• The Korean Journal of Physiology and Pharmacology
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• v.16 no.2
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• pp.131-138
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• 2012

Alcoholic hepatitis is a leading cause of liver failure in which the increased production of tumor necrosis factor ${\alpha}$ (TNF${\alpha}$) plays a critical role in progression of alcoholic liver disease. In the present study, we investigated the effects of cilostazol, a selective inhibitor of type III phosphodiesterase on ethanol-mediated TNF${\alpha}$ production in vitro and $in$ $vivo$, and the effect of cilostazol was compared with that of pentoxifylline, which is currently used in clinical trial. RAW264.7 murine macrophages were pretreated with ethanol in the presence or absence of cilostazol then, stimulated with lipopolysacchride (LPS). Cilostazol significantly suppressed the level of LPS-stimulated TNF${\alpha}$ mRNA and protein with a similar degree to that by pentoxifylline. Cilostazol increased the basal AMP- activated protein kinase (AMPK) activity as well as normalized the decreased AMPK by LPS. AICAR, an AMPK activator and db-cAMP also significantly decreased TNF${\alpha}$ production in RAW264.7 cells, but cilostazol did not affect the levels of intracellular cAMP and reactive oxygen species (ROS) production. The $in$ $vivo$ effect of cilostazol was examined using ethanol binge drinking (6 g/kg) mice model. TNF${\alpha}$ mRNA and protein decreased in liver from ethanol gavaged mice compared to that from control mice. Pretreatment of mice with cilostazol or pentoxifylline further reduced the TNF${\alpha}$ production in liver. These results demonstrated that cilostazol effectively decrease the ethanol-mediated TNF${\alpha}$ production both in murine macrophage and in liver from binge drinking mice and AMPK may be responsible for the inhibition of TNF${\alpha}$ production by cilostazol.

• Toxicological Research
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• v.22 no.4
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• pp.365-373
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• 2006

The present study was designed to characterize the effects of estrogen receptor agonist (4,4',4'-(4-Propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol, PPT) on liver and kidney in male mouse using a light microscopic analysis. PPT was subcutaneously given to adult male mice at a weekly dosage of 178.6mg/kg in a volume 0.08 ml of vehicle for 3, 5 and 8 weeks. There were differences in body and organ weights between control and the treated groups. Body and kidney weights were decreased in treated group whereas, liver weight was increased. In microscopic observations, sinusoidal diameter in liver of treated group was increased 156%, 216% and 255% on week 3, 5 and 8 respectively. Compared to the control, diameter of proximal convoluted tubules in kidney was increased 37% and 43% or week 5 and 8 in treated group. Whereas, height of epithelial cells in the proximal tubules was reduced at all time points. These results suggest that microstructure of liver and kidney was changed by treatment of estrogen receptor agonist PPT in the male mice.

• Korean Journal of Clinical Laboratory Science
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• v.43 no.3
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• pp.113-119
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• 2011

This study was designed to determine the effects of larval extracts from Protaetia brevitarsis seulensis shade dried larva from Korea and China on liver tissues of hepatic injury groups. The experimental groups are divided into five groups; Normal, carbon tetrachloride single injection ($CCl_4$), Pb-CHI ($CCl_4$ + P. brevitarsis shade dried larva from China), Pb-KOR ($CCl_4$ + P. brevitarsis shade dried larva from Korea) and SIL ($CCl_4$ + 0.35% silymarin) groups. Sprague Dawley rats were oral injected with $CCl_4$ at a dose l mg/kg (20% in corn oil) for induction of liver damage for 4 weeks. Each experimental group was fed with a dose 50 mg/kg of larval extracts based on medicinal preparations from 3 weeks to 4 weeks after $CCl_4$ treatment. At the end of 4 weeks, we evaluated the serum levels of glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate transferase (GPT), alkaline phosphatase (ALP) and blood urea nitrogen (BUN) in serum and the cytokine levels of tumor necrosis factor-${\alpha}$) (TNF-${\alpha}$) and transforming growth factor-${\beta}$ (TGF-${\beta}$) in the cells isolated from spleen and liver. The histological analysis was also conducted. The $CCl_4$ injection reduced body weight, induced congestion of middle lobe and hepatocytic degeneration, resulting in disintegration of hepatic cords, and increased biochemical markers of blood related to hepatic injury. On the other hand, the Pb-CHI and Pb-KOR group decreased the levels of biochemical markers in blood and cytokine levels in spleen and liver. Especially, the Pb-KOR group facilitated the recovery of biochemical values of blood related to hepatic injury, hepatic lesions and fibrosis. Taken together, larval extract from P. brevitarsis might prevent acute hepatotoxicity and enhance the recovery of liver fibrosis and cirrhosis induced by $CCl_4$, and the ingredients could be a promising candidate for the prevention and treatment of hepatic disorders.

