• 약학회지
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• 제37권4호
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• pp.317-324
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• 1993

The metabolic profile of carbinoxamine, 2-[(4-chlorophenyl)-2-pyridinyi-methoxy] N, N-dimethylethanamine, was determined in rat urine. Urinary extracts obtained with or without enzyme hydrolysis were derivatized with MSTFA/TMSCI (N-methyl-N-trimethylsilyl trifluoroacetamide/Trimethylchlorosilane) and analyzed by GC/MSD. In rat urine, which obtained after oral treatment with carbinoxamine maleate, chlorobenzolyl pyridine, (4-chlorophenyl)-2-pyridinyl methanol : carbinol, 2-[(4-chlorophenyl)-2-pyridinylmethoxy]-N-methylethanamine : norcarbinoxamine, 2-[(4-chlorophenyl)2-pyridinylmethoxy]ethanamine : bis-norcarbinoxamine and parent carbinoxamine were detected in free form. Norcarbinoxamine and bisnorcarbinoxamine were also detected in conjugated form(acetylation). These data suggest that in the rat, hydroxylation of either the benzyl or pyridinyl ring can occur during carbinoxamine elimination. O-demethylation and subsequent conjugation represents the primary pathway of carbinoxamine elimination in the rat.

• 한국환경보건학회:학술대회논문집
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• 한국환경보건학회 2003년도 Challenges and Achievements in Environmental Health
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• pp.157-157
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• 2003

To evaluate an effect of pathological liver damage on the cyclohexane metabolism, rats were pretreated with 50% $CCl_4$ dissolved in olive oil (0.1$\mell$/100g body weight) 10 or 17 times intraperitoneally at intervals of every other day. On the basis of liver function and histological findings, 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, with fibrosis, biliary abnormality and mild injury both in the kidneys and the lungs. To these liver damaged animals, cyclohexane (a single dose of 1.56g/kg body weight, i.p.) was administrated at 48 hours after the last injection of $CCl_4$. The rats were sacrificed at 4 or 8 hours after injection of cyclohexane. The cyclohexane metabolites; cyclohexanol (CH-ol), cyclohexane-1, 2-diol (CH-1, 2-diol), cyclohexane-l, 4-diol (CH-1, 4-diol), and their glucuronyl conjugates and cyclohexanone (CH-one) were detected in the urine of cyclohexane treated rats. After cyclohexane treatment, the serum levels of CH-ol and CH-one were remarkably increased at 4 hours and then decreased at 8 hours in normal group. Whereas in liver damaged rats, these cyclohexane metabolites were higher at 8 hours than at 4 hours. The excretion rate of cyclohexane metabolites from serum into urine was more decreased in liver damaged animals than normal group, with the levels of excretion rate being lower in $CCl_4$ 17 times injected animals than 10 times injected ones. However, it was interesting that 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 rats, especially $CCl_4$ 17 times treated ones, had an enhanced ability of glucuronyl conjugation to cyclohexanol 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. In conclusion, the metabolic rate of cyclohexane was unexpectably accelerated and it may be caused by physiological adaptation of adjacent intact hepatocyte in damaged liver.

• BMB Reports
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• 제29권2호
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• pp.105-110
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• 1996

