Co-exposure to lead, mercury, and cadmium induces neurobehavioral impairments in mice by interfering with dopaminergic and serotonergic neurotransmission in the striatum.

Humans are exposed to lead (Pb), mercury (Hg), and cadmium (Cd) through various routes, including drinking water, and such exposure can lead to a range of toxicological effects. However, few studies have investigated the toxic effects of exposure to mixtures of metals, particularly in relation to neurotoxicity. In this study, 7-week-old male mice were exposed to Pb, Hg, and Cd individually or in combination through their drinking water for 28 days. The mice exposed to the metal mixture exhibited significantly reduced motor coordination and impaired learning and memory abilities compared to the control group and each of the single metal exposure groups, indicating a higher level of neurotoxicity of the metal mixture. The dopamine content in the striatum was significantly lower in the metal mixture exposure group than in the single metal exposure groups and the control group. Furthermore, compared to the control group, the metal mixture exposure group showed a significantly lower expression level of tyrosine hydroxylase (TH) and significantly higher expression levels of dopamine transporter (DAT), tryptophan hydroxylase 1 (TPH1), and serotonin reuptake transporter (SERT). Notably, there were no significant differences in SERT expression between the single metal exposure groups and the control group, but SERT expression was significantly higher in the metal mixture exposure group than in the single metal and control groups. These findings suggest that the key proteins involved in the synthesis and reuptake of dopamine (TH and DAT, respectively), as well as in the synthesis and reuptake of serotonin (TPH1 and SERT, respectively), play crucial roles in the neurotoxic effects associated with exposure to metal mixtures. In conclusion, this study demonstrates that simultaneous exposure to different metals can impact key enzymes involved in dopaminergic and serotonergic neurotransmission processes, leading to disruptions in dopamine and serotonin homeostasis and consequently a range of detrimental neurobehavioral effects.

Trends and Factors Associated with Oral Contraceptive Use among Korean Women.

Although oral contraceptives (OC) are widely used, few national-level epidemiologic studies have evaluated the prevalence of OC use and factors related to their use in Korea. We performed a population-based cross-sectional study on OC use by premenopausal women aged 20-59 years residing in Korea. We used secondary data from the 2010-2019 National Health and Nutrition Examination Survey to examine trends in the annual prevalence of OC use between 2010 and 2019, and factors influencing OC use. Based on data from 14,386 premenopausal women, the average annual prevalence of OC use was 8.2-10.7% between 2010 and 2014; it increased to 12.6-14.4% during 2015-2019. The prevalence of OC use was significantly higher in women with higher (≥5) than lower gravidity (<5). In addition, among sociodemographic factors, education level, household income, cigarette smoking, and alcohol drinking were significantly associated with OC use in Korean women. As OC use is affected by sociodemographic factors, a contraceptive plan that considers sociodemographic factors is needed to establish an effective family planning policy.

Comparisons among Machine Learning Models for the Prediction of Hypercholestrolemia Associated with Exposure to Lead, Mercury, and Cadmium.

Lead, mercury, and cadmium are common environmental pollutants in industrialized countries, but their combined impact on hypercholesterolemia (HC) is poorly understood. The aim of this study was to compare the performance of various machine learning (ML) models to predict the prevalence of HC associated with exposure to lead, mercury, and cadmium. A total of 10,089 participants of the Korea National Health and Nutrition Examination Surveys 2008-2013 were selected and their demographic characteristics, blood concentration of metals, and total cholesterol levels were collected for analysis. For prediction, five ML models, including logistic regression (LR), k-nearest neighbors, decision trees, random forests, and support vector machines (SVM) were constructed and their predictive performances were compared. Of the five ML models, the SVM model was the most accurate and the LR model had the highest area under receiver operating characteristic (ROC) curve of 0.718 (95% CI: 0.688-0.748). This study shows the potential of various ML methods to predict HC associated with exposure to metals using population-based survey data.

