• 대한핵의학회지
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• 제3권1호
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• pp.1-12
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• 1969

Liver functions in diffuse parenchymal liver disease such as cirrhosis of the liver depend largely on the effective hepatic blood flow rather than on the individual cell functions. Clinical methods of measuring the hepatic blood flow were developed recently by the application of colloidal disappearance rate. In order to correlate the radiogold disappearance rate to conventional biochemical liver function tests, 21 normal subjects and 80 cases of cirrhosis of the liver were studied with both methods. The results are summarized as following: 1. The validity of external counting method to measure the blood disappearance rate of colloidal radiogold was confirmed by in vitro counting of the serial blood samples. 2. The blood disappearance rate of collidal radiogold was essentially the same. as the liver uptake rate of colloidal radiogold in normal and cirrhotic subjects with various degrees of functional disturbance. And it seemed there was no serious extrahepatic removal of the colloidal radiogold. 3. The disappearance rate of colloidal radiogold was not significantly changed by the posture change, but was enhanced by ingestion of 500 ml of water. 4. The disappearance rate of colloidal radiogold was not influenced by single dose of Telepaque, while BSP retention was increased after Telepaque. 5. The mean disappearance half time of colloidal radiogold in normal subjects was $2.49{\pm}0.391$(S.D.) minutes. The mean normal disappearance rate constant (K value) was $0.285{\pm}0.0428$(S.D.)/minute. 6. The colloidal radiogold disappearance half time was abnormally prolonged (over 3.2 min.) in $87.7{\pm}3.68$(S.D.) % of cirrhotic subjects. 7. In patients of liver cirrhosis the blood disappearance rate of colloidal radiogold correlated well to serum albumin and globulin levels and BSP retention which were considered to reflect functions of hepatic parenchymal cells. There was, however, no correlation between colloidal disappearance rate and thymol turbidity test, serum glutamic pyruvic transaminase, and serm alkaline phosphatase activities. The latters were considered to be associated with the activity of liver disease.

• 대한한방내과학회지
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• 제27권4호
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• pp.962-968
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• 2006

Background : Liver cirrhosis is a disease of the liver in which normal cells are replaced by scar tissue. This condition results in the failure of the liver to perform many of its usual functions. Liver cirrhosis includes ascites, jaundice, portal hypertension, varices etc. Objectives : This study was to see if there is a decrease in ascites of liver cirrhosis to under acupuncture and herbal treatment to test their validity. Methods : Measuring the response to treatment of ascites by giving pyengwie-san hap wieryungtang gamibang and treating the patient with acupuncture, these clinical symptoms were observed: weight, abdominal circumference, abdominal SONO, chest X-ray, and lab findings. Results : Over 18 days the daily average loss of weight and abdominal circumference 0.43kg and 0.56cm, respectively. Lab findings of liver functions showed improvement. Conclusions : This report shows a role for acupuncture and herbal treatment for treating ascites in liver cirrhosis.

• BMB Reports
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• 제38권3호
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• pp.300-306
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• 2005

Tamoxifen citrate is an anti-estrogenic drug used for the treatment of breast cancer. It showed a degree of hepatic carcinogenesis, when it used for long term as it can decrease the hexose monophosphate shunt and thereby increasing the incidence of oxidative stress in liver rat cells leading to liver injury. In this study, a model of liver injury in female rats was done by intraperitoneal injection of tamoxifen in a dose of 45 mg/kg body weight for 7 successive days. This model produced a state of oxidative stress accompanied with liver injury as noticed by significant declines in the antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and catalase) and reduced glutathione concomitant with significant elevations in TBARS (thiobarbituric acid reactive substance) and liver transaminases; sGPT (serum glutamate pyruvate transaminase) and sGOT (serum glutamate oxaloacetate transaminase) levels. The oral administration of dimethyl dimethoxy biphenyl dicarboxylate (DDB) in a dose of 200 mg/kg body weight daily for 10 successive days, resulted in alleviation of the oxidative stress status of tamoxifen-intoxicated liver injury in rats as observed by significant increments in the antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and catalase) and reduced glutathione concomitant with significant decrements in TBARS and liver transaminases; sGPT and sGOT levels. The administration of DDB before tamoxifen intoxication (as protection) is more little effective than its curative effect against tamoxifen-induced liver injury. The data obtained from this study speculated that DDB can mediate its biochemical effects through the enhancement of the antioxidant enzyme activities and reduced glutathione level as well as decreasing lipid peroxides.

