• Nutritional Sciences
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• 제5권1호
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• pp.3-8
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• 2002

The purpose of this study was to investigate the effects of L-carnitine administration on lipid metabolism in streptozotocin-induced diabetes. Diabetes was induced by a single intraperitoneal injection of streptozotocin (50 mg/kg b.w.) and was confirmed by determination of urinary glucose secretion. Diabetic rats in the three L-carnitine treated groups were given L-carnitine, 50(D5O), 100(D100) and 200 (D200) mg/kg body weight, by subcutaneously every other day for four weeks, while animals in normal (N) and diabetic (DM) groups for control received saline by the same method. The daily weight gain was not different between normal and diabetic rats, but daily dietary intake was significantly higher in diabetic rats than in normal rat. Diabetic rats had a significantly lower carnitine concentration in both serum and liver compared to normal rats. Total carnitine concentration in serum was increased dose dependently upon carnitine administration, but statistic significance was shown only in D200 group. Diabetic rats had significantly higher serum triglyceride and cholesterol concentrations compared to normal rats. However there were no significant differences in liver L-carnitine administration to diabetic rats significantly decreased serum triglyceride but not cholesterol concentrations. In liver, triglyceride and cholesterol concentrations were not attired by L-carnitine administration. These results indicated that streptozotocin induced-diabetic rats have decreased carnitine and increased lipid concentrations compared with normal rats. Also it indicated that L-carnitine administration has an effect on the normalization of serum triglyceride concentrations in diabetic rats.

• Archives of Pharmacal Research
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• 제26권8호
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• pp.631-637
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• 2003

Chloroquine has been used for many decades in the prophylaxis and treatment of malaria. It is metabolized in humans through the N-dealkylation pathway, to desethylchloroquine (DCQ) and bisdesethylchloroquine (BDCQ), by cytochrome P450 (CYP). However, until recently, no data are available on the metabolic pathway of chloroquine. Therefore, the metabolic pathway of chloroquine was evaluated using human liver microsomes and cDNA-expressed CYPs. Chloroquine is mainly metabolized to DCQ, and its Eadie-Hofstee plots were biphasic, indicating the involvement of multiple enzymes, with apparent $K_m and V_{max}$ values of 0.21 mM and 1.02 nmol/min/mg protein 3.43 mM and 10.47 nmol/min/mg protein for high and low affinity components, respectively. Of the cDNA-expressing CYPs examined, CYP1A2, 2C8, 2C19, 2D6 and 3A4/5 exhibited significant DCQ formation. A study using chemical inhibitors showed only quercetin (a CYP2C8 inhibitor) and ketoconazole (a CYP3A4/5 inhibitor) inhibited the DCQ formation. In addition, the DCQ formation significantly correlated with the CYP3A4/5-catalyzed midazolam 1-hydroxylation (r=0.868) and CYP2C8-catalyzed paclitaxel 6$\alpha$-hydroxylation (r = 0.900). In conclusion, the results of the present study demonstrated that CYP2C8 and CYP3A4/5 are the major enzymes responsible for the chloroquine N-deethylation to DCQ in human liver microsomes.

• 한국융합학회논문지
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• 제12권9호
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• pp.179-183
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• 2021

본 연구는 다양한 항암성분을 함유한 Celeriac Extract의 암세포 증식에 미치는 영향을 살펴보기 위하여 실시되었다. 실험에 사용한 암 세포주는 5종으로 폐암세포 A549, 전립샘암세포 DU-145, 자궁암세포 HeLa, 유방암세포 MCF-7, 간암세포 SNU-182 로 모두 인체 유래 암 세포주를 사용하였으며 Celeriac Extract 10ug/mL, 100ug/mL, 1000ug/mL 에 대한 암세포의 증식 억제는 CCK-8 방법을 이용하여 측정하였다. 암세포 증식 억제를 살펴본 결과 Celeriac Extract 1000ug/mL는 폐암세포 A549, 전립샘암세포 DU-145, 자궁암세포 HeLa, 간암세포 SNU-182에서 유의한 증식 억제를 보였으며 농도 의존성을 나타냈다. 그러나 유방암세포 MCF-7 에서는 농도 의존적인 감소만 보였다. 결론적으로, 다양한 인간유래 암 세포주를 이용한 Celeriac Extract의 세포 증식 억제기전들은 암 예방효과 및 치료제 개발의 잠재력을 제공한다고 볼 수 있다.

