• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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• pp.109-109
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• 2001

The present study was done to investigate the relationship between Kupffer cells and alteration of cytochrome P-450 (CYP)-dependent drug metabolizing enzyme activities during polymicrobial sepsis. Male rats were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP) followed by fluid resuscitation. The gadolinium chloride (GdC1$_3$, 10 mg/kg), blocker of Kupffer cells, was pretreated intravenously at 48 h and 24 h prior to the induction of CLP. All assay parameters were determined at 24 h after CLP or sham operation. In CLP-treated rats, the mortality rate of animals increased to 50% and serum alanine (ALT) and aspartate aminotransferase (AST) levels also significantly elevated. However, this increase was not suppressed by GdC1$_3$ pretreatment. Microsomal lipid peroxidation markedly increased after CLP operation. This increase was significantly attenuated by pretreatment. Total cytochrome P-450 content and NADPH-cytochrome P-450 reductase activity were not changed after CLP operation, but GdC1$_3$pretreatment reduced total cytochrome P-450 content, The hepatic microsomal CYP 1A1, 1A2, 2Bl and 2El activities in CLP-induced rats were also not significantly different from sham-operated rats. However, GdC1$_3$pretreatment showed a moderate increase in CYP1A1 and 1A2 activities. Our findings suggest that Kupffer cells may be partly responsible for producing hepatocellular dysfunction during sepsis.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6851-6856
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• 2013

In the present report we determined the protective capacity of grapefruit juice (GJ) against molecular and cellular damage in azoxymethane (AOM) treated mice. Animals were daily administered GJ orally (0.8, 4.1, and 8.2 ${\mu}l/g$) for seven weeks, as well as intraperitoneally (ip) injected with AOM twice (weeks 2 and 3 of the assay). Control groups administered with water, with the high dose of GJ, and with AOM injected in weeks 2 and 3 were also included. The results showed a significant, dose-dependent protection of GJ on the number of colon aberrant crypts (AC) induced by AOM. The highest inhibitory effect was reached with the highest tested dose of GJ, decreasing ACF by 51% and 43% at weeks 4 and 7 of the assay. Regarding protein and lipid oxidation we also found a dose-dependent decrease caused with GJ in comparison with the increased levels produced by AOM. Therefore, our results established chemopreventive potential for GJ, and suggested effects related to its antioxidant capacity. Finally, we found that the tested agents induced neither micronuclei increase nor alteration in bone marrow cytotoxicity.

• Biomolecules & Therapeutics
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• 제26권1호
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• pp.45-56
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• 2018

Cancer is the leading cause of human deaths worldwide. Understanding the biology underlying the evolution of cancer is important for reducing the economic and social burden of cancer. In addition to genetic aberrations, recent studies demonstrate metabolic rewiring, such as aerobic glycolysis, glutamine dependency, accumulation of intermediates of glycolysis, and upregulation of lipid and amino acid synthesis, in several types of cancer to support their high demands on nutrients for building blocks and energy production. Moreover, oncogenic mutations are known to be associated with metabolic reprogramming in cancer, and these overall changes collectively influence tumor-microenvironment interactions and cancer progression. Accordingly, several agents targeting metabolic alterations in cancer have been extensively evaluated in preclinical and clinical settings. Additionally, metabolic reprogramming is considered a novel target to control cancers harboring un-targetable oncogenic alterations such as KRAS. Focusing on lung cancer, here, we highlight recent findings regarding metabolic rewiring in cancer, its association with oncogenic alterations, and therapeutic strategies to control deregulated metabolism in cancer.

• Preventive Nutrition and Food Science
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• 제4권3호
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• pp.200-202
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• 1999

The effectsof garlic vinegar supplementation on body weight, blood blucose, and plasma triglyceride and cholesterol were investigated in streptozotocin -induced diabetic rats fed high-cholesterol(1%) diet for 4 wk. The garlic vinegar was made by fermenting 20% frsh garlic juice. There was no effect of garlic vinegar on body weight, plasma glucose or triglyceride concentrations in the diabetic rats. Plasma total -cholesterol concentrations were unaffected by garlic vinegarr supplementation. However, plasma LDL-cholesterol concentrations and atherogenic index were significantly lower in the diabetic rats supplemented with garlic vinegar diet than tin the cotnrol rats. The diabetic-rats supplemented with garlic vinegar not only had increased HDL-cholesterol levels but had decreased LDL-cholesterol. This alteration in the HDL/LDL-cholesterol ratio in the diabetic rats may decrease the risk of atheroscelrosis. Therefore, the over-all effect of garlic vinegar supplement may contribute to the antiatherogenic role in streptozotocin-induced diabetic rats.

