• Journal of Microbiology and Biotechnology
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• 제14권4호
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• pp.693-697
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• 2004

YH-1715R, (2R,3R)-2-(2,4-difluorophenyl)-3-(3-methoxy-1,2,4-isothiazol-3-yl-thio)-1-( 1H-1,2,4-triazol-l-yl)-2-butanol, a new triazole derivative obtained by the structural modification of fluconazole, was found to exhibit potent anti-Candida activity against a wide variety of Candida albicans (C. albicans) (MIC: 0.4-12.5 mg/l). To investigate the mode of action of YH-1715R, its effect on ergosterol biosynthesis in cell-free extracts and whole cells of C. albicans was examined. The inhibitory activity of YH-1715R was approximately ten-fold higher than that of fluconazole. To determine the primary action mechanism of YH-1715R, its inhibitory activity against lanosterol $14\alpha$-demethylase (14$\alpha$-DM), a major target for azole, was measured using gas-liquid chromatography. YH-1715R and fluconazole were found to inhibit 14a-DM with an $IC_{50}$ of 0.015 $\mu$M and 0.01$8\mu$M, respectively, plus the mode of inhibition of YH-1715R and fluconozole was noncompetitive with a $K_i$ of 0.0533$\mu$M and 0.0975$\mu$M.

• 환경위생공학
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• 제12권3호
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• pp.87-94
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• 1997

Influences of clotrimazole on the blood cholesterol and HDL-cholesterol level were studied in rats. Rats were provided food and water ad libitum and clotrimazole and methylcellulose were gavaged for 6 days. Clotrimazole was suspended in 1% methylcellulose solution as and administered at concentration 20mg/Kg, 40mg/Kg, 60mg/Kg. Body weight gain and liver weight/body weight ratio, serum cholesterol level, serum HDL-cholesterol level, serum triglyceride level, the activity of cytochrome p450 and erythromycin demethylase were determined at 6th day. Clotrimazole decreased the body weight gain a little as compared with control group and did not show any influence on liver weight/body weight ratio. Clotrimazole increased the serum HDL-cholesterol and serum triglyceride level significantly. Clotrimazole increased the microsomal cytochrome P450 significantly and increased the erythromycin demethylase (cytochrome P450 IIIA) significantly too. It might be conclued that clotrimazole showed a little influence on body weight and increased the serum lipid, especially HDL-cholesterol level. It also increased microsomal cytochrome P450 IIIA significantly. It might be concluded that clotrimazole showed a corelative influence between HDL-cholesterol and cytochrome P450 IIIA. In these results clotrimazole can be used as an anti-atherosclerotic agent by increasing the HDL-cholesterol but it is necessary that cloreimazole will show any adverse or side action on body or not.

• 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.

• Molecules and Cells
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• 제37권1호
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• pp.43-50
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• 2014

Jumonji domain-containing proteins (JMJD) catalyze the oxidative demethylation of a methylated lysine residue of histones by using $O_2$, ${\alpha}$-ketoglutarate, vitamin C, and Fe(II). Several JMJDs are induced by hypoxic stress to compensate their presumed reduction in catalytic activity under hypoxia. In this study, we showed that an H3K27me3 specific histone demethylase, JMJD3 was induced by hypoxia-inducible factor (HIF)-$1{\alpha}/{\beta}$ under hypoxia and that treatment with Clioquinol, a HIF-$1{\alpha}$ activator, increased JMJD3 expression even under normoxia. Chromatin immunoprecipitation (ChIP) analyses showed that both HIF-$1{\alpha}$ and its dimerization partner HIF-$1{\beta}$/Arnt occupied the first intron region of the mouse JMJD3 gene, whereas the HIF-$1{\alpha}/{\beta}$ heterodimer bound to the upstream region of the human JMJD3, indicating that human and mouse JMJD3 have hypoxia-responsive regulatory regions in different locations. This study shows that both mouse and human JMJD3 are induced by HIF-1.

