• BMB Reports
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• 제45권7호
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• pp.419-424
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• 2012

High-fat diets (HFD) and high-carbohydrate diets (HCD)-induced obesity through different pathways, but the metabolic differences between these diets are not fully understood. Therefore, we applied proton nuclear magnetic resonance ($^1H$ NMR)-based metabolomics to compare the metabolic patterns between C57BL/6 mice fed HCD and those fed HFD. Principal component analysis derived from $^1H$ NMR spectra of urine showed a clear separation between the HCD and HFD groups. Based on the changes in urinary metabolites, the slow rate of weight gain in mice fed the HCD related to activation of the tricarboxylic acid cycle (resulting in increased levels of citrate and succinate in HCD mice), while the HFD affected nicotinamide metabolism (increased levels of 1-methylnicotineamide, nicotinamide-N-oxide in HFD mice), which leads to systemic oxidative stress. In addition, perturbation of gut microflora metabolism was also related to different metabolic patterns of those two diets. These findings demonstrate that $^1H$ NMR-based metabolomics can identify diet-dependent perturbations in biological pathways.

• 한국환경보건학회지
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• 제44권6호
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• pp.572-580
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• 2018

Objectives: Human biomonitoring (HBM) is a measurement of the chemicals and their metabolites in human biological samples and has been successfully employed to determine the exposure levels of environmental chemicals. In this study, we analyzed seasonal variations of the blood or urinary levels of chemicals, and assessed that these differences could affect the results of association study. Methods: The Korea National Environmental Health Survey (KoNEHS) is a nationwide survey that analyzes exposure levels of environmental pollutants, 19 kinds of chemicals including heavy metals and organic chemicals, and the exposure factors in the general population. Based on KoNEHS data, we analyzed the levels of chemicals concentrations over the total survey period (2012-2014) and each season, and assessed the association of thyroid measures with phthalate metabolite and BPA. Results: Exposure levels of blood mercury and lead were lower in summer compare to winter. Bisphenol A and PAHs metabolites were higher in spring and summer, but lower in autumn. VOCs metabolites were generally lower in summer and autumn. Phthalate metabolites were higher in all other seasons than in winter. Pyrethroid metabolite, 3-PBA, was higher in summer and autumn. Regarding seasonal variation of chemical exposures, the statistical significance and size of effects between thyroid measures and phthalate and BPA were changed with season. Conclusion: Seasonal variations of chemical exposure and health outcome should be considered for interpreting biomonitoring results from a public health context.

• 실내환경 및 냄새 학회지
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• 제17권4호
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• pp.315-321
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• 2018

Phthalate is an endocrine disruptor that interferes with homeostasis and developmental regulation. It is highly toxic to the environment and is associated with various diseases of the human body. Using biological samples from 140 adult subjects, to evaluate the influencing factors which are related to contaminant concentration levels, we used correlation analysis and multiple regression analysis. Lastly, in order to analyze the health effects related to exposure to phthalates, we conducted a risk assessment by estimating acceptable daily intake exposure according to the influential factors. When we compared the concentration level according to influential factors, in general, the subjects who had engaged in home remodeling work had higher urinary phthalate metabolite concentrations levels than the subjects who had not engaged in home remodeling work. We can confirm statistically significant differences in DBP metabolites. In addition, we can confirm the concentration appeared higher in the categories such as using air freshener, sofa and foods. Through conducting a risk assessment of DEHP, BBzP, DiBP, and DnBP by using data on phthalate metabolite concentration in urine, it was found that the average concentration of all metabolites did not exceed TDI.