Polyclonal antiserum R101 against aflatoxin $B_1$ ($AFB_1$) was raised in New Zealand white rabbits after injection of bovine serum albumin-$AFB_1$ conjugate. Competitive ELISA (enzyme linked immuno-sorbent assay) demonstrated that antiserum R101 has the highest binding for $AFB_1$ (50% inhibition at 170 fmol) and aflatoxicol II (50% inhibition at 112 fmol). It also reacts with other aflatoxins such as $AFB_2$, $AFG_1$, $AFG_2$, and aflatoxin metabolites ($AFM_1$, $AFM_2$, $AFP_1$, and $AFQ_1$), but it does not cross-react with $AFG_2a$. Using this antiserum, aflatoxins were quantitated in 100 urine samples of undergraduate students at the College of Pharmacy, Sung Kyun Kwan University, Republic of Korea. By ELISA, $AFB_1$ and its metabolites were detected in human urine samples (N=100, male=89, female=11, ages=20~31 yrs) with a range of 1.4~200.6 ng/kg/day (mean$\pm$SD=$18.11{\pm}33.01\;ng\;AFB_1/kg/day$ in males, $3.82{\pm}2.65\;ng/kg/day$ in females). Assuming that urinary excretion is about 7.6% of $AFB_1$ intake (Groopman et al., 1992), we estimated that Koreans were daily exposed to a total dietary $AFB_1$ of $240.20{\pm}438.67\;ng/kg/day$ in males and $50.35{\pm}29.88\;ng/kg/day$ in females, respectively. When the human monitoring data was applied to a linear regression model of Y=21.67X-10.04 {Y=liver cancer incidence per 100,000, X=Log $AFB_1$ intake (ng/kg/day), r=0.99} developed from previously reported epidemiological data, calculated liver cancer incidences attributed to $AFB_1$ exposure were 41.56/100,000 in males and 26.84/100,000 in females. The incidences were similarly correlated with liver cancer mortality rates of 43.43/100,000 in males and 11.23/100,000 in females in Korea. These results suggest that aflatoxin exposure may be an important risk factor for the high incidence of liver cancer in Korea.

• 한국환경보건학회지
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• 제47권2호
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• pp.131-143
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• 2021

Objectives: This study aims to investigate the atmospheric concentration of polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs) and the urinary concentration of biomarkers in residents near the Shinpyeong·Jangrim Industrial Complex to compare them with those of residents in a control area. Methods: Hazardous air pollutants (PAHs and VOCs) were measured in an exposure area (two sites) and a control area (one site). Urine samples were collected from residents near the industrial complex (184 persons) and residents in the control area (181 persons). Multiple linear regression analysis was used to identify which factors affected the concentration of PAHs and VOCs metabolites. Results: The average atmospheric concentration of PAHs in Shinpyeong-dong and Jangrim-dong was 0.45 and 0.59 ppb for pyrene, 0.15 and 0.16 ppb for benzo[a]pyrene, and 0.29 and 0.35 ppb for dibenz[a,h]anthracene. The average atmospheric concentration of VOCs was 1.10 and 0.99 ppb for benzene, 8.22 and 11.30 ppb for toluene, and 1.91 and 3.05 ppb for ethylbenzene, respectively. The concentrations of PAHs and VOCs in residents near the Shinpyeong·Jangrim Industrial Complex were higher than those of residents in the control area. Geometric means of urinary 2-hydroxyfluorene, 1-hydroxypyrene, methylhippuric acid, and mandelic acid concentrations were 0.45, 0.22, 391.51, and 201.36 ㎍/g creatinine, respectively. Those levels were all significantly higher than those in the control area (p<0.05). In addition, as a result of multiple regression analysis, even after adjusting for potential confounding factors such as gender and smoking, the concentration of metabolites in urine was high in residents near the Shinpyeong·Jangrim Industrial Complex. Conclusion: The results of this study show the possibility of human exposure to VOCs in residents near the Shinpyeong·Jangrim Industrial Complex. Therefore, continuous monitoring of the local community is required for the management of environmental pollutant emissions.

• 한국환경농학회지
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• 제15권1호
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• pp.70-76
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• 1996

