• 대한의생명과학회지
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• 제6권3호
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• pp.193-199
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• 2000

실험동물에 있어서 연령 차이에 따라서 xylene 독성이 어떠한 차이가 있는지를 검토하는 일환으로 5주령 및 12주령 흰쥐에 50% m-xylene을 체중 100 g 당 0.25 ml씩 1회 투여한 다음 24시간 후에 처치하여 다음과 같은 결과를 얻었다. Xylene투여로 인한 요 중 methylhippuric acid 함량은 5주령군이 12주령군에 비해 현저하게 높게 나타났다. 그리고 간조직 중 cytochrome P-450 함량은 대조군에 있어서 5주령군이 12주령군 보다 약 50% 정도 낮게 나타났으나 xylene 투여로 인한 cytochrome P-450 함량 증가율은 12주령군 보다 5주령군에서 높게 나타났다. 간 alcohol dehydrogenase 활성치도 대조군에 있어서는 5주령군이 12주령 보다 약 35% 정도 낮게 나타났으나 xylene 투여로 인한 본 효소의 활성 증가율은 5주령군에서 오히려 높게 나타났다. 그러나 간 aldehyde dehydrogenase 활성치는 대조군 및 xylene 투여군 모두 5주령과 12주령간에 유의한 차이를 나타내지 않았다. 한편 xylene 투여시 체중 당 간무게, 간조직 malondialdehyde 함량 및 혈청 ALT 활성 변동을 통하여 간손상 정도를 상호 비교 관찰하였을 때, 12주령군이 5주령 실험동물 보다 간손상이 다소 심하게 나타남을 알 수가 있었다. 이상 실험결과는 연령에 따라 xylene에 의한 간손상의 차이는 이물질의 생체내 대사율이 달리 나타나기 때문일 것으로 생각된다.

• 대한약리학회지
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• 제21권1호
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• pp.34-48
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• 1985

항균제 nitrofurantion에 의한 폐독작용의 생화학적 기전을 규명하기 위한 연구 일환으로 in vitro에서 폐장 microsome 지질의 과산화 및 반응성 산소 radical $(O^{-}_{2}{\cdot},\;H_2O_2,\;OH{\cdot},\;^1O_2)$의 생성에 대한 nitrofurantion의 영향과 양자 간의 상호 관련성을 검토하였다. Nitrofurantion은 호기성 반응 조건에서 돼지 폐장 microsome의 NADPH 의존성 지질 과산화를 용량 의존적으로 증가시킬 뿐 아니라 $O^{-}_{2}{\cdot},\;H_2O_2$ 및 두 radical의 상호 작용으로 2차적으로 형성되는 $OH{\cdot}$의 생성 또한 촉진하였으며 $^1O_2$생성은 관찰되지 않았다. 이와 같은 폐장 microsome지질 과산화 증가는 SOD 및 catalase에 의하여 억제될 뿐만 아니라 $OH{\cdot}$ 제거 물질인 mannitol, thiourea에 의하여도 현저히 억제되었으며, $^1O_2$ 제거 물질에 의하여는 영향을 받지 않았던 한편 염기성 반응 조건에서는 nitrofurantoin에 의한 지질 과산화가 관찰되지 않았다. 이상의 결과로 미루어 보아 nitrofurantoin은 폐장 microsome의 NADPH 의존적이 반응성산소 radical $(O^{-}_{2}{\cdot},\;H_2O_2$ 및 $OH{\cdot})$의 생성을 증가시키며 이들 중 특히 $OH{\cdot}$ 에 의한 microsome막 지질 과산화를 촉진하는 것으로 결론지었고, 이와 같은 in vivo 현상은 nitrofurantion의 in vitro 폐독작용의 기전을 설명하는 일부가 될 것으로 사료하였다.

• Biomolecules & Therapeutics
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• 제26권5호
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• pp.512-519
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• 2018

Phthalates widely used in the manufacture of plastics have deeply penetrated into our everyday lives. Recently, a concern over the toxicity of phthalates on thyroid, has been raised but in most of cases, the doses employed were unrealistically high. To investigate the effects of phthalates on thyroid, we investigated the effects of the repeated oral exposure to low to high doses (0.3, 3, 30 and 150 mg/kg) di-2-ethylhexylphthalate (DEHP) from weaning to maturity for 90 days in juvenile rats on the thyroid. The histological examination revealed that DEHP significantly induced hyperplasia in the thyroid from the doses of 30 mg/kg, which was confirmed with Ki67 staining. In line with this finding, increased mRNA expression of thyrotropin releasing hormone (Trh) was observed in the thyroid of female at 0.3 mg/kg and 150 mg/kg as determined by RNAseq analysis. Moreover, significantly increased expression of parathyroid hormone (Pth) in the female at 0.3 mg/kg, and thyroglobulin (Tg) and thyroid hormone responsive (Thrsp) in the male at 0.3 mg/kg were noted in the blood, of which changes were substantially attenuated at 150 m/kg, alluding the meaningful effects of low dose DEHP on the thyroid hormone regulation. Urinary excretion of mono-2-ethylhexyl-phthalate (MEHP), a major metabolite of DEHP was determined to be 4.10 and 12.26 ppb in male, 6.65 and 324 ppb in female at 0.3 and 30 mg/kg DEHP, respectively, which fell within reported human urine levels. Collectively, these results suggest a potential adverse effects of low dose phthalates on the thyroid.