• 대한세포병리학회지
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• 제7권1호
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• pp.79-83
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• 1996

Gaucher's disease is an autosomal recessive disorder resulting from mutation at the glucocerebrosidase locus on chromosome 1q21. As a result, glucocerebroside accumulates principally in the phagocytic cells known as Gaucher cells. In our case, a five-year old girl was admitted with seven days' history of fever and abdominal distension. At physical examination the patient had hepatosplenomegaly. Laboratory tests revealed a hemoglobin concentration of 2.8g/L: platelet counts of $23,000/{\mu}l$: normal range of white cell and differential counts, and negative Coombs' test. Liver enzymes were normal. For the evaluation of hepatosplenomegaly, fine needle aspiration was performed blindly against the palpable spleen. Wet-fixed hematoxylin and eosin-stained smears are made. The smears from the spleen showed predominantly macrophages with abundant cytoplasm and rather small, uniform, often eccentric nuclei with small nucleoli. The multinucleated cells were often found. The cytoplasm was pale, with more or less distinct fibrillarity. The cells had the characteristic appearance of Gaucher cells. Gaucher cells were also found in the tissue section from the liver, spleen and lymph node and the bone marrow aspirate. The diagnosis was later confirmed by determination of bela-glucosidase activity in peripheral blood leucocytes. Fine needle aspiration of the spleen is considered as a convenient procedure with a low complication rate for the diagnosis of lysosomal storage disease.

• Journal of Microbiology and Biotechnology
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• 제25권3호
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• pp.413-417
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• 2015

Recently, we isolated HY253, a novel decahydrofluorene analog with a molecular structure of 7,8a-divinyl-2,4a,4b,5,6,7,8,8a,9,9a-decahydro-1H-fluorene-2,4a,4b,9a-tetraol from the roots of Aralia continentalis, which is known as Dokwhal (獨活), a traditional medicinal herb. Moreover, we previously reported its cytotoxic activity on cancer cell proliferation in human lung cancer A549 and cervical cancer HeLa cells. The current study aimed to evaluate its detailed molecular mechanisms in cell cycle arrest and apoptotic induction in human hepatocellular carcinoma HepG2 cells. Flow cytometric analysis of HepG2 cells treated with $60{\mu}M$ HY253 revealed appreciable cell cycle arrest at the G1 phase via inhibition of Rb phosphorylation and down-regulation of cyclin D1. Furthermore, using western blots, we found that up-regulation of cyclin-dependent kinase inhibitors, such as p21^CIP1 and p27^KIP1, was associated with this G₁ phase arrest. Moreover, TUNEL assay and immunoblottings revealed apoptotic induction in HepG2 cells treated with $60{\mu}M$ HY253 for 24 h, which is associated with cytochrome c release from mitochondria, via down-regulation of anti-apoptotic Bcl-2 protein, which in turn resulted in activation of caspase-9 and -3, and proteolytic cleavage of poly(ADP-ribose) polymerase (PARP). Accordingly, we suggest that HY253 may be a potent chemotherapeutic hit compound for treating human liver cancer cells via up-regulation and activation of the p53 gene.

