• 생명과학회지
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• 제19권10호
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• pp.1438-1443
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• 2009

이 연구는 신장섬유아 세포를 이용하여 LPS에 의해 유도된 신장섬유화 표적유전자인 plasminogen activator inhibitor (PAI-1) 발현과 Ascofuranone (AF)에 의한 신장섬유화 저해효과를 연구하였다. 이 연구를 통해 LPS가 PAI-1의 발현을 농도 및 시간 의존적으로 증가시켜 LPS가 신장섬유화 유도물질임을 확인 할 수 있었다. 또한 LPS로 유도된 PAI-1 mRNA 및 단백질 발현 레벨이 AF에 의해 저해되었으며, 신장섬유화의 또 다른 대표유전자인 fibronectin의 단백질 발현도 AF에 의해 억제되어 AF가 신장섬유화를 저해하는 사실을 확인할 수 있었다. 그리고 AF에 대한 PAI-1 프로모터 활성을 조사하기 위하여 p800-PAI-1-luc을 신장섬유아 세포에 형질전환 시킨 결과, AF가 PAI-1의 전사 활성 조절을 통해 발현을 억제한다는 것을 확인하였다. ERK-1/2의 상위에 존재하는 MEK inhibitor를 처리하여 PAI-1의 발현을 확인한 결과에서도 AF를 처리한 경우와 동일하게 PAI-1 발현이 저해되어 LPS로 유도된 PAI-1의 발현이 ERK-1/2에 의해 조절됨을 알 수 있었다. 또한 LPS로 유도된 ERK-1/2의 인산화가 AF 농도의존적으로 저해된 결과는, AF가 ERK-1/2의 활성저해를 통하여 PAI-1 발현을 조절한다는 사실을 확인 할 수 있었다. 따라서 이러한 연구결과 AF가 신장섬유화를 저해하는 유력한 후보물질로서의 가능성을 제시하였다.

• 한국환경보건학회지
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• 제16권1호
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• pp.29-43
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• 1990

The purpose of this study is to investigate the vairous change in the toxicity of cadmium by the simultaneous administration of selenium and zinc, which have been reported to change -the toxicity of cadmium through the interaction with cadmium, to rat. For the experiment, 42 rats of Sprague-Dawley strain were used. The experimental groups were divided into 6 groups: a control group, a cadmium (100ppm) alone treatment group, a cadmium (100ppm) and zinc (100ppm) combined treatment group, and three cadmium (100ppm), zinc (100ppm) and selenium (1, 4, and 8ppm) combined treatment groups. The rats were allocated seven to each group and observed for seven weeks. The results of experiment are as follows: 1. The food consumptions of each group were reduced, compared with a control group, especially, in a cadmium and zinc combined treatment group and a cadmium $\cdot$ zinc and selenium(1ppm) combined treatment group to the significant level compared with a control group (p < 0.05). The water consumptions of each group were reduced to the very significant level compared with a control group (p < 0.01). The feed efficiencies of each group were lower than a control group, and among them the highest group was cadmium $\cdot$ zinc and selenium (8ppm) combined treatment group as 90% of a control group. 2. In all groups, the weight gains were highest in the second week and the total weight gains were reduced to the very significant level compared with a control group (p < 0.01). 3. In all groups, the relative weights of liver were reduced, compared with a control group, especially, a cadmium alone treatment group was reduced to the significant level (p < 0.05). The relative weight of kidney was high to the significant level in a cadmium alone treatment group (p < 0.05) compared with a control group. In all groups, the relative weights of testis were reduced, compared with a control group, but the levels were not significant. 4. The accumulation of cadmium was highest in the kidney and the order of height was in liver, testis and blood, respectively. In all groups, the amount of cadmium accumulation was high to the very significant level compared with a control group (p < 0.01). In liver, the amount of acdmium accumulation in. a cadmium alone treatment group was high to the significant level compared with a cadmium $\cdot$ zinc and selenium (8ppm) combined treatment group (p < 0.05), and in kidney, the amount of cadmium accumulation in a cadmium alone tretment group was high to the very significant level compared with the cadmium $\cdot$ zinc and selenium (4, 8ppm) combined treatment groups (p < 0.01). However, in testis, among the treatment groups the level was not significant and in blood, a cadmium alone treatment group was low to the significant level compared with the cadmium $\cdot$ zinc and selenium (4, 8ppm) combined treatment groups (p < 0.05). 5. According to the histopathological finding on the testis, some of the seminiferous tubules of a group treated with cadmium alone showed severe necrosis and atrophy. But the testis of cadmium $\cdot$ zinc and selenium (8ppm) combined treatment group was similar to that of a control group. From the results of this study, it can be concluded that the repeated simultaneous oral administration of large doses of selenium with the cadmium produces the partial amelioration of cadmium toxicity, whereas zinc does not.

