Jung-Duck Park

Risk assessment of low-level cadmium and arsenic on the kidney.

Cadmium (Cd) and arsenic (As) are widely distributed in the environment and are known human carcinogens. Several studies reported that chronic exposure to Cd and As produced renal injuries in humans. As one of the mechanisms, oxidative stress was suggested to play a role in the early process of Cd- and/or As-induced tubular damage in the kidney. This study was performed to evaluate the significance of urinary biomarkers, role of oxidative stress, and effect of coexposure to environmental low-level exposure to Cd and/or As in the general population. Urine samples were collected from 290 adults (86 males and 204 females). Urinary concentrations of Cd and As were measured, and kidney biomarkers of toxicity such as ß2-microglobulin and N-acetyl-β-D-glucosaminidase (NAG) activity determined in urine. Urinary malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels were measured as oxidative stress indices. The mean concentration of Cd was 1.21 μg/L, 0.84 μg/g creatinine, and As was 5.7 μg/L, 3.95 μg/g creatinine in urine. NAG, MDA, and 8-OHdG were positively correlated with both Cd and As in urine. Positive correlations were also observed between NAG and oxidative indices. The effects of coexposure to Cd and As on biomarkers are more pronounced than for exposure to each metal alone. These findings suggest that chronic exposure to low levels of Cd and/or As might produce tubular damage in the kidney through oxidative stress in humans.

Evaluation of factors associated with cadmium exposure and kidney function in the general population.

Cadmium (Cd) is a nonessential toxic metal which is widely distributed in the environment. The general population is exposed to low levels of Cd and the kidney is the organ most sensitive to Cd toxicity. This study was performed to simultaneously evaluate Cd exposure, kidney function, and oxidative stress biomarkers in the general population. A total of 643 adults were interviewed to document demographic characteristics, lifestyles, past‐medical history, and diet during the last 24 h. We estimated daily Cd intake based on the diet of study subjects who had not been exposed to Cd occupationally. Whole blood and urine samples were collected and analyzed to determine Cd concentrations and kidney function indices (β2‐microglobulin [β2‐MG], N‐acetyl‐β‐D‐glucosaminidase [NAG], metallothionein [MT]). The oxidative stress index (malondialdehyde [MDA]) was determined from the urine. The daily Cd intake from diet was established as 7.07 μg/day. The mean concentration of Cd measured in the blood was 1.22 μg/L and urine was 0.95 μg/g creatinine. The concentrations of Cd in blood and urine were higher in females than in males. The blood levels of Cd were affected by sex, age, and smoking, and urine Cd was influenced by sex, age, and blood Cd. The urine Cd was positively correlated with MT, NAG activity, and MDA in females, but with NAG only in males. The blood Cd was associated with MT in males. Increased NAG activity was observed when Cd in urine reached 1.0 μg Cd/g creatinine and was also affected by age, hypertension, and diabetes mellitus. Urinary MT only responded to Cd in urine or blood. In summary, exposure to Cd in the general population was influenced by various factors including sex, age, and smoking habits. Such exposure might eventually cause tubular damage in the kidneys through the oxidative stress mechanism, and females might be more susceptible than males to Cd exposure under the environment.

Inorganic Arsenite Potentiates Vasoconstriction through Calcium Sensitization in Vascular Smooth Muscle

Chronic exposure to arsenic is well known as the cause of cardiovascular diseases such as hypertension. To investigate the effect of arsenic on blood vessels, we examined whether arsenic affected the contraction of aortic rings in an isolated organ bath system. Treatment with arsenite, a trivalent inorganic species, increased vasoconstriction induced by phenylephrine or serotonin in a concentration-dependent manner. Among the arsenic species tested—arsenite, pentavalent inorganic species (arsenate), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV)—arsenite was the most potent. Similar effects were also observed in aortic rings without endothelium, suggesting that vascular smooth muscle plays a key role in enhancing vasoconstriction induced by arsenite. This hypercontraction by arsenite was well correlated with the extent of myosin light chain (MLC) phosphorylation stimulated by phenylephrine. Direct Ca2+ measurement using fura-2 dye in aortic strips revealed that arsenite enhanced vasoconstriction induced by high K+ without concomitant increase in intracellular Ca2+ elevation, suggesting that, rather than direct Ca2+ elevation, Ca2+ sensitization may be a major contributor to the enhanced vasoconstriction by arsenite. Consistent with these in vitro results, 2-hr pretreatment of 1.0 mg/kg intravenous arsenite augmented phenylephrine-induced blood pressure increase in conscious rats. All these results suggest that arsenite increases agonist-induced vasoconstriction mediated by MLC phosphorylation in smooth muscles and that calcium sensitization is one of the key mechanisms for the hypercontraction induced by arsenite in blood vessels.