• 대한한방내과학회지
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• 제37권3호
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• pp.442-452
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• 2016

Objectives: This study was performed to investigate the anti-lipogenic effect and the mechanism of Jungmanbunso-hwan extract (JMBSH) on a cellular model of non-alcoholic fatty liver disease (NAFLD) caused by palmitate in HepG2 cells.Methods: The JMBSH was prepared, andHepG2 cells were treated with various concentrations of JMBSH in order to perform an MTT assay. The HepG2 cells were cultivated in palmitate-containing media with or without extract of JMBSH. The intracellular lipid content in the HepG2 cells was examined. The effects of JMBSH on sterol regulatory element-binding transcription factor-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), and AMP-activated protein kinase (AMPK) activation in HepG2 cells were measured.Results: JMBSH did not reduce HepG2 cell viability under 1,000 μg/mL. JMBSH considerably decreased intracellular lipid accumulation caused by palmitate in HepG2 cells. JMBSH repressed expression of SREBP-1c, which mediates the induction of lipogenic genes (ACC, FAS, and SCD-1). JMBSH also activated AMPK, which plays animportant role in the regulation of hepatic lipid metabolism.Conclusions: This study suggested that JMBSH relieves hepatic steatosis by repressing SREBP-1c, which mediates the induction of lipogenic genes. The anti-lipogenic effect of JMBSH may also be related to the activation of AMPK. Therefore, JMBSH could potentially be applied to NAFLD treatment after further clinical studies.

• BMB Reports
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• 제41권2호
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• pp.119-125
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• 2008

Our previous work confirmed that Sph2/LA1029 was a sphigomyelinase-like hemolyisn of Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai. Characteristics of both hemolytic and cytotoxic activities of Sph2 were reported in this paper. Sph2 was a heat-labile neutral hemolysin and had similar hemolytic behavior as the typical sphingomyelinase C of Staphylococcus aureus upon sheep erythrocytes. The cytotoxic activity of Sph2 was shown in mammalian cells such as BALB/C mouse lymphocytes and macrophages, as well as human L-02 liver cells. Transmission electron microscopic observation showed that the Sph2 treated BALB/C mouse lymphocytes were swollen and ruptured with membrane breakage. They also demonstrated condensed chromatin as a high-density area. Cytoskeleton changes were observed via fluorescence confocal microscope in Sph2 treated BALB/C mouse lymphocytes and macrophages, where both cytokine IL-$1{\beta}$ and IL-6 were induced. In addition, typical apoptotic morphological features were observed in Sph2 treated L-02 cells via transmission electron microscope and the percentage of apoptotic cells did increase after the Sph2 treatment detected by flow cytometry. Therefore, Sph2 was likely an apoptosis-inducing factor of human L-02 liver cells.

• 한국환경성돌연변이발암원학회지
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• 제24권4호
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• pp.171-179
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• 2004

Cytochrome P4503A4(CYP3A4) is the most abundnat CYPs in human liver, comparising approximately 30% of the total liver CYPs contents ans is involbed in the metabolism of more than 60% of currently used therapeutic drugs. The expression of CYP3A4 is induced by a variety of structurally unrelated xonobiotics including the antibiotic rifampicin and endogenous hormones, and might be mediated through steroid and xenobiotic receptor(SXR) system. The molecular mechanisms underlying regulation of CYP3A4 gene expression hae not been understood. In order to gain the insight of the molecular mechanism of CYP3A4 gene expression, study has been undertaken to investigate if the histone deacelylation is involved in the regulation of CYP3A4 gene expression by proximal promoter or not. Also SXR was investigated to see if they were involved in the regulation of CYP3A4 proximal promoter activity. HepG2 or Hena-I cells were transfected with a plasmid containing~1kb of the CYP3A4 proximal promoter region (-863 to +64bp) cloned in front of a reporter gene, luciferase, in the presence or absence of SXR or hER. Transfected cells were treated with CYP3A4 inducers such as rifampicin, PCN and RU 486, or with estradiol, in order to exmine to regulation of CYP3A4 gene expression in the presence or absence of trichostatin A (TSA). In HepG2 cells, CYP3A4 inducers and estradiol increased significantly the luciferase activity by CYP3A4 proximal promoter, only when TSA was co-treated after SXR cotransfection. In the case of Hepa-I cells CYP3A4 inducers and estradiol incressed modestly the luciferase activity when TSA was co-treated, but this increment was not enhanced by SXR cotransfection in contrast to HepG2 cells. Taken together, these results indicated that the inhibition of histone deacetylation was required to SXR-mediated increase in CYP3A4 proximal promoter region when rifampicin, or PCN was treated. Futher a trans-activation by SXR may demand other species-specific transcription factors.

