• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3131-3135
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• 2015

Objective: To investigate whether the expression of serum soluble neural cell adhesion molecule (sNCAM) is associated with hepatic encephalopathy (HE) in hepatocelular carcinoma (HCC) patients. Materials and Methods: The Oncomine Cancer Microarray database was used to determine the clinical relevance of NCAM expression in different kinds of human cancers. Sera from 75 HCC cases enrolled in this study were assessed for expression of sNCAM by enzyme linked immunosorbent assay (ELISA). Results: Dependent on the Oncomine Cancer Microarray database analysis, NCAM was down regulated in 10 different kinds of cancer, like bladder cancer, brain and central nervous system cancer, while up-regulated in lung cancer, uterine corpus leiomyoma and sarcoma, compared to normal groups. Puzzlingly, NCAM expression demonstrated no significant difference between normal and HCC groups. However, we found by quantitative ELISA that the level of sNCAM in sera from HCC patients with HE ($347.4{\pm}151.9ng/ml$) was significantly more up-regulated than that in HCC patients without HE ($260.3{\pm}104.2ng/ml$), the p-value being 0.008. sNCAM may be an important risk factor of HE in HCC patients, the correlation coefficients was 0.278 (P<0.05) on rank correlation analysis. Conclusions: This study highlights that up-regulated level of serum sNCAM is associated with HE in HCC patients and suggests that the high expression can be used as an indicator.

• Journal of Veterinary Clinics
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• v.7 no.1
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• pp.381-390
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• 1990

In order to study the effects of administration of carbon tetrachloride(CCI$_4$) and 1-naphthylisothiocyanate(ANIT) on the liver of Korean black goats, some liver function tests and liver biopsy were done on 4 Korean black goats dosed with CCI$_4$(0.4m1/kg of body weight) in-traruminally and 4 Korean black goats dosed with ANIT(400mg/kg of body weight) by stomach tube. BSP Tl/2 and serum total bilirubin concentration in goats dosed with CCI$_4$ were increased gradually, reached to maximum value on 2nd and 1st day, respectively, and then began to decrease in normal range, gradually. In goats dosed with ANIT, BSP Tl/2 and serum total bilirubin concentration were increased rapidly, reached to maximum value on 0.5 and 1st day, respectively, and then returned to normal ragne, rapidly. Serum SDH, AST and GGT activities in goats dosed with CCI$_4$ were increased rapidly and reached to maximum value on 3rd, 1st and 2nd day, respectively. Thereafter, the serum enzyme activities began to decrease in normal range gradually. In goats dosed with ANIT, however, serum SDH, AST and GGT activities were not changed. The histopathologic changes in goats dosed with CCI$_4$ were lipidosis and centrilobular nee-rosis of the hepatic parenchyma. In goats dosed with ANIT, hyperplasia of bile duct epithelium was noticeable, but pathologic changes in liver parenchyma were not noticed. Conclusively, in Korean black goats dosed with CCI$_4$, main finding was necrosis of hepatic parenchyma. In Korean black goats dosed with ANIT, main finding was cholestasis.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.71-71
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• 1993

