Objective: To study the effects of cadmium chloride (CdCl(2)) exposure on testicular autophagy levels and blood-testis barrier integrity in prepubertal male SD rats and testicular sertoli (TM4) cells. Methods: In July 2021, 9 4-week-old male SD rats were randomly divided into 3 groups: control group (normal saline), low dose group (1 mg/kg·bw CdCl(2)) and high dose group (2 mg/kg·bw CdCl(2)), and were exposed with CdCl(2) by intrabitoneal injection. 24 h later, HE staining was used to observe the morphological changes of testis of rats, biological tracer was used to observe the integrity of blood-testis barrier, and the expression levels of microtubule-associated protein light chain 3 (LC3) -Ⅰ and LC3-Ⅱ in testicular tissue were detected. TM4 cells were treated with 0, 2.5, 5.0 and 10.0 μmol/L CdCl(2) for 24 h to detect the toxic effect of cadmium. The cells were divided into blank group (no exposure), exposure group (10.0 μmol/L CdCl(2)), experimental group[10.0 μmol/L CdCl(2)+60.0 μmol/L 3-methyladenine (3-MA) ] and inhibitor group (60.0 μmol/L 3-MA). After 24 h of treatment, Western blot analysis was used to detect the expression levels of LC3-Ⅱ, ubiquitin binding protein p62, tight junction protein ZO-1 and adhesion junction protein N-cadherin. Results: The morphology and structure of testicular tissue in the high dose group were obvious changed, including uneven distribution of seminiferous tubules, irregular shape, thinning of seminiferous epithelium, loose structure, disordered arrangement of cells, abnormal deep staining of nuclei and vacuoles of Sertoli cells. The results of biological tracer method showed that the integrity of blood-testis barrier was damaged in the low and high dose group. Western blot results showed that compared with control group, the expression levels of LC3-Ⅱ in testicular tissue of rats in low and high dose groups were increased, the differences were statistically significant (P<0.05). Compared with the 0 μmol/L, after exposure to 5.0, 10.0 μmol/L CdCl(2), the expression levels of ZO-1 and N-cadherin in TM4 cells were significantly decreased, and the expression level of p62 and LC3-Ⅱ/LC3-Ⅰ were significantly increased, the differences were statistically significant (P<0.05). Compared with the exposure group, the relative expression level of p62 and LC3-Ⅱ/LC3-Ⅰ in TM4 cells of the experimental group were significantly decreased, while the relative expression levels of ZO-1 and N-cadherin were significantly increased, the differences were statistically significant (P<0.05) . Conclusion: The mechanism of the toxic effect of cadmium on the reproductive system of male SD rats may be related to the effect of the autophagy level of testicular tissue and the destruction of the blood-testis barrier integrity.
Rats ; Male ; Animals ; Testis ; Cadmium Chloride/metabolism* ; Cadmium ; Blood-Testis Barrier/metabolism* ; Rats, Sprague-Dawley ; Cadherins/metabolism* ; Autophagy

