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      A Biomarker Found in Cadmium Exposed Residents of Thailand by Metabolome Analysis

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          Abstract

          First, the urinary metabolic profiling by gas chromatography-mass spectrometry (GC-MS), was performed to compare ten cadmium (Cd) toxicosis cases from a Cd-polluted area in Mae Sot (Thailand) with gender-matched healthy controls. Orthogonal partial list square-discrimination analysis was used to identify new biomarker candidates in highly Cd exposed toxicosis cases with remarkable renal tubular dysfunction. The results of the first step of this study showed that urinary citrate was a negative marker and myo-inositol was a positive marker for Cd toxicosis in Thailand. In the second step, we measured urinary citrate in the residents (168 Cd-exposed subjects and 100 controls) and found significantly lower levels of urinary citrate and higher ratios of calcium/citrate and magnesium/citrate, which are risk factors for nephrolithiasis, in highly Cd-exposed residents. Additionally, this inverse association of urinary citrate with urinary Cd was observed after adjustment for age, smoking and renal tubular dysfunction, suggesting a direct effect of Cd on citrate metabolism. These results indicate that urinary citrate is a useful biomarker for the adverse health effects of Cd exposure in a Thai population with a high prevalence of nephrolithiasis.

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          Gas chromatography/mass spectrometry in metabolic profiling of biological fluids.

          One of the objectives of metabonomics is to identify subtle changes in metabolite profiles between biological systems of different physiological or pathological states. Gas chromatography mass spectrometry (GC/MS) is a widely used analytical tool for metabolic profiling in various biofluids, such as urine and blood due to its high sensitivity, peak resolution and reproducibility. The availability of the GC/MS electron impact (EI) spectral library further facilitates the identification of diagnostic biomarkers and aids the subsequent mechanistic elucidation of the biological or pathological variations. With the advent of new comprehensive two dimensional GC (GC x GC) coupled to time-of-flight mass spectrometry (TOFMS), it is possible to detect more than 1200 compounds in a single analytical run. In this review, we discuss the applications of GC/MS in the metabolic profiling of urine and blood, and discuss its advances in methodologies and technologies.
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            Elevated levels of cadmium and zinc in paddy soils and elevated levels of cadmium in rice grain downstream of a zinc mineralized area in Thailand: implications for public health.

            Prolonged consumption of rice containing elevated cadmium (Cd) levels is a significant health issue particularly in subsistence communities that are dependent on rice produced on-farm. This situation is further exacerbated in areas of known non-ferrous mineralization adjacent to rice-based agricultural systems where the opportunity for contamination of rice and its eventual entry into the food chain is high. In the current study, an assessment of the degree of soil Cd and Zn contamination and associated rice grain Cd contamination downstream of an actively mined zone of Zn mineralization in western Thailand was undertaken. Total soil Cd and Zn concentrations in the rice-based agricultural system investigated ranged from 0.5 to 284 mg kg(-1) and 100 to 8036 mg kg(-1), respectively. Further, the results indicate that the contamination is associated with suspended sediment transported to fields via the irrigation supply. Consequently, the spatial distribution of Cd and Zn is directly related to a field's proximity to primary outlets from in-field irrigation channels and inter-field irrigation flows with 60-100% of the Cd and Zn loading associated with the first three fields in irrigation sequence. Rice grain Cd concentrations in the 524 fields sampled, ranged from 0.05 to 7.7 mg kg(-1). Over 90% of the rice grain samples collected contained Cd at concentrations exceeding the Codex Committee on Food Additives and Contaminants (CCFAC) draft Maximum Permissible Level for rice grain of 0.2 mg Cd kg(-1). In addition, as a function of demographic group, estimated Weekly Intake (WI) values ranged from 20 to 82 mug Cd per kg Body. This poses a significant public health risk to local communities. The results of this study suggest that an irrigation sequence-based field classification technique in combination with strategic soil and rice grain sampling and the estimation of WI values via rice intake alone may be a useful decision support tool to rapidly evaluate potential public health risks in irrigated rice-based agricultural systems receiving Cd contaminated irrigation water. In addition, the proposed technique will facilitate the cost effective strategic targeting of detailed epidemiological studies thus focusing resources to specific 'high risk' areas.
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              Metabolic profiling detects early effects of environmental and lifestyle exposure to cadmium in a human population

              Background The 'exposome' represents the accumulation of all environmental exposures across a lifetime. Top-down strategies are required to assess something this comprehensive, and could transform our understanding of how environmental factors affect human health. Metabolic profiling (metabonomics/metabolomics) defines an individual's metabolic phenotype, which is influenced by genotype, diet, lifestyle, health and xenobiotic exposure, and could also reveal intermediate biomarkers for disease risk that reflect adaptive response to exposure. We investigated changes in metabolism in volunteers living near a point source of environmental pollution: a closed zinc smelter with associated elevated levels of environmental cadmium. Methods High-resolution 1H NMR spectroscopy (metabonomics) was used to acquire urinary metabolic profiles from 178 human volunteers. The spectral data were subjected to multivariate and univariate analysis to identify metabolites that were correlated with lifestyle or biological factors. Urinary levels of 8-oxo-deoxyguanosine were also measured, using mass spectrometry, as a marker of systemic oxidative stress. Results Six urinary metabolites, either associated with mitochondrial metabolism (citrate, 3-hydroxyisovalerate, 4-deoxy-erythronic acid) or one-carbon metabolism (dimethylglycine, creatinine, creatine), were associated with cadmium exposure. In particular, citrate levels retained a significant correlation to urinary cadmium and smoking status after controlling for age and sex. Oxidative stress (as determined by urinary 8-oxo-deoxyguanosine levels) was elevated in individuals with high cadmium exposure, supporting the hypothesis that heavy metal accumulation was causing mitochondrial dysfunction. Conclusions This study shows evidence that an NMR-based metabolic profiling study in an uncontrolled human population is capable of identifying intermediate biomarkers of response to toxicants at true environmental concentrations, paving the way for exposome research.
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                Author and article information

                Journal
                Int J Environ Res Public Health
                Int J Environ Res Public Health
                ijerph
                International Journal of Environmental Research and Public Health
                MDPI
                1661-7827
                1660-4601
                02 April 2014
                April 2014
                : 11
                : 4
                : 3661-3677
                Affiliations
                [1 ]Environmental Science Program, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand; E-Mail: dhitiwass@ 123456gmail.com
                [2 ]Department of Public Health, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan; E-Mail: hnakagaw@ 123456kanazawa-med.ac.jp
                [3 ]Mae Sot General Hospital, Mae Sot District, Tak 63110, Thailand; E-Mail: swaddi@ 123456hotmail.com
                [4 ]Department of Nursing, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan; E-Mail: ryumon@ 123456kanazawa-med.ac.jp
                [5 ]Japan Clinical Metabolomics Institute, Kahoku, Ishikawa 929-1174, Japan; E-Mails: jcmi-ohse@ 123456heart.ocn.ne.jp (M.O.); jcmi-kuhara@ 123456bell.ocn.ne.jp (T.K.)
                [6 ]Department of Forensic Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; E-Mail: ruangyuttikarn@ 123456gmail.com
                Author notes
                [* ] Author to whom correspondence should be addressed; E-Mail: ni-koei@ 123456kanazawa-med.ac.jp ; Tel.: +81-76-286-2211 (ext. 3033); Fax: +81-76-286-3728.
                Article
                ijerph-11-03661
                10.3390/ijerph110403661
                4025033
                24699029
                © 2014 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

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