• Genomics & Informatics
• /
• 제7권2호
• /
• pp.97-106
• /
• 2009

Epigallocatechin gallate (EGCG), a well-known antioxidant molecule, has been reported to cause hepatotoxicity when used in excess. However, the mechanism underlying EGCG-induced hepatotoxicity is still unclear. To better understand the mode of action of EGCG-induced hepatotoxicity, we examined the effect of EGCG on human hepatic gene expression in HepG2 cells using microarrays. Analyses of microarray data revealed more than 1300 differentially expressed genes with a variety of biological processes. Upregulated genes showed a primary involvement with protein-related biological processes, such as protein synthesis, protein modification, and protein trafficking, while downregulated genes demonstrated a strong association with lipid transport. Genes involved in cellular stress responses were highly upregulated by EGCG treatment, in particular genes involved in endoplasmic reticulum (ER) stress, such as GADD153, GADD34, and ATF3. In addition, changes in genes responsible for cholesterol synthesis and lipid transport were also observed, which explains the high accumulation of EGCG-induced lipids. We also identified other regulatory genes that might aid in clarifying the molecular mechanism underlying EGCG-induced hepatotoxicity.

• Asian-Australasian Journal of Animal Sciences
• /
• 제26권8호
• /
• pp.1080-1088
• /
• 2013

Our previous results showed that kisspeptin-10 (Kp-10) injections via intraperitoneal (i.p.) once daily for three weeks notably promoted the egg laying rate in quails. In order to investigate the mechanism behind the effects of Kp-10 on enhancing the egg laying rate in birds, this study focused on the alternations of lipids synthesis in liver after Kp-10 injections. 75 female quails (22 d of age) were allocated to three groups randomly, and subjected to 0 (control, Con), 10 nmol (low dosage, L) and 100 nmol (high dosage, H) Kp-10 injections via i.p. once daily for three weeks, respectively. At d 52, quails were sacrificed and sampled for further analyses. Serum $E_2$ concentration was increased by Kp-10 injections, and reached statistical significance in H group. Serum triglyceride (TG) concentrations were increased by 46.7% in L group and 36.8% in H group, respectively, but did not reach statistical significance, and TG contents in liver were significantly elevated by Kp-10 injections in a dose-dependent manner. Serum total cholesterol (Tch) concentrations significantly decreased in H group, while in H group the hepatic Tch content was markedly increased. The level of non-esterified fatty acid (NEFA), apolipoprotein A1 and B (apoA1 and apoB) were not altered by Kp-10 injections. The genes expression of sterol regulatory element binding protein-1 (SREBP-1), fatty acid synthetase (FAS), apolipoprotein VLDL-II (apoVLDL-II), cholesterol $7{\alpha}$-hydroxylase (CYP7A1) and vitellogenin II (VTG-II) were significantly up-regulated by high but not low dosage of Kp-10 injection compared to the control group. However, the expression of SREBP-2, acetyl-CoA carboxylase ($ACC_{\alpha}$), malic enzyme (ME), stearoyl-CoA (${\Delta}9$) desaturase 1 (SCD1), apolipoprotein A1 (apoA1), fatty acid binding protein 2 (FABP2), 3-hydroxyl-3-methyl glutaryl-coenzyme A reductases (HMGCR), estrogen receptor ${\alpha}$, ${\beta}$($ER{\alpha}$ and ${\beta}$) mRNA were not affected by Kp-10 treatment. In line with hepatic mRNA abundance, hepatic SREBP1 protein content was significantly higher in H group. Although the mRNA expression was not altered, the content of $ER{\alpha}$ protein in liver was also significantly increased in H group. However, SREBP-2 protein content in liver was not changed by Kp-10 treatment. In conclusion, exogenous Kp-10 consecutive injections during juvenile stage significantly advanced the tempo of egg laying in quails, which was associated with the significant elevation in hepatic lipids synthesis and transport.