Objective: To investigate the role of inflammatory biomarkers in the relationship between blood lead levels and blood pressure changes. Methods: A total of 9 910 people aged 18-79 years who participated in the China National Human Biomonitoring in 2017-2018 were included in this study. A self-made questionnaire was used to collect demographic characteristics, lifestyle and other information, and the data including height, weight and blood pressure were determined through physical examination. Blood and urinary samples were collected for the detection of blood lead and cadmium levels, urinary arsenic levels, white blood cells, neutrophils, lymphocytes, and hypersensitive C-reactive protein (hs-CRP). Weighted linear regression models were used to evaluate the associations between blood lead, inflammatory biomarkers and blood pressure. Mediation analysis was performed to investigate the role of inflammation in the relationship between blood lead levels and blood pressure changes. Results: The median (Q₁, Q₃) age of all participants was 45.4 (33.8, 58.4)years, including 4 984 males accounting for 50.3%. Multivariate logistic regression model analysis showed that after adjusting for age, gender, residence area, BMI, education level, smoking and drinking status, family history of hypertension, consumption frequency of rice, vegetables, and red meat, fasting blood glucose, total cholesterol, triglycerides, blood cadmium and urinary arsenic levels, there was a positive association between blood lead levels, inflammatory biomarkers and blood pressure (P<0.05). Each 2.71 μg/L (log-transformed) increase of the lead was associated with a 2.05 (95%CI: 0.58, 3.53) mmHg elevation in systolic blood pressure (SBP), 2.24 (95%CI: 1.34, 3.14) mmHg elevation in diastolic blood pressure (DBP), 0.25 (95%CI: 0.05, 0.46) mg/L elevation in hs-CRP, 0.16 (95%CI: 0.03, 0.29)×10⁹/L elevation in white blood cells, and 0.11 (95%CI: 0.02, 0.21)×10⁹/L elevation in lymphocytes, respectively. Mediation analysis showed that the levels of hs-CRP significantly mediated the association of blood lead with SBP, with a proportion about 3.88% (95%CI: 0.45%, 7.32%). The analysis also found that the levels of hs-CRP and neutrophils significantly mediated the association of blood lead with SBP, with a proportion about 4.10% (95%CI: 1.11%, 7.10%) and 2.42% (95%CI: 0.07%, 4.76%), respectively. Conclusion: This study suggests that inflammatory biomarkers could significantly mediate the association of blood lead levels and blood pressure changes.
Adult ; Male ; Humans ; Blood Pressure/physiology* ; C-Reactive Protein/analysis* ; Lead ; Arsenic/analysis* ; Cadmium ; Biomarkers ; Hypertension/epidemiology* ; China/epidemiology*

BACKGROUND: Previous studies have suggested that exposures to heavy metals (arsenic, cadmium, lead, and selenium) may be associated with differences in blood pressure. However, the findings of these studies have been inconsistent. This study was performed to examine the associations between urinary heavy metal concentrations and blood pressure among residents of four Asian countries (Bangladesh, Indonesia, Nepal, and Vietnam). METHODS: This cross-sectional study examined 1899 adults in four Asian countries. Urinary concentrations of heavy metals were measured by inductively coupled plasma mass spectrometry. A questionnaire survey was administered regarding individual characteristics. Anthropometric measurements (height and weight) were performed. Systolic and diastolic blood pressures were measured after a short rest. Multiple linear regression models were applied to investigate associations between urinary heavy metal concentrations and blood pressure after adjustments for age, sex, and body mass index. RESULTS: The geometric means of the urinary concentrations of arsenic, cadmium, lead, and selenium were 84.6, 0.885, 2.09, and 16.5 μg/g creatinine, respectively. The urinary arsenic concentrations were slightly higher than those typically reported in non-polluted populations, while urinary cadmium, lead, and selenium concentrations were equivalent or slightly lower. The urinary lead concentrations were positively associated with both systolic and diastolic blood pressure, but urinary selenium concentrations were negatively associated with them. CONCLUSIONS Variations in the urinary concentrations of lead and selenium were associated with blood pressure at low levels of exposure/intake.
Adult ; Arsenic/urine* ; Bangladesh ; Blood Pressure ; Cadmium/urine* ; Cross-Sectional Studies ; Environmental Exposure ; Female ; Humans ; Indonesia ; Lead/urine* ; Linear Models ; Male ; Metals, Heavy/urine* ; Middle Aged ; Nepal ; Selenium/urine* ; Vietnam