생쥐 체내에서 $^{14}C-{\alpha}-Endosulfan$의 흡수, 분포, 대사, 배설 등의 동태를 구명하기 위하여 약제를 7.5mg $kg^{-1}$ 수준으로 복강주사 처리하여 수행한 시험 결과를 요약하면 다음과 같다. 1. 약제처리 후 4 일 이내에 처리 방사능의 63.9%가 소변을 통해 배설되었고, 그 후부터는 배설율이 일정하였다. 2. 약제처리 후 각 조직별 방사능의 분포는 처리 30분 이내에는 심장에 가장 높게 분포하였으며, 2시간에는 간과 신장에서 그 분포율이 현저하게 증가하였으며, 시간이 경과함에 따라 그 분포율은 점점 감소하였다. 3. $^{14}C-{\alpha}-endosulfan$은 생쥐 체내에서 ${\beta}-endosulfan({\beta}-E)$, endosulfan ether(EE), endosulfan sulfate(ES), 그리고 endosulfan alcohol(EA)로 대사되었으며 주요 대사산물은 간에서 EA(13.25%) 그리고 신장에서는 EHE(19.37%)였다. 4. 소변중에 배설된 대사산물로는 EA(43.21%), ES(4.78%), ${\beta}-E$(7.21%), EE(3.72%), EHE(18.04%) 등이었다.

• Asian-Australasian Journal of Animal Sciences
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• 제23권4호
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• pp.465-474
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• 2010

The effects of four types of tropical protein-rich trees on nutrient digestibility, nitrogen (N) balance, urinary purine derivative (PD) excretion and blood metabolites in four Thai Brahman cattle (290${\pm}$2.5 kg) were studied. The animals were fed twice daily, with each feeding consisting of 1 kg (fresh weight) rice straw and one of the four dietary supplements: i) 1.98 kg oven-dried rain tree pods (RTP) and 20 g premix (RTPP), ii) 980 g RTP and 1 kg sun-dried leucaena leaves and 20 g premix (LLRT), iii) 980 g RTP and 1 kg sun-dried cassia leaves and 20 g premix (CLRT) and iv) 980 g RTP and 1 kg sun-dried mulberry leaves and 20 g premix (MLRT). The apparent dry matter (DM) and organic matter (OM) digestibilities were higher (p<0.05) in cattle fed the CLRT supplement than in those fed the other supplements, whilst the apparent digestibility of neutral detergent fibre (NDF) was higher (p<0.05) in cattle fed the CLRT and MLRT supplements than in those fed the other supplements. The N-balance of cattle fed LLRT and CLRT supplements was higher (p<0.05) than in cattle fed RTPP and MLRT supplements, whilst the apparent digestibility of N was highest (p<0.05) in cattle fed RTPP supplement, compared to the other supplements. Allantoin and PD excretion in the urine, and the ratios of allantoin/DOMI and PD/DOMI were higher (p<0.05) in cattle fed RTPP and MLRT than for those fed LLRT and CLRT supplements. Plasma ${\beta}$-hydroxy butyrate (${\beta}$-HBA) and insulin concentrations were higher (p<0.05) in cattle fed RTPP supplement than in those fed the other supplements. The study demonstrated the value of using local multipurpose trees (MPTs) to improve Brahman cattle feeding systems in the tropics.

• 농약과학회지
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• 제18권1호
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• pp.41-47
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• 2014

생체시료를 이용하여 화훼 농작업자와 플로리스트의 유기인계와 피레스로이드 살충제 노출 평가를 하였다. 유기인계는 소변중 DMP, DEP, DMTP, DETP를 피레스로이드계 살충제는 Cis/Trans DCCA, DBCA 그리고 3-PBA를 대상으로 평가 하였다. 연구 결과 DMP는 화훼 농작업자에서 가장 높았으며, 반면 DETP는 소매자에서 유의하게 높았다. 피레스로이드계 살충제의 대사물질은 3-PBA가 화훼 농작업자에서 통계적으로 유의하게 높았다. 화훼 농작업자는 살충제에 고농도로 노출됨을 알 수 있으며, 화훼를 대량으로 취급하는 도매상들도 살충제에 많이 노출됨을 알수 있었다.

