Kowit Nambunmee

Bone resorption acceleration and calcium reabsorption impairment in a Thai population with high cadmium exposure

Some residents of the Mae Sot district in Thailand have suffered long-term exposure to elevated dietary levels of cadmium. To test the hypothesis that chronic dietary cadmium exposure can cause imbalance in calcium dynamics and accelerate bone resorption, a group of these residents (156 men and 256 women aged ≥ 50) were selected on the basis of previous records of elevated urinary cadmium and tested for urinary and blood cadmium, bone formation and resorption markers, and the renal tubular dysfunction markers. Both genders had high levels of blood and urinary cadmium and high urinary levels of the markers for renal dysfunction and bone resorption in a dose–response relationship to urinary cadmium. The excretion of bone resorption markers was positively correlated to the ratio of excreted calcium and urinary cadmium. The results of a multivariate regression analysis indicated that bone resorption was accelerated by impaired calcium reabsorption in renal tubules.

Use of the kidney injury molecule-1 as a biomarker for early detection of renal tubular dysfunction in a population chronically exposed to cadmium in the environment

Cadmium (Cd) has been found as an environmental pollutant in Mae Sot district, Tak province, Thailand. Prolong exposure to high levels of Cd of the resident increases high risk of Cd toxicity especially to kidney which is the primary target of Cd. In order to investigate the early effect of Cd induced renal dysfunction, a kidney injury molecule-1 (KIM-1), a novel biomarker of renal tubular dysfunction, was measured using an enzyme linked immunosorbent assay (ELISA). The method was validated and used to quantify the KIM-1 concentrations in the urine of 700 subjects (260 men, 440 women) who lived in the Cd contaminated area. The KIM-1 concentrations were compared to the concentrations of two conventional renal tubular dysfunction biomarkers, N-acetyl-β-D-glucosaminidase (NAG) and β2-microglobulin (β2-MG). Urinary KIM-1 was correlated with urinary and blood Cd as well as NAG. After adjustment of age and smoking, urinary KIM-1 was correlated with blood Cd more than urinary NAG did. Clear dose response relationships of urinary KIM-1 with urinary Cd were shown in both men and women. These results indicate that the urinary KIM-1 might be more sensitive biomarker than urinary NAG and β2-MG for an early detection of renal tubular dysfunction. It is useful as a tool to detect renal effect of toxicity due to chronic Cd exposure at high level.

Gender-Specific Impact of Cadmium Exposure on Bone Metabolism in Older People Living in a Cadmium-Polluted Area in Thailand

To elucidate the influence of cadmium exposure on bone metabolism, associations between urinary/blood cadmium and bone resorption/formation markers were investigated in older cadmium exposed men and women. Increased urinary cross-linked N-telopeptide of type I collagen (NTx), a bone resorption marker, was found to be associated with increased levels of parathyroid hormone, fractional excretion of calcium, and urinary/blood cadmium after adjusting for confounding factors in men. In women, urinary NTx was significantly associated with only urinary cadmium and a strong relationship with increased fractional excretion of calcium. Risk for bone metabolic disorders, indicated by high urinary NTx, significantly increased in men with blood cadmium ≥ 10 μg/L or urinary cadmium ≥ 10 μg/g creatinine. Increased osteocalcin level was significantly associated with increased blood cadmium in men. In conclusion, cadmium exposure appeared to have an influence on bone remodeling both bone resorption and formation in this population of older Thai men, and blood cadmium was more closely associated with bone metabolism than urinary cadmium.

Cadmium exposure and age-associated DNA methylation changes in non-smoking women from northern Thailand

Abstract DNA methylation changes with age, and may serve as a biomarker of aging. Cadmium (Cd) modifies cellular processes that promote aging and disrupts methylation globally. Whether Cd modifies aging processes by influencing establishment of age-associated methylation marks is currently unknown. In this pilot study, we characterized methylation profiles in > 450 000 CpG sites in 40 non-smoking women (age 40–80) differentially exposed to environmental Cd from Thailand. Based on specific gravity adjusted urinary Cd, we classified them as high (HE) and low (LE) exposed and age-matched within 5 years. Urinary Cd was defined as below 2 µg/l in the LE group. We predicted epigenetic age (DNAm-age) using two published methods by Horvath and Hannum and examined the difference between epigenetic age and chronologic age (Δage). We assessed differences by Cd exposure using linear mixed models adjusted for estimated white blood cell proportions, BMI, and urinary creatinine. We identified 213 age-associated CpG sites in our population (P < 10−4). Counterintuitively, the mean Δage was smaller in HE vs. LE (Hannum: 3.6 vs. 7.6 years, P = 0.0093; Horvath: 2.4 vs. 4.5 years, P = 0.1308). The Cd exposed group was associated with changes in methylation (P < 0.05) at 12, 8, and 20 age-associated sites identified in our population, Hannum, and Horvath. From the results of this pilot study, elevated Cd exposure is associated with methylation changes at age-associated sites and smaller differences between DNAm-age and chronologic age, in contrast to expected age-accelerating effects. Cd may modify epigenetic aging, and biomarkers of aging warrant further investigation when examining Cd and its relationship with chronic disease and mortality.

