• 한국식품영양과학회지
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• 제40권8호
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• pp.1099-1106
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• 2011

본 연구는 다량으로 폐기되는 오이를 이용하기 위하여 개발한 오이 발효원액을 주원료로 제조한 숙취해소 음료의 간보호 효능을 검증하기 위하여 만성적으로 에탄올을 섭취시킨 흰쥐에서 에탄올 대사, 항산화 방어계, 간독성 관련지표 및 지질함량 변화를 살펴보았다. 실험동물은 4주령의 수컷 SD계 흰쥐 24마리를 1주간 고형식이로 적응시킨 후 난괴법에 의하여 에탄올대조군(Control) 및 에탄올 섭취 흰쥐에게 헛개열매 추출물을 주원료로 하여 개발한 숙취해소 물질인 SKM 급여군(SKM) 또는 SKM을 함유한 오이 발효음료 급여군(CF+SKM)으로 나누었다. SKM과 CF+SKM은 사람의 하루 섭취량을 기준으로 체중 kg당 7 mL씩 매일 일정시각에 경구투여 하였다. SKM과 CF+SKM은 체중과 식이섭취에는 영향을 미치지 않았으며, CF+SKM군의 신장무게가 대조군보다 낮았다. 혈장 중 에탄올 함량은 대조군에 비하여 CF+SKM군에서 유의적으로(p<0.05) 낮았으며, SKM군은 낮은 경향을 보였다. 혈장 중의 아세트알데히드 함량은 대조군에 비하여 SKM과 CF+SKM군 모두 각각 40.6%와 48.4% 유의적인(p<0.05) 개선 효과를 보였다. 간조직 중의 ADH 활성은 실험군간 유의적인 변화가 없었으나 CYP2E1 활성은 SKM과 CF+SKM 모두 대조군에 비하여 유의적으로 (p<0.05) 낮았다. 간조직의 CYP2E1 활성은 혈장 중의 아세트알데히드 함량과 양의 상관관계(r=0.566, p<0.01)였다. 간조직의 ALDH 활성은 SKM과 CF+SKM 모두 대조군에 비하여 유의적으로(p<0.05) 높았으며 혈장의 아세트알데히드 농도와 유의적 음의 상관관계(r=-0.564, p<0.01)를 보였다. SKM군과 CF+SKM군의 간조직내 SOD와 CAT 활성과 GSH 함량이 대조군에 비하여 유의적으로 높았다. 반면, SKM과 CF+SKM은 간조직 중의 지질과산화물 생성을 대조군에 비하여 각각 유의적으로 낮추었다. SKM과 CF+SKM 급여 시 에탄올대조군에 비하여 각각 AST 활성은 29%와 44% 낮았으며, ALT 활성은 42%와 34% 낮았다. 혈장의 총 콜레스테롤과 간조직의 콜레스테롤 함량은 대조군에 비하여 SKM과 CF+SKM군에서 유의적으로(p<0.05) 낮았으며 특히, CF+SKM의 간조직내 중성지질 함량은 대조군에 비하여 유의적으로(p<0.05) 낮았다. SKM군과 CF+SKM군의 간조직 중 지방축적이 대조군에 비하여 감소되었다. 이와 같이 SKM과 CF+SKM은 간조직의 CYP2E1 활성을 억제하고 ALDH 활성과 항산화 방어계를 향상시킴으로써 에탄올로 인한 간독성을 보호할 수 있을 것으로 사료된다.

• 생명과학회지
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• 제28권7호
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• pp.835-840
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• 2018

본 연구는 시토크롬 P450 단백질을 암호화하는 애기장대 유래의 AtCYP78A7을 과발현하는 형질전환 식물체로부터 AtCYP78A7 단백질을 특이적으로 인식하는 단일큰론 항체의 제조와 그 항체를 AtCYP78A7 단백질과 접촉시켜 항원-항체 복합체 형성을 검출함으로써 AtCYP78A7 단백질을 효소면역학적(ELISA) 방법으로 검출하는 진단 키트를 개발하기 위하여 수행하였다. 재조합한 GST-AtCYP78A7 단백질을 항원으로 사용하여 단일클론 항체를 분비하는 융합세포주를 제조한 후 비오틴화 및 페어링 테스트를 통해 포획항체와 검출항체를 선정하였으며, GST-AtCYP78A7 정제 단백질을 기준으로 일품벼, 화영벼, AtCYP78A7 과발현 벼(10B-5, 18A-4)의 용해물을 검출항원으로 사용하여 product test를 진행하였다. 그 결과 AtCYP78A7 단백질에 특이적으로 결합하는 4개의 단클론 항체(mAb 6A7, mAb 4C2, mAb 11H6, mAb 7E8)를 생산하였고, 포획항체 mAb 4C2와 검출항체 mAb 7E8-biotin의 조합으로 ELISA 키트를 개발하였다. 개발된 ELISA 키트를 이용한 벼 시료의 분석 결과 AtCYP78A7 과발현 벼는 전체 단백질 대비 AtCYP78A7 단백질의 비율이 0.1% 이상인 양성으로, 일품벼와 화영벼는 0.1% 미만인 음성으로 나타나 키트를 이용한 AtCYP78A7 단백질의 검출이 가능하였으며, 따라서 본 키트는 향후 AtCYP78A7를 과발현하는 형질전환 작물을 대상으로 하는 환경 모니터링 또는 인체 위해성 평가에 유용하게 활용될 수 있을 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권11호
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• pp.4689-4695
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• 2014