• Laboraroty Animal Research
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• 제34권4호
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• pp.140-146
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• 2018

Though bile acids have been well known as digestive juice, recent studies have demonstrated that bile acids bind to their endogenous receptors, including Farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (GPBAR1; TGR5) and serve as hormone to control various biological processes, including cholesterol/bile acid metabolism, glucose/lipid metabolism, immune responses, and energy metabolism. Deficiency of those bile acid receptors has been reported to induce diverse metabolic syndromes such as obesity, hyperlipidemia, hyperglycemia, and insulin resistance. As consistent, numerous studies have reported alteration of bile acid signaling pathways in type II diabetes patients. Interestingly, bile acids have shown to activate TGR5 in intestinal L cells and enhance secretion of glucagon-like peptide 1 (GLP-1) to potentiate insulin secretion in response to glucose. Moreover, FXR has been shown to crosstalk with TGR5 to control GLP-1 secretion. Altogether, bile acid receptors, FXR and TGR5 are potent therapeutic targets for the treatment of metabolic diseases, including type II diabetes.

• Asian-Australasian Journal of Animal Sciences
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• 제29권3호
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• pp.419-427
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• 2016

There is a high association of heat shock on the alteration of energy and lipid metabolism. The alterations associated with thermal stress are composed of gene expression changes and adaptation through biochemical responses. Previous study showed that Angelica gigas Nakai (AGN) root extract promoted adipogenic differentiation in murine 3T3-L1 preadipocytes under the normal temperature condition. However, its effect in heat shocked 3T3-L1 cells has not been established. In this study, we investigated the effect of AGN root hot water extract in the adipogenic differentiation of murine 3T3-L1 preadipocytes following heat shock and its possible mechanism of action. Thermal stress procedure was executed within the same stage of preadipocyte confluence (G0) through incubation at $42^{\circ}C$ for one hour and then allowed to recover at normal incubation temperature of $37^{\circ}C$ for another hour before AGN treatment for both cell viability assay and Oil Red O. Cell viability assay showed that AGN was able to dose dependently (0 to $400{\mu}g/mL$) increase cell proliferation under normal incubation temperature and also was able to prevent cytotoxicity due to heat shock accompanied by cell proliferation. Confluent preadipocytes were subjected into heat shock procedure, recovery and then AGN treatment prior to stimulation with the differentiation solution. Heat shocked preadipocytes exhibited reduced differentiation as supported by decreased amount of lipid accumulation in Oil Red O staining and triglyceride measurement. However, those heat shocked preadipocytes that then were given AGN extract showed a dose dependent increase in lipid accumulation as shown by both evaluation procedures. In line with these results, real-time polymerase chain reaction (RT-PCR) and Western blot analysis showed that AGN increased adipogenic differentiation by upregulating heat shock protection related genes and proteins together with the adipogenic markers. These findings imply the potential of AGN in heat shock amelioration among 3T3-L1 preadipocytes through heat shock factor and proteins augmentation and enhanced adipogenic marker expression.

• Journal of Nutrition and Health
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• 제35권1호
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• pp.5-14
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• 2002