• Preventive Nutrition and Food Science
• /
• 제2권2호
• /
• pp.121-128
• /
• 1997

this study was conducted to examine the atherogenic effect of high cholesterol diet (experimental diet) that influences changes of lipoprotein cholesterol metabolism and arterial wall. Seven NewZealand white rabbits were fed control diet, an the other 7 rabbits 2% cholesterol diet for 10 weeks. Results obtained from this study are as follows: 1) High cholesterol diet resulted in a gradual increase of plasma total cholesterol level, reaching upto 1422 mg/dl at the seventh week. 2) CETP (cholesteryl ester transfer protein) activity was significantly higher in high cholesterol group (64.9% at the 7th week) than control group (49.3% at the 7th week) during most of the experimental period except the 6th week. 3) The cholesterol supplementation induced fatty liver and a decrease of hepatic HMG-CoA reductase activities (2.1 moles vs. 0.3nmoles) compared to control group. 4) Bands of apo B-100 and apo E in plasma lipoprotein were thicker in high cholesterol-fed animals tan control animals as visualized by SDS-PAGE. 5) Oxidizability of plasma lipoproteins measured in vitro was greater in high cholesterol group tan control group, but vitamin E level higher in control group. 6) he effect of cholesterol feeding for 10 weeks also led to early fatty streaks in aortic intima. High cholesterol feeding was atherogenic to rabbits, an this seems to be mediated through elevated CETP activities that regulate plasma HDL cholesterol level and decrease an efficiency of reverse cholesterol transport in lipoprotein cholesterol metabolism. The enhanced oxidizability of plasma lipoproteins and lowered vitamin E level may also contribute to the formation of faaty streaks in aorta of cholesterol-fed rabbits.

• 분석과학
• /
• 제5권1호
• /
• pp.83-90
• /
• 1992

$^{14}C$-warfarin을 흰쥐에 경구투여 후 4시간 경과시 혈액에서 최고치를 나타내었으며, coumarin과 그 유도체인 warfarin에 의한 간조직 microsome 내의 Cyt. p-450은 이들 화합물에 의해 microsomal electron transport system이 증가됨과 Cyt. p-450의 isozyme들이 유도됨을 확인할 수 있었다.

• Clinical and Experimental Pediatrics
• /
• 제51권5호
• /
• pp.538-541
• /
• 2008

멘케스병은 성염색체 열성으로 유전되는 질환으로 APT7A 유전자의 돌연변이에 의해 발생한다. 기전은 장에서의 구리 흡수와 운반에 결손이 있는 것으로 혈청 구리 및 ceruloplasmin 이 낮다. 특징적인 임상양상은 경련발작, 근육긴장저하, 저체온증을 나타내며 얼굴은 특징적으로 통통하며 저색소 피부색, 꼬이고 윤택이 없고 잘 부스러지는 머리카락을 보인다. 성장장애를 보이는 경우가 흔하며 심한 정신지체와 발달장애를 동반한다. 멘케스병에서 간비대가 간병증을 보이는 경우는 현재까지 보고되지 않았다. 저자들은 유전자 검사를 통해 멘케스병으로 확진된 4개월 소아가 영아연축, 발달장애, 머리카락 이상 외에도 이전에 잘 알려져 있지 않은 간비대를 보인 1례를 보고하는 바이다.

• 대한핵의학회지
• /
• 제32권1호
• /
• pp.114-119
• /
• 1998

반복적인 수혈을 받은 급성전격성간염 환자에서 Ga-67 체내분포의 양상을 추적하였다. 급성기에 시행한 갈륨스캔에서 간의 악성종양을 의심하게 하는 간섭취증가와 신장, 뼈섭취증가가 관찰되었다. 간섭취증가는 철운반단백질에 결합하지 않은 Ga-67이 염증이 일어난 간세포에 섭취되었기 때문으로 해석되었다. 신장과 뼈섭취증가는 반복적인 수혈에 의한 철운반단백질의 포화에 따른 Ga-67의 세포내운반저하에 의한 것으로 생각되었다. 10개월 후에 다시 시행한 갈륨스캔에서 간섭취는 더욱 증가되었으며 골수섭취의 증가가 관찰되었다. 반면 신장섭취는 정상화되었다. 이러한 소견은 철결핍성 빈혈에 의한 것으로 해석되었다. 이 증례는 체내 철의 양과 이에 따른 철운반단백질 포화도의 변화에 의한 Ga-67의 체내분포의 변화를 예시해 준다.

• Archives of Pharmacal Research
• /
• 제28권3호
• /
• pp.330-334
• /
• 2005

The effect of a new hepatoprotective agent, YH-439, on the hepatobiliary transport of a model organic cation (OC), TBuMA (tributylmethylammonium), was investigated. The area under the plasma concentration-time curve (AUC) from time zero to 4 h following iv administration of TBuMA (6.6 $\mu$mol/kg) was increased significantly when YH-439 in corn oil (300 mg/kg) was orally administered to rats 24 h prior to the experiment. Nevertheless, the cumulative biliary excretion of TBuMA remained unchanged. As a consequence, the apparent biliary clearance ($CL_b$) of TBuMA was decreased significantly as a result of YH-439 pretreatment, consistent with the fact that the in vivo excretion clearance of TBuMA across the canalicular membrane ($CL_{exc}$) was not changed by the pretreatment. The in vitro uptake of TBuMA into isolated hepatocytes was decreased by one half by the pretreatment, owing to a decrease in the apparent V$_{max}$ and $CL_{linear}$, but the $K_m$ for the process remained constant. Most interestingly, however, the sinusoidal uptake of glucose, a nutrient, into hepatocytes was not influenced by the pretreatment, suggesting the YH-439 pretreatment specifically impaired the sinusoidal uptake of OCs. Thus, the OC-specific inhibition of hepatic uptake, without influencing the uptake of glucose, a nutrient, appeared to be associated with the hepatoprotective activity of YH-439.