• Nutrition Research and Practice
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• 제5권1호
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• pp.20-27
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• 2011

We conducted this study to examine the effects of safflower seed granular tea containing physiologically active polyphenols on antioxidative activities and bone metabolism. Forty postmenopausal women ages 49 to 64-years were recruited from Daegu and Gyeongbuk and were randomly assigned to either a safflower tea supplement (Saf-tea) group (n=27) or a placebo group (n=13). The Saf-tea group received 20 g of safflower seed granule tea per day containing a 13% ethanol extract of defatted safflower seeds, whereas the placebo group received a similar type of tea that lacked the ethanol extract. No significant changes in nutrient intake for either the placebo or Saf-tea groups were observed before or after the study period, except vitamin A intake increased after 6 months in the Saf-tea group. Dietary phytoestrogen intakes were similar in the Saf-tea group (60.3 mg) and placebo group (52.5 mg). Significant increases in plasma genistein and enterolactone were observed in the Saf-tea group. After 6 months of supplementation, serum levels of antioxidant vitamins such as a-tocopherol and ascorbic acid increased significantly, and TBARS levels decreased in the Saf-tea group compared to the placebo group. Serum osteocalcin levels were reduced (P<0.05) in the Saf-tea group after 6 months, whereas serum osteocalcin did not change in the placebo group. Urinary deoxypyridinoline/creatinine excretion was not different between the two groups at baseline, and did not change in either group after 6 months. Bone mineral density decreased significantly in the placebo group (P<0.01) but not in the supplemented group. It was concluded that polyphenols (72 mg/day), including serotonin derivatives, in the Saf-tea had both antioxidant and potential bone protecting effects in postmenopausal women without liver toxicity.

• The Korean Journal of Physiology and Pharmacology
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• 제1권5호
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• pp.597-602
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• 1997

Cytochrome P450 2E1 (CYP2E1) is involved in the toxicity and carcinogenicity of a number of solvents and xenobiotics. Like the various types of oxidation pharmacogenetics, the activity of the enzyme shows a discernible interindividual and interethnic variation. However, no pharmacogenetic information on CYP2E1 polymorphism has been available from a Korean population. The aim of this study was to explore the pharmacogenetics of CYP2E1 polymorphism in a native Koreans after an oral 400 mg dose of chlorzoxazone administered to 128 subjects. Urine samples were collected during the subsequent 8-hour period and urinary concentrations of chlorzoxazone and 6-hydroxychlorzoxazone were determined by a high performance liquid chromatography with an ultraviolet detector. The limit of detection in the samples was found to be $0.5\;{\mu}g/ml$. The mean value of the 6-hydroxychlorzoxazone excreted in 8 hr urine expressed as the percentage was 48.2 13.8%. The frequency distribution of percentage of the administered dose excreted as the 6-hydroxy metabolite was unimodally distributed in the subjects studied. However, the values showed wide (7-fold) interindividual difference, ranged from 11.6% to 79.8% of the dose of chlorzoxazone. Thus, it was considered that the pharmacogenetic characteristics of CYP2E1 in a Korean population did not represent multimodal distribution in the 6-hydroxychlorzoxazone excreted in 8-hr urine expressed as the percentage. And the activity of the CYP2E1 in a Korean population seemed to be less compared with that of the Caucasian subjects.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제11권sup1호
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• pp.72-82
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• 2008

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism that results in accumulation of copper primarily in the liver, the brain and the cornea. Mutations in the WD gene, ATP7B cause failure of copper excretion from hepatocyte into bile and a defective synthesis of ceruloplasmin. More than 370 mutations are now recognized, scattering throughout the ATP7B gene. Since WD has protean clinical presentations, awareness of WD in clinical practice is important for the early diagnosis and prevention of accumulated copper toxicity. None of the laboratory parameters alone allows a definite diagnosis of WD. There are numerous pitfalls in the diagnosis of WD. Low serum ceruloplasmin concentrations, increased 24 hour urinary copper excretion, increased hepatic copper concentrations and the presence of Kayser-Fleischer rings in the cornea are major diagnostic points. A combination of any two of these 4 laboratory findings is strong support for a diagnosis of WD. Molecular methods are now being used to aid diagnosis. Molecular genetic testing has confirmed the diagnosis in individuals in whom the diagnosis is not clearly established biochemically and clinically. Siblings should be screened for WD once an index case has been diagnosed. Discrimination of heterozygotes from asymptomatic patients is essential to avoid inappropriate lifelong therapy for heterozygotes. Genetic testing, either by haplotype analysis or by mutation analysis, is the only reliable tool for differentiating heterozygote carriers from affected asymptomatic patients. Currently, genetic testing is of limited value in the primary diagnosis. However, genetic testing will soon play an essential role in diagnosing WD as rapid advancement of biomedical technology will allow more rapid, easier and less expensive mutation detection.

