[Blood cadmium level and the change of cadmium exposure risk in Chinese urban school-age children in 2002 and 2012].

OBJECTIVE: To investigate the blood cadmium concentrations and the related change in Chinese urban children derived from the China Nutrition and Health Survey 2002 and 2012(CNHS 2002 and CNHS 2012). METHODS: The Chinese urban children aged 6-11 years were selected according to gender, age and regional distribution using the multi-stage stratified cluster random sampling method, as well as the corresponding whole blood samples. The blood cadmium concentration was carefully determined by the quadrupole inductively coupled plasma mass spectrometry(ICP-MS) and the percentage of blood cadmium over 2 µg/L was subsequently estimated. In addition, the upper limit values of the 95%CI of the 95th percentiles of available blood cadmium data was assessed as the threshold of cadmium exposure. RESULTS: Totally, 2182 Chinese urban children were included, and of these, 1036 children were from the CNHS 2002 and 1146 children were from the CNHS 2012. From the CNHS 2002 to the CNHS 2012, the median blood cadmium concentration was increased from 0.28 µg/L to 0.95 µg/L, and the percentage of blood cadmium with over 2 µg/L was elevated from 1.45% to 10.47%. In addition, the new estimated threshold of blood cadmium was ascended from 1.24 µg/L up to 2.89 µg/L. CONCLUSION: The risk of cadmium exposure in Chinese urban children aged 6-11 years was increasingly aggravated from the CHNS 2002 to the CNHS 2012.

Exploring the association of metal mixture in blood to the kidney function and tumor necrosis factor alpha using machine learning methods.

This research aimed to approach relationships between metal mixture in blood and kidney function, tumor necrosis factor alpha (TNF-α) by machine learning. Metals levels were measured by Inductively Couple Plasma Mass Spectrometry in blood from 421 participants. We applied K Nearest Neighbor (KNN), Naive Bayes classifier (NB), Support Vector Machines (SVM), random forest (RF), Gradient Boosting Decision Tree (GBDT), Categorical boosting (CatBoost), eXtreme Gradient Boosting (XGBoost), Whale Optimization-based XGBoost (WXGBoost) to identify the effect of plasma metals, TNF-α, and estimated glomerular filtration rate (eGFR by CKD-EPI equation). We conducted not only toxic metals, lead (Pb), arsenic (As), cadmium (Cd) but also included trace essential metals, selenium (Se), copper (Cu), zinc (Zn), cobalt (Co), to predict the interaction of TNF-α, TNF-α/white blood count, and eGFR. The high average TNF-α level group was observed among subjects with higher Pb, As, Cd, Cu, and Zn levels in blood. No associations were shown between the low and high TNF-α level group in blood Se and Co levels. Those with lower eGFR group had high Pb, As, Cd, Co, Cu, and Zn levels. The crucial predictor of TNF-α level in metals was blood Pb, and then Cd, As, Cu, Se, Zn and Co. The machine learning revealed that As was the major role among predictors of eGFR after feature selection. The levels of kidney function and TNF-α were modified by co-exposure metals. We were able to acquire highest accuracy of over 85% in the multi-metals exposure model. The higher Pb and Zn levels had strongest interaction with declined eGFR. In addition, As and Cd had synergistic with prediction model of TNF-α. We explored the potential of machine learning approaches for predicting health outcomes with multi-metal exposure. XGBoost model added SHAP could give an explicit explanation of individualized and precision risk prediction and insight of the interaction of key features in the multi-metal exposure.

Comparison of the accumulation of toxic metal biomarkers in Asian subgroups and other races in the United States: NHANES 2015-2016.

