• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Current Trends in Toxicological Sciences
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• pp.24-42
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• 2002

Antioxidant responsive element (ARE) mediates the transcriptional activation of the genes encoding phase II drug metabolizing enzymes and antioxidative stress genes. The ARE consensus sequence shows high similarity to NF-E2 binding sequence, a cisacting erythroid gene regulatory element.(omitted)

• 동의생리병리학회지
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• 제16권5호
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• pp.911-913
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• 2002

Rubi Fructus (fruit of Rubus coreanus Miq.), oriental medicine, has been used for remedy of the liver diseases and for tonic. In order to investigate the oxygen free radical, a harmful factor of aging, in liver of rats fed diets supplemented with the Rubi Fructus water extract(RX), Sprague-Dawley male rats have been fed a diet supplemented with 3% or 5% RX for a month. In rats fed 3% RX supplemented diet, hepatic cytochrome P-450 contents appeared to be increased, and catalase and superoxide dismutase activities were significantly increased compared with the control. There was no difference in glutathione peroxide and glutathione-S-transferase activities between the rats fed RX supplemented diets and the control diet. In conclusion, it is likely that rats fed a diet supplemented with RX may have the oxygen free radicals detoxication potential.

• Biomolecules & Therapeutics
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• 제2권1호
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• pp.11-15
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• 1994

The detoxifying properties of cruciferous vegetables components have been the subject of several recent investigations. Evidences from many biochemical and pharmacological studies indicated that higher consumption of cruciferous vegetables is associated with lower incidence of harmful actions such as hepatotoxicity and oxidative stress in animal and human populations. Recently, it has been reported that drug metabolizing and detoxifying enzyme activities were increased by cruciferous vegetable extract in which sinigrin is known to be a main active component, accounting for about 2 to 3 percents of total extract. The detoxifying effect of sinigrin has been well reported in several literatures. The metabolism of sinigrin in animal, however, has not been reported yet. That led us to study the metabolism of sinigrin in rat. Sinigrin is nown to be metabolized into three compounds, i.e., allyl isothiocyanate, glucose and potassium phosphate in cruciferous vegetables. Allyl isothiocyanate was formed in rat hepatic mitochondrial fraction in dose and incubation time dependent manner, that was confirmed by HPLC. Glucose formation was came up with results similar to that of allyl isothiocyanate. Three hours after i.p. administration of sinigrin to rat, allyl isothiocyanate appeared in rat liver, and five hours later it was detected in liver and blood. The above results suggested that sinigrin might be metabolized into allyl isothiocyanate, glucose and potassium phosphate in rat.

• 약학회지
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• 제48권5호
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• pp.266-271
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• 2004

Ginger (Zingiber officinale Roscoe) is widely used as a common condiment for a variety of foods and beverages. In addition to its extensive utilization as a spice, the fresh or the processed rhizome is a useful crude drug in traditional Chinese medicine. It is considered to possess stomachic, carminative, stimulant, diuretic and antiemetic properties. Chemical studies on the pungent principles of ginger have been carried out by a number of investigators, and 6-gingerol and 6-shogaol as a major pungent substance have been isolated. In this study, the constituents inhibiting a drug metabolizing enzyme CYP3A4 from ginger were investigated. CYP3A4 is responsible for drug metabolism as heme-containing monooxygenases. As a result of experiment, 10-gingerol (lC$_{50}$ 5.75$\mu$M) isolated from EtOAc extract of ginger showed remarkable inhibitory activity compared to 6-gingerol ($IC_{50}$/ 14.56 $\mu$M) and zingerone ($IC_{50}$/ 379.63 $\mu$M). This paper describes the isolation, structure elucidation, and CYP3A4 inhibitory activity of these compounds. The structure of the compounds were identified by instrumental analysis such as LC-mass spectrometer and NMR.R.