BACKGROUND: In health examinations for local inhabitants in cadmium-polluted areas, only healthy people are investigated, suggesting that patients with severe cadmium nephropathy or itai-itai disease may be overlooked. Therefore, we performed hospital-based screening to detect patients with cadmium nephropathy in two core medical institutes in cadmium-polluted areas in Akita prefecture, Japan. METHODS: Subjects for this screening were selected from patients aged 60 years or older with elevated serum creatinine levels and no definite renal diseases. We enrolled 35 subjects from a hospital in Odate city and 22 from a clinic in Kosaka town. Urinary ß-microglobulin and blood and urinary cadmium levels were measured. RESULTS: The criteria for renal tubular dysfunction and the over-accumulation of cadmium were set as a urinary ß-microglobulin level higher than 10,000 μg/g cr. and a blood cadmium level higher than 6 μg/L or urinary cadmium level higher than 10 μg/g cr., respectively. Subjects who fulfilled both criteria were diagnosed with cadmium nephropathy. Six out of 57 patients (10.5% of all subjects) had cadmium nephropathy. CONCLUSIONS: This hospital-based screening is a very effective strategy for detecting patients with cadmium nephropathy in cadmium-polluted areas, playing a complementary role in health examinations for local inhabitants. REGISTRATION NUMBER No. 6, date of registration: 6 June, 2010 (Akita Rosai Hospital), and No. 1117, date of registration: 26 December, 2013 (Akita University).
Aged ; Aged, 80 and over ; Cadmium ; adverse effects ; urine ; Cadmium Poisoning ; blood ; complications ; urine ; Creatinine ; urine ; Environmental Exposure ; adverse effects ; Environmental Monitoring ; Environmental Pollutants ; adverse effects ; urine ; Female ; Hospitals ; Humans ; Japan ; Kidney Diseases ; chemically induced ; urine ; Male ; Middle Aged ; Sex Distribution

There have been few studies investigating the association between atopic dermatitis (AD) and prenatal exposure to heavy metals. We aimed to evaluate whether prenatal exposure to heavy metals is associated with the development or severity of AD in a birth cohort study. A total of 331 subjects were followed from birth for a median duration of 60.0 months. The presence and severity of AD were evaluated at ages 6 and 12 months, and regularly once a year thereafter. The concentrations of lead, mercury, chromium, and cadmium in umbilical cord blood were measured by inductively coupled plasma mass spectrometry. Cord blood mononuclear cells (CBMCs) were isolated and stimulated for analysis of cytokine production using ELISA. Heavy metal levels in cord blood were not associated with the development of AD until 24 months of age. However, a positive correlation was observed between the duration of AD and lead levels in cord blood (p=0.002). AD severity was also positively associated with chromium concentrations in cord blood (p=0.037), while cord blood levels of lead, mercury, and cadmium were not significantly associated with AD severity (p=0.562, p=0.054, and p=0.055, respectively). Interleukin-13 production in CBMCs was positively related with lead and chromium levels in cord blood (p=0.021 and p=0.015, respectively). Prenatal exposure to lead and chromium is associated with the persistence and severity of AD, and the immune reaction toward a Th2 polarization.
Cacao ; Cadmium ; Chromium ; Cohort Studies ; Dermatitis, Atopic ; Enzyme-Linked Immunosorbent Assay ; Fetal Blood ; Interleukin-13 ; Mass Spectrometry ; Metals, Heavy ; Parturition ; Plasma ; Umbilical Cord

BACKGROUND: We evaluated the association of blood pressure (BP) with blood levels of cadmium, lead, and cadmium and lead together (cadmium + lead) in a representative sample of adolescents from Korea. METHODS: We used 2010–2016 data from the Korean National Health and Nutrition Examination Survey. This cross-sectional study enrolled adolescents aged at 10–18 years-old who completed a health examination survey and had blood measurements of lead and cadmium. The association of adjusted mean differences in diastolic and systolic BP with doubling of blood lead and cadmium were estimated by regression of BP against log2-transformed blood metals and their quartiles after covariate adjustment. Adjusted odds ratio for prehypertension were calculated for log2-transformed blood levels of lead and cadmium and their quartiles. RESULTS: Our analysis of adolescents in Korea indicated that blood levels of lead and cadmium were not significantly associated with increased BP or risk of prehypertension. However, the cadmium + lead level was associated with prehypertension. Previous studies showed that blood levels of lead and cadmium were associated with increased BP and risk of hypertension in adult populations. We found no such association in Korean adolescents. CONCLUSION: We found that the cadmium + lead level was associated with prehypertension. The differences between adults and adolescents are because adolescents generally have lower levels of these blood metals or because adolescents only rarely have hypertension.
Adolescent* ; Adult ; Blood Pressure* ; Cadmium* ; Cross-Sectional Studies ; Humans ; Hypertension ; Korea ; Metals ; Nutrition Surveys* ; Odds Ratio ; Prehypertension