Toxic metals such as lead (Pb), cadmium (Cd), mercury (Hg) and arsenic (As) that lead to many visceral organ and nervous system diseases have attracted global attention due to their gradual accumulation in human bodies. The tolerance levels of exposure to toxic metals among race/ethnic groups are different due to the variance of sociodemographic, dietary, and behavioral characteristics. Few studies focused on investigating the biomarker levels of toxic metals in different race/ethnic groups and the potential mechanisms for controlling the accumulation in human bodies. Therefore, we selected eight biomarkers for four toxic metals from the National Health and Nutrition and Examination Survey (NHANES) in the 2-year data cycle of 2015-2016 to reveal the accumulation levels in different races. According to the NHANES rules, we applied probability sampling weights. The geometric mean levels of these biomarkers were calculated in all five race/ethnic groups (Mexican American, white, black, Asian, and other Hispanic) and two Asian subgroups (U.S.-born Asian, and other-born Asian), and compared with each other. The results showed that all the biomarkers in other-born Asians were 1.1-6.7 times in blood and 1.1-3.6 times in urine higher than other race/ethnic groups. Except Hg and As, the lowest biomarker levels were recorded in U.S.-born Asians, only 0.6-0.9 times of lead and 0.3-0.8 times of cadmium than other race/ethnic groups. Furthermore, the major factors of higher Hg and As biomarker levels in Asians were dietary intake of seafood and rice, indicating different accumulation mechanisms among Asians and other race/ethnic groups, especially for U.S.-born Asians. These findings provided new insight into a deeper understanding the accumulation of toxic metals and human health.

The Time Trend of Blood Lead and Cadmium Levels in Rural Chinese Children: China Nutrition and Health Survey 2002 and 2012.

This study was to investigate blood lead (Pb) and cadmium (Cd) levels and time trend in rural Chinese children derived from the China Nutrition and Health Survey 2002 and 2012 (CNHS 2002, CNHS 2012). In total, 1698 and 1581 of rural Chinese children were selected from the CNHS 2002 and the CNHS 2012 databases, respectively. The blood Pb and Cd levels were determined by inductively coupled plasma mass spectrometer (ICP-MS), whilst the prevalence of blood Pb levels >5 µg/dL and blood Cd levels >0.5 µg/L and the corresponding reference values (RV95s: the upper limit of 95% confidence interval of 95th percentile) were together calculated. From the CNHS 2002 to the CNHS 2012, median concentrations in blood were severally decreased from 6.3 to 3.1 µg/dL for Pb and from 0.64 to 0.39 µg/L for Cd. The prevalence of blood Pb levels >5 µg/dL had decreased from 63.6 to 14.2%, together with blood Cd levels >0.5 µg/L prevalence from 62.7 to 33.5%, respectively. The RV95s of blood Pb and Cd levels were 15.2 µg/dL and 1.54 µg/L in the CNHS 2002, as well as 6.3 µg/dL and 1.12 µg/L in the CNHS 2012. In conclusion, blood Pb and Cd levels had been obviously improved in rural Chinese children during the past 10 years. However, the risks of Pb and Cd exposure are still serious and required to have continuous health monitoring and evaluation, even call for greater collaboration of the government and society.

Comparison of monoamine oxidase and selected heavy metal levels in the blood and the workplace among e-waste sorting workers in Ubon Ratchathani Province, Thailand.