Urinary Levels of 4-Nonylphenol and 4-t-Octylphenol in a Representative Sample of the Korean Adult Population.

4-Nonylphenol (4-NP) and 4-t-octylphenol (4-t-OP) are xenoestrogen compounds to which humans are exposed via contaminated food, water, and air. This study assessed the body burden of 4-NP and 4-t-OP in Koreans aged 18-69 years using data from the Korean National Human Biomonitoring Survey conducted in 2009. Based on data from 1865 representative Koreans, 83.2% and 91.8% had urinary 4-NP and 4-t-OP concentrations >0.05 ng/mL (limit of detection). Of the Korean adult population, the geometric mean urinary concentrations of 4-NP and 4-t-OP were 3.70 ng/mL (95% confidence interval (CI) = 3.20-4.27) and 0.60 ng/mL (95% CI = 0.55-0.66), respectively. Urine 4-NP concentrations were significantly associated with place of residence and smoking status, whereas urine 4-t-OP concentrations were not correlated with any of the demographic factors. These findings suggest that most Koreans have detectable levels of 4-NP and 4-t-OP in their urine and that the body burden of 4-NP, but not 4-t-OP, varies according to some demographic factors.

Gender differences in the association between self-reported stress and cigarette smoking in Korean adolescents.

BACKGROUND: The aim of this study was to examine the relationship between stress and smoking among Korean adolescents, as well as the influence of gender on this relationship. METHODS: A cross-sectional study was conducted using data from 3930 adolescents aged 12-18 years, collected in the 2007-2012 Korea National Health and Nutrition Examination Surveys. RESULTS: An increased level of self-reported stress was positively associated with increasing levels of smoking in both girls and boys (p for trend < 0.001). After adjusting for age, the odds ratios of smoking among girls and boys reporting very high levels of stress were 15.99 (95 % confidence interval (CI), 4.17-61.30) and 2.34 (95 % CI, 1.07-5.11), respectively, compared with those who reported low levels of stress. CONCLUSIONS: This study found a statistically significant association between stress and smoking among Korean adolescents and this association was stronger in girls than boys. Further research is needed to understand more fully the link between stress and smoking in adolescents, with particular attention to sex differences.

Effect of topical dimethylarsinic acid on the expression of apoptosis-related proteins in mouse skin.

We investigated the effect of the topical application of dimethylarsinic acid (DMA) on skin thickness and the expression of several apoptosis-related proteins in skin. After administration of DMA during pregnancy, skin thickness and skin expression of Bcl-2, Bcl-3, Bad, Bid, and caspases-3, -6, -8, -9, and -12 were examined in dams and their offspring. DMA treatment caused significant increases in skin thickness (p < 0.05) and the expression of Bcl-2, Bad, and capase-12 in the skin of dams at the mRNA and protein levels (p < 0.01). However, maternal exposure to DMA did not significantly alter the expression of the studied apoptosis-related factors in the skin of the offspring. These findings indicate that DMA may induce skin apoptosis, in part, by modulating the expression of Bcl-2, Bad, and caspase-12 in maternal skin. Additionally, our results suggest that maternal exposure to DAM during pregnancy may not induce apoptosis in the skin of the offspring.

Blood cadmium concentration and lipid profile in Korean adults.