• 대한약리학회지
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• 제26권1호
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• pp.83-90
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• 1990

Cimetidine이 theophylline의 약동학적 특성과 대사과정에 미치는 효과를 검토코자 6마리의 개를 대상으로 일주일간 정맥내 cimetidine(30mg/kg/day)투여 전후에 단일 용량의 정맥투여에 따른 theophylline의 약동학적 parameter 및 뇨중 theophylline 대사물 배설의 변화를 교차 실험을 통하여 관찰하였다. 대조실험에 비해 cimetidine투여후 theophylline의 청소율은 평균 31%(P<0.05)감소하였고 혈장반감기는 29%(P<0.01)연장되었다. 그러나 steady-state의 분포용적 및 혈장 단백 결합의 변화는 관찰할 수 없었다. Theophylline의 주 대사물인 3-methylxanthine, 1-methyluric acid 및 1,3-dimethyluric acid의 24시간 뇨증 배설량은 cimetidine투여후 모두 감소 하였으나 통계적으로 유의한 변화는 아니었으며 개별대사물의 배설 분획은 변화가 없었다. 이상의 결과로 부터 cimetidine이 theophylline의 demethylation과 8-hydroxylation대사과정 모두를 비선택적으로 억제함으로써 청소율을 감소시키고 반감기를 증가시킬 것으로 추정되었다.

• Preventive Nutrition and Food Science
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• 제7권1호
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• pp.67-71
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• 2002

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenarnide), a major pungent component of hot pepper, is known to exert antioxidative properties. In this study, we investigated the protective effects of capsaicin against chemical carcinogen-induced oxidative damage in rats. Male Sprague Dawley rats weighting 230~250 g were treated with chemical carcinogens such as 2-nitropropane (2NP) or n-methyl-N'-nitro-N-nitrosoguanidine (MNNG) after (or before) the administration of capsaicin at doses of 0.5, 1,5 mg/kg. The level of lipid peroxidation in rat liver was estimated by measuring the amounts of thiobarbituric acid reactive substances. The degree of oxidative DNA damage was evacuated by measuring a DNA adduct, 8-hydroxydeoxyguanosine (8-OHdG), in urine. Antioxidative activities of capsaicin and its metabolites in vitro were determined by the measurement of DPPH (1,1-diphenyl-2-picrylhydrazyl), a radical quencher. Significant inhibition of 2-NP induced lipid peroxidation was observed in the liver of the rat when treated with capsaicin. MNNG-induced urinary excretion of 8-OHdG was decreased by capsaicin treatment. Capsaicin and its metabolites inhibited net only the formation of free radicals, but also lipid peroxidation in vitro. Our results show that capsaicin may function as a free radical scavenger against chemical carcinogen-induced oxidative cellular damage in vivo. The observed antioxidative activities of capsaicin may play an important role in the process of chemoprevention.

• Biomolecules & Therapeutics
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• 제17권2호
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• pp.188-198
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• 2009

This work was conducted to investigate the effect of bisphenol A (BPA) on estradiol (E2) 2-and 4-hydroxylase activities in the liver, kidney and lung tissues of male and female rats. After intraperitoneal administration of BPA to male and female rats for 4 days at 0, 10, and 50 mg/kg, the conversion of the substrate for hepatic and extra-hepatic enzyme activities was measured by GC/MSD. The result showed decreases of body and organ weights at 50 mg/kg BPA of male and female rats. Male hepatic E2 2-hydroxylase activity was inhibited by 68% at 10 mg/kg and by 82% at 50 mg/kg BPA. Female hepatic E2 2-hydroxylase activity was decreased by 46% at 10 mg/kg and by 56% at 50 mg/kg to the control. E2 4-hydroxylase was inhibited by 57 and 57% at 10 mg/kg and 54 and 78% at 50 mg/kg in liver of female and male, respectively. The urinary excretion rate of 2-hydroxyestradiol (2-OHE), androsterone and testosterone in urine of female rats with 50 mg/kg BPA were decreased significantly. The results showed that 50 mg/kg BPA was decreased E2 2-and 4-hydroxylase activities in liver, but not in other tissues. The urinary excretion rates of 2-OHE, androsterone and testosterone were also decreased. In liver, estrogenic enzyme activity were higher in male than female. These results suggest that BPA can disrupt estrogen metabolism by suppressing E2 2-and 4-hydroxylase activities in the liver of male and female rats.