• Nutrition Research and Practice
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• v.15 no.1
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• pp.1-11
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• 2021

BACKGROUND/OBJECTIVES: It is difficult to consistently demonstrate the health effects of soy isoflavones owing to the multitude of factors contributing to their bioavailability. To accurately verify these health effects, dietary isoflavone intake should be measured using a biologically active dose rather than an intake dose. This concept has been expanded to the development of new exposure biomarkers in nutrition research. This review aims to provide an overview of the development of exposure biomarkers and suggest a novel research strategy for identifying the health effects of soy isoflavone intake. MATERIALS/METHODS: We cover recent studies on the health effects of soy isoflavones focusing on isoflavone metabolites as exposure biomarkers. RESULTS: Compared to non-fermented soy foods, fermented soy foods cause an increased concentration of isoflavones in the biofluid immediately following ingestion. The correlation between exposure biomarkers in blood and urine and the food frequency questionnaire was slightly lower than that of corresponding 24-h dietary recalls. Urinary and blood isoflavone levels did not show a consistent association with chronic disease and cancer risk. CONCLUSION: It is crucial to understand the variable bioavailabilities of soy isoflavones, which may affect evaluations of soy isoflavone intake in health and disease. Further studies on the development of valid exposure biomarkers are needed to thoroughly investigate the health effects of isoflavone.

• Analytical Science and Technology
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• v.12 no.3
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• pp.190-195
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• 1999

The metabolism of testosterone ($17{\beta}$-hydroxy-androst-4-en-3-one) was confirmed in horse after a single intramuscular administration of testosterone cypionate (750 mg). Solvent extracts of urine obtained with enzymatic hydrolysis and methanolysis were analyzed by GC/MS after oxime t-butyldimethylsilyl (oxime-TBDMS) derivatization. The structures of four urinary metabolite after testosterone administration in horse were determined based on EI mass spectra and $5{\alpha}$-androstane-$3{\beta}$, $17{\alpha}$-diol and $5{\alpha}$-androstane-$3{\beta}$-ol-17-one as major was confirmed with authentic standard. Also the concentrations of $5{\alpha}$-androstane-$3{\beta}$, $17{\alpha}$-diol, $5{\alpha}$-androstane-$3{\beta}$, $17{\beta}$-diol, dehydroepiandrosterone (DHEA), $5{\alpha}$-androstane-$3{\beta}$-ol-17-one and testosterone were determined in the urine of normal subjects and the urine after administration. The recovery and detection limit in the most drugs were 86.3~94.7% and 1~3 ppb, respectively. Correlation coefficients for calibration were in the range of 0.984~0.999. Excretion profile of testosterone presents the rapid and large increasement up to maximum values at days 5 after administration and the slow regression. The relative ratios of testosterone, its metabolites over DHEA were determined for indication of testosterone administration in horse doping.

• Journal of Pharmaceutical Investigation
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• v.9 no.2
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• pp.11-21
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• 1979

It has been reported from our department that a few agents, such as $K_2S_2O_5,\;NaHSO_3,$ nicotinamide have a marked stabilizing effect in vitro on metoclopramide which is relatively unstable compound. In order to study the effect of these stabilizers on the action of metoclopramide in vitro, the fate of this compound combined with $K_2S_2O_5,\;NaHSO_3$ and nicotinamide, respectively, was studied and furthermore, the change of the biological activity of metoclopramide due to these stabilizers was studied by using the isolated stomach strip of rat. The blood concentration of metoclopramide was measured by using Bakke's method at the various time after intravenous injection of the mixed metoclopramide solution with the stabilizers. In order to study the excretion of the drug, rabbits were anesthesized and catheterized into bladder for withdrawal of urine. After intravenous injection of the mixed metoclopramide solution, urine was collected for 5 hours and the conjugated forms of metoclopramide as well as the free form were determined by using Arita's method. In the biological study of the metoclopramide combined with stabilizers, the contractability of the isolated rat stomach strip was observed by using polygraph recorder. The results were following: 1. When metoclopramide was administered with nicotinamide as stabilizer, the blood concentration of the unchanged from and the rate of the clearance of this compound were very similar to that of metoclopramide alone. On the other hand, other stabilizers, $K_2S_2O_5\;and\;NaHSO_3$, brought about 40% decrease in blood concentration of the unchanged form at 15 min after intravenous injection however, the rate of clearance of metoclopramide with $K_2S_2O_5\;or\;NaHSO_3$ was very slow. 2. In the case of urinary excretion, the excretory pattern of the metabolites of metoclopramide with $NaHSO_3$ or nicotinamide was very similar to that of metoclopramide alone. But metodopramide plus $K_2S_2O_5$ group showed the maked depression of excretion for first 1 hour. 3. In composition of metabolites, when metoclopramide was administered with $K_2S_2O_5$ or $NaHSO_3$, the sulfonate conjugation was predominant. But the glucuronic acid conjugation was predominant in metoclopramide plus nicotinamide gronp. 4. In the experiments on the biological activity of the metoclopramide, this compound exhibited the marked contracting effect in isolatd rat stomach strip. Specially, the meetoclopramide combined with $K_2S_2O_5$ showed the strong contraction of the isolated strip, suggesting the potenciating effect of $K_2S_2O_5$ on the action of metoclopramide in the isolated strip.