• Nutrition Research and Practice
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• 제12권6호
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• pp.503-511
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• 2018

BACKGROUND/OBJECTIVES: Ginger, a root vegetable, is known to have antioxidant and antiobesity effects. Preparation, such as by steaming, can affect the chemical composition of prepared root vegetables or herbs and can change their functional activities. In the present study, we investigated the protective effects of steamed ginger against oxidative stress and steatosis in C57BL/6J mice fed a high-fat diet. MATERIAL/METHODS: The levels of polyphenols and flavonoids in two different extracts of steamed ginger, i.e., water extract (SGW) and ethanolic extract (SGE); as well, their antioxidant activities were examined. Forty male C57BL/6J mice were fed a normal diet (ND, n = 10), high-fat diet (HFD, 60% fat, w/w, n = 10), HFD supplemented with 200 mg/kg of SGE or garcinia (GAR) by weight (SGED or GARD, respectively, n = 10) for 12 weeks. Serum chemistry was examined, and the expressions of genes involved in lipid metabolism were determined in the liver. Histological analysis was performed to identify lipid accumulations in epididymal fat pads and liver. RESULTS: The SGE had higher contents of polyphenols and flavonoids and higher DPPH and $ABTS^+$ free radical scavenging activities compared to those of SGW. Treatment with SGE or GAR significantly decreased the HFD-induced weight gain. Both SGE and GAR significantly reduced the high serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein levels induced by HFD. Compared to ND, HFD significantly increased hepatic TC and TG levels. SGE or GAR supplementation significantly decreased the increase of hepatic lipids by HFD. Interestingly, SGE had a more significant effect in reducing hepatic TC and TG levels than GAR. Furthermore, hepatic genes involved in lipogenesis and lipolysis were altered in both the SGED and GARD groups. CONCLUSIONS: The present study indicates that steamed ginger supplementation can decrease plasma TC and TG and can inhibit liver steatosis by regulating the expressions of hepatic genes.

• 한국환경성돌연변이발암원학회지
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• 제23권3호
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• pp.99-102
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• 2003

IARC classified areca quid as a human carcinogen. Areca quid chewed in Taiwan includes Piper betle inflorescence, which contains high concentrations of safrole (15 mg/fresh weight). Safrole is a documented rodent hepatocarcinogen, and chewing areca quid may contribute to human exposure (420 $\mu$m in saliva). The carcinogenicity of safrole is mediated through 1'-hydroxysafrole formation, followed by sulfonation to an unstable sulfate that reacts to form DNA adducts. Using human liver microsomes and Escherichia coli membranes expressing bicistronic human P450s, CYP2E1 and CYP2C9 were identified as the main P450s involved in the activation of safrole. We have demonstrated the presence of stable safrole-dGMP adducts in human oral tissues following areca quid chewing using $^{32}$ P-postlabeling and HPLC mass spectrometry methods. By studying 88 subjects with a known AQ chewing history and 161 matched controls, we have demonstrated that the presence of safrole-DNA adducts in peripheral blood cells was correlated to AQ chewing, and CYP2E1 seemed to play an important role in the modulation of safrole-DNA adduct formation. We have also shown that safrole can form stable safrole-DNA adducts as well as oxidative damages in rodent liver. However, the stable safrole-DNA adducts may represent a more significant initial lesion as compared to the rapidly repaired safrole-induced 8-hydroxy-2'-deoxyguanosine. This oxidative DNA damage is mediated through the formation of hydoryxchavicol, the major safrole metabolite in human urine. Hydroxychavicol may have gone through two-electron oxidation to the o-quinone; then via one-electron reduction to semiquinone radicals to generate oxidative DNA damage. However, these reactive metabolites can be efficiently conjugated by GSH. These data suggest that safrole may contribute to the initiation of oral carcinogenesis through safrole-DNA adduct and not oxidative DNA damage. In addition, CYP2E1 may modulate this adduct formation.