Alteration in the syntesis or enhanced inactivation of nitric oxide(NO) can induce impairment of endothelial cell function. Insulin dependent diabetes mellitus(IDDM) is characterized by impaired endothelial function and vascular disease. NO is produced through L-arginine pathway To elucidate the hypothesis that the decreased production on NO in IDDM reflects vascular damage and the NO production can be manipulated by either dietary fat(7% of kg diet) or the oral supplementation with L-arginine(2g/kg bw), plasma markers for vascular endothelial damage and plasma lipid profiles were measured in streptozotocin(STZ)-induced diabetic rats. Diabetic or normal Sprague-Dawley rats were fed 6 different experimental diets for 4 weeks(SO : soybean oil, SOA: soybean oil + L-arginine supplementation, BT : beef tallow, BTA_ beef tallow + L-arginine supplementation, OV olive oil, OVA : olive oil + L-arginine supplementation). Plasma glucose, total cholesterel, HDL-cholesterol, LDL-cholesterol and triglyceride were measured. Endothelial markers, plasma von Willebrand factor(vWf), thromboxane B$_2$, and 6-keto PGF1$\alpha$ of aorta were measured by ELISA. Plasma NO production was evaluated through the measurement of nitrite by EIA. Feeding saturated fatty acid(SFA, BT) increased relative liver size(RLS) in diabetic rats compared to either polyunsatunted fatty acid(PUFA, SO) or monounsaturated fatty acid(MUFA, OV) The supplementation of L-arginine inhibited the liver and kidney enlargement in olive oil find diabetic rats. Plasma glucose was lower in diabetic animal find the olive oil compared to fed beef tallow and the supplementation L-arginine decreased it in diabetic rats find beef tallow significantly(p < 0.05). Plasma TXB$_2$ levels were increased due to diabetes and the value of beef tallow group showed highest value. Plasma vWf concentration of beef tallow group was higher value in normal rats and was elevated more in diabetes. In diabetic groups, the vWf concentration of olive oil group was lower than beef tallow or soybean oil group. The supplementation of L-arginine in diabetic rats decreased plasma TXB$_2$ and vWf levels significantly(p < 0.05). NO production was higher in normal olive oil fed rats and was tend to be decreased in diabetic rats and the supplementation of L-arginine recovered to normal value(p < 0.05), Olive oil supplemented with L-arginine tended to lower plasma total cholesterol and LDL-cholesterol after 4 week treatment. These results suggest that generalized vascular endothelial changes based on plasma TXB$_2$and vWf occurs in diabetic rats. and olive oil with L-arginine supplementation contributes to a better control of the hyperglycemia, endothelial changes and hypercholesterolemia accompanying diabetes as compared with beef tallow or soy bean oil in this rat model.

• Applied Microscopy
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• 제38권4호
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• pp.353-361
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• 2008

구기자와 구기엽이 난소를 적출한 흰쥐의 간에 미치는 영향을 규명하고자 체중, 혈청 콜레스테롤, 간세포의 미세구조 변화를 관찰하였다. 실험군은 가장수술군 (Sham), 난소적출군 (OVX), 난소적출 후 구기자 투여군(LCF)과 구기엽 투여군(LCL), 에스트로겐 투여군 ($E_2$)의 5개 군으로 분류하였다. 난소를 적출한 다음날부터 Sham군은 음용수로 물을 투여하였으며, LCF군과 LCL군은 음용수에 건조분말 100 mg/kg을 희석하여 매일 공급하였다. $E_2$군은 에스트로겐 0.01 mg/kg을 1일 1회 8주간 복강 주사하였다. 체중은 OVX군이 가장 높았으며, $E_2$군이 가장 낮았다. 총 cholesterol의 농도는 OVX군 ($105{\pm}4.2\;mg/dL$)이 Sham군 ($91{\pm}4.5\;mg/dL$)에 비하여 유의성 있게 증가하였으며, LCF군 ($86{\pm}3.9\;mg/dL$)과 LCL군 ($94{\pm}4.3\;mg/dL$)이 OVX군에 비해 낮게 나타났다. HDL cholesterol 함량은 OVX군 ($63.3{\pm}5.21\;mg/dL$)에 비하여 LCF군($64.9{\pm}4.04\;mg/dL$)과 LCL군($70.4{\pm}4.90\;mg/dL$)이 다소 높았으며, LDL cholesterol 농도는 OVX군 ($12.6{\pm}0.89\;mg/dL$)에 비하여 LCF군 ($8.8{\pm}0.45\;mg/dL$)과 LCL군 ($9.7{\pm}0.52\;mg/dL$)이 낮았다. 간세포의 미세구조를 전자현미경으로 관찰한 결과 OVX군에서는세포질에서 다양한 크기의 지방적들이 다수 관찰되었으나 LCF군에서는 지방적들이 거의 관찰되지 않았으며, LCL군은 세포질 전반에 걸쳐 지방적들이 관찰되었는데 크기는 OVX군에 비하여 작았다. 이상의 결과로 보아 구기자와 구기엽의 투여가 난소를 적출한 흰쥐의 혈청 콜레스테롤 함량을 낮출 뿐만 아니라 간세포의 손상과 지방적 생성을 억제하는 것으로 사료되었다.