Background: E-waste sorting workers usually separate electronic waste. Therefore, they can be exposed to heavy metals. Objectives: This study compared monoamine oxidase (MAO) levels affected by the levels of lead (Pb), cadmium (Cd), and nickel (Ni) in the blood and their workplace among e-waste sorting workers (EWSW). Material and methods: The exposed group included 76 EWSW, and the non-exposed group included 49 village health volunteers. An interview form was used to assess the risk factors. We measured Pb, Cd, and Ni on the work surfaces and in the blood, and MAO levels as a neurological enzymes. Results: Among the EWSW, 42 were males (55.3%), and the mean age (SD) 48.0 (12.64) years, and income were 156.37 ± 88.08 USD. In the work areas of the exposed group, the concentration of Pb, Cd, and Ni were 245.042 (± 613.910), 0.375 (± 0.662), and 46.115 (± 75.740) µg/100 cm2, respectively, while the non-exposed group, the concentration of Pb, Cd, and Ni were 0.609 (± 0.934), 0.167 (± 1.171) and 1.020 (± 0.142) µg/100 cm2. Pb and Ni concentrations in the workplace of the exposed groups were statistically different from that of the non-exposed group. Pb, Cd, and Ni concentrations in serum were 6.411 ± 1.492 µg/dL, 0.9480 ± 0.350 µg/L, 2.568 ± 0.468 µg/L, respectively, while in the non-exposed group, the heavy metal concentrations were 6.411 ± 1.620 µg/dL, 0.909 ± 0.277 µg/L, 2.527 ± 0.457 µg/L. The MAO in the exposed group was 362.060 ± 97.981 U/L, while that in the non-exposed group was 369.771 ± 86.752 U/L. Moreover, MAO concentration was significantly different from Ni concentration (p < 0.05). Conclusion: The electronic waste sorting workers should clean their work areas to reduce the Pb, Cd, and Ni levels on the working surfaces, and health surveillance should be performed.

Blood cadmium, lead, manganese, mercury, and selenium levels in American Indian populations: The Strong Heart Study.

BACKGROUND: Many American Indian (AI) communities are in areas affected by environmental contamination, such as toxic metals. However, studies assessing exposures in AI communities are limited. We measured blood metals in AI communities to assess historical exposure and identify participant characteristics associated with these levels in the Strong Heart Study (SHS) cohort. METHOD: Archived blood specimens collected from participants (n = 2014, all participants were 50 years of age and older) in Arizona, Oklahoma, and North and South Dakota during SHS Phase-III (1998-1999) were analyzed for cadmium, lead, manganese, mercury, and selenium using inductively coupled plasma triple quadrupole mass spectrometry. We conducted descriptive analyses for the entire cohort and stratified by selected subgroups, including selected demographics, health behaviors, income, waist circumference, and body mass index. Bivariate associations were conducted to examine associations between blood metal levels and selected socio-demographic and behavioral covariates. Finally, multivariate regression models were used to assess the best model fit that predicted blood metal levels. FINDINGS: All elements were detected in 100% of study participants, with the exception of mercury (detected in 73% of participants). The SHS population had higher levels of blood cadmium and manganese than the general U.S. population 50 years and older. The median blood mercury in the SHS cohort was at about 30% of the U.S. reference population, potentially due to low fish consumption. Participants in North Dakota and South Dakota had the highest blood cadmium, lead, manganese, and selenium, and the lowest total mercury levels, even after adjusting for covariates. In addition, each of the blood metals was associated with selected demographic, behavioral, income, and/or weight-related factors in multivariate models. These findings will help guide the tribes to develop education, outreach, and strategies to reduce harmful exposures and increase beneficial nutrient intake in these AI communities.

Effects of heavy metals in acute ischemic stroke patients: A cross-sectional study.

ABSTRACT: Cerebrovascular disease is the second commonest cause of mortality globally and among the commonest causes of disability. However, research executed to probe the heavy metal exposure-stroke incidence relationship is scarce. Accordingly, we executed our study to probe the relationship of heavy metal concentrations (ie, concentrations of lead [Pb], mercury [Hg], cadmium [Cd], and arsenic) in the serum and urine of acute ischemic stroke (AIS) patients with several patient variables.For enrollment, we chose patients who had a first AIS within 7 days after the onset of a stroke. Thus, 33 newly diagnosed patients with AIS were recruited. We determined the aforementioned metals' concentrations by executing inductively coupled plasma mass spectrometry. We also gauged the association between such metal concentrations and patient variables by employing Spearman correlation coefficient. To examine the differences in metal concentrations between the different variables, we implemented an independent Mann-Whitney U test.In our cohort analysis, we noted serum Pb and Cd concentrations to be positively correlated with serum creatinine and hemoglobin. Serum and urine Cd concentrations had a negative correlation with impaired HbA1c in AIS patients. Urine Hg had a positive correlation with C-reactive protein in the participants. Participants who smoked or consumed alcohol had significantly higher Pb and Cd levels in serum than did those who neither smoked nor drank. Patients with AIS who smoked or consumed alcohol had high levels of serum Pb and serum Cd than did those who did not. Patients with AIS who consumed alcohol had significantly higher Pb and Hg urine concentrations than did those who did not.Our study indicated that serum Cd and Pb elevation increased the AIS risk in southern Taiwan patients.