Although animal experiments have shown that cadmium exposure induces alterations in lipid profiles, no epidemiological study of this relationship has been performed. The objective of this study was to evaluate the association between blood cadmium concentration and blood lipid levels in Korean adults. A cross-sectional study comprising participants (n=3903) aged 20 years or older from the 2005, 2008, and 2009 Korea National Health and Nutrition Examination Surveys was conducted. Demographic characteristics and dietary intake were obtained from the participants by questionnaire, and cadmium and lipid levels were determined by analysis of blood samples. After adjusting for demographic and dietary factors, blood concentration of cadmium was positively associated with the risk of low high-density lipoprotein cholesterol (HDL-C) in a dose-dependent manner (p for trend <0.001). In addition, the odds ratios (ORs) of a high triglyceride to HDL-C ratio was significantly increased in the high blood cadmium groups [OR=1.36; 95% confidence interval (CI), 1.03-1.79 for fourth quintile and OR=1.41; 95% CI, 1.07-1.86 for fifth quintile] compared with the lowest quintile group. However, high blood cadmium was not associated with a risk of high total cholesterol, high low-density lipoprotein cholesterol, or high triglycerides. These data suggest that an increased cadmium body burden increases the risk of dyslipidemia, mainly due to the increased risk of low HDL-C and the high ratio of triglycerides to HDL-C.

Urinary concentrations of bisphenol A and triclosan and associations with demographic factors in the Korean population.

Bisphenol A (BPA) and triclosan are synthetic phenolic compounds to which the general public can be extensively exposed via consumer products and environmental contamination. In this study, we assessed exposure to BPA and triclosan in the Korean adult population aged 18-69 based on the Korean National Human Biomonitoring Survey conducted in 2009. Relying on data from 1870 representative Koreans, we found that the geometric mean urinary concentrations of BPA and triclosan were 1.90 ng/ml [95% confidence interval (CI): 1.81-1.99] and 1.68 ng/ml (95% CI: 1.48-1.90), respectively. The creatinine-adjusted geometric means of BPA and triclosan were 1.79 µg/g creatinine (95% CI: 1.70-1.90) and 1.58 µg/g creatinine (95% CI: 1.39-1.81), respectively. About 99.8% of the Korean adult population had urinary concentrations of BPA and about 92.6% of the Korean adult population had urinary concentrations of triclosan above the level of 0.05 ng/ml (limit of detection, LOD). Urinary BPA concentrations were higher in residents of rural areas, whereas urinary triclosan concentrations were significantly associated with cigarette smoking. These findings suggested that most Koreans had detectable levels of BPA and triclosan in their urine and that the body burden of BPA and triclosan varied according to demographic and geographic factors.

Association of blood mercury concentrations with atopic dermatitis in adults: a population-based study in Korea.

Atopic dermatitis is one of the most common inflammatory skin diseases among children and adults. Although the risk factors for atopic dermatitis have not yet been fully identified, exposure to mercury may be an important environmental risk factor. The objective of this study was to evaluate the association between mercury body burden and prevalence of atopic dermatitis in an adult population. We recruited participants (n=1990) aged 20 years or older, using stratified random sampling of Korean census blocks. Demographic characteristics and medical history of atopic dermatitis were collected from participants by questionnaire, and mercury levels were determined by an analysis of blood samples. We found that demographic factors such as sex, age, alcohol drinking status, income, and fish or shellfish consumption were important covariates determining blood mercury concentration. Sex and cigarette smoking status were important demographic variables affecting the prevalence of atopic dermatitis. After adjusting for demographic factors, blood mercury concentrations were positively associated with lifetime prevalence of atopic dermatitis [odds ratio (OR), highest vs. lowest tertile=1.50; 95% confidence interval (CI), 1.02-2.21; p for trend=0.057]. This association became stronger for 1-year prevalence of atopic dermatitis (OR, highest vs. lowest tertile=1.82; 95% CI, 1.17-2.83; p for trend=0.026). Mercury body burden and atopic dermatitis prevalence vary across demographic characteristics, and increased blood level of mercury was related to an incidence of atopic dermatitis in this adult population.

Biomonitoring of lead and cadmium in the hair and fingernails of elderly Korean subjects.