• Archives of Pharmacal Research
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• 제27권1호
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• pp.111-117
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• 2004

Hepatic microcirculatory failure is a major component of reperfusion injury in the liver. Recent data provided some evidence that endothelium-derived vasoconstrictors and vasodilators may be functionally important to the control of the total hepatic blood flow under these conditions of circulatory failure. Since Kupffer cells provide signals that regulate the hepatic response in ischemia/reperfusion (I/R), the aim of this study was to investigate the role of Kupffer cells in the I/R-induced imbalance of vasoregulatory gene expression. Rats were subjected to 60 min hepatic ischemia, followed by 5 h of reperfusion. The Kupffer cells were inactivated by gadolinium chloride ($GdCl_3$, 7.5 mg/kg body weight, intravenously) 1 day prior to ischemia. Liver samples were obtained 5 hrs after reperfusion for RT-PCR analysis of the mRNA for genes of interest: endothelin-1 (ET-1), its receptors $ET_A and ET_B$, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1). ET-1 mRNA expression was increased by I/R. mRNA levels for $ET_A$ receptors showed no change, whereas $ET_B$ receptor transcripts increased in the I/R group. The increases in ET-1 and $ET_B$ mRNA were not prevented by the $GdCI_3$ pretreatment. The mRNA levels for iNOS and eNOS significantly increased within the I/R group with no significant difference between the I/R group and the $GdCl_3$-treated I/R group. HO-1 mRNA expression significantly increased in the I/R group and this increase was attenuated by $GdCI_3$. In conclusion, we have demonstrated that an imbalance in hepatic vasoregulatory gene expression occurs during I/R. Our findings suggest that the activation of Kupffer cells is not required for I/R-induced hepatic microvascular dysfunction.

• 대한통합의학회지
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• 제11권3호
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• pp.59-67
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• 2023

Purpose : Epithelial-to-mesenchymal transition (EMT) is recognized as an important cellular response in metastatic proceduresand characterized by loss of cellular polarity as well as gain of mesenchymal features, which enables migration and invasion. Hepatocellular carcinoma (HCC) is one of the most common primary carcinomas in the liver and exhibits a poor prognosis due to frequent extrahepatic metastasis. Taraxacum officinale has been used for a long time in oriental medicine because of its various pharmacological activitiessuch as anti-rheumatic, anti-inflammatory, antioxidative, and anticarcinogenic activities. In this study, the anti-metastatic activity of T. officinale water extract (TOWE) and ethanol extract (TOEE) was investigated through the regulation of EMT in the Huh7 cells. Methods : The effects of TOWE and TOEE on migratory and invasive activities were investigated by wound healing and in vitro invasion assays. Western blot analysis was also applied to analyze protein expression levels associated with EMT and their upstream transcription factors in Huh7 cells. Results : TOWE and TOEE treatment potently inhibited migration and invasion of Huh7 cells compared to the untreated group. Both extracts treatment inhibited protein expression levels of N-cadherin, matrix metalloproteinase (MMP)-9, and vimentin while E-cadherin was significantly accelerated. In addition, the activated status of transcription factors, Snail, nuclear factor (NF)-κ B, and zinc finger E-box binding homeobox (ZEB)1 was also inhibited with statistical significance. In comparison to both extracts, TOEE more potently attenuated migration, invasion, and EMT markers as well as their transcription factors in Huh7 cells than TOWE, which means that TOEE might possess more functional phytochemicals than TOWE. Conclusion : Consequently, TOWE and TOEEattenuated metastatic activity of hepatocellular carcinoma through the regulation of EMT markers and their transcription factors in Huh7 cells, which means that T. officinale might be a promising strategy for a chemopreventive agent against HCC metastasis.