Background: A great number of studies have shown that cytochrome P450 1A1 (CYP1A1) genetic polymorphisms, CYP1A1 Msp I and CYP1A1 Ile/Val, might be risk factors for digestive tract cancers, including esophageal cancer (EC), gastric cancer (GC), hepatic carcinoma (HC), as well as colorectal cancer (CC), but the results are controversial. In this study, a meta-analysis of this literature aimed to clarify associations of CYP1A1 genetic polymorphisms with digestive tract cancers susceptibility in Chinese populations. Materials and Methods: Eligible case-control studies published until December 2013 were retrieved by systematic literature searches from PubMed, Embase, CBM, CNKI and other Chinese databases by two investigators independently. The associated literature was acquired through deliberate search and selection based on established inclusion criteria. Fixed-effects or random-effects models were used to estimate odds ratios (ORs and 95%CIs). The meta-analysis was conducted using Review Manager 5.2 and Stata 12.0 softwares with stability evaluated by both stratified and sensitivity analyses. Moreover, sensitivity analysis and publication bias diagnostics confirmed the reliability and stability. Results: Eighteen case-control studies with 1,747 cases and 2,923 controls were selected for CYP1A1 MspI polymorphisms, and twenty case-control studies with 3, 790 cases and 4, 907 controls for the CYP1A1 Ile/Val polymorphisms. Correlation associations between CYP1A1 Ile/Val polymorphisms and digestive tract cancers susceptibility were observed in four genetic models in the meta-analysis (GG vs AA:OR= 2.03, 95%CI =1.52- 2.72; AG vs AA: OR=1.26, 95%CI =1.07-1.48; [GG+AG vs AA] :OR =1.42, 95%CI=1.20-1.68, [GG vs AA+AG]:OR=1.80, 95%CI =1.40-2.31). There was no association between CYP1A1 Msp I polymorphisms and digestive tract cancers risk. Subgroup analysis for tumor type showed a significant association of CYP1A1 Ile/Val genetic polymorphisms with EC in China. However, available data collected by the study failed to reveal remarkable associations of GC or HC with CYP1A1 Ile/Val genetic polymorphisms and EC, GC or CC with CYP1A1 MspI genetic polymorphisms. Conclusions: Our results indicated that CYP1A1 Ile/Val genetic polymorphisms, but not CYP1A1 Msp I polymorphisms, are associated with an increased digestive tract cancers risk in Chinese populations. Additional well-designed studies, with larger sample size, focusing on different ethnicities and cancer types are now warranted to validate this finding.

• 한국임상약학회지
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• 제30권1호
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• pp.31-35
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• 2020

Objective: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are frequently prescribed medications worldwide for the treatment of hypercholesterolemia. Statins are considered to be well tolerated; however, they have a potential for myotoxicity. Concomitant drugs that inhibit cytochrome P450 3A4 can increase the concentration of statins and thus the risk of developing myotoxicity. The purpose of this study was to evaluate risk factors associated with potential drug-drug interactions in patients receiving statins. Methods: The subjects of this study were patients aged more than 18 years who received at least one prescription of statins in a general hospital located in Chuncheon-si, Korea, between January 1, 2018, and March 31, 2018. Data regarding statin use and baseline characteristics was collected from the computerized hospital database. Logistic regression analysis was used to identify risk factors associated with potential drug-drug interactions. Results: A total of 1061 patients were finally included in the study. The incidence of potential drug-drug interactions was 45% in all subjects. According to the results of the multivariate logistic regression analysis, myocardial infarction as the indication of statin, arrhythmia or heart failure as a comorbidity, and aspartate aminotransferase levels higher than 40 IU/L were significant risk factors for potential drug-drug interactions in study subjects. Diltiazem was the most commonly co-prescribed drug that caused potential drug-drug interactions with statins. Conclusion: There was a considerable rate of potential drug-drug interactions in patients receiving statins. Health care professionals should attempt to reduce potential drug-drug interactions during statin administration.