• Journal of Pharmaceutical Investigation
• /
• 제7권1_4호
• /
• pp.13-21
• /
• 1977

This study on the biliary excretion of sulfadiazine has been established in the rats. 1. Sulfadiazine, administered intravenously to rats with ligated renal pedicles and a cannulated bile duct, rapidly appeared in the bile in high concentration. 2. Between 0-30min. and 30-60 min. after administration, the bile-to-plasma concentration ratios(B/P) of the sulfadiazine were 1. 02-2.67, 1.14-3.79 for 1mg/kg dose, 1.48-3.89, 1.30-3.81 for 10mg/kg, 1.97-4.27, 2.11-4.07 for 50mg/kg, and 1.70-4.21, 1.71-5.34 for 100mg/kg. Thus, B/P ratios at any doses of sulfadiazine greatly exceeded 1.0 at all experimental periods. 3. Furthermore, the biliary excretion of sulfadiazine was inhibited by probenecid significantly. 4. Hepatic clearance of sulfadiazine in the rats was increased from 0.515 to 1.780 ml/60 min. when the dose was raised from 1.0mg/kg to 50.0mg/kg of sulfadiazine, but at 100mg/kg, decreased to 1.250ml/60min. All these results indicate that sulfadiazine is excreted into the bile by active transport process in the rats with ligated renal pedicles and a cannulated bile duct.

• Toxicological Research
• /
• 제11권2호
• /
• pp.199-203
• /
• 1995

The focus of this study was to investigate that cellular parameters and glucose uptake might be altered by extracellular calcium and starvation. Addition of 1 mM $Ca^{++}$ to hepatocytes (equalling to the free calcium concentration of blood) significantly increased intracellular $Na^+$ and decreased $Na^+$ & LDH leakage. This pertains to the hepatocytes of control rats as well as those of rats fasted for 24 and 48. hr. These effects might be come from the membrane-stabilizing effects of calcium. But calcium had no effects on cell volumes, superoxide-formation and glucose uptake. Actually hepatocytes of starved rats showed changes in several cellular parameters. Starvation increased LDH leakage, glucose uptake and the total concentration of $Na^+$ and $Na^+$ whereas it markedly decreased cell volumes. Since total tonicity remained unchanged, intracellular $Na^+$ and $Na^+$ could contribute to a higher share of total osmolarity in starvation. Starvation increased the cytoplasmic pH because $R-NH^{3+}$ions and their corresponding counterions disappeared. This increase may be related to suppress the protonization of amino groups in proteins. Starvation decreased hepatic glycogen, a major compound that affects cytosolic volume of hepatocytes. The data indicate that starvation increases the glucose transport activity. The possible molecular basis will be discussed.

• 대한핵의학회지
• /
• 제20권1호
• /
• pp.33-37
• /
• 1986

It is well known that $^{99m}Tc-sulfur$ colloid or phytate hepatic scintigraphy is highly sensitive but not specific. Both $^{99m}Tc-DISIDA$ and bilirubin have been shown to share the same anionic transport pathway in the liver. Hepatocellular carcinoma(HCC) retains the ability to produce bile but has marked limitation to excreting it resulting in accumulation of bile within the tumor cells. Based upon such a fact, $^{99m}Tc-DISIDA$ hepatobiliary scintigraphy is used for the diagnosis of HCC. The present communication deals with our experience of DISIDA scintigraphic exploration of 9 cases of HCC in a retrospective way. We have made an observation on intensity of positive radio nuclide accumulation in the cold area of HCC as it is demonstrated by phytate scintigraphy. In addition we have semi quantitatively analyzed time-activity pattern and the following results were obtained. (1) All of 9 cases showed an increased uptake of $^{99m}Tc-DISIDA$ in delayed scintigrams. Of these 5 cases showed accumulation less than, 3 equal to, 1 more than the surrounding liver tissue. (2) The mean of the first appearing time of $^{99m}Tc-DISIDA$ activity in tumoral region was 2 hours and 20 minutes. (3) DISIDA scintigraphy provides us with positive informations of diagnostic value.