• Preventive Nutrition and Food Science
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• 제16권2호
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• pp.95-103
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• 2011

This study was performed to investigate the antioxidant mechanism of tomato wine with varying lycopene content in rats fed a high fat diet (HFD). Male Sprague-Dawley rats were randomly divided into five groups (n=10 per group) and fed an HFD (35% of total energy from fat) plus ethanol (7.2% of total energy from alcohol), tomato wine with varying lycopene content (0.425 mg%, 1.140 mg% or 2.045 mg% lycopene) or an isocaloric control diet for 6 weeks. Mice fed HFD plus ethanol significantly increased erythrocyte hydrogen peroxide and thiobarbituric acid reactive substances (TBARS) levels with increases in activities of erythrocyte antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) compared to pair-fed rats. Supplementation of tomato wine with varying lycopene content decreased ethanol-mediated increases of erythrocyte lipid peroxidation and antioxidant enzyme activities in HFD-fed rats, and tomato wine with higher lycopene appeared to be more effective. Tomato wine also dose-dependently lowered TBARS levels with decreased pro-oxidant enzyme, xanthine oxidase (XOD) activity in plasma of HFD-fed rats. In contrast to erythrocytes, the inhibitory effects of tomato wine on hepatic lipid peroxidation were linked to increased hepatic antioxidant enzymes (SOD and CAT) and alcohol metabolizing enzyme (alcohol dehydrogenase and aldehyde dehydrogenase) activities. There were no significant differences in hepatic XOD and cytochrome P450-2E1 activities among the groups. Together, our data suggest that tomato wine fortified with lycopene has the potential to protect against ethanol-induced oxidative stress via regulation of antioxidant or pro-oxidant enzymes and alcohol metabolizing enzyme activities in plasma, erythrocyte and liver.

• 한국식품영양과학회지
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• 제43권9호
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• pp.1363-1368
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• 2014

우리나라 남해안 연안에서 주로 양식되는 진주담치(국산 홍합)와 세계적으로 기능성이 잘 알려진 뉴질랜드 초록입 홍합의 열수 추출물을 제조하여 생리활성을 비교하였다. 모든 홍합 추출물들은 알코올대사와 관련한 alcohol dehydrogenase(ADH)와 acetaldehyde dehydrogenase(ALDH)의 활성을 상승시켰으며, 특히 ADH의 활성을 크게 향상시켰다. 국산 홍합의 육질 추출물은 초록입 홍합의 육질 추출물에 비하여 ADH 상승 효과는 비슷하였으며, ALDH 상승 효과는 약간 낮았다. DPPH 라디칼 소거능으로 조사한 항산화능은 국산 홍합의 육질 추출물이 초록입 홍합의 육질 추출물 보다 높았다. 항고혈압과 관련한 ACE 저해능의 경우에는 국산 홍합 육질 추출물이 초록입 홍합의 육질 추출물에 비해 10 mg/mL 농도에서는 낮았으나 20 mg/mL 이상의 농도에서는 유의차(P<0.05)를 보이지 않았다. 이상의 결과는 국내에서 양식되고 있는 홍합도 세계적으로 초록입 홍합에 못지않은 생리활성을 가지고 있음을 시사한다.

• Molecules and Cells
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• 제38권6호
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• pp.482-495
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• 2015

Sphingolipids such as ceramide, sphingosine-1-phosphate and sphingomyelin have been emerging as bioactive lipids since ceramide was reported to play a role in human leukemia HL-60 cell differentiation and death. Recently, it is well-known that ceramide acts as an inducer of cell death, that sphingomyelin works as a regulator for microdomain function of the cell membrane, and that sphingosine-1-phosphate plays a role in cell survival/proliferation. The lipids are metabolized by the specific enzymes, and each metabolite could be again returned to the original form by the reverse action of the different enzyme or after a long journey of many metabolizing/synthesizing pathways. In addition, the metabolites may serve as reciprocal biomodulators like the rheostat between ceramide and sphingosine-1-phosphate. Therefore, the change of lipid amount in the cells, the subcellular localization and the downstream signal in a specific subcellular organelle should be clarified to understand the pathobiological significance of sphingolipids when extracellular stimulation induces a diverse of cell functions such as cell death, proliferation and migration. In this review, we focus on how sphingolipids and their metabolizing enzymes cooperatively exert their function in proliferation, migration, autophagy and death of hematopoetic cells, and discuss the way developing a novel therapeutic device through the regulation of sphingolipids for effectively inhibiting cell proliferation and inducing cell death in hematological malignancies such as leukemia, malignant lymphoma and multiple myeloma.