Serum cadmium is associated with hepatic steatosis and fibrosis: Korean national health and nutrition examination survey data IV-VII.

ABSTRACT: Although cadmium (Cd) is correlated with elevated levels of hepatic amino transferases, its influence on the degree of liver steatosis and fibrosis are unknown yet. We aimed to investigate the associations between the serum level of Cd and degree of liver steatosis/fibrosis.Clinical data were obtained from Korean National Health and Nutrition Examination Surveys IV-VII. Alanine aminotransferase (ALT) elevation was defined as ≥ 33 IU/L for men and ≥ 25 IU/L for women. Significant steatosis was defined as a hepatic steatosis index ≥ 36, while significant fibrosis was defined as a fibrosis index (FIB-4) ≥ 2.67 and as an aspartate aminotransferase and platelet ratio index ≥ 0.7. Adjusted odds ratios and 95% confidence intervals were calculated after adjustment.The levels of serum Cd were assessable in 15,783 subjects. The serum cadmium concentrations were significantly associated with ALT elevation, significant liver steatosis and fibrosis. Multivariate logistic regression analysis demonstrated serum Cd level in the forth quartile had a positive correlation with ALT elevation, hepatic steatosis index ≥ 36, FIB-4 ≥ 2.67 and aspartate aminotransferase-to-platelet ratio ≥ 0.7 using the first quartile of serum Cd level as the reference, (adjusted odds ratios 1.90, 1.26, 1.73, and 2.53, respectively; P values <.001).The serum level of Cd was associated with liver steatosis and fibrosis. The evaluation of serum Cd may help for assessing an unexplained liver steatosis and fibrosis, and further prospective studies are needed to confirm our findings.

Effects of lead and cadmium co-exposure on liver function in residents near a mining and smelting area in northwestern China.

Chronic exposure to environmental cadmium (Cd) and lead (Pb) may have adverse effects on the human health. In this study, we aimed to determine the primary and interactive effects of Cd and Pb exposure on liver function in residents near a mining and smelting area in northwestern China. A total of 451 subjects were recruited, from which blood samples were collected to determine the levels of Cd, Pb, and liver function indices. Additionally, the association between the levels of exposure markers and liver function indices was analysed. Cd and Pb levels were significantly higher in subjects living in the polluted area than in those living in the non-polluted reference area. The liver function levels of subjects in the polluted area were poor compared with those in the reference area. In addition, Cd and Pb levels in the blood were positively associated with gamma glutamyl transpeptidase (GGT) levels and negatively associated with direct bilirubin (DBil) levels. Cd and Pb may be risk factors for abnormal liver function. The risk of abnormal liver function was higher in subjects with moderate Cd and Pb levels, high Cd levels, high Pb levels, and high Cd and Pb levels than in those with low Cd and Pb levels. Our data show that exposure to Cd and/or Pb can cause abnormal liver function. Cd and Pb may have an antagonistic effect on liver function, and high Cd exposure alone has a more profound effect on abnormal liver function compared with co-exposure to Pb and Cd.

Cadmium and lipid balance in outdoor workers exposed to urban stressor.

