• Title/Summary/Keyword: cholesterol clearance

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Medium-chain fatty acid enriched-diacylglycerol (MCE-DAG) accelerated cholesterol uptake and synthesis without impact on intracellular cholesterol level in HepG2 (중쇄지방산 강화 디아실글리세롤(MCE-DAG)이 간세포 내 콜레스테롤 흡수 및 합성 기전에 미치는 영향)

  • Kim, Hyun Kyung;Choi, Jong Hun;Kim, Hun Jung;Kim, Wooki;Go, Gwang-woong
    • Korean Journal of Food Science and Technology
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    • v.51 no.3
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    • pp.272-277
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    • 2019
  • The effects of medium-chain enriched diacylglycerol (MCE-DAG) oil on hepatic cholesterol homeostasis were investigated. HepG2 hepatocytes were treated with either 0.5, 1.0, or $1.5{\mu}g/mL$ of MCE-DAG for 48 h. There was no evidence of cytotoxicity by MCE-DAG up to $1.5{\mu}g/mL$. The level of proteins for cholesterol uptake including CLATHRIN and LDL receptor increased by MCE-DAG in a dose-dependent manner (p<0.05). Furthermore, proprotein convertase subtilisin/kexin type 9, an inhibitor of LDLR, was dose-dependently diminished (p<0.05), indicating cholesterol clearance raised. MCE-DAG significantly increased 3-hydroxy-3-methylglutaryl-coenzyme A reductase and acetyl-CoA acetyltransferase2 (p<0.05), required for cholesterol synthesis, and their transcriptional regulator sterol regulatory element-binding protein2 (p<0.05). These findings suggest that given conditions of prolonged sterol fasting in the current study activated both hepatic cholesterol synthesis and clearance by MCE-DAG. However, total intracellular level of cholesterol was not altered by MCE-DAG. Taken together, MCE-DAG has the potential to prevent hypercholesterolemia by increasing hepatic cholesterol uptake without affecting intracellular cholesterol level.

Effects of the Fermented Extract Using the Leaves of Pinus densiflora on Hyperlipidemia Rats (솔잎 발효액이 백서의 고지혈증 미치는 영향)

  • Kang Dae Gill;Lee Yun Mi;Oh Hyun Cheol;Mun Yeun Ja;Lee Ho Sub;Woo Won Hong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.1
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    • pp.140-145
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    • 2003
  • The present study was designed to examine whether the fermented extract using the leaves of Pinus densiflora (FPD), has an ameliorative effect on the lipid metabolism in rats with hyperlipidemia. The body weight gain was attenuated by the adminstration of either 1-dose (2 ml/kg/day) or 2-dose (4 ml/kg/day) of FPD for 2 weeks compared with that of control or hyperlipidemia rats, while blood glucose, systolic blood pressure, sGOT, and sGPT were not altered. Serum total cholesterol, LDL-cholesterol, and athelosclerotic index were partially restored by the administration of 2-dose of FPD in rats with hyperlipidemia without changes of serum HDL-cholesterol, total lipid, and triglyceride concentration. The FPD also partially ameliorated renal functional parameters including plasma cleatinine and creatinine clearance which were attenuated in rats with hyperlipidemia. These results suggest that FPD has an ameliorative effect on the lipid metabolism and renal function in rats with hyperlipidemia.

Pharmacokinetic Analysis of the Effect of Extrahepatic Cholestasis by Common Bile Duct Ligation on Hepatic Function in Rats (총수담관 결찰에 의한 간외 담즙분비정체가 흰쥐의 간기능에 미치는 영향에 대한 약물속도론적 분석)

  • Lee, Yong-Bok;Na, Eun-Yeong;Joo, Eun-Hee;Jeong, Sug-Jin;Koh, Ik-Bae
    • Journal of Pharmaceutical Investigation
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    • v.25 no.3
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    • pp.193-204
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    • 1995
  • In order to examine the effect of extrahepatic cholestasis induced by common bile duct ligation on the hepatic function, the pharmacokinetics of antipyrine and d-propranolol were investigated in rats. In addition, in an attempt to observe the degree of direct hepatic injury, light and electron microscopic observations and conventional pathologic test using serum were performed. Five days after common bile duct ligation, antipyrine(15 mg/kg) and d-propranolol(3 mg/kg) were intravenously administrated to the rats, respectively. The total clearances of antipyrine and d-propranolol were significantly(p<0.05) decreased. Because hepatic clearance of antipyrine poorly extracted by the liver and that of d-propranolol highly extracted by the liver are respectively dependent on the hepatic intrinsic clearance and the hepatic blood flow, it may be concluded that extrahepatic cholestasis following five days after common bile duct ligation decreased the hepatic intrinsic clearance and the hepatic blood flow. SGPT, SGOT, cholesterol, bilirubin(total bilirubin, direct bilirubin) and alkaline phosphatase were significantly increased(p<0.05). The proliferation of bile ducts was prominent, and degeneration and necrosis of hepatocytes were observed by light microscope. Also, ultrastructurally, bile canaliculi were containing the amorphous materials and losing microvilli, and SER and RER in hepatocytes were dilated and vacuolated.