• 생약학회지
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• 제28권4호
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• pp.280-285
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• 1997

Pectenotoxin 2 (PTX2), isolated from marine sponges, was examined for its hepatotoxic potential using male ICR mice. PTX2 $(20\;or\;100\;{\mu}g/kg/day,\;ip)$ was administered to mice repeatedly for one or two week. Histopathological examination revealed an increase in granularity in the liver from the mice treated with PTX2. PTX2 did not alter the parameters for hepatotoxicity and nephrotoxicity such as sorbitol dehydrogenase (SDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and blood urea nitrogen (BUN). Cytochrome P-450, cytochrome $b_5$, or NADPH cytochrome c reductase was net changed by repeated administration of PTX2. Hepatic microsomal activity of p-nitroanisole O-demethylase, but not aminopyrine N-demethylase, was slightly depressed by PTX2 administerd repeatedly $(100\;{\mu}g/kg/day,\;ip)$ fur 2 weeks. The toxicity of PTX2 $(200\;{\mu}g/kg/day,\;ip)$ was determined in mice pretreated with a metabolic inducer or inhibitor such as phenobarbital, 3-methyl-cholanthrene, $CoCl_2$, or SKF 525-A. Significant alterations in lethality and hepatotoxicity of PTX2 were observed in mice pretreated with a metabolic modulator. The results suggest that liver seems to be the target organ for PTX2 toxicity and also that induction of the PTX2 toxicity may be associated with hepatic drug metabolizing activity.

• 대한약리학회지
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• 제18권1호
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• pp.65-72
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• 1982

It has been known that retinoids are intrinsically of critical importance for control of premalignant epithelial cell differentiation. In the absence of retinoids, normal cellular differentiation and growth does not occur in epithelia such as those of trachea and bronchi. Furthermore, it was also reported that retinoid deficiency enhanced susceptibility to chemical carcinogenesis in the respiratory system, in the bladder, and in the colon of the experimental animal. In 1974, Bollag examined the effects of synthetic retinoids in prevention of development of cancer and demonstrated synthetic retinoids to have more favorable therapeutic index than retinoic acid for causing regression of skin papilloma in mice. Therefore, it was assumed that this anticarcinogenic effect of vitamin A derivatives could be due to modification of the metabolism of the carcinogenic polycyclic hydrocarbon, which must first be activated to exert their effect. Hill and Shih reported that vitamin A compounds and analogs had inhibitory effect on drug metabolizing enzyme from liver and lung tissue of mouse and hamster. Lucy suggested that the chemoprevention effect of vitamin A derivatives is due to reaction with molecular oxygen, and it is possible that inhibition of hydroxybenzpyrene formation is a result of this property. On the other hand, butylated hydroxytoluene which is a potent antioxidant strongly inhibited the formation of mammary tumor induced by dimethylbenranthracene. Also, it was observed that this antioxidant inhibited cancer induction in rats by N-2-fluo-renylacetamide. The purpose of this experiment was to investigate the effect of vitamin A derivatives such as retinoic acid and retinoid on drug-metabolizing enzyme and to determine whether riboflavin tetrabutylate or vitamin E could prevent of modify any changes induced by vitamin A delivatives in the rats. The results obtained were as followings. 1) Body weight was significantly reduced by retinoic acid, but not by retinoid. 2) Retinoic acid markedly increased liver weight while retincid showed no effect on liver weight. Treatment of riboflavin tetrabutylate did not affect retinoic acid-induced change in both body weight and liver weight. 3) Both retinoic acid and retinoid remarkably decreased the activity of aminopyrine demethylase. Pretreatment of riboflavin tetrabutylate, however, prevented inhibitory effect of retinoic acid on the enzyme activity. 4) No significant effect of vitamin E on aminopyrine demethylase was observed in both groups treated with retinoic acid and retinoid.

• 대한예방한의학회지
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• 제13권2호
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• pp.51-64
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• 2009

Objective : This research was aimed to investigate the anti-tumor effect, safety, mechanism and metabolizing enzyme of Agrimonia pilosa LEDEB(APL) in female C57B/L mouse. Methods : At first, to evaluate the anti-tumor activity of APL, we divided into four groups, normal, control, APL100(100mg/kg), APL150(150mg/kg). LLC obtained American Type Culture Collection was used. LLC had been inoculated to induce tumor. To measure the anti-tumor effect of APL, we calibrate tumor size and weight. To study for mechanism of anti-tumor in APL, we used western blotting and to know metabolizing enzyme in APL we used to real-time PCR. Results : APL100, APL150 inhibited tumor growth after medicine injected. APL did not only induced caspase-dependent apoptosis in LLC-bearing mouse tumor. In APL100, it were decreased 72% in CYP3A11. In APL150, it were decreased 62%, 75% in CYP3A11 and MRP1a respectively. Conclusion : These results suggests that APL has some anti-tumor effects in female C57B/L mouse tumor. APL should be careful use with other drugs related with CYP3A11 or MRP1a.