The aim of our study was to evaluate the association between levels of blood and urinary cadmium and lipid balance in a group of outdoor workers. The study was conducted on a group of 146 individuals (average age 45,1 ± 8,5). Blood and urinary samples were collected for the detection of total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, blood cadmium and urinary cadmium. We divided the group of workers into two subgroups according to the task:75 traffic policemen and 71 police drivers. Gender differences were found. The Pearson correlation coefficient showed a positive association between blood and urinary cadmium levels and total cholesterol, LDL and triglycerides levels. Total cholesterol, LDL cholesterol and triglycerides were significantly higher in the group of traffic policemen than in police drivers. In conclusion, the results suggest a statistically significant association between blood and urinary cadmium levels and lipid balance contributing to an increase of the cardiovascular risk.

Biomarkers of cadmium exposure and renal function in estuarine adult villagers.

OBJECTIVE: Assess cadmium (Cd) exposure of adults living in two estuarine communities in Aratu bay, Bahia, Brazil and its association with effects on renal function. METHODS: This cross-sectional study included 88 volunteers aged 17-55 years, living in the following two communities: Santa Luzia (SL) located more intimately in the bay and Cotegipe (CT), a bit further and closer to a ferro-manganese alloy plant. Cd in blood (CdB) and urine (CdU), along with blood lead (PbB) levels were determined by graphite furnace atomic absorption spectrometry. Renal function was evaluated by the estimated glomerular filtration rate (eGFR) and tubular cell biomarkers: retinol binding protein (RBP), ß2-microglobulin (ß2M), and N-acetyl-ß-D-glucosaminidase (NAG). RESULTS: The median CdU levels in villagers of the two communities were 0.20 and 0.44 µg/g creat. and SL vs CT, respectively. Age range (> 35 years), cigarette smoking and lower family income were significantly associated with more elevated CdU levels. Multiple linear regression analysis demonstrated a significant association between LnCdU and LnRBP levels (ß = 0.200, 95%CI 0.074-0.365) after adjusted for sex, urinary creatinine and blood lead levels. CONCLUSION: These data show consistent evidences of association between Cd exposure and elevated tubular cell biomarker excretion in estuarine villagers living close to an industrial site.

Prenatal metal mixture concentrations and reward motivation in children.

Reward motivation is a complex umbrella term encompassing the cognitions, emotions, and behaviors involved in the activation, execution, and persistence of goal-directed behavior. Altered reward motivation in children is characteristic of many neurodevelopmental and psychiatric disorders. Previously difficult to operationalize, the Progressive Ratio (PR) task has been widely used to assess reward motivation in animal and human studies, including children. Because the neural circuitry supporting reward motivation starts developing during pregnancy, and is sensitive to disruption by environmental toxicants, including metals, the goal of this study was to examine the association between prenatal concentrations of a mixture of neurotoxic metals and reward motivation in children. We measured reward motivation by administering a PR test to 373 children ages 6-8 years enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) Study in Mexico City. Children were asked to press a response lever for a token reward; one press on the response lever was required to earn the first token and each subsequent token required an additional 10 lever presses. Maternal blood concentrations of lead, manganese, zinc, arsenic, cadmium, and selenium were measured using inductively-coupled plasma mass spectrometry during the 2nd and 3rd trimesters of pregnancy. We performed generalized Weighted Quantile Sum (gWQS) regression analyses to examine associations between the prenatal metal mixture and reward motivation; adjusting for child sex, birthweight and age; and maternal IQ, education, and socioeconomic status. The prenatal metal mixture was significantly associated with higher motivation as indicated by more lever presses (ß = 0.02, p < 0.001) and a shorter time between receiving the reinforcer and the first press (ß = 0.23, p = 0.01), and between subsequent presses (ß = 0.07, p = 0.005). Contributions of different metals to this association differed by trimester and child sex. These findings suggest that children with increased exposure to metal during the 2nd and 3rd trimesters of gestation demonstrate increased reward motivation, which may reflect a tendency to perseverate or hypersensitivity to positive reinforcement.

Iron deficiency as promoter of heavy metals-induced acute myeloid leukemia.