Carboxylesterase is widely distributed in the tissues of vertebrates, insects, plants and mycobacteria. Among various tissues of animals and humans, the highest esterase activity with various substrates is found in the liver. Kidney has moderate carboxylesterase activity in the proximal tubules. Considerable esterase activity is also found in the small intestine epithet elial cells and serum of mammals. Besides these tissues, carboxylesterase has been found in the lung, testis, adipose tissue, nasal mucosa and even in the central nervous system. Hepatic microsomal carboxylesterase catalyzes the hydrolysis of a wide variety of endogenous and exogenous compounds such as carboxylester, thioester and aromatic amide. Since carboxylesterases are important for metabolic activation of prodrugs and detoxification of xenobiotics, differences in substrate specificity and immunological properties of this enzyme are important in connection with choosing a suitable laboratory animal for the evaluation of biotransformation and toxicity of drugs. On the other hand, liver, kidney, intestine and serum were found to contain multiple forms of carboxylesterases in animal species and humans. In fact, we have purified more than fifteen isoforms of carboxylesterases from microsomes of liver, kidney and intestinal mucosa of nine animal species and humans. and characteristics of these isoforms were compared each other in terms of their physical and immunochemical properties. On the other hand, we have reported that hepatic microsomal carboxylesterases are induced by many exogenous compounds such as phenobarbital, polycyclic aromatic hydrocarbons, Aroclor 1254, aminopyrine and clofibrate. Later, we showed that some isoforms of hepatic carboxylesterase were induced by glucocorticoids such as dexamethasone and 16 ${\alpha}$-carbonitrile, but other isoforms were rather inhibited by these compounds. These findings indicate that involvement of carboxylesterases in the metabolism and toxicity of drugs should be explained by the isoforms involved. Since 1991, we have carried out detailed research investigating the types of carboxylesterases involved in the metabolic activation of CPT-11, a derivative of camptothecin, to the active metabolite, SN-38. The results obtained strongly suggest that some isoforms of carboxylesterase of liver microsomes and intestinal mucosal membrane are exclusively involved in CPT-11 metabolism. In this symposium, the properties of carboxylesterase isoforms purified from liver, kidney and intestine of animal species and humans are outlined. In addition, metabolism of CPT-11, a novel antitumor agent, by carboxylesterases in relation to the effectiveness will also be discussed.

• Korean Journal of Clinical Laboratory Science
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• v.36 no.1
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• pp.55-63
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• 2004

The hepatotherapeutic effect of the extract of Lycii fructus has been studied in rats against $CCl_4$ induced liver toxicity. The rats were orally treated with $CCl_4$ (corn oil/$CCl_4$ 1:1, $1m{\ell}/kg$) and then $CCl_4$ ($0.5m{\ell}/kg$) administered four times for 2 weeks. The extracts of L. fructus have been administered every day for 2 weeks after the last $CCl_4$ injection. The experimental groups consisted of negative control (G1), positive control ($CCl_4$ alone; G2), extract of L. fructus (50 mg/kg; G3, 100 mg/kg; G4, 200 mg/kg; G5), respectively. There was a significant decrement to G2 on the serum level of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase in G5. Also, the content of thiobarbituric acid reactive substance, and phosphatidylcholine hydroperxidase, a marker of lipid peroxidation, in the liver were decreased significantly G5 and G4 compared with G2. Although, catalase or superoxide dismutase, antioxidant enzyme, in the liver were decreased significantly too, it would not be a good sign for the liver. In histopathological findings, such a hepatocellular vacuolar degeneration, lobular restructure, cellular infiltration, necrosis, and so on were shown severely in G2. However, G4 and G5 was shown a mild cytoplasmic vacuolation and inflammatory cell. In conclusion, as a protection against cell damage, lipid peroxidation and serum level, it suggested that the extract of Lycii fructus would have been a therapeutic effect of liver injury directly.

• Korean Journal of Clinical Pharmacy
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• v.18 no.1
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• pp.60-67
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• 2008

This study aimed to compare a microparticle enzyme immunoassay (MEIA) with a liquid chromatography-tandem mass spectrometry (LC/MS/MS) technique for the measurement of tacrolimus concentrations in adult liver transplant recipients, to investigate how the assay choice influenced the population pharmacokinetics of tacrolimus and to identify patient characteristics that affected pharmacokinetic parameters in each assay. Tacrolimus concentrations from 29 liver (n=52 paired-samples) transplant recipients measured by both MEIA and LC/MS/MS were used to evaluate the performance of these methods in the clinical setting. Tacrolimus pharmacokinetics was studied independently using MEIA and LC/MS/MS data in 70 adult patients using a population approach performed with NONMEM. Patient characteristics which influenced pharmacokinetic parameters in each assay were compared. The relation between LC/MS/MS and MEIA measurements was best described by the regression equation MEIA=1.465*LC/MS/MS-1.336 (r=0.91). Multiple linear regression analysis showed significant inverse relationships between assay difference and hematocrit (Hct) (p<0.025) in liver graft recipients. In MEIA, the population estimate of tacrolimus CL/F and apparent volume of distribution (Vd/F) were found to be 10.1 L/h and 226 L, and in LC/MS/MS, 13 L/h and 305 L respectively. Neither patient's age, weight, gender, grafted hepatic weight, albumin concentration, nor markers of liver function influenced tacrolimus CL/F The final model of CL/F was found to be 10.1+(Hct/Hct mean)$^{12.0}$ in MEIA and 13+(1+Hct/578) in LC/MS/MS indicating that CL/F was influenced by hematocrit.