• Translational and Clinical Pharmacology
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• v.25 no.2
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• pp.67-73
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• 2017

Glimepiride, a third generation sulfonylurea, is an antihyperglycemic agent widely used to treat type 2 diabetes mellitus. In this study, an untargeted urinary metabolomic analysis was performed to identify endogenous metabolites affected by glimepiride administration. Urine samples of twelve healthy male volunteers were collected before and after administration of 2 mg glimepiride. These samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and then subjected to multivariate data analysis including principal component analysis and orthogonal partial least squares discriminant analysis. Through this metabolomic profiling, we identified several endogenous metabolites such as adenosine 3', 5'-cyclic monophosphate (cAMP), quercetin, tyramine, and urocanic acid, which exhibit significant metabolomic changes between pre- and posturine samples. Among these, cAMP, which is known to be related to insulin secretion, was the most significantly altered metabolite following glimepiride administration. In addition, the pathway analysis showed that purine, tyrosine, and histidine metabolism was affected by pharmacological responses to glimepiride. Together, the results suggest that the pharmacometabolomic approach, based on LC-MS/MS, is useful in understanding the alterations in biochemical pathways associated with glimepiride action.

• Analytical Science and Technology
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• v.11 no.5
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• pp.374-385
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• 1998

Phytoestrogens are biologically active compounds derived from plants foods. It had been suggested that phytoestrogens, by inhibiting aromatase in peripheral and/or cancer cells and lowering estrogen levels, may play a protective role as antipromotional compounds during growth of estrogen-dependent cancers. Therefore, simultaneous analysis of estrogens and phytoestrogens is necessary to elucidate the possible involvement of phytoestrogens in estrogen metabolism. In this view, we developed a simple and reproducible procedure to quantitatively determine estrogen and phytoestrogen metabolites. The proposed method consisted of solid phase extraction using preconditioned Serdolit AD-2 resin, enzyme hydrolysis with ${\beta}$-glucuronidase/arylsulfatase from Helix pomatia, liquid-liquid extraction and TMS-ether derivatization. And the final determination was carried out by gas chromatography/mass spectrometry (GC/MS) in selected ion monitoring mode (SIM). The precision and accuracy of this method was evaluated through within-a-day and day-to-day test. Recovery range and detection limit were 71.96~105.66%, 2~4 ng/mL, respectively. Using this method, 17 estrogen and 5 phytoestrogen compositions in urine of normal subjects were analyzed. It was found that amounts and relative distribution of urinary phytoestrigens and estrogens showed different pattern in male and female subjects.

• Journal of the Korean Electrochemical Society
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• v.17 no.3
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• pp.172-178
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• 2014

In this work, we describe an electrochemical immunosensor for simple, fast and quantitative detection of a urinary hippuric acid (HA). Urinary HA, of molecular weight 180 DA, is one of the major metabolites and biological indicators in toluene-exposed humans. Simple and ubiquitous monitoring of exposure to toluene is very important in occupational health care. We propose the electrochemical immunoassay based on the dopamine-antigen conjugate for detecting hippuric acid. Our electrochemical immunoassay system employs a conjugate of dopamine (DA) as an electrochemical active molecule and hippuric acid (HA) as an antigen. As an electrochemical aspect, dopamine (DA) containing two hydroxyl group can show excellent redox signal. Also, dopamine-tethered hippuric acid (DA-HA) shows the reversible redox signal in the immunoassay. The competition between HA and DA-HA generated electric signals proportional to HA concentration. The electrochemical immunoassay was performed with DA-HA on the screen printed carbon electrodes (SPCEs), and then applies the mixture antigen (HA) and HA-antibody. The electrical signals were proportional to HA in the range of 0.010~2.500 mg/mL which is enough range to be used for the point-of-care.