Lead and cadmium are toxic to humans at excessive levels, and monitoring the human body burden of these metals is important in preventing adverse health effects. In this study, we assessed the exposure to lead and cadmium among an elderly population 60 years of age or older. Based on data from 115 participants, we found that the geometric mean lead concentrations in hair and fingernails were 1.11 µg/g [95% confidence interval (CI) 0.78-1.58] and 1.11 µg/g (95% CI 0.81-1.51), respectively. The lead concentrations in hair and fingernails were significantly related to cigarette smoking. The geometric mean cadmium concentrations in hair and fingernails were 52.6 ng/g (95% CI 42.0-65.9) and 40.1 ng/g (95% CI 29.9-53.9), respectively. Cadmium concentrations in hair were significantly related to body mass index and cigarette smoking, whereas higher fingernail cadmium concentrations were related to alcohol drinking. Correlations between hair and fingernail concentrations of lead and of cadmium were slightly positive. Our findings suggest that the body burden of lead and cadmium varies according to demographic factors, and hair and fingernails could be used differentially as a biological medium for metal exposure.

Effect of lavender oil on motor function and dopamine receptor expression in the olfactory bulb of mice.

AIM OF THE STUDY: Although treatment with the essential oil of lavender induces neuroemotional changes, there is a lack of data regarding its specific effects on neurotransduction, especially dopaminergic neurotransduction. We investigated the relationship between altered motor activity and changes in the expression of dopamine receptors (DR), particularly the receptor subtypes D2 and D3, in lavender oil-treated mice. MATERIALS AND METHODS: After the administration of lavender oil (intraperitoneal injections of 10-1000 mg/kg lavender oil once per day for 5 days), motor coordination and dopamine receptor expression were examined in the olfactory bulb and the striatum of the mouse brain. RESULTS: After 5 days, mice treated with 1000 mg/kg lavender oil showed significantly increased rotarod activity when compared to controls. Although DRD2 expression showed no change in the olfactory bulb or striatum of lavender-treated mice, DRD3 expression increased significantly in the olfactory bulb; this increase was dose-dependent and was observed at both the mRNA and protein levels. CONCLUSIONS: These data indicate that altered dopamine D3 receptor subtype homeostasis in the olfactory bulb may contribute to lavender oil-induced behavioral change.

Aluminum exposure decreases dopamine D1 and D2 receptor expression in mouse brain.

Aluminum (Al) has been identified as a potential contributing factor in the etiology of several neurodegenerative disorders, but data regarding specific effects on neurotransduction, especially on dopaminergic neurotransduction, are lacking. The objective of this study was to determine the extent of expressional alterations in dopamine receptors (DRs) in two dopaminergic subtypes, D1 and D2, in low and high dose Al-treated mice. After administration of Al (four intraperitoneal injections of 30 or 60 mg/kg AlCl3.6H2O at 2 h intervals), expression of the dopamine D1-like and D2-like receptors (DRD1, DRD2) was examined in the cortex and striatum of mouse brain at bregma levels of 1.10, -0.10 and -1.34 mm. In the cortex, Al treatment decreased densities of DRD1 and DRD2 in a dose-dependent manner at all three bregma levels, especially in the high-dose Al group. Similarly, DRD1 and DRD2 expression in the striatum also exhibited dose dependency and statistically significant decreases were seen in the high-dose group, except in the striatum at bregma level - 1.34. These findings suggest that DR in the caudal striatum is more resistant to the effects of Al exposure than DR in the cortex or rostral striatum. In addition, our results suggest that disturbance of dopaminergic neurotransmission mediated by DRD1 and/or DRD2 may be involved in the pathogenesis of Al neurotoxicity.

The effect of PARP inhibitor on ischaemic cell death, its related inflammation and survival signals.

