, LDL cholesterol, C-reactive protein (CRP), total cholesterol, and triglycerides. Methods: This study explored the relationship between outcome cardiovascular variables (SBP, CRP, LDL, HDL, triglycerides, and total cholesterol) and predictor metal/metalloid variables (cadmium, mercury, and arsenic) among 136 participants (53.4 percent women). We initially conducted linear regression to determine the association between variables of interest. Bayesian Kernel Machine Regression (BKMR) analysis was subsequently performed to capture potential non-linear relationships, as well as interactions among metal/metalloid exposures. In the BKMR analysis, posterior inclusion probabilities (PIPs) quantified the contribution of each metal/metalloid to the outcomes, with higher PIP values indicating a greater likelihood of a specific exposure being a key predictor for a given cardiovascular biomarker. Within the BKMR framework, univariate, bivariate, and overall exposure–response analyses provided insights into the individual and combined effects of metal/metalloid exposures. These analyses identified the factors with the strongest associations and highlighted interactions between exposures. Results: In this study, the average age of male participants was 58.2 years, while female participants had an average age of 55.6 years. The study population included 104 individuals identifying as White (mean age: 57.5 years), 10 as Black or African American (mean age: 63.2 years), 7 as Hispanic (mean age: 48.2), 3 as Asian (mean age: 49.7 years), and 12 as Other race (mean age: 48.8 years). In our study, men exhibited higher levels of SBP, triglycerides, mercury, and arsenic, while women had higher levels of CRP, LDL cholesterol, HDL cholesterol, total cholesterol, and cadmium. Black people exhibited higher levels and greater variability in markers of cardiovascular risk and inflammation (e.g., blood pressure and CRP), Asians consistently showed the lowest levels across most biomarkers, while White people, Hispanics, and the “Other” group demonstrated moderate levels with some variability. In linear regression, we identified significant positive associations between mercury and HDL cholesterol, arsenic and triglycerides, and arsenic and total cholesterol. In BKMR analysis, PIP results revealed that mercury had the highest predictive contribution for SBP, HDL cholesterol, and triglycerides; cadmium for CRP; and arsenic for LDL and total cholesterol. Univariate and bivariate exposure–response analyses in BKMR demonstrated non-linear exposure–response patterns, including U-shaped and inverted U-shaped patterns for cadmium, particularly CRP and total cholesterol. Traditional linear regression techniques would have missed these patterns. Conclusion: Our study results highlight the influence of environmental metal/metalloid exposures on cardiovascular biomarkers, providing evidence of non-linear and interactive effects that warrant further investigation to understand their role in cardiovascular disease risk better. Full article

Background: Cigarette smoking is a leading cause of preventable mortality, largely due to the absence of effective, non-invasive biomarkers for early disease detection. Profiling serum metabolomics to identify metabolic changes holds the potential to accelerate the detection process and identify individuals at risk of developing smoking-related diseases. Objectives: This study investigated the biochemical and metabolomic changes induced by nicotine exposure, with a focus on disruptions in amino acid, lipid, and carbohydrate metabolism. Methods: Liquid chromatography–tandem mass spectrometry (LC-MS/MS) was employed to observe significant disruptions in lipid and amino acid metabolism, along with alterations in key metabolic pathways. A total of 400 smokers and 100 non-smokers were included to evaluate the biomarkers related to insulin resistance, blood lipid profile, inflammation, and kidney and liver function. Results: The results demonstrated significantly elevated (p < 0.05) levels of glycemic markers in smokers, including fasting blood glucose; glycated hemoglobin (HbA1c); and inflammatory markers such as interleukin-6 (IL-6) and C-reactive protein (CRP). Smokers also exhibited dyslipidemia, with increased total cholesterol (154.888 ± 35.565) and LDL levels (117.545 ± 24.138). Impaired liver and kidney function was evident, with significantly higher levels (p < 0.05) of AST, ALP, ALT, blood urea nitrogen, and creatinine in smokers. A total of 930 metabolites were identified, of which 343 exhibited significant alterations (p < 0.05) in smokers compared to non-smokers. Among these, 116 metabolites were upregulated, and 127 were downregulated. Metabolomic pathway analysis revealed eight significant pathways. The study also identified three lipid metabolites specific to smokers and seven unique to non-smokers. Through LC-MS/MS, fragments of phenylalanine, tryptophan, valine, histidine, carnitine, and sphinganine were detected. Several lipidomic changes associated with insulin resistance and cardiovascular complications were observed. Cadmium (Cd) levels were higher in smokers than non-smokers (1.264 ppb vs. 0.624 ppb) and showed a strong negative correlation (R² = 0.8061, p-value = 0.015) with serum zinc (Zn), likely due to Cd displacing Zn in proteins and causing nephrotoxicity through accumulation. Conclusions: This study highlights the distinct metabolic disruptions caused by smoking that could serve as potential biomarkers for the early detection of metabolic diseases. It emphasizes the importance of metabolomics in identifying systemic indicators of smoking-related health issues, providing new opportunities for preventive and therapeutic interventions. Full article