• 한국환경농학회지
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• 제36권4호
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• pp.293-298
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• 2017

BACKGROUND: Pyrethroids (PYRs) are a widely used insecticide in agriculture and household area. In mammals, PYRs such as deltamethrin is metabolized to 3-phenoxybenzoic acid (3-PBA) in liver that is mainly excreted in urine. This study is designed to single exposure of deltamethrin to rats in a dose-dependent manner and identify the correlation between deltamethrin exposure and its metabolite (3-PBA) in urine. METHODS AND RESULTS: Exposure levels of deltamethrin were control (0 mg/kg bw), low (0.0705 mg/kg bw), medium (0.705 mg/kg bw) and high (7.05 mg/kg bw) dose. Low concentration was derived by ussing Korea predictive operator exposure model (KoPOEM). Dermal exposure persisted for 6 h, and urine specimens were collected for 24 h. The urine matrix was removed after a series of procedures and 3-PBA was analyzed by gas chromatography/mass spectrometry. CONCLUSION: There was a strong correlation ($R^2=0.83$) between the amount of oral exposure to delta me thrin and urinary levelof3-PBAexcreted. In dermal exposure groups of deltamethrin except high-dose, also there was a good correlation between urinary 3-PBA and deltamethrin exposure, but not stronger than in oral deltamethrin exposure groups. Based on these results, therefore, the amount of 3-PBA in urine can be used as a good monitoring indicator that reflexing the exposure level of deltamethrin to human body.

• 한국식품과학회지
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• 제33권6호
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• pp.784-788
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• 2001

최근 고추섭취량과 위암과의 양의상관도를 보이는 역학조사 결과가 발표되었는데 이런 자료를 신뢰하기 위해서는 향신료로 쓰이는 고추의 섭취량이 정확히 측정되어야 할 것이다. 이에 고추의 매운맛 성분 capsaicin의 인체대사산물을 확인하고 이를 응용하여 생리학적으로 의미있는 섭취량을 측정하려는 취지에서 실험을 계획하였다. 먼저 동물실험에서 관찰된 capsaicin의 대사체들을 소변에서 HPLC로 동시에 검출하는 방법을 고안하고 이들 대사체의 신속한 검색을 위해, 이전부터 사용하던 유기용매 추출을 지양하고 효소 glucuronidase 처리한 소변희석액을 바로 HPLC에 주입하는 방법을 사용하였다. 20대의 젊은 여성 5-6명을 대상으로, 이틀 간의 capsaicin 고갈식이 이후 capsaicin이 포함되지 않은 식사시 capsacin의 제공원으로서 고추장을 섭취하게 하였다. 60g씩 사홀 고추장을 섭취한 실험시 여섯명의 참가자 중 네명에게서 섭취를 시작한지 3일 째 4-hydroxy-3-methoxybenzoic acid가, 한 명에게서 3일 째 capsaicin이 검출되었다. 80g씩 나흘을 섭취한 2차 실험시는 세 명의 피실험자에게서 4-hydroxy-3-methoxybenzoic acid가 나흘째 소변에서 검출되었다. 2차 실험에서 나흘째 검출된 4-hydroxy-3-methoxybenzoic acid의 총량은 실험기간 중 섭취한 capsaicinoids 총량의 85% 이상이었다. 따라서 쥐 등을 이용한 capsaicinoid 대사 실험에서는 4-hydroxy-3-methoxybenyl alcohol이 주대사물질이었으나 인체에서는 그와 달리 4-hydroxy-3-methoxybenzoic acid가 주대사산물이라고 여겨진다. 그러나 1, 2차 실험식이를 충실히 따른 두명의 소변에서는 4-hydroxy-3-methoxybenzoic acid를 포함한 어떤 대사체도 찾을 수 없었기 때문에 개인간의 흡수 대사 차이가 크게 기여한다고 추정되며 생리적으로 의미 있는 capsaicin 섭취의 지표 물질은 인체를 대상으로 처음 얻어진 이 결과에 기반으로 한 계속 실험을 통해 선정되리라 기대한다.