• Toxicological Research
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• 제32권1호
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• pp.73-80
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• 2016

Chronic exposure to cadmium (Cd) is known to adversely affect renal function. Our previous studies indicated that Cd induces p53-dependent apoptosis by inhibiting gene expression of the ubiquitin-conjugating enzyme (Ube) 2d family in both human and rat proximal tubular cells. In this study, the effects of Cd on protein expression of p53 and apoptotic signals in the kidney and liver of mice exposed to Cd for 12 months were examined, as well as the effects of Cd on p53 protein levels and gene expression of the Ube2d family in various cell lines. Results showed that in the kidney of mice exposed to 300 ppm Cd for 12 months, there was overaccumulation of p53 proteins in addition to the induction of apoptosis, which was triggered specifically in the proximal tubules. Interestingly, the site of apoptosis was the same as that of p53 accumulation in the proximal tubules. In the liver of mice chronically exposed to Cd, gene expression of the Ube2d family tended to be slightly decreased, together with slight apoptosis without the accumulation of p53 protein. In rat small intestine epithelial (IEC-6) cells, Cd decreased not only the p53 protein level but also gene expression of Ube2d1, Ube2d2 and Ube2d4. In human brain microvascular endothelial cells (HBMECs), Cd did not suppress gene expression of the Ube2d family, but increased the p53 protein level. In human brain astrocytes (HBASTs), Cd only increased gene expression of UBE2D3. These results suggest that Cd-induced apoptosis through p53 protein is associated with renal toxicity but not hepatic toxicity, and the modification of p53 protein by Cd may vary depending on cell type.

• 한국식품영양과학회지
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• 제15권3호
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• pp.235-242
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• 1986

chloroform으로 인한 간(肝) 및 위장조직(胃臟組織)에 미치는 영향을 알기 위해 rat에 농도별로 Chloroform을 투여(投與)하고, 또 이들에 화분립(花粉粒)을 함께 투여(投與)한 결과는 다음과 같다. 1. 간(肝) 및 위장(胃臟)의 total lipid함량(含量)이 chloroform만 투여(投與)한 실험군(實驗群)에서는 그 투여(投與)농도가 높아질수록 증가하였으며, chloroform과 화분립(花粉粒)과 함께 투여(投與)한 군(群)에서는 chloroform의 투여(投與)농도가 낮을수록 대조군(對照群)과 비슷한 함량(含量)을 나타내었다. 2. total cholesterol함량(含量)은 혈청(血淸), 간(肝) 및 위장(胃臟) 모두 chloroform만 투여(投與)한 실험군(實驗群)에서는 대조군(對照群)보다 많았으나, 화분립(花粉粒)을 함께 투여(投與)함으로 그 함량(含量)이 감소하는 경향을 보였으며, I-P군(群)의 혈청(血淸)은 대조군(對照群)보다도 더 낮은 수치를 나타내기도 했다. 3. sGOT, sGPT 및 LDH 모두 chloroform의 투여(投與)농도 증가에 비해하여 활성(活性)의 증가를 나타냈으며, 화분립(花粉粒)을 함께 투여(投與)한 군(群)에서는 대조군(對照群)과 거의 비슷한 활성(活性)으로의 저하가 보였으나, Chloroform 투여(投與)농도가 클수록 활성(活性) 저하 정도는 감소하였다. 4. LDH isozyme의 Cellulose acetate electrophoresis결과(結果), 간(肝)에서는 choroform을 투여(投與)함으로 $LDH_5$의 증가가, 화분립(花粉粒)을 함께 투여(投與)함으로 $LDH_5$의 감소가 나타났으나 유의성(有意性)은 없었으며 위장(胃臟)에서도 isozyme 상호간의 유의적(有意鈴)인 변화(變化)는 나타나지 않았다.

• 대한본초학회지
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• 제37권1호
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• pp.1-9
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• 2022