Biomonitoring of urinary di(2-ethylhexyl) phthalate metabolites of mother and child pairs in South Korea

Di(2-ethylhexyl) phthalate (DEHP) is one of the common phthalate plasticizers used primarily in soft polyvinyl chloride, which is a plastic polymer that makes up the total weight of goods from 1% up to 40% in many consumer products. The aims of this study were to examine the urinary DEHP metabolites in South Korean children and to investigate the correlation between mother and child DEHP urine excretion. Three kinds of urinary DEHP metabolites: mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (5-OH-MEHP) and mono(2-ethyl-5-oxohexyl) phthalate (5-oxo-MEHP), were analyzed. The total of 954 samples (nChildren=392, nMothers=265, nAadults=297), including 258 mother and child pairs, were analyzed using isotope dilution gas chromatography-mass spectrometry. Many studies present higher concentration of DEHP metabolites detected from adults in reproductive age than adults in other ages. Therefore, adults who are age-matched to mothers were evaluated to serve as a standard of comparison against mothers. All statistical analysis was made by adjusting detected volume concentrations (μg/L) with respect to creatinine concentrations (mg/dL) since urinary DEHP metabolites were studied using human reference. The difference in median levels of sum of urinary DEHP metabolites was only significant when children were analyzed in relation to region (p-value≤0.005). Among the three DEHP metabolites, only MEHP of children was significantly correlated to that of paired mothers (p-value≤0.01). The present paper defines the relative metabolic rate (RMR) of DEHP metabolism for the first time in study on phthalates. Children had faster RMR than mothers and adults, specifically in the first step of DEHP metabolism (RMR1: MEHP hydroxylation to 5-OH-MEHP), and RMR1 of children between 1 and 24 months was the fastest. The above results may be used to study and assess human health risk from DEHP exposures, especially among mothers and children in Korea.

Urinary Arsenic Concentrations and their Associated Factors in Korean Adults

Arsenic (As) is a well-known human carcinogen and its dietary exposure has been found to be the major route of entry into general population. This study was performed to assess the body levels of As and their associated factors in Korean adults by analyzing total As in urine. Urine and blood samples were collected from 580 adults aged 20 years and older, who had not been exposed to As occupationally. Demographic information was collected with the help of a standard questionnaire, including age, smoking, alcohol intake, job profiles, and diet consumed in the last 24 hrs of the study. Total As, sum of As(III), As(V), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), in urine was determined using atomic absorption spectrometer involving hydride generation method. The geometric mean concentration of total As in urine was 7.10 μg/L. Urine As was significantly higher in men (7.63 μg/L) than in women (6.75 μg/ L). Age, smoking, alcohol consumption, and job profiles of study subjects did not significantly affect the concentration of As in urine. No significant relationship was observed between body mass index (BMI), Fe, and total cholesterol in serum and urinary As. Urine As level was positively correlated with seaweeds, fishes & shellfishes, and grain intake. A negative correlation between urinary As level and HDL-cholesterol in serum and meat intake was observed. Overall, these results suggest that urinary As concentration could be affected by seafood consumption. Therefore, people who frequently consume seafood and grain need to be monitored for chronic dietary As exposure.

Co-administration of toluene and xylene antagonized the testicular toxicity but not the hematopoietic toxicity caused by ethylene glycol monoethyl ether in Sprague–Dawley rats

Occupational painters are exposed to ethylene glycol monoethyl ether (EGEE), a widely used emulsifying solvent known to cause testicular degeneration and bone marrow depression, together with toluene (TOL) and xylene (XYL) as a mixture. In the previous study (Chung et al., Tox. Lett. 104:143, 1999), testicular atrophy caused by EGEE (200 mg/kg) was shown to be antagonized by co-administration of TOL (250 mg/kg) and XYL (500 mg/kg). This study was conducted to provide histological support for the previously observed antagonistic protective effect of TOL + XYL on EGEE inducible testicular toxicity and to determine whether a similar antagonistic effect can be demonstrated against the EGEE derived hematopoietic toxicity. Compared to the extent of seminiferous tubule degeneration caused by EGEE (150 mg/kg, six times per week for 4 weeks), testes of rats given co-administration of TOL (250 mg/kg) + XYL (500 mg/kg) showed dramatically reduced tubular degeneration. Hyperplasia of Leydig cells in the interstitium was observed in both EGEE and EGEE + TOL + XYL-treated rats. Although a minimal dose of EGEE causing testicular atrophy was used, WBC and platelet counts were decreased significantly. In the TOL + XYL-treated control group, the WBC and platelet counts were not decreased. However, the bone marrow depression caused by EGEE was not reversed by the combined administration of TOL + XYL. In all experimental groups (EGEE alone, TOL + XYL, EGEE + TOL + XYL), plasma levels of creatinine and alkaline phosphatase were significantly decreased. In addition to the marked testicular atrophy, EGEE also decreased the weights of adrenal glands and epididymis. In conclusion, while the testicular degeneration caused by EGEE was antagonized by TOL + XYL, the EGEE derived hematopoietic suppression was not reversed.

Estimation of the Biological Half-Life of Methylmercury Using a Population Toxicokinetic Model.