• 한국산업보건학회지
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• 제21권1호
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• pp.49-54
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• 2011

In order to develop the methods for exposure assessment and find susceptibility markers for the workers who are exposed to low doses of toluene, xylene and other chemical in petroleum industries, we investigated the application of P-450 expression in human lymphocytes utilizing mouse monoclonal anti-rat CYP2B1/2, the levels of toluene and xylene in air and their metabolite levels in urine with the levels of expressed CYP2B1/2 proteins. The general characteristics such as age, smoking and drinking habit were no significant difference between the control and exposed workers, but the working durations and working hours were significantly different. Workers in exposed group were exposed to the mean of 2.1 ppm (range, 0.00-4.54) of toluene and 0.3 ppm (rang, 0.00-1.23) of xylene. The mean concentration of urinary hippuric acid was low and less than 1/5 of the biological exposure index recommended by the Ministry of Employment and Labor Korea. Methyl hippuric acid in urine was not detected in control and exposed workers. Also, there were no significant differences in the levels of the urinary metabolites between the control and exposed group. When chemiluminescence dot blottings were carried out utilizing mouse monoclonal antibody against CYP2B1/2, the strong density dots corresponding to a mouse monoclonal antibody was observed in the human lymphocytes from the exposed workers. These results suggested that the chemiluminescence dot blot assay for CYP of lymphocytes should be valuable for identifying CYP expression as biomarkers in the workers exposed to toluene and xylene.

• 대한의생명과학회지
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• 제12권4호
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• pp.361-370
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• 2006

To evaluate an effect of pathological liver damage on the conjugation of cyclohexane metabolites, rats were pretreated with 50% $CCl_4$ dissolved in olive oil (0.1 ml/100 g body weight) 10 or 17 times intraperitoneally at intervals of every other day. On the basis of liver function, the animals pretreated with $CCl_4$ 10 times were identified as acutely liver damaged ones and the animals pretreated with $CCl_4$ 17 times were identified as severly liver damaged ones. To these liver damaged animals, cyclohexane (a single dose of 1.56 g/kg body weight, i.p.) was administered at 48 hr after the last injection of $CCl_4$. The rats were sacrificed at 4 or 8 hr after injection of cyclohexane. The cyclohexane metabolites, cyclohexanol (CH-ol), cyclohexane-1,2-diol (CH-1,2-diol), cyclohexane-1,4-diol (CH-1,4-diol), and their glucuronyl conjugates and cyclohexanone were detected in the urine of cyclohexane treated rats. The urinary concentration of cyclohexane metabolites was generally more increased in liver damaged animals than normal ones, and the increasing rate was higher in $CCl_4$ 17 times injected rats than 10 times injected ones. And liver damaged.ats, especially $CCl_4$ 17 times treated ones, had an enhanced ability of glucuronyl conjugation to CH-ol analogues compared with normal group. Futhermore, CH-1,2 and 1,4-diol were all conjugated with glucuronic acid in $CCl_4$ 17 times injected animals. On the other hand, the increasing rate of activities of hepatic cytochrome P450 dependent aniline hydroxylase, alcohol dehydrogenase and urine diphosphate glucuronyl transferase was higher in 17 times $CCl_4$-treated rats compared with normal and $CCl_4$ 10 times injected animals. Taken all together, it is assumed that an increased urinary excretion amount of cyclohexane metabolites in liver damaged rats might be caused by an increase in the activities of cyclohexane metabolizing enzymes. And enhanced conjugating ability of CH-ol in liver damaged animals and novel finding of conjugating form of CH-1,2 and 1,4-diol might be caused by increase in the activity of hepatic diphosphouridine glucuronyltransferase.