• Parasites, Hosts and Diseases
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• 제33권4호
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• pp.395-398
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• 1995

강원도 홍천에 거주하는 56세 구부가 갑자기 우상부 복통 고열 오한을 주소로 내원하였고 복 꾸 초음파검사와 콤퓨터단층촬영 결과 2-3 cm 직경의 불규칙한 꼴의 동공이 간 우엽에서 여러개 관찰되었다. 간생검상 샤르코-라이덴 결정을 포함한 심한 중심성 괴사 주위로 조직구. 호산구등 염 증세포가 침윤되어 주위 조직과 명확히 구분되었다. 효소면역측정법을 이총한 간질 특이 항체 혈청 걸사에서 양성이었다. 간 병변은 프라지관텔 투약 6개웍 후에 모두 사라졌으나. 특이 항체가와 호산구 증가는 투약 6개월 16개월 후에도 정상화 되지 않았다. 방사선학적 소견 조직병리학 소견 및 혈청학 검사 결과를 종합할 때. 초기 침습성 간질증으로 진단하였으며 프라지콴텔에 의하여 치료되지 않은 예이었다.

• 대한전자공학회논문지
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• 제12권1호
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• pp.1-6
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• 1975

잡음을 포함한 저화질의용화상의 배경과 목적대상정을 분할하는 환경영역은 중요한 정보로 의학상 진단에 큰 의의를 갖고 있다. 이 논문의 목적은 화상의 농도변화를 정총화하여 통계적수법에 의해 환경영역을 결정하는 threshold를 구하는 방법을 제시하고 이를 비 scintigram에 적용하여 실험을 행했다. 전화상을 64개의 소영역으로 나누고 경계영역이 존재하는 부분온 선택하며 이 부분에 maximum likelihood법을 적용하여 threshold를 결정한뒤 내삽법에 의해 전화소에 대한 threshold를 구하고 수곽을 포함한 2식화면을 구했다. 이의 결과는 인간의 인식과 거의 같은 결과로 동적해석방법의 유효성이 증명되었다. The boundary has been one of the most important information in radiographic images and the degrees of difficulty involved varies greatly with the quality of the picture. These Buantifications are the means to diagnoses. The purpose of this paper is to quantify intensity variation and the threshold decision which is based on statistical principles and is developed to detect limits in liver scintigrams the entire picture is devide4 into 64 small regions. The kurtosis and variances for each smal region are used as indications to select the histograms the thresholds are computed according to the method o(maximum likelihood which minimizes the probability o( misclassification. Therefore Ive have demonstrated the applicability of the boundary detection and proved good agreement with human recognition, and we can use it for the diagnosis data of liver disease.

• 보험의학회지
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• 제4권1호
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• pp.24-37
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• 1987

During the period from september, 1985 to september, 1986, 1,005 cases(475cases in male, 529 cases in female) of employees and family member were observed for the general physical examination(Human-dock) in Medical Department of Daehan Life Insurance Co. Ltd. The results were as follows. 1) The occurrence of obesity cases were observed as 130 cases(12.9%), and among the 130 cases, 34 cases(26.2%) were male and 96 cases(73.8%) were female. 2) Diabetes mellitus patients were detected as 93 cases(9.3%), and 53 cases(57.1%) were male and 40 cases(43.0%) were female. The most frequent age groups were demonstrated in age of 5th and 6th decades. 3) Hypertension patients were 85 cases(8.5%), and among the 85 cases, 42 cases (49.4%) were male and 43 cases(50.6%) were female. The most frequent age groups were 5th and 6th decades, and complication of hypertensive retinopathy revealed 54 cases(63.5%). 4) Hyperlipidemia cases were observed as 71(7.1%), and 42 cases(59.2%) were male and 29 cases(40.8%) were female. The most frequent age groups were 5th and 6th decades. 5) 69 cases(6.9%) of positive reaction of HBs Ag and 46 cases(4.6%) of abnormal erectrocardiography were detected in the total examination cases. 6) Abnormalities of liver function were observed as 58 cases(5.8%), and 46 cases(79.3%) were male and 12 cases(20.7%) were female. In ultrasonographic study, 25 cases of fatty liver were obtained in the abnormality cases of liver function. 7) Cholelithiasis and gastroduodenal ulcer patients were detected as 2 cases(2.0%) respectively. 8) In the total examination cases, pulmonary tuberculosis, positive reaction of syphilis and renal cysts(ultrasonography) were obtained as 9 cases(0.9%), 7 cases(0.7%) and 4 cases(0.4%) respectively. 9) In the total examination cases, gastric cancer and liver cancer patients were detected as 2 cases(0.2%) respectively.