Objective : This study was designed to investigate anti-diabetic effects of fermented soy bean extract with herbal medicines (Godjang) in diabetic rat models induced by streptozotocin (STZ) injection. Method : Changes in body weight, drinking water, and food intake were observed for 4 weeks before and after induction of diabetes mellitus in rats. The anti-diabetic capacity of Godjang was analyzed by fasting blood glucose (FBG) every week. Also, after 4 weeks of administration, the oral glucose tolerance test (OGTT) was performed, and then blood levels of insulin were checked. And serum levels of total cholesterol and triglycerides were determined. Histomorphological changes of liver, kidney and pancreatic tissues were also observed in STZ-induced diabetic rats and Godjang administered rats. Result : In Godjang administered group, body weight and water intake were more lower than that of STZ-induced diabetic rats. FBG was decreased in the Godjang administered group than STZ-induced diabetic group. According to OGTT, blood glucose levels at 30 minutes and 60 minutes significantly decreased in Godjang administered group than in STZ-induced diabetic control group. Administration of Godjang extract for 4W significantly decreased levels of serum glucose, total cholesterol (TC), triglycerides (TG) in diabetic rats. In histomorphological analysis of kidney, liver, Godjang administrated groups showed the inhibition of pathological damage. Conclusion : These results suggest that Godjang extract has an anti-diabetic action through decrease in serum glucose, TC, TG levels and recovery of the morphological changes in kidney and liver in STZ-induced diabetic rats.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 1999년도 학술발표회 진행표 및 논문초록
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• pp.61-62
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• 1999

;The mechanisms inducing hypertension are actively investigated and are still challenging topics. Basically hypertension must be caused by the disorder of $Ca^{2+}$ metabolism in vascular smooth muscle, such as the increase of $Ca^{2+}$ influx, the decrease of ci+ efflux, or the change of sensitivity of contractile protein etc. The one of cause of the increase of ci+ influx may be the change of ci+ channel activity. Even though the relationships of ci+ channel activity and hypertension were studied using various hypertension models, still it is not clear how much change of $Ca^{2+}$ channel activity in diabetes mellitus (DM) induced hypertension is occurred. We induced DM hypertension in SD rat and compared the $Ca^{2+}$ channel activity with age-matched normotensive SD rat. For inducing DM hypertension, left kidney was removed with 200 gm rat and, after 1 month, 60 mg/kg of streptozotocin was injected into peritoneal space to induce diabetes mellitus. Usually after 4-6 weeks, hypertension was fully induced. For isolating vascular smooth muscle cells (VSMC), we used mesenteric arteriole (3rd - 4th branch of mesenteric artery) of which diameter is below 150 urn. VSMCs were isolated enzymatically. $Ca^{2+}$ current was measured using whole cell patch clamp technique. All experiments were performed at $37^{\circ}C$. The cell membrane area of VSMC of DM hypertensive rat is larger than that of control VSMC($36.6{\pm}3.64{\;}pF{\;}vs{\;}22.4{\pm}1.29{\;}pF, {\;}mean{\pm}S.E.$) When we compared the current amplitude, the $Ca^{2+}$ current amplitude in VSMC of DM hypertensive rat is much larger than that in VSMC of normotensive age-matched rat. After $Ca^{2+}$ current amplitude was normalized by cell membrane area, the current amplitude in DM hypertension is increased to $249.1{\pm}15.9{\;}%{\;}(mean{\pm}S.E.M)$, which means the ;absolute current amplitude is about 4 times larger in DM hypertension. When we compared the steady state activation and inactivation. there were no noticeable differences. From these results. one of cause of the DM hypertension is due to the increase of $Ca^{2+}$ current amplitude. But it need further study why the $Ca^{2+}$ current is so large in VSMC of DM hypertension and how much $Ca^{2+}$ influx through $Ca^{2+}$ channel contribute to the increase of intracellular $Ca^{2+}$ and eventually contribute to development of hypertension.ypertension.

• The Korean Journal of Physiology and Pharmacology
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• 제7권4호
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• pp.207-210
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• 2003

Lipids play many structural and metabolic roles, and dietary fat has great impact on metabolism and health. Fatty acid oxidation rate is dependent on tissue types. However there has been no report on the relationship between the rate of fatty acid oxidation and carnitine transport system in outer mitochondrial membrane of many tissues. In this study, the rate of fatty acid oxidation and carnitine palmitoyltransferase (CPT) I activity in the carnitine transport system were measured to understand the metabolic characteristics of fatty acid in various tissues. Palmitic acid oxidation rate and CPT I activity in various tissues were measured. Tissues were obtained from the white and red skeletal muscles, heart, liver, kidney and brain of rats. The highest lipid oxidation rate was demonstrated in the cardiac muscle, and the lowest oxidation rate was in brain. Red gastrocnemius muscle followed to the cardiac muscle. Lipid oxidation rates of kidney, white gastrocnemius muscle and liver were similar, ranging from 101 to 126 DPM/mg/hr. CPT I activity in the cardiac muscle was the highest, red gastrocnemius muscle followed by liver. Brain tissue showed the lowest CPT I activity as well as lipid oxidation rate, although the values were not significantly different from those of kidney and white gastrocnemius muscle. Therefore, lipid oxidation rate was highly (p＜0.001) related to CPT I activity. Lipid oxidation rate is variable, depending on tissue types, and is highly (p＜0.001) related to CPT I activity. CPT I activity may be a good marker to indicate lipid oxidation capacity in various tissues.