BACKGROUND: Lead and cadmium are harmful heavy metals that are used for a variety of occupational purposes. Considering their potentially hazardous effects on health, studies on the association between exposure to these two heavy metals and health disorders have been actively conducted. This study aimed to determine the association between blood lead and cadmium levels and blood pressure in workers exposed to lead and cadmium in a smelter. METHODS: Nine hundred and sixty-three male workers who worked in a smelter, and underwent medical examinations at the Ulsan University Hospital between January 1 and December 31, 2014, were selected as participants. Among them, 310 subjects whose data on height, weight, blood pressure, fasting blood glucose, lipid profile, and blood lead and cadmium levels were available and who answered the questionnaire were selected as the final participants. We investigated the drinking habit, smoking status, exercise adequacy, and family history of hypertension of these workers using formal questionnaires. A statistical analysis was conducted using Student's t-test, analysis of variance, and linear or logistic regression. RESULTS: The association between blood lead and cadmium levels and blood pressure was analyzed through statistical adjustment of the risk factors of hypertension. Results showed an association between blood cadmium level and blood pressure elevation. However, blood lead level was found to be not correlated with blood pressure elevation. CONCLUSIONS: This study shows the association between blood cadmium level and systolic blood pressure (SBP) and diastolic blood pressure (DBP) elevation. TRIAL REGISTRATION: IRB No. 2017–03-037. Retrospectively Registered 30 March 2017.
Blood Glucose ; Blood Pressure* ; Cadmium* ; Cross-Sectional Studies* ; Drinking ; Ethics Committees, Research ; Fasting ; Humans ; Hypertension ; Logistic Models ; Male ; Metals, Heavy ; Osmeriformes* ; Retrospective Studies ; Risk Factors ; Smoke ; Smoking ; Ulsan

OBJECTIVES: This study was conducted to evaluate a relationship between the blood concentrations of toxic metals and the blood pressure in people living near the copper smelter. METHODS: The study included 570 adults living within 4km of the smelter. We compared systolic and diastolic blood pressure between tertiary groups for blood cadmium, mercury and lead levels, respectively. Multiple regression analysis was performed to identify risk factors affecting systolic and diastolic blood pressures. RESULTS: In male subjects, there is a significant difference in the mean of systolic and diastolic blood pressure between tertiary groups of blood cadmium and mercury levels, but in women, there was no significant difference in the mean systolic and diastolic blood pressures in all tertiary groups of heavy metals. The results of multiple regression analysis showed that age, BMI, and cadmium concentration in men were risk factors for blood pressure. CONCLUSIONS: Residents living near the Janghang smelter showed high concentrations of blood lead and cadmium, suggesting that they were exposed to high concentrations of heavy metals released from the smelter in the past. Such exposure may have caused some blood pressure increase. Especially, the concentration of cadmium in the case of men and the concentration of mercury in blood in the case of women were found to be significantly related to the increase of blood pressure. The local population should be advised to make efforts to reduce exposure to environmental contaminants, in order to minimize cardiovascular disease, and to pay close attention to any health problems possibly related to toxic metal exposure.
Adult ; Blood Pressure* ; Cadmium ; Cardiovascular Diseases ; Copper* ; Female ; Humans ; Korea* ; Male ; Metals* ; Metals, Heavy ; Risk Factors