• Molecular & Cellular Toxicology
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• 제5권4호
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• pp.310-316
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• 2009

Some environmental chemicals have been shown to cause liver-toxicity as the result of bioaccumulation. Particularly, fungicides have been shown to cause varying degrees of hepatictoxicity and to disrupt steroid hormone homeostasis in in vivo models. The principal objective of this study was to evaluate the liver-toxic responses of environmental chemicals-in this case selected fungicides and parasiticides-in order to determine whether or not this agent differentially affected its toxicogenomic activities in hepatic tumor cell lines. To determine the gene expression profiles of 3 fungicides (triadimefon, myclobutanil, vinclozolin) and 1 parasiticide (dibutyl phthalate), we utilized a modified HazChem human array V2. Additionally, in order to observe the differential alterations in its time-dependent activities, we conducted two time (3 hr, 48 hr) exposures to the respective IC20 values of four chemicals. As a result, we analyzed the expression profiles of a total of 1638 genes, and we identified 70 positive significant genes and 144 negative significant genes using four fungicidic and parasiticidic chemicals, using SAM (Significant Analysis of Microarray) methods (q-value<0.5%). These genes were analyzed and identified as being related to apoptosis, stress responses, germ cell development, cofactor metabolism, and lipid metabolism in GO functions and pathways. Additionally, we found 120 genes among those time-dependently differentially expressed genes, using 1-way ANOVA (P-value<0.05). These genes were related to protein metabolism, stress responses, and positive regulation of apoptosis. These data support the conclusion that the four tested chemicals have common toxicogenomic effects and evidence respectively differential expression profiles according to exposure time.

• Toxicological Research
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• 제18권4호
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• pp.331-339
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• 2002

Phenoxy compounds, 2,4-Dichlorophenol acetoxy acid (2,4-D) and 2,4-dichlorophenol (DCP), are widely used as a hormonal herbicide and intermediate for pesticide manufacturing, respectively. In order to assess the potential of these compounds as endocrine disruptors, we studied the androgenicity of them wing in vivo and in vitro androgenicity assay system. Administration of 2,4-D (50 mg/kg/day, p.o.) or DCP (100 mg/kg/day, p.o.) to rats caused an increase in the tissue weight of ventral prostate, Cowpers gland and glands penis. These increase of androgen-dependent tissues were additively potentiated when rats were simultaneously treated with low dose of testosterone (1 g/kg, s.c.). 2,4-D increased about 350% of the luciferase activity in the PC cells transiently cotransfected phAR and pMMTV-Luc at concentration of $10^{-9}$ M. In 2,4-D or DCP-treated castrated rats, testosterone 6$\beta$-hydroxylase activity was not significantly modulated even when rats were co-treated with testosterone. In vitro incubation of 2,4-D and DCP with microsomes at 50 $\mu$M inhibited testosterone 6$\beta$-hydroxylase activity about 27% and 66% in rat liver microsomes, about 44% and 54% in human liver microsomes and about 50% and 45% in recombinant CYP3A4 system, respectively. The amounts of total testosterone metabolites were reduced about 33% and 75% in rat liver microsomes, 69% and 73% in human liver microsomes and 54% and 64% in recombinant CYP3A4 by 2,4-D or DCP, respectively. Therefore, the additive androgenic effect of 2,4-D or DCP by the co-administration of the low dose of testosterone may be due to the increased plasma level of testosterone by inhibiting the cytochrome P450-mediated metabolism of testosterone. These results collectively suggested that 2,4-D and DCP may act as androgenic endocrine disrupter by binding to the androgen receptor as well as by inhibiting the metabolism of testosterone.