• Herbal Formula Science
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• v.24 no.3
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• pp.131-152
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• 2016

Objectives ： This study was to evaluate Sibjeondaebo-tang’s(Shiquan dabutang) effect to rat hypothyroidism which induced by 6-n-propyl-2-thiouracil(PTU)Methods ： Aqueous extracts of Sibjeondaebo-tang(Shiquan dabutang)(21.29%) were administered by oral dose of 300 and 150 mg/kg(rat’s body weight) for 42 days from 2 weeks before start of PTU treatment. During this moment the body weight, thyroid gland weights, liver weight, serum thyroid hormone, lipid content and liver antioxidant defense system were measured with histopathological changes of thyroid glands, Liver and these result were compared with LevoT₄ 0.5mg/kg treated ratsResults ： As a result of PTU treatment, marked decreases of body weight, liver weight, serum thyroid hormone levels of T₃, T₄, triglyceride content and liver CAT activation were observed with marked increases of thyroid gland weight, thyroid gland hormone TSH, activate liver H₂O₂ and SOD, serum Total cholesterol, HDL and AST amount were admitted. In addition, marked hyperplasia of follicular cells with reduce of follicular colloid contents and sizes were showed at histopathological inspections. These PTU-induces histopathological changes related to hypothyroidism were significantly reduced by treatment of both different dosages of Sibjeondaebo-tang(Shiquan dabutang).Conclusions： This study suggest that Sibjeondaebo-tang(Shiquan dabutang) extracts have favorable effect on the thyroid hormone productions with beneficial effect on hypothyroidism medicated by modulatory effects on antioxidant defense system.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1396-1402
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• 1997

Epithelioid Hemangioendothelioma(EH) is a rare vascular tumor, originating from endothelial cells. The principal locations are lung, soft tissue, bone and liver. This tumor is of borderline malignancy, relatively benign course. In the lung, the tumor is often multifocal, bilateral and frequently lead to the mistaken diagnosis of metastatic carcinoma. Although EH of the lung is relatively slow growing tumor, extensive pulmonary involvement, systemic metastasis, mainly to the liver have been documented. A 26-year-old man with EH involving the lung and liver was reported. Chest X-ray and chest CT showed multiple nodules in both lung fields and Abdominal CT multiple round low densities in liver. Transbronchial lung biopsy was performed. The patient diagnosed as EH by light microscopic finding and immunohistochemical study for Factor VIII-related antigen.

• Molecules and Cells
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• v.38 no.10
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• pp.843-850
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• 2015

The1hepatic cell death induced by acetaminophen (APAP) is closely related to cellular adenosine triphosphate (ATP) depletion, which is mainly caused by mitochondrial dysfunction. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a key sensor of low energy status. AMPK regulates metabolic homeostasis by stimulating catabolic metabolism and suppressing anabolic pathways to increase cellular energy levels. We found that the decrease in active phosphorylation of AMPK in response to APAP correlates with decreased ATP levels, in vivo. Therefore, we hypothesized that the enhanced production of ATP via AMPK stimulation can lead to amelioration of APAP-induced liver failure. A769662, an allosteric activator of AMPK, produced a strong synergistic effect on AMPK Thr172 phosphorylation with APAP in primary hepatocytes and liver tissue. Interestingly, activation of AMPK by A769662 ameliorated the APAP-induced hepatotoxicity in C57BL/6N mice treated with APAP at a dose of 400 mg/kg intraperitoneally. However, mice treated with APAP alone developed massive centrilobular necrosis, and APAP increased their serum alanine aminotransferase and aspartate aminotransferase levels. Furthermore, A769662 administration prevented the loss of intracellular ATP without interfering with the APAP-mediated reduction of mitochondrial dysfunction. In contrast, inhibition of glycolysis by 2-deoxy-glucose eliminated the beneficial effects of A769662 on APAP-mediated liver injury. In conclusion, A769662 can effectively protect mice against APAP-induced liver injury through ATP synthesis by anaerobic glycolysis. Furthermore, stimulation of AMPK may have potential therapeutic application for APAP overdose.

• Korean Journal of Transplantation
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• v.32 no.4
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• pp.108-112
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• 2018

Antibody-mediated rejection (AMR) is a major complication after ABO-incompatible liver transplantation. According to the 2016 Banff Working Group on Liver Allograft Criteria for the diagnosis of acute AMR, a positive serum donor specific antibody (DSA) is needed. On the other hand, the clinical significance of the histological findings of AMR in the absence of DSA is unclear. This paper describes a 57-year-old man (blood type, O+) who suffered from hepatitis B virus cirrhosis with hepatocellular carcinoma. Pre-operative DSA and cross-matching were negative. After transplantation, despite the improvement of the liver function, acute AMR was observed in the protocol biopsy on postoperative day 7; the cluster of differentiation 19+ (CD19+) count was 0% and anti-ABO antibody titers were 1:2. This paper presents the allograft injury like AMR in the absence of DSA after ABOi living donor liver transplantation with low titers of anti-ABO antibody and depleted serum CD19+ B cells.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.5
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• pp.385-393
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• 2021