Methylmercury is well known for causing adverse health effects in the brain and nervous system. Estimating the elimination constant derived from the biological half-life of methylmercury in the blood or hair is an important part of calculating guidelines for methylmercury intake. Thus, this study was conducted to estimate the biological half-life of methylmercury in Korean adults. We used a one-compartment model with a direct relationship between methylmercury concentrations in the blood and daily dietary intake of methylmercury. We quantified the between-person variability of the methylmercury half-life in the population, and informative priors were used to estimate the parameters in the model. The population half-life of methylmercury was estimated to be 80.2 ± 8.6 days. The population mean of the methylmercury half-life was 81.6 ± 8.4 days for men and 78.9 ± 8.6 days for women. The standard deviation of the half-life was estimated at 25.0 ± 8.6 days. Using the direct relationship between methylmercury concentrations in blood and methylmercury intake, the biological half-life in this study was estimated to be longer than indicated by the earlier studies that have been used to set guideline values.

Tissue Distribution of Manganese in Iron-Sufficient or Iron-Deficient Rats After Stainless Steel Welding-Fume Exposure

Welders can be exposed to high levels of manganese through welding fumes. Although it has already been suggested that excessive manganese exposure causes neurotoxicity, called manganism, the pathway of manganese transport to the brain with welding-fume exposure remains unclear. Iron is an essential metal that maintains a homeostasis in the body. The divalent metal transporter 1 (DMT1) transports iron and other divalent metals, such as manganese, and the depletion of iron is known to upregulate DMT1 expression. Accordingly, this study investigated the tissue distribution of manganese in iron-sufficient and iron-deficient rats after welding-fume exposure. The feeding of an iron-deficient diet for 4 wk produced a depletion of body iron, such as decreased iron levels in the serum and tissues, and upregulated the DMT1 expression in the rat duodenum. The iron-sufficient and iron-deficient rats were then exposed to welding fumes generated from manual metal arc stainless steel at a concentration of 63.5 ± 2.3 mg/m3 for 2 h per day over a 30-day period. Animals were sacrificed on days 1, 15, and 30. The level of body iron in the iron-deficient rats was restored to the control level after the welding-fume exposure. However, the tissue distributions of manganese after the welding-fume exposure showed similar patterns in both the iron-sufficient and iron-deficient groups. The concentration of manganese increased in the lungs and liver on days 15 and 30, and increased in the olfactory bulb on day 30. Slight and heterogeneous increases of manganese were observed in different brain regions. Consequently, these findings suggest that the presence of Fe in the inhaled welding fumes may not have a significant effect on the uptake of Mn into the brain. Thus, the condition of iron deficiency did not seem to have any apparent effect on the transport of Mn into the brain after the inhalation of welding fumes.

EFFECTS OF ULTRAVIOLET LIGHT ON THE TENSION OF ISOLATED HUMAN CAVERNOSAL SMOOTH MUSCLE FROM NON-DIABETIC AND DIABETIC IMPOTENT MEN

The effects of ultraviolet (UV) light (310 nm) on human cavernosal smooth muscles were investigated. Cavernosal strips were obtained from men during penile prosthetic surgery. When the cavernosal strips were irradiated with UV light in an organ bath, after precontraction by norepinephrine (100 nM) for 10, 20, 40 and 90 s at intervals of 3 min, the contracted cavernosal smooth muscles from the impotent men without vascular risk factors (controls) showed relaxation depending on the duration of irradiation. However, the relaxation was not found when the strips were pretreated with methylene blue (10 μM) or their epithelia were denuded. The relaxation response of the cavernosal strips from the patients with diabetogenic impotence was significantly reduced compared with that of the controls. Photorelaxation of human cavernosal strips therefore seems to be dependent on endothelium.

Korean research project on the integrated exposure assessment of hazardous substances for food safety.

Objectives: This survey was designed to conduct the first nationwide dietary exposure assessment on hazardous substances including the intakes of functional food and herbal medicine. In this paper, we introduced the survey design and the results of the dietary exposure status and internal exposure levels of lead (Pb), cadmium (Cd), and mercury (Hg). Methods: We selected 4867 subjects of all ages throughout Korea. We conducted a food survey, dietary survey, biomonitoring, and health survey. Results: Pb and Cd were the highest (median value) in the seaweed (94.2 μg/kg for Pb; 594 μg/kg for Cd), and Hg was the highest in the fish (46.4 μg/kg). The dietary exposure level (median value) of Pb was 0.14 μg/kg body weight (bw)/d, 0.18 μg/kg bw/d for Cd, and 0.07 μg/kg bw/d for Hg. Those with a blood Pb level of less than 5.00 μg/dL (US Centers for Disease Control and Prevention, reference value for those 1 to 5 years of age) were 99.0% of all the subjects. Those with a blood Cd level with less than 0.30 μg/L (German Federal Environmental Agency, reference value for non-smoking children) were 24.5%. For those with a blood Hg level with less than 5.00 μg/L (human biomonitoring I, references value for children and adults, German Federal Environmental Agency) was 81.0 % of all the subjects. Conclusions: The main dietary exposure of heavy metals occurs through food consumed in a large quantity and high frequency. The blood Hg level and dietary exposure level of Hg were both higher than those in the European Union.