Our objective is to evaluate the relationships between prenatal maternal stress and depressive symptoms, respectively, and infant neurodevelopment at 6 months, adjusted for heavy metals and oxidative stress. This research is a part of a multi-center birth cohort study in South Korea. Information on stress and depressive symptoms was collected during the first trimester using Psychosocial Well-Being Index Short Form (PWI-SF) and Center for Epidemiological Studies Depression Scale (CES-D). The Korean Bayley Scales of Infant Development-II assessment (BSID-II), which includes the standardized mental development index (MDI) and psychomotor developmental index (PDI), and Korean Ages & Stages Questionnaires (K-ASQ) were applied to infants at six months of age. A higher index score indicates better development. Among 641 babies, 320 were female (50%). Maternal PWI ≥ 29 (vs. PWI ≤ 18) during early pregnancy was associated with a decrease in MDI scores of 5.37 points (P = 0.02) after adjusting for socioeconomic factors. Maternal CES-D ≥ 26 (vs. CES-D ≤ 10) during early pregnancy was associated with a decrease in MDI scores of 8.18 points (P = 0.01). The associations remained significant even after adjustment for lead, cadmium, and MDA levels (P < 0.05). However, no association was found between maternal PWI/CES-D and PDI score. No interaction was observed between stress and lead exposure. We found an inverse association between prenatal maternal stress and depressive symptoms, and MDI scores in 6-month-old infants after adjustment for prenatal lead exposure, which is known to affect cognitive function negatively.
Adult ; Cadmium/blood ; Child Development/*physiology ; Cohort Studies ; Depression/epidemiology/*pathology ; Female ; Humans ; Infant ; Lead/blood ; Linear Models ; Male ; Malondialdehyde/blood ; Mothers/*psychology ; Prospective Studies ; *Stress, Psychological ; Surveys and Questionnaires

Anemia, iron deficiency (ID), and iron deficiency anemia (IDA) are common disorders. This study was undertaken to determine the prevalence of anemia, ID, and IDA in Korean females. We examined the associations between IDA, heavy metals in blood, vitamin D level and nutritional intakes. The study was performed using on data collected from 10,169 women (aged > or =10 yr), including 1,232 with anemia, 2,030 with ID, and 690 with IDA during the fifth Korea National Health and Nutrition Examination Survey (KNHANES V; 2010-2012). Prevalence and 95% confidence intervals were calculated, and path analysis was performed to identify a multivariate regression model incorporating IDA, heavy metals in blood, vitamin D level, and nutritional intakes. The overall prevalence of anemia, ID and IDA was 12.4%, 23.11%, and 7.7%, respectively. ID and IDA were more prevalent among adolescents (aged 15-18 yr; 36.5% for ID; 10.7% for IDA) and women aged 19-49 yr (32.7% for ID; 11.3% for IDA). The proposed path model showed that IDA was associated with an elevated cadmium level after adjusting for age and body mass index (beta=0.46, P<0.001). Vitamin D levels were found to affect IDA negatively (beta=-0.002, P<0.001). This study shows that the prevalence of anemia, ID, and IDA are relatively high in late adolescents and women of reproductive age. Path analysis showed that depressed vitamin D levels increase the risk of IDA, and that IDA increases cadmium concentrations in blood. Our findings indicate that systematic health surveillance systems including educational campaigns and well-balanced nutrition are needed to control anemia, ID, and IDA.
Adolescent ; Adult ; Aged ; Anemia, Iron-Deficiency/*blood/*epidemiology ; Body Mass Index ; Cadmium/*blood ; Cross-Sectional Studies ; Female ; Humans ; Immunoradiometric Assay ; Middle Aged ; Nutrition Surveys ; Prevalence ; Regression Analysis ; Republic of Korea/epidemiology ; Risk ; Vitamin D/*blood ; Young Adult