Tissue factor (TF) activates the coagulation system and has an important role in the pathogenesis of various diseases. Our previous study stated that retinoid receptors (RAR-α and RXR-α) are released as a lipid droplet in monocrotaline/lipopolysaccharide-induced idiosyncratic liver toxicity in mice. Herein, the interdependence between the release of retinoid receptors RAR-α and RXR-α and TF in N-acetyl-p-aminophenol (APAP)-induced mice liver toxicity, is investigated. Serum alanine transaminase (ALT) level, platelet and white blood cells (WBCs) counts, protein expression of fibrin, TF, cyclin D1 and cleaved caspase-3 in liver tissues are analyzed. In addition, histopathological evaluation and survival study are also performed. The results indicate that using of TF-antisense (TF-AS) deoxyoligonucleotide (ODN) injection (6 mg/kg), to block TF protein synthesis, significantly restores the elevated level of ALT and WBCs and corrects thrombocytopenia in mice injected with APAP. TF-AS prevents the peri-central overexpression of liver TF, fibrin, cyclin D1 and cleaved caspase-3. The release of RXR-α and RAR-α droplets, in APAP treated sections, is inhibited upon treatment with TF-AS. In conclusion, the above findings designate that the released RXR-α and RAR-α in APAP liver toxicity is TF dependent. Additionally, the enhancement of cyclin D1 to caspase-3-dependent apoptosis can be prevented by blocking of TF protein synthesis.

• Journal of Ginseng Research
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• v.47 no.3
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• pp.429-439
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• 2023

Background: The incidence and clinical importance of nonalcoholic fatty liver disease (NAFLD) has emerged. However, effective therapeutic strategies for NAFLD have yet to be found. Panax ginseng (P. ginseng) is a traditional herb in Eastern Asia with therapeutic effects in many chronic disorders. However, the precise effects of ginseng extract on NAFLD are currently unknown. In present study, the therapeutic effects of Rg3-enriched red ginseng extract (Rg3-RGE) on the progression of NAFLD were explored. Methods: Twelve-week-old C57BL/6 male mice were fed a chow or western diet supplemented with high sugar water solution with or without Rg3-RGE. Histopathology, immunohistochemistry, immunofluorescence, serum biochemistry, western blot analysis, and quantitative RT-PCR were used for in vivo experiment. Conditionally immortalized human glomerular endothelial cell (CiGEnC) and primary liver sinusoidal endothelial cells (LSECs) were used for in vitro experiments. Results: Eight weeks of Rg3-RGE treatment significantly attenuated the inflammatory lesions of NAFLD. Furthermore, Rg3-RGE inhibited the inflammatory infiltrate in liver parenchyma and the expression of adhesive molecules to LSECs. Moreover, the Rg3-RGE exhibited similar patterns on the in vitro assays. Conclusion: The results demonstrate that Rg3-RGE treatment ameliorates NAFLD progression by inhibiting chemotaxis activities in LSECs.

• YAKHAK HOEJI
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• v.12 no.1_2
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• pp.1-15
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• 1968

The levels of activities of amylase, lipase and trypsin in both the pancreatic tissue and serum of 18 species of vertebrate animals were measured and enzymologically compared with each other. 1) The value of amylase in the pancreas of experimental mammalia has been found decreasing in the order pig, rat, dog, cat, rabbit and cow; that of pancreatic lipase has been found decreasing in the order of pig, dog, cat, rat, rabbit and cow; and that of trypsin has been found decreasing in the order of pig, cow, dog, rat, rabbit. Thus the value of all the above three kinds of enzymes were observed highest in pig, but in cow amylase and lipase were observed lowest while trypsin were observed considerably high. 2) In view of diets, the comparatively high values of pancreatic enzyme were observed in the ommivorous animals such as pig, rat, dog, while the values observed low in the herbivorous animals, such as cow and rabbit. 3) In the bovine, the values were observed moderately high except lipase which were found comparatively low. 4) In the Reptilia and Amphibia such a mud turttle and frog, the values were shown in similar measure with each other, that is, the pancreatic amylase and trypsin were observed considerably high while the lipase was found low. 5) In the species of Reptilia such as a viper and snake, the activities of pancreatic enzymes were not detected. But in the tissue of liver, stomach, activities of the enzymes were found considerably high. Lacertilia animals such as lizard the values of pancreatic enzymes were little observed. 6) In the fish in which the pancreatic tissue is scattered in the liver, the pancreatic enzymes were found in the liver tissue considerably higher than in the other tissues but lower than in the warm-blooded animals, especially the lipase was lower. 7) In generally the values of serum amylase and lipase were observed higher than those of man; and even in the cold-blooded animals in which the values of pancreatic enzymes were shown low or none, the values were also observed high. 8) The above three kinds of pancreatic enzyme values of those experimental animals have shown a tendency of higher degree in higher taxa than in lower taxa according to taxonomical order. 9) In view of tissue, the pancreatic cell was observed large in the mammalian animals such as rat and pig and cytoplasm was also abundantly contained in the acinous cell; and the bovine and the snake haave the pancreatic cells of the similar rosette form the comparatively large acinous cells of long rhombic form in the comparatively large acinous cells of long rhombic form in which the spindle shaped neucleus and the abundant cytoplasm were contained. In the fish the pancreatic cell were found scattered in the liver in which the very large pancreatic islet were found.