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The Significance of Hyperlipidemia as a Predictive Factor of Relapse in Corticosensitive Nephrotic Syndrome (스테로이드에 반응을 보인 신증후군 환아에서 재발 예측인자로서 고지혈증의 중요성)

  • Jung, Soon-Pil;Hong, Soon-Cheul;Lim, Seong-Joon;Lim, In-Seok;Choi, Eung-Sang
    • Childhood Kidney Diseases
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    • v.5 no.2
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    • pp.136-146
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    • 2001
  • Purpose : One of the most difficult problems in the care of children with nephrotic syndrome remains the occurrence of relapses, despite initial response to steroids. Constantinescu reported that rapidity of initial response to steroid therapy could predict fewer relapses in the first year. So we evaluated the changes in serum lipid abnormalities in children with corticosensitive nephrotic syndrome before steroid treatment and the correlation between serum lipid levels and renal function, days to remission. Methods . We analyzed the Medical records of children who were managed by us between October 1994 and August 2000. In 33 patients with corticosensitive nephrotic syndrome, we evaluated the correlation between serum lipid levels and renal function [Creatinine clearance(Ccr)] and proteinuria before steroid treatment, and days to remission defined as the third day when the patient's urine becomes protein free. Results : There were 21 males and 12 females. Median age at presentation was 6.4 years (range: 1.8-17.3 years). Median days to remission were 15.4 days (range 4-42 days) on Prednisolone $60mg/m^2$ daily. The increased levels of triglyceride, total cholesterol, LDL cholesterol, apolipoprotein B, total cholesterol/HDL cholesterol, Lipoprotein(a) were observed. But the level of HDL cholesterol was not increased. Serum albumin was decreased a]id proteinuria was increased before steroid treatment. But Ccr was not decreased. There were negative correlation between serum albumin and total cholesterol (r = -0.5157, P<0.005), LDL cholesterol (r = -0.5543, P<0.005), total cholesterol/HDL cholesterol (r = -0.4506, P<0.01), lipoprotein(a) (r = -0.4570, P<0.025), apolipoprotein B (r = -0.5297, P<0.025), apolipoprotein B/apolipoprotein Al (r = -0.5851, P<0.01), apolipoprotein B/HDL cholesterol (r = -0.4961, P<0.05) before steroid treatment. There was no correlation between proteinuria and serum lipid profiles. Also Ccr and serum lipid profiles were not correlated. There was positive correlation between days to remission and HDL cholesterol (r = +0.4511, P<0.05), apolipoprotein B (r = +0.5190, P<0.05), apolipoprotein B/HDL cholesterol (r = +0.7169, P<0.005). Conclusions : This results reveal that HDL cholesterol, apolipoprotein B and apolipoprotein B/HDL cholesterol can be used as a predictive factor in corticosensitive nephrotic syndrome. We could not determine the significant level of these lipids for insufficient patients number, but these level may predict future relapses of corticosensitive nephrotic syndrome patients and thus may allow to better management and treatment protocols. More data and long term follow up studies should be needed. (J Korean Soc Pediatr Nephrol 2001;5 : 136-46)

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Pharmacological Activities of a New Glycosaminoglycan, Acharan Sulfate Isolated from the Giant African Snail Achatina fulica

  • Shim, Jin-Young;Lee, Yeon-Sil;Jung, Sang-Hoon;Choi, Hyung-Seok;Shin, Kuk-Hyun;Kim, Yeong-Shik
    • Archives of Pharmacal Research
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    • v.25 no.6
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    • pp.889-894
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    • 2002
  • Acharan sulfate (AS) is a glycosaminoglycan (GAG) prepared from the giant African snail, Achatina fulica. In this study, some biological activities of AS were evaluated on the basis of structural similarities to heparin/heparan sulfate and the biological functions of GAGs. We demonstrated that it exhibited strong immunostimulating activities as measured by carbon clearance test in mice and in vivo phagocytosis. It also exhibited a significant hypoglycemic activity in epinephrine (EP)-induced hyperglycemia as well as antifatigue effects by weight-loaded forced swimming test. And it showed hypolipidemic activities in cholesterol-rich mixture induced hyperlipidemia in rats. The above results indicate that AS has diverse biological activities and suggest therapeutically important target molecules.