Iron deficiency (ID) and iron deficiency anemia (IDA) have many adverse effects on human health. Also, iron deficiency anemia and anemia in general are linked with an increased risk of various cancers, particularly blood cancers. It is known that subjects with IDA as well as smokers have elevated blood levels of toxic divalent cations, particularly cadmium (Cd2+) and lead (Pb2+). Cadmium is a proven carcinogen. Most of the circulating cadmium is bound to transferrin and apart from the target organs of cadmium accumulation, kidney and liver, tissues (cells) which highly express transferrin receptor 1 (TfR1) may also accumulate high levels of circulating cadmium. Density of TfR1, glycoprotein that is expressed on cell surface, is not uniform in bone marrow cells. Namely, megakaryocyte/erythrocyte progenitors and pro-erythroblasts express TfR1 incomparably more than other cell lines within the bone marrow and we hypothesize that the mentioned cell lines will uptake most of the circulating cadmium and lead, and will consequently be most suitable for malignant transformation. In this review, we discuss in detail the mechanisms involved in accumulation of cadmium in particular cell lines of the bone marrow and the consequent occurrence of acute myeloid leukemia (AML).

Effect of heavy metals on ventricular repolarization and depolarization in the Metropolitan Manila Development Authority (MMDA) traffic enforcers' health study.

We examined the relationships between blood heavy metals [cadmium (B-Cd), mercury (B-Hg), and lead (B-Pb)] and heart rate-corrected QT interval (QTc), JT interval (JTc), and QRS complex duration (QRSc), electrocardiogram markers of ventricular repolarization and depolarization among 60 traffic enforcers in the MMDA traffic enforcers' health study. We fitted regression models to estimate the mean change effect on QTc, JTc, and QRSc, of B-Cd, B-Hg, and B-Pb concentrations, adjusted for potential confounding factors. We looked at effect modification by sex and smoking status. An interquartile range increase in B-Cd (0.9 µg/L) was related to a 6.6% increase in mean QRSc [95% confidence interval (CI): 2.5, 10.8], and a 1.7% increase in mean QTc (95% CI: 0.2, 3.3). We also found that the associations between B-Cd and QRSc and QTc were higher among participants who were never smokers than ever smokers. Moreover, the association between B-Cd and QRSc was also higher among males than females.

Increased incidence of spontaneous abortions on exposure to cadmium and lead: a systematic review and meta-analysis.

BACKGROUND: Spontaneous abortions are the most severe complication of early pregnancy and are a major reproductive health problem. Although this could be caused due to various cytogenetic, immunological, or endocrinological reasons, role of environmental toxicants cannot be ruled out. In order to explore the role of cadmium and lead in causing spontaneous abortions, current systematic review and meta-analysis had been carried out. METHODOLOGY: Literature search was performed using appropriate keywords in PubMed, Science Direct, Cochrane Library, and Google Scholar databases up to December 25 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). Metananalysis was carried out with the help of RevMan software (version 5.3). RESULTS: Meta-analysis of nine studies on cadmium concentrations in blood of women with at least one spontaneous abortions and controls revealed standardized mean difference (SMD)=3.39, 95% CI (2.17, 4.61), with p < .05. Similarly, meta-analysis of eight studies on lead concentrations revealed standardized mean difference (SMD)=6.24, 95% CI (4.34, 8.14), with p < .05. CONCLUSION: Populations exposed to heavy metals such as cadmium and lead are at higher risk of pregnancy loss. Therefore, couples experiencing repeated pregnancy losses may be screened for heavy metal load.

Influence of serum ferritin combined with blood cadmium concentrations on blood pressure and hypertension: From the Korean National Health and Nutrition Examination Survey.