• Environmental Analysis Health and Toxicology
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• 제31권
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• pp.10.1-10.8
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• 2016

Objectives Aromatase inhibitors that block estrogen synthesis are a proven first-line hormonal therapy for postmenopausal breast cancer. Although it is known that standardized extract of Ginkgo biloba (EGb761) induces anti-carcinogenic effects like the aromatase inhibitors, the effects of EGb761 on steroidogenesis have not been studied yet. Therefore, the effects of EGb761 on steroidogenesis and aromatase activity was studied using a H295R cell model, which was a good in vitro model to predict effects on human adrenal steroidogenesis. Methods Cortisol, aldosterone, testosterone, and $17{\beta}$-estradiol were evaluated in the H295R cells by competitive enzyme-linked immunospecific assay after exposure to EGb761. Real-time polymerase chain reaction were performed to evaluate effects on critical genes in steroid hormone production, specifically cytochrome P450 (CYP11/ 17/19/21) and the hydroxysteroid dehydrogenases ($3{\beta}$-HSD2 and $17{\beta}$-HSD1/4). Finally, aromatase activities were measured with a tritiated water-release assay and by western blotting analysis. Results H295R cells exposed to EGb761 (10 and $100{\mu}g/mL$) showed a significant decrease in $17{\beta}$-estradiol and testosterone, but no change in aldosterone or cortisol. Genes (CYP19 and $17{\beta}$-HSD1) related to the estrogen steroidogenesis were significantly decreased by EGb761. EGb761 treatment of H295R cells resulted in a significant decrease of aromatase activity as measured by the direct and indirect assays. The coding sequence/Exon PII of CYP19 gene transcript and protein level of CYP19 were significantly decreased by EGb761. Conclusions These results suggest that EGb761 could regulate steroidogenesis-related genes such as CYP19 and $17{\beta}$-HSD1, and lead to a decrease in $17{\beta}$-estradiol and testosterone. The present study provides good information on potential therapeutic effects of EGb761 on estrogen dependent breast cancer.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2001년도 추계학술발표대회
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• pp.867-870
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• 2001

아급성 독성 시험으로부터, 미립구내의 레티노익 산을 기준으로 한 투여량이 100mg/kg 일때는 4마리의 치사 개체가 보이는 등의 심각한 독성 효과가 유발되었으며, 25 및 50mg/kg인 경우에 독성 효과가 거의 나타나지 않음을 관찰하였다. 50mg/kg의 투여량의 경우, 일부 동물에서 뼈골절 현상이 나타났지만, 이러한 독성효과는 항염증제를 같이 투여함으로써 극복될 수 있을 것으로 생각되어졌다. 따라서, 앞으로의 실험에서는 항염증제를 이용하여, 가능한 독성을 억제하연서, 보다 빠른 기간 내에 상태가 회복될 수 있도록 하는 연구를 행할 것이다.

• 한국식품위생안전성학회지
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• 제26권3호
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• pp.235-241
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• 2011

아직 분명히 규명되지 않은 부분이 많지만, 신선초가 다양한 측면에서 건강증진 효과가 있다고 믿어져 왔고 따라서 일반인들이 지금까지 사용해 오고 있다. 이 연구에서는 신선초의 메타놀 추출물을 투여한 후, 전형적인 간독성 유발물질인 갈락토사민과 사염화탄소를 투여한 랫드에서 일반적 간독성지표와 지질대사능 지표를 측정함으로써 간장 보호작용이 있는지 시험하였다. 신선초를 독성유발전 7일간 매일 1회씩 200 및 500mg/kg의 용량으로 경구투여 하고, 간독성물질을 복강내로 투여 한 후 독성유발 24시간에 혈장과 간장조직에 대한 분석을 수행하였다. 시험한 두 용량(200 및 500 mg/kg)은 갈락토사민에 의해 유발된 지질과 산화물 증가, 혈장 AST 및 ALT 활성의 증가를 감소시켰다. 또한 신선초 500mg/kg은 갈락토사민이 유발한 혈장 중성지질, 총 콜레스테롤 및 저밀도지단백 콜레스테롤의 농도 증가현상을 감소시켰다. 갈락토사민에 의해 유발된 독성에 대한 효과와는 달리, 사염화탄소로 유발된 AST, ALT 및 과산화지질의 증가현상이 신선초 전투여에 의해 더욱 증가하였다. 이 결과는 갈락토사민에 의한 독성을 신선초 전투여가 감소시킬 수 있지만, 반대로 사염화탄소 유발 독성은 더 악화시킴을 의미한다. 신선초의 사염화탄소 유발 간독성 증강효과에 대한 기전을 이해하기 위해 신선초를 투여한 랫드의 간장내 aninline hydroxyiase의 활성을 측정하였다. 그 결과 사염화탄소가 간독성을 발휘하는 데에 필요한 조건인 대사체로의 변환을 매개하는 이 효소의 간장내 활성이 증가함을 관찰하였다. 종합적으로 신선초가 간장보호효과를 발휘하지만 간독성이 어떤 독소에 의해 유발되었느냐에 따라 향상 보호효과가 있지는 않음을 의미한다.