• The Korean Journal of Zoology
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• v.32 no.1
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• pp.48-54
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• 1989

Several proteolytic activities and the level of and-trypsin in neoplastic tissues of human cervix and liver were compared to those in normal tissues to examine if any correlation exists between malignant behavior of the tumors and the changes in overall proteolytic capacity. Proteolysis against casein and insulin in cervix tumor was increased to 2-to 3-fold while that in liver tumor was reduced to one-tenth to one-half. By contrast, the level of anti-trypsin in cervix tumor was lowered to nearly one-tenth of that in normal tissues while the level rose to about 2-fold in malignant tissues of liver. On the other hand, the activities of plasmin-like protease and plasminogen activator were enhanced 10-20% over the activities in normals. These results suggest that the changes in proteolytic capacity are at least in part due to outbalance in either of proteolytic or its inhibitory activity over the other and occur distinctively to each tumor systems for their malignant behavior.

• Journal of Society of Preventive Korean Medicine
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• v.12 no.2
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• pp.37-49
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• 2008

In this study, we experimented the influence of three herbal medicines, which are Saussurea lappa Clarke, Poncirus trifoliata Rafin, Citrus aurantium Linne, which are called 'Yigiyak(理氣藥)' on drug metabolizing enzyme cytochrome P450 3A4 in Human Liver Microsome. Above all, the reason for this study is that herbal medicines can be assumed that herbs might have interactions with drugs, other herbs, alcohol and chemicals whether those are much better synergy effects than expected effects when the medicine was treated alone or not. As a result, we showed that all of five traditional herbal medicines had no CYP 3A4 inhibition effect on 10, 20, 30, 40, $50{\mu}g/m{\ell}$ doses in Human Liver Microsome even Saussurea lappa Clarke showed a little inhibition as about 93% and 79% inhibition rate of control. However, this result are mostly not enough to prove that SLC has a CYP 3A4 inhibition effect. Moreover, it is not that those rates showed that those herbal medicines have CYP 3A4 induction effect. In conclusion, the result could support that those herbal medicines are more safe than chemical drugs even if this is the basic step to prove that result. Therefore, more specific studies to support this result, which are Kinetic study, cell and animal study then finally until clinical research, are required.

• Journal of Nutrition and Health
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• v.32 no.2
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• pp.137-149
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• 1999

This study was performed to investigate the effets of hesperidin extracted from tangerine peel on Cadmium (Cd) and lipid metabolism lipid peroxide formation, and antioxidative enzyme activities in rats. Forty-eight male Sprague-Dawley rats weighing 158.3$\pm$3.5g were blocked into eight groups according to body weight. Rats were raised for three weeks with diets containing 0 or 0.04%(w/w) cadmium chloride and 1%(w/w) extracted hesperidin from tangerine peel, commercial hesperidin or naringin. Food intake, weight gain and food efficiency ratio were significantly lower in the Cd-administered groups. The Cd concentrations in blood and liver and the Cd excretions in urine and feces were significantly higher in the Cd-administered groups. Among the Cd groups, blood Cd concentrations were decreased, fecal Cd excretions were increased, and Cd retenition ratios were decreased by feeding flavonoid diets. Plasma total lipid concentrations were significantly lower in the extracted hesperidin group, plasma triglyceride concentrations were significantly lower in the extracted hesperidin and naringin groups. Plasma HDL-cholesterol concentrations and HDL : total cholesterol ratios were increased by feeding flavonoids. Among the Cd groups, liver total lipid concentratons were decreased by feeding flavonoids. Fecal total lipid, fecal cholesterol, and fecal triglyceride excretions were significantly higher in the naringin group, and they were increased by feeding flavonoids among Cd groups. Thiobarbituric acid reactive substance concentrations in plasma and liver were higher in Cd groups, and were significantly decreased by feeding flavonoids. The activities of erythrocyte catalase, superoxide dismutase and glutathione peroxidase showed a tendency to increase by feeding. The activities of liver catalase, superoxide dismutase and glutathione peroxidase were not significantly affected by administering Cd or flavonoids. In conclusion, all flavonoids that were used in this experiment inhibited lipid peroxide formation in plasma and liver, but this effect was not caused by the increased in the activities of antioxidative enzymes.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.3
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• pp.177-187
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• 2021