BACKGROUND: Previous studies have suggested that cadmium (Cd) exposure and serum ferritin levels may influence the development of hypertension. OBJECTIVE: We evaluated whether the association between blood Cd levels and the development of hypertension could be modified by serum ferritin levels in a representative sample of the adult population of South Korea. METHODS: We used data from the Korean National Health and Nutrition Examination Survey (2008-2012), a nationally representative, cross-sectional, population-based study. We included 5752 adults aged 19 years and older who had records of blood Cd and ferritin levels and blood pressure measurements. Multiple logistic regression was used to examine the association between Cd exposure and the development of hypertension, as well as the modifying effects of serum ferritin. RESULTS: Men had higher levels of serum ferritin, and women had higher levels of Cd. Smoking in men was significantly associated with high blood pressure and risk of hypertension. Significantly fewer women were smokers, and the combination of abnormal serum ferritin levels and high Cd levels was significantly associated with high systolic blood pressure [odds ratio (OR) = 2.11; 95% confidence interval (CI) = 1.04-4.28], high diastolic blood pressure (OR = 2.07; 95% CI = 1.04-4.12), and increased hypertension risk (OR = 1.83; 95% CI = 1.03-3.25) in women who never smoked. CONCLUSIONS: Our results provide further evidence that individuals with abnormal serum ferritin levels should limit their exposure to Cd to prevent hypertension.

Alcohol Consumption Moderated the Association Between Levels of High Blood Lead or Total Urinary Arsenic and Bone Loss.

Metal exposure and lifestyle are important risk factors for osteoporosis. Our study aimed to investigate the association between red blood cell lead and cadmium, total urinary arsenic, and plasma selenium levels and bone mineral density (BMD). In addition, we explored whether alcohol and coffee consumption modified the association between BMD and metals and metalloids. In total, 437 participants who underwent adult or senile physical examinations were recruited. Bone loss was defined as a calcaneus BMD T-score of <-1. Blood cadmium and lead and plasma selenium levels were measured using inductively coupled plasma mass spectrometry. Levels of urinary arsenic species were determined using high-performance liquid chromatography-hydride generator-atomic absorption spectrometry. The total urinary arsenic level was defined as the sum of the levels of urinary arsenic species. The BMD T-scores decreased significantly with increasing blood lead levels. The BMD T-scores also showed a downward trend with increasing total urinary arsenic levels. The odds ratio (OR) and 95% confidence interval (CI) for bone loss in patients with blood lead levels >57.58 versus 35.74 µg/dL were 1.98 and 1.17-3.34. In addition, the greater the lead or arsenic exposure and alcohol intake was the higher the OR for bone loss with multivariate ORs of 2.57 (95% CI 1.45-4.56) and 2.96 (95% CI 1.67-5.22), respectively. To the best of our knowledge, this study is the first to demonstrate that high total urinary arsenic or blood lead levels and frequent or occasional alcohol consumption had a significant multiplicative interaction for increasing the OR for bone loss.

Antioxidant status in relation to heavy metals induced oxidative stress in patients with polycystic ovarian syndrome (PCOS).

Polycystic ovary syndrome (PCOS) is a global health concern for women of reproductive age, as 6.5% of women worldwide are affected by this syndrome. PCOS is marked by hyperandrogenism, anovulation, menstrual abnormalities, and polycystic ovaries. Metals such as arsenic, cadmium, lead and mercury are considered to be systemic toxicants/human carcinogens and seem to have devastating effects on humans, even at minimal exposures. One of the probable aetiological factors for PCOS has been identified as oxidative stress. In view of the probable associations among oxidative stress, metal toxicity and PCOS, the present study examined the role of heavy metals in the generation of oxidative stress among females. This prospective study included 106 women (56 women diagnosed with PCOS and 50 women who were not diagnosed with PCOS as control women). There were no significant differences in the sociodemographic characteristics between the two groups except for the irregularity of menses and the presence of acne. The serum As, Cd, Pb, and Hg levels increased and the serum glutathione (GSH) and superoxide dismutase (SOD) levels diminished significantly in the PCOS group compared to the control group at P < 0.001. The SOD levels were negatively correlated with the As and Pb levels at P < 0.05. Additionally, the PCOS group exhibited a strong negative correlation between the GSH and As levels (P < 0.01), GSH and Pb levels (P < 0.05) and GSH and Hg levels (P < 0.01). Furthermore, the As levels were positively correlated with increased levels of Cd, Pb and Hg among PCOS women. Significant positive correlations were observed between Pb and Cd and between Cd and Hg at P < 0.001. The outcome of the study provides clear insight into the role of metal-induced oxidative stress, which plays a vital role in the pathophysiology underlying PCOS and suggests the use of these markers as prognostic tools to reduce the consequences of high-risk exposure to these metals among females.