• 미생물학회지
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• 제55권1호
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• pp.83-85
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• 2019

남극 연안 툰드라 토양에서 리그닌 분해능이 있는 Pseudomonas sp. PAMC 29040를 분리하였으며, 이후 토양 유기물의 주요 구성성분인 복합유기화합물 부식질 분해능을 확인하였다. 부식질 초기 저분자화 효소(예, dye-decolorizing peroxidase)와 부식질 유래의 다양한 저분자 분해산물들을 분해하는 효소들(예, vanillate O-demethylase)를 탐색하기 위해 PAMC 29040 게놈 염기서열을 분석하였다. 분석을 통해서 최종 확보한 효소유전자 정보는 저온환경에 서식하는 토양 세균의 부식질 분해경로 제안에 활용될 것이다.

• 미생물학회지
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• 제55권2호
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• pp.177-179
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• 2019

미국 뉴저지주 중위도 산림토양에서 부식산(천연 복합유기화합물인 부식질의 주요 구성성분) 분해능이 있는 세균 균주 Pseudomonas kribbensis CHA-19를 분리하였으며, 이후 또 다른 토양 유기물인 리그닌과 리그닌 유래의 페룰산(ferulic acid)과 바릴린산(vanillic acid)의 분해능을 확인하였다. 부식질 초기 저분자화 효소(예, dye-decolorizing peroxidase와 laccase-like multicopper oxidase)와 부식질 유래의 다양한 저분자 분해산물들을 분해하는 효소(예, vanillate O-demethylase와 biphenyl 2,3-dioxygenase)를 탐색하기 위해 CHA-19 게놈염기서열을 분석하였다. 최종 확보한 효소유전자 정보는 토양세균의 부식질 분해경로 제안에 사용되었다.

• 대한약리학회지
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• 제18권1호
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• pp.55-63
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• 1982

Lipid peroxidation is the reaction of oxidative deterioration of polyunsaturated lipids and this peroxidation involves the direct reaction of oxygen and lipid to form free radical intermediates, which can lead to autocatalysis. As results of the extensive studies on the lipid peroxidation by many authors, the relationship between lipid peroxidation and the drug metabolizing system as well as the actions of free radicals on the peroxidation was reasonably well known. For a long time, the mechanism of hepatotoxicity of $CCl_4$ was not clearly understood. However, it is now quite well established that $CCl_4$ is activated in vivo to a free radical which is a highly reactive molecule. Therefore, lipid peroxidation which induces the reduction of cytochrome P-450 and aminopyrine demethylase activity is known as decisive event of $CCl_4$ hepatotoxicity. On the other hand, it was also reported that singlet molecular oxygen produces lipid peroxidation in liver microsomes. In this study the effects of benzoyl peroxide on the lipid peroxidation and drug-metabolizing enzyme were examined. Benzoyl peroxide mixed with starch and phosphates etc. is usually used as a food additive for flour bleaching and maturing purpose because of its oxidative property. Albino rats were used for the experimental animals. Benzoyl peroxide was suspended in soybean oil and sesame oil and administered intraperitoneally or orally. TBA value and aminopyrine demethylase activity were determined in liver microsomal fraction and serum. The results were summerized as following. 1) Body weights of animals administered benzoyl peroxide suspension were decreased while that of oil administered group were increased. 2) The activity of aminopyrine demethylase was generally decreased in animals administered oil suspension of benzoyl peroxide. Furthermore, the marked reduction of the enzyme activity was observed in animals administered benzoyl peroxide intraperitoneally. 3) Generally, microsomal TBA values as well as serum TBA were significantly elevated in benzoyl peroxide group in comparison with the control group. However, the more remarkable increase of serum TBA than microsomal TBA was observed in animals administered orally for 6 days. 4) Specifically, the changing pattern of TBA value was notable in serum rather than in liver microsome by intraperitoneal administration of benzoyl peroxide.

• 한국식품영양과학회지
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• 제25권6호
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• pp.976-980
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• 1996