• 동의생리병리학회지
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• 제16권2호
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• pp.389-396
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• 2002

In the present work, we examined the mechanism of vasorelaxant effect of scopoletin, an active constituent of Artemisia capillaris on rat thoracic descending aortic rings. Scopoletin induced a concentration-dependent relaxation in rat thoracic descending aortic rings pre-contracted with phenylephrine (EC/sub 50/ = 238.94±37.4 μM), while it was less effective in rat thoracic descending aortic rings precontracted with high potassium solution (KCI 30 mM). Vasorelaxation by scopoletin was significantly inhibited after endothelial removal, but recovered at high concentration. Pretreatment of rat thoracic descending aortic rings with N/sup G/-nitro-L-arginine (100 μM), a nitric oxide synthase inhibitor, and atropine (1 μM), a muscarinic receptor antagonist, significantly inhibited scopoletin-induced relaxation of rat thoracic descending aortic rings. Neither indomethacin (3 μM), an inhibitor of cydooxygenase, nor propranolol (1 μM), a β -adrenoceptor antagonist, modified the effect of scopoletin. The combination of N/sup G/ -nitro-L-arginine (100 μ M) and miconazole (10 μ M), an inhibitor of cytochrome P 450, did not modify the effect of scopoletin, when compared with pretreatment with N/sup G/-nitro-L-arginine(100 μM) alone. Vasorelaxant effect of scopoletin was inverted by pretreatment with diltiazem (10 μM), a Ca/sup 2+/-channel blocker, at low concentration, while restored at high concentration. Apamin (K/sub ca/-channel blocker, 1 μM), 4-aminopyridine (4-AP, K/sub v/-channel blocker, 1 mM), and tetrodotoxin (TTX, Na/sup +/-channel blocker 1 μM) potentiated the vasorelaxant effect of scopoledn, but glibendamide (K/sub ATP/-channel blocker, 10 μM), tetraetylammonium(TEA, non-selective K-channel blocker, 10 mM) did not affect the relaxation of scopoletin. Free radical scavengers (TEMPO, catalase, mannitol) did not modify vascular tone. These results suggest that nitric oxide, Ca/sup 2+/ -channels play a role in endothelium-dependent relaxations to scopoletin in rat aortas, that apamin, 4-AP, TTX but not glibenclamide, TEA potentiated relaxation to scopoletin mediated by these channels, and that free radicals do not concern to the vasorelaxant effect of scopoletin.

• 한국식물생명공학회:학술대회논문집
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• 한국식물생명공학회 2002년도 추계학술대회
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• pp.69-75
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• 2002

Sterols play two major roles in plants: a bulk component in biological membranes and precursors of plant steroid hormones. Physiological effects of plant steroids, brassinosteroids (BRs), include cell elongation, cell division, stress tolerance, and senescence acceleration. Arabidopsis mutants that carry genetic defects in BR biosynthesis or its signaling display characteristic phenotypes, such as short robust inflorescences, dark-green round leaves, and sterility. Currently there are more than 100 dwarf mutants representing 7 genetic loci in Arabidopsis. Mutants of 6 loci, dwf1/dim1/cbb1, cpd/dwf3, dwf4, dwf5, det2/dwf6, dwf7 are rescued by exogenous application of BRs, whereas bri1/dwf2 shares phenotypes with the above 6 loci but are resistant to BRs. These suggest that the 6 loci are defective in BR biosynthesis, and the one locus is in BR signaling. Biochemical analyses, such as intermediate feeding tests, examining the levels of endogenous BR, and molecular cloning of the genes revealed that dwf7, dwf5, and dwf1 are defective in the three consecutive steps of sterol biosynthesis, from episterol to campesterol via 5-dehydroepisterol. Similarly, det2/dwf6, dwf4, and cpd/dwf3 were shown to be blocked in $D^4$ reduction, 22a-hydroxylation, and 23 a-hydroxylation, respectively. A signaling mutant bri1/dwf2 carries mutations in a Leucine-rich repeat receptor kinase. Interestingly, the bri1 mutant was shown to accumulate significant amount of BRs, suggesting that signaling and biosynthesis are dynamically coupled in Arabidopsis. Thus It is likely that transgenic plants over-expressing the rate-limiting step enzyme DWF4 as well as blocking its use by BRI1 could dramatically increase the biosynthetic yield of BRs. When applied industrially, BRs will boost new sector of plant biotechnology because of its potential use as a precursor of human steroid hormones, a novel lead compound for cholesterol-lowering effects, and a various application in plant protection.

• 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.