Long non-coding RNA ENST00000414355 as a biomarker of cadmium exposure regulates DNA damage and apoptosis.

Human exposure to cadmium (Cd) may induce severe effects in different organs. Recent studies suggest that long non-coding RNAs (lncRNAs) are closely involved in the pathophysiological mechanisms of Cd-related diseases. This study evaluated the use of lncRNA (ENST00000414355) as an expression signature of Cd exposure and assessed its ability to modulate DNA damage and apoptosis by measuring the expression of ATM serine/threonine kinase (ATM) and mitochondrial membrane potential (ΔΨm) in Cd-exposed workers. A total of 139 (74 non-smokers and 65 smokers) participants from a Cd battery manufacturer were included in the study. Venous blood samples were collected to determine the blood Cd level and detect blood ENST00000414355 and its target gene (ATM) using real-time reverse transcription-polymerase chain reaction (qRT-PCR). Mitochondrial membrane potential was used to assess the Cd effect on mitochondrial permeability. Our results indicated a significant positive correlation between blood Cd level and lncRNA-ENST00000414355 and ATM expression and a significant negative correlation between blood Cd level and ΔΨm (p < 0.0001). Moreover, significant correlations were observed between the expression of lncRNA-ENST00000414355 and ATM expression and ΔΨm (p < 0.0001). Statistical significance was found in the blood Cd level, lncRNA-ENST00000414355 expression, ATM expression, and ΔΨm (p < 0.0001) between smokers and non-smokers. This study confirmed the upregulation of the lncRNA-ENST00000414355 expression, DNA damage-checkpoint-related gene (ATM), and decreased ΔΨm in Cd-exposed workers. Thus, lncRNA-ENST00000414355 may serve as a valuable biomarker for the exposure and toxicity of Cd.

Changes in DNA methylation in APOE and ACKR3 genes in multiple sclerosis patients and the relationship with their heavy metal blood levels.

Multiple sclerosis (MS) is a chronic inflammatory disease with demyelinated lesions in the central nervous system caused by genetic and environmental factors. DNA methylation as an epigenetic change influenced by environmental factors, including heavy metals has been implemented in MS disease. We investigated the correlation of DNA methylation changes in APOE and ACKR3 genes in MS patients and the possible association with blood concentration of arsenic (As), cadmium (Cd) and lead (Pb) as major heavy metal pollutants. This study included 69 relapsing-remitting multiple sclerosis (RR-MS) patients and 69 age/gender-matched healthy subjects. The HRM real-time PCR method was used to investigate the changes in DNA methylation and heavy metal concentrations were measured by electrothermal atomic absorption spectrometry. Our results showed that the methylation pattern in the ACKR3 gene of the patient group was more hypomethylated, while in the case of the APOE gene, this pattern was more towards hypermethylation compared to healthy subjects. Moreover, the blood levels of As and Cd metals, but not Pb, were significantly higher in the patient group compare to the control group (p ≤ 0.05). The data indicate that the increase in expression of ACKR3 gene by hypomethylation and the decrease in expression of APOE gene via hypermethylation are possibly involved in the onset and progression of inflammatory processes in MS patients. The level of As can also lead to hypomethylation by disrupting the methylation patterns of the ACKR3 gene, resulting in increased expression in MS patients. Finally, we have shown that epigenetic changes can be an important factor in increasing and decreasing the expression of genes involved in the onset and/or progression of inflammatory processes in MS. Furthermore, exposure to heavy metals, especially As, by changing the natural patterns of DNA methylation can be effective in this disease.