• 한국식품영양과학회지
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• 제36권5호
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• pp.540-547
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• 2007

본 연구에서는 고지방식이 흰쥐에서 녹차 catechin의 체지방 조성 및 지방조직에 미치는 영향을 규명하고자 혈중 및 간조직의 지질조성과 지방조직의 세포 수 및 크기를 관찰하였다. 실험동물은 체중 $100{\pm}10g$내외의 Sprague-Dawley종 흰쥐를 이용하여 catechin의 공급수준에 따라 각각 10마리씩 총 8군으로 나누어 4주간 자유섭식시킨 후 지질대사를 관찰하였다. 체중증가량을 관찰한 결과 HFCM 및 HFCH군에서 HF군에 비해 체중이 유의적으로 감소됨을 관찰할 수 있었다. 단위 체중당 복부지방 및 부고환지방 무게는 NC군에 비해 HF군에서 각각 103%, 106%씩 증가되었으나, HFCM 및 HFCH군은 HF군에 비해 각각 15%, 23% 및 21%, 33%씩 감소되었다. 혈중 중성지방, 총 콜레스테롤, LDL-콜레스테롤 및 동맥경화지수는 HF군에 비해 HFCH군에서 유의적으로 감소되었으나, HDL-콜레스테롤은 증가되었다. 간조직의 총 지방 함량은 NC군에 비해 HF군에서 유의적으로 증가되었으나 HFCH군은 정상식이군 수준이었다. 중성지방 함량은 고지방식이 실험군간의 유의적인 차이는 없었다. 콜레스테롤 함량은 NC군에 비해 HF군은 29% 증가되었으나, HFCM 및 HFCH군은 HF군에 비해 유의적으로 감소되었다. 부고환지방의 세포수 및 세포크기도 HFCM 및 HFCH군이 HF군에 비해 유의적으로 감소되었다. 결론적으로 녹차 catechin은 혈청에서 총콜레스테롤, 중성지방 및 동맥경화지수를 감소시키고 부고환지방의 세포수 및 크기의 감소를 유도하여 비만을 억제시키는 효과가 규명되었다.

• The Korean Journal of Physiology and Pharmacology
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• 제4권3호
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• pp.185-195
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• 2000

Vascular diseases are significant complications of diabetes mellitus (DM), and the endothelial cells may play a pivotal role in the development of vascular disease in DM. Endothelin-1 (ET-1) released from endothelium is a potent vasoconstrictor peptide and circulating level of ET-1 is increased in a variety of disease states. The purpose of this study was to determine the changes of responsiveness to ET-1 in DM, and we experimented on the changes in the ET-1-induced contraction, levels of nitrite and lipid peroxidation, and ET-1 immunoreactivity in aorta from streptozotocin-induced DM rats. DM was induced by single injection of streptozotocin (55 mg/kg, i.p.). The immunoreactive ET-1 levels in endothelial layer of thoracic aorta were much higher in DM rats than control rats. Nitrite in tissue homogenate was decreased and plasma nitrite was increased in DM rats. Malondialdehyde (MDA) was significantly increased in DM rats and cGMP was not significantly different between control and DM rats. ET-1 produced concentration- dependent contractile responses that are significantly attenuated in DM rats compared to controls. In the presence of selective $ET_A$ receptor antagonist BQ610, the maximum contraction was decreased and the concentration ratios for BQ610 yielded $pA_2$ values of 7.3 (slope, 0.65) in control rats, whereas BQ610 had no antagonistic effect on ET-1-induced contraction in DM rats. However, pretreatment with BQ788, an $ET_B$ receptor antagonist, maximum response was decreased and the dose-response curves for ET-1 were shifted to the right in both groups and $pA_2$ values were 7.9 and 7.7 (slope, 1.05 in control and DM rats), respectively. IRL 1620 and sarafotoxin S6c, $ET_B$ agonists, induced relaxation in control rats but not in DM rats. These results indicate that endothelial cell dysfunction and enhanced immunoreactivity of ET-1 have been found in DM rat and ET-1-induced contraction was attenuated in DM rat. These attenuated responses might be at least in part caused by the alteration of $ET_A$ receptor properties (e.g. desensitization), and partly related with an alteration in intracellular mechanism for contraction to ET-1.