Poly(ADP-ribose) polymerase (PARP) plays an important role in ischaemic cell death, and 3-aminobenzamide (3-AB), one of the PARP inhibitors, has a protective effect on ischaemic stroke. We investigated the neuroprotective mechanisms of 3-AB in ischaemic stroke. The occlusion of middle cerebral artery (MCA) was made in 170 Sprague-Dawley rats, and reperfusion was performed 2 h after the occlusion. Another 10 Sprague-Dawley rats were used for sham operation. 3-AB was administered to 85 rats 10 min before the occlusion [3-AB group (n = 85) vs. control group without 3-AB (n = 85)]. Infarct volume and water content were measured, brain magnetic resonance imaging, terminal deoxynucleotidyltransferase (TdT)-mediated dUTP-biotin nick end-labelling (TUNEL) and Cresyl violet staining were performed, and immunoreactivities (IRs) of poly(ADP-ribose) polymer (PAR), cleaved caspase-3, CD11b, intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), phospho-Akt (pAkt) and phospho-glycogen synthase kinase-3 (pGSK-3) were compared in the peri-infarcted region of the 3-AB group and its corresponding ischaemic region of the control group at 2, 8, 24 and 72 h after the occlusion. In the 3-AB group, the infarct volume and the water content were decreased (about 45% and 3.6%, respectively, at 24 h), the number of TUNEL-positive cells was decreased (about 36% at 24 h), and the IRs of PAR, cleaved caspase-3, CD11b, ICAM-1 and COX-2 were significantly reduced, while the IRs of pAkt and pGSK-3 were increased. These results suggest that 3-AB treatment could reduce the infarct volume by reducing ischaemic cell death, its related inflammation and increasing survival signals. The inhibition of PARP could be another potential neuroprotective strategy in ischaemic stroke.

3-monochloropropane-1,2-diol does not cause neurotoxicity in vitro or neurobehavioral deficits in rats.

3-monochloro-1,2-propanediol (3-MCPD) is a contaminant of acid-hydrolyzed vegetable protein. Several reports have suggested that chronic exposure to 3-MCPD could produce neurotoxicity in vitro or neurobehavioral effects in experimental animals. The present study further explored the in vitro neurotoxic effects of 0.1-100 microM 3-MCPD on PC12 and N18D3 cell lines. In addition, to investigate the effects of repeated ingestion of 3-MCPD on neurobehavioral impairments parameters in rats, motor activity, landing foot splay, and grip strength tests were performed, following treatment with 3-MCPD at dose levels of 10, 20, and 30 mg/kg per day for 11 weeks. We demonstrated that no significant neurotoxic effects were present in 3-MCPD-treated rats compared to saline-treated control rats, whereas, acrylamide, used as a positive control, induced significant deficits in all neurobehavioral parameters in both male and female rats. On the other hand, body weight gain was significantly decreased in high dose 3-MCPD-treated male rats as well as in acrylamide-treated rats. Taken together, these results suggest that 3-MCPD, at the dose levels used for this study, does not produce in vitro neurotoxicity or neuromotor deficits in vivo.

Perinatal exposure to aluminum alters neuronal nitric oxide synthase expression in the frontal cortex of rat offspring.

Disturbance of the neuronal nitric oxide signaling pathway by chronic exposure to aluminum (Al) in drinking water may be a causal factor of neurological disorders in offspring. In order to investigate the relationship between Al administration and expression of neuronal nitric oxide synthase (nNOS), the numbers and distribution patterns of nNOS-immunoreactive neurons were examined in the frontal cortex of offspring after exposure to 0, 5, and 10 mM of Al in drinking water during prenatal and neonatal periods. At the bregma 0.20 level, the number of nNOS-positive neurons was significantly increased (10%) and decreased (17%) following exposure to 5 and 10 mM of Al in drinking water, respectively. The change was more severe in the upper layer than in deep layer of the cortex. In contrast, at the bregma -2.80 level, the number and distribution pattern was not significantly changed following exposure to Al. These data suggest that Al toxicity may be mediated through disturbances to the nitric oxide signaling pathway and exhibits a biphasic effect, especially in the frontal area of the cortex. In addition, the results suggest that impaired expression of nNOS plays an important role in the development of neurological syndrome caused by an exposure to Al during the early developmental stage.