Metabolic syndrome (MBS) is a widespread disease that has strongly related to unhealthy diet and low physical activity, which initiate more serious conditions such as obesity, cardiovascular diseases and type 2 diabetes mellitus. This study aimed to examine the therapeutic effects of morin, as one of the flavonoids constituents, which widely exists in many herbs and fruits, against some metabolic and hepatic manifestations observed in MBS rats and the feasible related mechanisms. MBS was induced in rats by high fructose diet feeding for 12 weeks. Morin (30 mg/kg) was administered orally to both normal and MBS rats for 4 weeks. Liver tissues were used for determination of liver index, hepatic expression of glucose transporter 2 (GLUT2) as well as both inflammatory and fibrotic markers. The fat/muscle ratio, metabolic parameters, systolic blood pressure, and oxidative stress markers were also determined. Our data confirmed that the administration of morin in fructose diet rats significantly reduced the elevated systolic blood pressure. The altered levels of metabolic parameters such as blood glucose, serum insulin, serum lipid profile, and oxidative stress markers were also reversed approximately to the normal values. In addition, morin treatment decreased liver index, serum liver enzyme activities, and fat/muscle ratio. Furthermore, morin relatively up-regulated GLUT2 expression, however, down-regulated NF-κB, TNF-α, and TGF-β expressions in the hepatic tissues. Here, we revealed that morin has an exquisite effect against metabolic disorders in the experimental model through, at least in part, antioxidant, anti-inflammatory, and anti-fibrotic mechanisms.

• BMB Reports
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• v.29 no.6
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• pp.555-563
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• 1996

A membrane-bound phosphatidylinositol 4-kinase (PI 4-kinase) was separated in a sucrose gradient and solubilized with 1% Triton X-100 from mouse brain. The enzyme was purified 2,952-fold by various chromatographic techniques including DEAE-cellulose, PI-Sepharose and Sephacryl S-200 gel filtration. The molecular weight of PI 4-kinase was approximately 76 kDa by gel filtration and 70.8 kDa by SDS-polyacrylamide gel electrophoresis. The purified enzyme exhibited specific activity of 11.2 nmol/min/mg protein and pi value of 4.7. Kinetic analysis of the PI 4-kinase indicated apparent $K_m$, values of 190 ${\mu}M$ and 120 ${\mu}M$ for phosphatidylinositol and ATP, respectively. The maximal activity of this purified enzyme was observed at pH 7.4 at an incubation temperature of $37^{\circ}C$. The enzyme activity was significantly activated by $Mg^{2+}$, $Mn^{2+}$ and $Fe^{2+}$, and inhibited severely by $Ca^{2+}$. PI 4-kinase was proved to be pure in its immunoblot test by polyclonal antibody prepared from immunized rabbit sera. By this test, we were able to detect the existence of the same type of PI 4-kinase from other mouse organ tissues, such as liver, heart, kidney and spleen. Furthermore, similar immunoblot analysis with the same antisera recognized the different epitopes of PI 4-kinase proteins from various organs of rabbit, chinese hamster and rat.