• Biomolecules & Therapeutics
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• 제21권1호
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• pp.1-9
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• 2013

Polyamines, putrescine, spermidine and spermine, are ubiquitous in living cells and are essential for eukaryotic cell growth. These polycations interact with negatively charged molecules such as DNA, RNA, acidic proteins and phospholipids and modulate various cellular functions including macromolecular synthesis. Dysregulation of the polyamine pathway leads to pathological conditions including cancer, inflammation, stroke, renal failure and diabetes. Increase in polyamines and polyamine synthesis enzymes is often associated with tumor growth, and urinary and plasma contents of polyamines and their metabolites have been investigated as diagnostic markers for cancers. Of these, diacetylated derivatives of spermidine and spermine are elevated in the urine of cancer patients and present potential markers for early detection. Enhanced catabolism of cellular polyamines by polyamine oxidases (PAO), spermine oxidase (SMO) or acetylpolyamine oxidase (AcPAO), increases cellular oxidative stress and generates hydrogen peroxide and a reactive toxic metabolite, acrolein, which covalently incorporates into lysine residues of cellular proteins. Levels of protein-conjuagated acrolein (PC-Acro) and polyamine oxidizing enzymes were increased in the locus of brain infarction and in plasma in a mouse model of stroke and also in the plasma of stroke patients. When the combined measurements of PC-Acro, interleukin 6 (IL-6), and C-reactive protein (CRP) were evaluated, even silent brain infarction (SBI) was detected with high sensitivity and specificity. Considering that there are no reliable biochemical markers for early stage of stroke, PC-Acro and PAOs present promising markers. Thus the polyamine metabolites in plasma or urine provide useful tools in early diagnosis of cancer and stroke.

• Preventive Nutrition and Food Science
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• 제5권2호
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• pp.105-108
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• 2000

To evaluate an effect of oxygen free radical on the toluence metabolism, the rats were fed on a tungstate sup-plemented diet(0.75g of tungstate included in 1kg of standard diet) or a standard diet. To the present xanthine oxidase deficient animal model, toluene(0.15ml/100g of body weight) was injected and then the animals were sacrificed after 24 hrs to determine the toluene metabolizing enzyme activities and toluene metabolite, hippuric acid concentration. The increasing rate of urinary hippuric acid concentration was significantly(p<0.01) higher in tungstate fed animals than in standard diet fed ones. Hepatic cytochrome P_450 contents were significantly higher(p<0.01) in tungstate fed animals than in standard diet fed ones. And tungstate fed animals showed a ten-dency of higher activities of benzylalcohol dehydrogenase while a significantly higher activites of benzaldehyde dehydrogenase (p<0.01) than standard diet fed animals. In conclusion, the more possibly reduced oxygen free radical in toluene-treated rats fed with a tungstate supplemented diet than in those fed with a standard diet would be responsible for the enhancement of toluene metabolism.

• 약학회지
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• 제44권5호
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• pp.379-383
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• 2000

Stanozolol (STZ, 17$\alpha$-methyl-17$\beta$-hydroxy-5$\alpha$-androstano-(3,2-c) pyrazole), an anabolic steroid, is an abused drug by body-builders or atheletes, as well as medicine for treatment of aplastic anemia and vascular thrombosis. In human volunteers, the major urinary metabolite of STZ was reported to be 3'-hydroxystanozolol that was identified by gas chromatography-mass selective detector (GC/MSD). The objective of this experiment is to investigate the in vitro metabolism of STZ in liver S-9 faction of polychlorinated biphenyl-induced rats. Reaction mixture including STZ as substrate and the S-9 faction was extracted with diethyl ether and quantified by the selected ion monitoring mode of GC/MSD. The selected concentration of substrate STZ is 100 nmole and the selected time for incubation in the reaction mixture was determined to 60 min. The amount of 3'-hydroxystanozolol produced was increased by about 6-fold in the reaction medium including the liver S-9 fraction of polychlorinated biphenyl-induced rats, compared to that of untreated rats. Inhibitors of cytochrome P450, SKF-525A and 7,8-benzoflavone, decreased the production of 3'-hydroxystanozolol by about 89~100% and 65~75%, respectively; In conclusion, hydroxylation of STZ into 3'-hydroxystanozolol is confirmed by GC/MSD and is catalyzed by cytochrome P450.