흰쥐를 대조군과 체중 100g 당 ethanol 0.3ml를 1일 1회 4일간 복강내로 투여한 실험군, 체중 100g당 toluene 0.3ml를 1일 1회 4일간 복강내로 투여한 실험군 및 ethanol 투여 2시간 후 toluene을 투여한 군으로 나누어 실험을 행하여 다음과 같은 결과를 얻었다. Alcohol 투여군, toluene투여군 모두 간 microsomal aniline hydroxylase(AH) 및 aminopyrine demethylase(AD) 활성도가 대조군 보다 유의한 증가를 보였다. Toluene과 ethanol의 병 행군은 toluene 투여군 보다 AH 및 AD 활성도가 다소 낮게 나타나는 경향을 보였다. 간조직 중 benzylalcohol dehydrogenase 활성도 역시 alcohol 및 toluene 투여군 모두 대조군에 비하여 높게 나타났으며 toluene과 alcoho의 병행투여군은 toluene 투여군 보다 본 효소 활성도가 다소 낮게 나타나는 경향을 보였다. 한편 간조직 중 benzaldehyde dehydrogenase 활성도는 alcohol 및 toluene 투여군 모두 대조군에 비하여 증가되는 경향을 보였으며 alcohol과 toluene의 병행투여군은 toluene 투여군 보다 유의한 감소를 보였다. 또한 간조직 중 xanthine oxidase 활성도는 alcohol과 toluene 병행 투여군이 toluene 투여군 보다 유의하게증가되었다. 이상 실험성적을 종합해 볼 때 alcohol의 전처치는 toluene 대사 효소 활성도를 억제시켜 toluene 대사에 영향을 미칠 것으로 생각된다.

• Biomolecules & Therapeutics
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• 제23권2호
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• pp.201-206
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• 2015

Scutellaria baicalensis is one of the most widely used herbal medicines in East Asia. Because baicalein and baicalin are major components of this herb, it is important to understand the effects of these compounds on drug metabolizing enzymes, such as cytochrome P450 (CYP), for evaluating herb-drug interaction. The effects of baicalin and baicalein on activities of ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), benzyloxyresorufin O-debenzylase (BROD), p-nitrophenol hydroxylase and erythromycin N-demethylase were assessed in rat liver microsomes in the present study. In addition, the pharmacokinetics of caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) in baicalin-treated rats were compared with untreated control. As results, EROD, MROD and BROD activities were inhibited by both baicalin and baicalein. However, there were no significant differences in the pharmacokinetic parameters of oral caffeine and its three metabolites between control and baicalin-treated rats. When the plasma concentration of baicalin was determined, the maximum concentration of baicalin was below the estimated $IC_{50}$ values observed in vitro. In conclusion, baicalin had no effects on the pharmacokinetics of caffeine and its metabolites in vivo, following single oral administration in rats.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.205-205
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• 1996

본 실험은 간장허혈 및 재관류시 야기되는 간장 손상에 대해 vitamin C와 E 각각의 효과와 이들의 병용효과를 알아보고자 하였다. 실험군은 흰쥐에 vitamin E(25mg/kg)를 실험전 3일간 투여한 군, vitamin C(100mg/kg)를 실험 5분전 경정맥주사한 군 및 vitamin C와 E의 병용 투여군등의 3군으로 하여 각각에 허혈을 유발시킨 후 (60분) 재관류 1시간, 5시간에 간세포 손상정도(AI.T, AST, liver wet-weight to dry-weight ratio), 지질과산화(MDA), 담즙분비변동(bile flow, bilirubin, cholate output) 및 약물대사효소계의 변동(cytochrome P$_{450}$, aminopyrine-N-demethylase, aniline p-hydroxylase activity) 등을 관찰하였다. 실험결과로는 허혈 및 재관류로 인한 ALT, AST MDA는 재관류 5시간에 최고치를 이루었으며 이는 vitamin C와 vitamin E의 각각 투여로 억제되었고, 특히 vitamin C와 E의 병용투여로 더욱 현저하게 억제되었다. 간세포 부종의 지표인 liver wet-weight to dry-weight ratio도 vitamin C와 E의 병용투어로 유의성있게 억제되었다. 담즙분비량 및 담즙산량은 vitamin C 투여와 vitamin C와 E 병용투여로 허혈 및 재관류로 감소된 양을 증가시켰고, 특히 vitamin C와 E의 병용투여는 담즙분비량에 있어 현저한 상승을 나타내었다. 허혈 및 재관류로 인한 cytochrome P$_{450}$양의 감소와 aminopyrine N-demethylase 활성의 억제는 vitamin C 투여와 vitamin C와 E의 병용투여에 의해 유의성 있게 증가하였다. 이상의 결과로 보아 vitamin C와 vitamin E는 각각 허혈 및 재관류로 인한 간장손상을 완화시켰으며 특히 vitamin C와 E의 병용투여는 상승적으로 적용하여 간세포손상을 더욱 억제시킴을 알 수 있었다.