Gene Targeting of Low Density Lipoprotein(LDL) Receptor Related Protein 5(LRP5) Involved in the Wnt Signaling Pathway

  • Jeong, Young-Hee;Kim, Suck-Ho;Kim, Dong-Ho;Moon, Seung-Ju;Tokuo Yamamoto;Kang, Man-Jong
    • Proceedings of the KSAR Conference
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    • 2002.06a
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    • pp.82-82
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    • 2002
  • The Wnt signaling pathway plays pivotal roles in embryonic development and oncogenesis through various signaling molecules inculding Frizzled receptor, recently characterized LRP5/6 and Dickkopf protein. Although Wnt signaling has been characterized in both developmental and oncogenic processes, little is known about its function in the normal adult. The ability of LRP5 to bind apolipoprotein E(apoE) and the abundant expression of LRP5 transcripts in hepatocytes, raise the possibility that LRP5 plays a role in the hepatic clearance of ApoE-containing chylomicron remonants, a major plasma lipoprotein carrying diet-derived cholesterol. (omitted)

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Effects of Parenteral Lipid Formulas on Seurm Lipids Clearance in Normal Volunteers (지질 수액체 투여가 정상인의 혈장 지질변화에 미치는 영향)

  • Choe Myeon·Kim
    • Journal of Nutrition and Health
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    • v.25 no.6
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    • pp.461-467
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    • 1992
  • Although intravenous fat emulsions are well accepted as a consituent of a total parenteral nutrition regimen it is still controversial how much it can be used and who to use it in consideration of physical situation of useres. In this study the effect of two marketed lipid formulas on serum lipids change was investigated. Each lipid formula was injected to twelve normal adult volunteers and a set of blood samples was drawn at 5 minute interval during the experiment. Changes of triglycerides. free fatty acids free glycerol total cholesterol and phospolipids in the serum wre determined. To calculate serum lipids clearance the phar-macokinetics of serum triglyceride fractional removal rate(k) and half-life time(t/2) were calculated using intravenous fat tolerance-test(IVFTT) None of the parameters determined in this experiment was statistically different between two marketed formulas. In summary the bolus injection of the lipid formulas did not produce any adverse effects and their elimination kinetics from the blood stream were similar.

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Hepatoprotective Effects of Pig Placental Hydrolysates on Liver Damage-induced Rats by Injecting Carbon Tetrachloride (사염화탄소 주입으로 간손상을 유발시킨 백서에서 돈태반가수분해 물 투여가 간기능 보호에 미치는 영향)

  • Park, Sun-Young;Kim, Da-Sol;Kang, Sun-A;Park, Sun-Min
    • Journal of Applied Biological Chemistry
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    • v.55 no.2
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    • pp.109-115
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    • 2012
  • The aim of this study was to determine hepatoprotective effects of pig placenta hydrolysates (PLA) on liver damage-induced rats. Sprague Dawley rats were subcutaneously injected with carbon tetrachlorides and divided into 4 groups: negative control (DMSO treated), two PLA treated groups, low dosage of PLA (LPLA; 300 mg/kg body weight) and high dosage of PLA (HPLA; 1000 mg/kg body weight), and silymarin treated group (80 mg/kg body weight). Rats in each group orally received assigned compounds for 3 weeks. For the normal control group vehicle (corn oil) was injected. After 3 weeks, liver and spleen weights were greater in the two PLA and silymarin groups than the negative control group. After bromosulfalein (BSP) treatment, the clearance rates were in the descending order of negative control > LPLA > HPLA = silymarin and serum BSP levels exhibited the opposite trends of the clearance rates. Serum levels of aspartate aminotransferase, alanine aminotransferase, triglyceride, and cholesterol lowered with PLA in a dose-dependent manner. The decrease with HPLA was similar to that with silymarin. In addition, triglyceride, cholesterol, lipid peroxides levels in the liver decreased in HPLA and silymarin compared to the negative control. The liver morphometry was improved in HPLA- or silymarin-treated rats in comparison to the negative control. In conclusion, HPLA administration ameliorated the hepatotoxicity as much as silymarin in rats injected with carbon tetrachlorides.