• 생명과학회지
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• 제11권6호
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• pp.543-553
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• 2001

마늘 속에서 중금속 중독 시에 킬에이트 작용을 일으킬수 있다는 다량의 황 화합물이 함유되어 있으므로 납 중독 흰쥐에서 그 효과를 확인하고자 본 연구를 실시한 결과 마늘 500mg/kg 투여 흰쥐군에서 유의한 납 배설량의 증가가 있었으며, 납과 마늘의 동시에 투여했을 경우에는 납 단독 투여군 보다 신장에서의 병리조직학적 변화가 경미한 것을 관찰할수 있었다. 이러한 결과는 마늘이 납 중독에대한 킬레이트제로서의 이용 가능성이 있음을 나타내고 있다.

• 한국환경보건학회지
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• 제27권2호
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• pp.10-16
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• 2001

To evaluate an effect of circadian variation on the xylene metabolizing enzyme activities, 50% m-xylene in olive oil(0.25 $m\ell$/100g body weight) was intraperitoneally administered to the rats every other day for 6 days both in the night; 24:00 and the day; 12:00. Then animals were sacrigiced at 8hr after last injection of m-xylene. Hepatic microsomal cytochrome p450 contents were more increased both in control and xylene treated rats of night phase than those of day phase. But the activity of hepatic alcohol dehydrogenase(ADH) in control of night phase showed the similar value with that in those of day phase and xylene treated rats of day phase showed an increasing tendency of hepatic ADH activity as those of night phase showing similar activity. Furthermore, control rats of night phase than those of day phase. And by xylene treatment, enzyme activities of rats of day phase were higher tendency in rats of control but those of night phase were somewhat inhibited. Besides, xylene-treated animals of night phase showed increasing tendency of urinary methylhippuric acid concentration compared with those of day phase. On the other hand, liver weight per body weight(%), hepatic lipid peroxide content and serum xanthine oxidase activity were higher in night phase. And the activities of hepatic oxygen free radical metabolizing enzymes such as xanthine oxidase, gluthathione S-transferase, and xylene-treated rats of night phase than those of day phase. In conclusion, it can be hypothesized on the basis of the results that the accumulation rate of m-xylene intermediate metabolite, i.e. m-methylbenzaldehyde in liver tissus may be higher in night phase than in day phase and it may be responsible for higher liver toxicity in bight phase than in day phase.

• Natural Product Sciences
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• 제25권3호
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• pp.200-207
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• 2019

Albizzia julibrissin (AJ) is an herbal medicine that shows low toxicity, promotes promoting blood circulation and mitigates the inflammation and has mild side effects. Benign prostate hyperplasia (BPH) is one of the most common diseases that occurs in older males and often results in lower urinary tract symptoms. This study was conducted to evaluate the protective effect of AJ against BPH using LNCaP cells and Sprague Dawley rats treated with testosterone. Treatment with AJ extract reduced the expression of androgen receptor (AR) and prostate-specific antigen (PSA) in vitro. In vivo, rats were divided into 6 groups: 1 (Normal Control); 2 (Testosterone propionate (TP) alone); 3 (TP + finasteride); 4 (TP + AJ 10 mg/kg); 5 (TP + AJ 50 mg/kg); 6 (TP + AJ 300 mg/kg). The groups treated with AJ showed reduced the relative prostate weights and BPH-related proteins were altered, with decreased AR, PSA and proliferating cell nuclear antigen (PCNA) observed by western blot. Histopathological analysis revealed the therapeutic effect of AJ, with a decreased thickness of epithelial cells and reduced level of PCNA and $5{\alpha}$-reductase type 2. These results suggest that AJ extract could ameliorate testosterone-induced benign prostatic hyperplasia.

• 한국산업보건학회지
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• 제29권2호
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• pp.195-207
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• 2019

Objectives: This study was performed to confirm whether plasma lead can be used as a chronic biomarker for the biological monitoring of exposure to lead. Methods: Lead concentrations in 66 plasma samples from retired lead workers (G.M. 60.25 years, Median 61.00 years) and 42 plasma samples from the general population (G.M. 53.76 years, Median 56.50 years) were measured using ICP/Mass. Tibia, whole blood, hemoglobin, hematocrit, and blood zinc protophorphyrin (ZPP) concentrations and urinary ${\delta}$-aminolevulinic acid (${\delta}-ALA$) were measured for correlation analysis with plasma lead. Results: The geometric mean concentration of lead in plasma was $0.23{\mu}g/L$ for the retired lead workers and $0.10{\mu}g/L$ for the general population sample. A simple correlation analysis of biomarkers showed that plasma lead concentration among the retired lead workers was highly correlated with lead concentration in the tibia and with blood lead concentration, and the plasma lead concentration among the general population correlated with ZPP concentration in the blood. The lead concentration in the tibia and the lead concentration in the whole blood increased with length of working period. As the period in the lead workplace increased, the ratio of lead in plasma to lead concentration in whole blood decreased. Conclusion: This study confirmed the possibility of a chronic biomarker of lead concentration in blood plasma as a biomarker. In the future, comparative studies with specific indicators will lead to more fruitful results.