• Journal of Preventive Medicine and Public Health
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• v.29 no.4 s.55
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• pp.863-875
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• 1996

In order to prepare the fundamental data for the health promotion by assessing the exposure level of styrene, the author determined the concentration of mandelic acid and phenylglyoxylic acid in urine of 42 workers who were exposed to styrene by high performance liquid chromatography and surveyed 16 symptoms, by questionnaire and also tested neurobehavioral test(digit symbol, benton visual retention) in 2 FRP plants of Kyung Nam area from July to September, 1995. Control was sampled by age sex matching method. The concentration of styrene in air was determined by gas chromatography. The results were as follows; 1. Geometric mean concentration of styrene in air was 17.4ppm, geometric mean concentration of mandelic acid(MA) in urine were 404.3mg/g creatinine for exposure group, 46.4mg/g creatinine for control group, geometric mean concentration of phenylglyoxylic acid(PGA) in urine were 57.5mg/g creatinine for exposure group, 9.5mg/g creatinine for control group. Mean concentration of MA and PGA showed statistically significant difference between exposure group and control group(p<0.01). 2. Number of symptom were 2.9 for exposure group, 3.3 for control group, number of digit symbol were 24.1 for exposure group, 32.5 for control group, number of Benton visual retention test were 6.1 for exposure group, 6.0 for control group, respectively. As result of adjusting the education year, number of Benton visual retention test showed statistically significant difference between exposure group and control group(p<0.05). 3. Excellent correlation were observed between environmental styrene exposure and urinary MA(r=0.80), PGA(r=0.73), and MA+PGA(r=0.81).

• Molecular & Cellular Toxicology
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• v.4 no.1
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• pp.5-10
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• 2008

The effect of obesity on the drug-metabolizing enzymes remains an important issue for clinician since obesity is a world wide epidemic problem. However, little is known about the effects of obesity on flavincontaining monooxygenase (FMO) production and activity. We show here for the first time that in vivo FMO activity determined by urinary ranitidine (RA) metabolites ratio in human, was higher in subjects with a high body mass index (BMI, kg/$m^2$, 21.97-30.32) than in those with an intermediate BMI (range 19.38-21.83). Moreover, there was a significant correlation between FMO activity and BMI in 209 subjects. In high fat diet-induced obese mice, we also observed that the hepatic expression of FMO (225% of lean mice) and the activity measured by the RA Noxidation rate ($513{\pm}58.1$ vs. $349{\pm}66.0$ pmol/hr per mg protein) were significantly higher than in lean mice fed a control diet. Unknown factors rather than leptin or insulin appeared to regulate the hepatic FMO production. Thus, FMO activity may be increased in obese or overweight individuals. Moreover, the regulation of FMO activity in subjects with morbid obesity, with or without complications and its clinical implications, should be investigated further.

• Environmental Mutagens and Carcinogens
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• v.22 no.4
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• pp.248-254
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• 2002

Single cell gel electrophoresis assay was carried out to evaluate DNA damage in T-and B-lymphocytes from rats exposed to benzene and the correlation between DNA damage and the level of t,t-muconic acids, which are urinary benzene metabolites, was investigated. In control rats, the mean values of Olive tail moments in T-and B-lymphocytes were 1.507$\pm$0.187 and 1.579$\pm$0.206 respectively. DNA damages of T-lymphocytes in rats exposed for 4 weeks showed the highest Olive tail moments at each benzene concentration examined (2.72-4.351). However this DNA damage was decreased after 6 weeks of exposure (1.74-2.09). DNA damages of B-lymphocytes did not show such differences with exposure time or benzene concentration (1.49-2.07) except at 200 ppm at 4 weeks. T-lymphocytes show significantly more damages than B-lymphocyte upon acute exposure to benzene.

• The Korean Journal of Pesticide Science
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• v.20 no.2
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• pp.172-180
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• 2016

This study was conducted to evaluate the relations between the exposure level of organophosphates (OPs) pesticide and application factors among rural farmers. The urinary dialkylphosphates, metabolites of organophosphorus pesticides, including DMP, DEP, DMTP and DETP were analyzed by GC/MSD and GC/MS/MS. The DMP and DMTP were detected more in the use of a speed sprayer without cap than with a capped one. Also, the less farmers wore the personal protective equipment (PPE), the more these were detected. The amount of organophosphorus exposure was the highest in the use of a power sprayer. However, it was low when a farmer applied pesticides with a speed sprayer with cap and wore more PPE. In this study, the detection rate was analyzed by chi-square test, the exposure level of OPs was analyzed by a generalized linear model.