Fenofibrate Reduces Age-related Hypercholesterolemia in Normal Rats on a Standard Diet

  • Han, Ying;Do, Mi-Hyang;Kim, Mi-Sun;Seo, Eun-Hui;Park, Mi-Kyoung;Kim, Duk Kyu;Lee, Hye-Jeong;Seo, Su-Yeong
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.2
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    • pp.77-81
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    • 2010
  • Plasma cholesterol is increased in normal aging in both rodents and humans. This is associated with reduced elimination of cholesterol and decreased receptor-mediated clearance of plasma low-density lipoprotein (LDL) cholesterol. The aims of this study were: (1) to determine age-related changes in plasma lipid profiles, and (2) to determine the effect of fenofibrate, an activator of peroxisome proliferator activated receptor alpha (PPAR $\alpha$), on plasma lipid profiles in normal rats on a standard diet. Male Sprague-Dawley (SD) rats (n=15) were fed standard chow and water from 10 to 25 weeks of age. During that period, we measured daily food intake, body weight, fasting and random blood glucose levels, plasma total cholesterol (TC), triglycerides (TG), and free fatty acid (FFA) levels. At 20 weeks of age, all rats were randomly divided into two groups: a fenofibrate group (in which rats were gavaged with 300 mg/kg/day of fenofibrate) and a control group (gavaged with water). Fenofibrate treatment lasted 5 weeks. There were no significant changes in daily food intake, blood glucose, and plasma TG level with age. Body weight, plasma TC, and FFA levels were significantly increased with age. Fenofibrate significantly decreased plasma concentrations of TC and FFA, which had been increased with age. However, fenofibrate did not influence the plasma concentration of TG, which had not increased with age. These results suggest that fenofibrate might have a novel role in preventing age-related hypercholesterolemia in SD rats on a normal diet.

Studies on the Distribution of Plasma Lipid Profiles and Body Fatness According to Apo E Polymorphism in Normolipidemic Korean Women

  • Lee, Myoung-Sook
    • Preventive Nutrition and Food Science
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    • v.2 no.4
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    • pp.338-347
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    • 1997
  • Apo E polymorphism(e2, e3, e4) was among the first reported genetic polymorphism that explained part of the normal vairation in plasma cholesterol concentrations. Both alleles E2 and E4 are significantly more frequent in patients with mixed forms of hyperlipidemia and contribute on the observed differences in CHD risk among different populations. Effects of apo E polymorphism on the distribution of plasma lipid profiles were studied in 89 normolipidemic healthy females, aged 19 up to 22 years. The relative frequencies of E3/3 was 0.787, E3/2 was 0.101, E3/4 allele was 0.112 and no E2/2, E2/4 and E4/4 were found. Weight, height and %LBM were elevated in E2 than those in E3&E4. No differences in the blood pressure among apo E isomers were found, otherwise the pulsation was higher in E4 than that in the others. There were no differences in plasma total-, total DL-, HDL$_3$-, HDL$_2$ cholesterol, apo B-100 and apo A-I, However, phenotype means rank E3/2>E3/3>E3/4 in average TG levels(p<0.0001) significantly, and rank E3/4>E3/3>E3/2 in LDL cholesterol levels. These results were related to the correlation between atherogenic indiced (AI) such as LDL/HDL, (TC-HDL)/HDL, HDL$_3$/HDL$_2$. The ratio of HDL$_3$& HDL$_2$was significantly increased in E2 & E4 than that in E3(P=0.043). LCAT activity was not different between E2 and E3 but was highly increased in E4 (p<0.0001 among apo E isomers), but CETP was not different. Since the negative correlation between LCAT and CETP in apo E2(r=-0.491) was stronger than that in apo E3, E2 allele impacts the clearance of plasma apo E mediated lipoproteins. In conclusion firstly, E4 mediated alteration through LDL or E receptors results in lower TG or higher $\beta$-lipoprotein levels and E2 shows reciprocal effects of E4, respectively. Second, E4 allele was more atherogenic than E2 allele because the higher levels of AI such as HDL$_3$/HDL$_2$ were criticized.

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