615 Bone metabolism abnormality and renal dysfunction in cadmium exposed farmer from thailand

Introduction Paddy fields in Mae Sot, Tak province of Thailand are polluted with cadmium (Cd) over safe level. Farmers exposed Cd from contaminated rice consumption and the high prevalence of kidney dysfunction was shown in the exposed population. Bone fracture is another Cd related pathology which shown in elderly with high exposure level. The identification of high risk individuals will be advantageous to provide suitable health promotion and to prevent severe pathology.This study was done to compare bone fracture risk between glomerular dysfunction, proximal tubular dysfunction and Calcium (Ca) handling abnormality. Methods Serum osteocalcin and cross-linked N-telopeptide of type I collagen to detect bone metabolism abnormalities, whereas glomerular filtration rate, serum cystatin C, urinary β2-microglobulin (β2-MG) and fractional excretion of calcium (FECa) were used to indicate renal dysfunction. Urinary Cd was used as exposure marker. Results We found that high FECa was related to high bone fracture risk in both genders. Proximal tubular dysfunction and glomerular dysfunction did not relate to bone fracture risk. Conclusion Abnormal Cd handling was a key risk factor for bone fracture in Cd exposed people. Men was at risk of bone fracture risk as similar as women. FECa was a specific indicator of Ca wasting and its determination cost was cheaper compare to β2-MG and serum cystatin C. We recommended to use FECa to monitor abnormal Ca metabolism and individual who showed high FECa should have a special health promotion to reduce bone fracture risk. Reduced renal toxicant exposure, and Ca supplementation were suggested as a health promotion for this Cd exposed farmer.

Respirable silica and noise exposures among stone processing workers in northern Thailand

ABSTRACT Silica and noise are highly prevalent occupational exposures in the stone processing industry. Monitoring for silica and noise are expensive tasks that may be especially difficult to perform in low-resource settings, but exposure awareness is vital for protecting worker health. This study evaluated personal noise and silica measurements at a stone processing facility in northern Thailand to investigate the differing exposure potentials and risk for overexposure among the varying job categories. Our research team performed repeated personal noise and respirable silica measurements on 46 workers, over three separate workshifts for each of 46 workers. While 36.2% of noise measurements exceeded the recommended exposure limit of 85 dBA, only three silica measurements (2.4%) were above the threshold limit value (TLV) of 25 µg/m3. Self-reported personal protective equipment use was low, with only 27.5% of participants wearing hearing protection in noisy environments during their monitored shift and 29.7% of workers wearing respiratory protection during dusty portions of their shift. We identified a significant positive correlation between measured noise and silica levels (r = 0.54, p < 0.01), with stone loaders having the highest average noise (mean = 89 dBA, standard deviation = 4.9 dBA) and silica (geometric mean = 6.4 µg/m3, geometric standard deviation = 1.8) exposure levels. In a multivariate model, the stone loader job category was a significant predictor of exposure to detectable levels of respirable silica (p < 0.01). These results provide useful guidance regarding the need for noise and silica exposure interventions in order to reduce incidences of workplace disease in the stone processing industry.

Fractional excretion of calcium, a sensitive marker for calcium wasting in cadmium-exposed women

In Cadmium (Cd)-exposed populations there is urinary calcium (Ca) loss which reflects Ca loss from the bone, decreased bone mass, and osteoporosis later in life, to which women are particularly vulnerable. A sensitive screening method to detect critical Ca wasting is required to provide warning of an increased osteoporosis risk. We used Fractional Excretion of Calcium (FECa) to study Ca wasting in Cd-exposed population. FECa sensitivity to Ca loss was compared to that of serum Ca, urinary Ca and intact parathyroid hormone. Mean FECa in the exposed group was 1.5 times higher than in the control group, and a dose-effect relationship to Cd exposure level was observed. FECa showed a relationship to Cd exposure level even following adjustment for a renal dysfunction marker. We conclude that FECa has a better sensitivity than urinary Ca and serum Ca. The use of FECa as an indicator of Ca wasting in Cd exposed women is recommended.

0397 Serum Heme Oxygenase-1 Level in Silicosis Patients and Stone Mortar and Pestle Production Workers

Objectives Silicosis is a chronic lung disease caused by silica dust exposure and is a significant health problem in industry involving stone crushing process such as mortar and pestle production industry. We proposed a use of Heme Oxygenase-1 (HO-1) to detect an early stage of silicosis. HO-1 is a lung inflammation and oxidative stress biomarker which has a potential to indicate silicosis. In this study, the serum level of HO-1 in exposed subjects (stone mortar and pestle production workers) was compared to a non-silica exposed subjects. Method Total crystalline silica was quantified by ultraviolet visible spectrometry. A chest radiograph was performed in a General Hospital by a trained radiologist to detect silicosis according to International Labour Organisation guideline. The serum HO-1 level was determined by sandwich enzyme immunoassay. Results There were 19 silicosis subjects in the exposed group which was categorised into the silicosis group. The process in stone mortar and pestle production industry produced high level of silica dust in the air ranging between 3.97–21.12 mg/m3. The level of HO-1 increased as the level of silica exposure increased even after adjusted for smoking and employment duration. The level of serum HO-1 level was, however, not significantly different between silicosis, exposed, and non-exposed groups, nor was the relationship between HO-1 and pulmonary function. Conclusions We propose that HO-1 reflects the lung inflammation caused by silica exposure although it is not specific to silicosis. HO-1 may be a useful parameter for monitoring lung inflammation in silica exposed population.