• The Korean Journal of Physiology and Pharmacology
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• 제1권2호
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• pp.151-159
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• 1997

In an attempt to investigate whether hemorrhage affects the gene expression of the renin-angioteusin system (RAS) components in the brain and peripheral angiotensin-generating tissues, changes in mRNA levels of the RAS components in response to hemorrhage were measured in conscious unrestrained rats. Wistar rats were bled at a rate of 3 ml/kg/min for 5 min, and then decapitated 7 h after hemorrhage. Levels of mRNA for renin, angiotensinogen and angiotensin $II-AT_1$ receptor subtypes ($AT_{1A}$ and $AT_{1B}$) were determined with the methods of northern blot and reverse transcriptase-polymerase chain reaction (RT-PCR). Hemorrhage produced a profound hypotension with tachycardia, but blood pressure and heart rate recovered close to the basal level at 7 h. Plasma and renal renin levels were significantly increased at 7 h. Hemorrhage induced rapid upregulation of gene expression of both $AT_{1A}$ and $AT_{1B}$ receptor subtypes in the brainstem and hypothalamus, downregulation of them in the adrenal gland and liver. However, renin mRNA level increased in the brainstem, decreased in the liver, but was not changed in the hypothalamus, kidney and adrenals after hemorrhage. Angiotensinogen mRNA level was not significantly changed in any of the tissue except a slight increase in the liver. The kidney and liver did not show any significant change in gene expression of the RAS components. These results suggest that gene expression of the RAS in central and peripheral tissues are, at least in part, under independent control and the local RAS in each organ plays specific physiologic role.

• Journal of Nutrition and Health
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• 제34권4호
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• pp.384-392
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• 2001

The purpose of this study was to investigate the effects of green tea catechin on the cadmium accumulation in body, cadmium excretion and detoxification functions in chronic cadmium poisoned rats. Sprague-Dawley male rats weighing 100$\pm$10g were randomly assigned to one normal group and three cadmium poisoned groups. Cadmium groups were classified to catechin free diet (Cd-0C group), 0.25% catechin diet(Cd-0.25C group) and 0.5% catechin diet(Cd-0.5C group) according to the levels of catechin supplement. Animals were maintained on 0, 0.25 and 0.5% catechin diets for 20 weeks and simultaneously administered 50ppm Cd(sup)2+ dissolved in the drinking water. Body weight, food intakes and food efficiency ratio in Cd-0C group was lower than the normal group. The accumulation of cadmium in rat liver, kidney, and blood was reduced by catechin supplementation. The excretion of cadmium in urine and feces was increased by catechin supplementation. The metallothionein(MT) contents in liver and kidney were increased in all cadmium groups compared with that of normal group. The ratios of cadmium absorption and retention ratios were significantly decreased in catechin supplementation groups. Accordingly, catechin supplementation resulted to an excretion of cadmium in urine and feces and a lowered accumulation of cadmium in liver and kidney by increasing methallothionein synthesis that led to the significant decrease in cadmium absorption and retention ratios.(Korean J Nutrition 34(4) : 384~392, 2001)

• Journal of Nutrition and Health
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• 제36권7호
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• pp.691-698
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• 2003

The purpose of this study was to investigate the effect of vitamin E on the cadmium accumulation in body, cadmium excretion and detoxification functions in chronic cadmium poisoned rats. Sprague-Dawley male rats weighing 100$\pm$10 g were randomly assigned to one normal group and three cadmium poisoned groups. Cadmium poisoned groups were classified to vitamin E free diet (Cd-0E group), vitamin E 40 mg/kg diet (Cd-400E group) and 400 mg/kg diet (Cd-400E group) according to the levels of vitamin E supplement. Animals were maintained on 0, 40 mg and 400 mg vitamin E/kg diets for 20 weeks and simultaneously administered 50 ppm Cd$^{2+}$ dissolved in the drinking water. Body weight, food intakes and food efficiency ratio were significantly decreased in all cadmium groups, compared with those of normal group. The accumulation of cadmium in rat liver, kidney and blood was reduced by sufficient vitamin E supplementation. The metallothionein (MT) content in liver and kidney were increased in all cadmium groups compared with that of normal group. The ratio of cadmium absorption and retention were significantly decreased in vitamin E supplementation groups. Accordingly, vitamin E supplementation resulted in an excretion of cadmium in urine and feces and a lowered accumulation of cadmium in liver and kidney. It can be suggested that increased MT synthesis lead to the significant decrease in cadmium absorption and retention ratios.s.