• Biomolecules & Therapeutics
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• 제17권4호
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• pp.438-445
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• 2009

We investigated global gene expression from both mouse liver and mouse hepatic cell lines treated with acetaminophen (APAP) in order to compare in vivo and in vitro profiles and to assess the feasibility of the two systems. During our analyses of gene expression profiles, we picked up several down-regulated genes, such as the cytochrome P450 family 51 (Cyp51), sulfotransferase family cytosolic 1C member 2 (Sult1c2), 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (Hmgcs1), and several genes that were up-regulated by APAP, such as growth arrest and DNA-damage-inducible 45 alpha (Gadd45a), transformation related protein 53 inducible nuclear protein 1 (Trp53inp1) and zinc finger protein 688 (Zfp688). For validation of gene function, synthesized short interfering RNAs (siRNAs) for these genes were transfected in a mouse hepatic cell line, BNL CL.2, for investigation of cell viability and mRNA expression level. We found that siRNA transfection of these genes induced down-regulation of respective mRNA expression and decreased cell viability. siRNA transfection for Cyp51 and others induced morphological alterations, such as membrane thickening and nuclear condensation. Taken together, siRNA transfection of these six genes decreased cell viability and induced alteration in cellular morphology, along with effective inhibition of respective mRNA, suggesting that these genes could be associated with APAP-induced toxicity. Furthermore, these genes may be used in the investigation of hepatotoxicity, for better understanding of its mechanism.

• KSBB Journal
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• 제23권5호
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• pp.381-386
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• 2008

본 연구에서는 암모니아에 의해 손상된 사람의 간세포주 Hep G2 cell과 rat의 hepatocyte에 대하여 metronidazole이 간 세포 손상을 억제하는 효과가 있음을 밝혔다. Metronidazole은 암모니아에 의한 세포 생존율 감소, 배지내의 암모니아 수준 및 지질과산화 증가 및 항산화 효소 발현 감소 그리고 세포 내 DNA 손상과 세포사멸을 억제하였다. 따라서 metronidazole은 암모니아로부터 기인하는 세포손상을 감소시켜 간세포 기능을 보호함으로써 간 기능의 저하로 발생한 과암모니아혈증에 효과적인 치료제로서의 가능성을 시사한다.

• Toxicological Research
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• 제29권3호
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• pp.187-193
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• 2013

The effects of toluene in dimethylformamide (DMF)-induced hepatotoxicity were investigated with respect to the induction of cytochrome P-450 (CYP) and the activities of related enzymes. The rats were treated intraperitoneally with the organic solvents in olive oil (Single treatment groups: 450 [D1], 900 [D2], 1,800 [D3] mg DMF, and 346 mg toluene [T] per kg of body weight; Combined treatment groups: D1+T, D2+T, and D3+T) once a day for three days, while the control group received just the olive oil. Each group consisted of 4 rats. The activities of the xenobiotic metabolic enzymes and the hepatic morphology were assessed. The immunoblots indicated that the expression of CYP2E1 was considerably enhanced depending on the dosage of DMF and the CYP2E1 blot densities were significantly increased after treatment with both DMF and toluene, compared to treatment with DMF alone. The activities of glutathione-S-transferase and glutathione peroxidase were either decreased or remained unaltered after treatment with DMF and toluene, whereas the lipid peroxide levels were increased with increasing dosage of DMF and toluene. The liver tissue in the D3 group (1,800 mg/kg of DMF) showed signs of microvacuolation in the central vein region and a large necrotic zone around the central vein, in rats treated with both DMF (1,800 mg/kg) and toluene (D3T). These results suggest that the expression of CYP2E1 is induced by DMF and enhanced by toluene. These changes may have facilitated the accelerated formation of N-methylformamide (NMF) from toluene, and the generated NMF may directly induce liver damage.

• 한국식품영양과학회지
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• 제14권1호
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• pp.27-32
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• 1985

화분립이 alcohol대사에 미치는 영향을 알기 위하여 아미노산을 분석하고, rat에 alcohol과 화분립을 각각 농도별로 투여하여 rat 간(肝) alcoholdehydrogenase (ADH)활성과 간(肝)조직 변화를 실험하였다. 1. 해바라기 화분립의 아미노산 조성을 분석하여 phenylalanine을 비롯한 18종의 아미노산을 정량하였으며, 필수 아미노산중 특히 phenylalanine, leucine, threonine, lysine의 함량이 많았다. 2. 실험동물의 간(肝) ADH활성은 alcohol 투여군이 alcohol농도에 비례하여 대조군 보다 현저히 저하하였으며, 화분립을 alcohol과 함께 투여함으로써, 대조군에는 미치지 않았지만 ADH활성이 증가하였고, alcohol의 농도가 낮을수록 그 증가율이 높았다. 3. 실험동물의 간(肝)조직은 alcohol투여군에서 지방침윤이 나타났으며, 화분립과 alcohol 복합투여군에서는 지방침윤이 현저히 적게 나타났다.

• 한국수의병리학회지
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• 제6권1호
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• pp.41-48
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• 2002

Oval cell is considered as facultative precursor cells for both hepatocytes and biliary cells, as well as origin of hepatocellar and cholangiocellular carcinoma (CCC) during carcinogenesis or toxic liver injury. To clarify the cellular origin or differentiation of cholagiocarcinogensis, the fate of carcinogen-induced oval cells was pathologically and phenotypically chased in Syrian golden hamster liver after Clonorchis sinensis (CS) infection which would give rise to a promoting effect. Two week treatment of hamsters with 0.005% diethylnitrosamine (DEN) followed by 2 week treatment of 1% 2-acetylaminofluorene (AAF) under choline deficient diet resulted in massive proliferation of BrdU labeleed and PCNA positive oval cells showing various distinct morphology, histochemical and immunohistochemical phenotypes for GGT, cytokeratin 19 and OV-6. Oval cells also frequently form ductular-like structures or phenotypically show hepatocyte-like characteristics. After CS infection, the oval cells showed sequential morphological changes to atypicl proliferating bile ductules and all hamsters thereafter developed well differentiated and anaplastic CCC at 16 week after CS infection. In electron microscopy, some bile ductules were constructed by intermediate oval cells and bile ductular cells surrounded by basement membrane. The results of this study strongly suggest that CCC developed in the present study were originated from hepatic stem-like oval cells, supporting the theory of stem cell origin of cancers. In addition, this hamster model would be valuable for the molecular mechanistic study during chemical-triggered cholangiocarcinogenesis.

• Preventive Nutrition and Food Science
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• 제9권4호
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• pp.361-366
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• 2004

Defatted methanol extracts of the medicinal plants, Rubus coreanus Miq. (RC) and Atractylodes japonica Koidzumi (AJ) were added at the levels of 0.1, 0.5, or $2\%$ (w/w) to high cholesterol diets and fed to ovariectomized Sprague-Dawley female rats, weighing 212.6 $\pm$ 1.8 g for four weeks. Weight gains were lower in RC and AJ groups than the control group, but there were no changes in uterus weights. Serum levels of triglyceride decreased by 20-$27\%$ in the experimental groups fed $0.1\%$ of each extract (O.1RC and O.1AJ), compared with that of control (Ovx). Serum cholesterol levels were not changed in the RC groups but increased in the group fed $2\%$ of the AJ extract. Liver levels of cholesterol and triglyceride were reduced in both the RC and AJ groups. Microscopic observation revealed that there were no morphological alterations in liver, lung, heart, spleen and kidney tissues of the experimental groups. Plasma levels of albumin, BUN, creatinine, sodium, potassium and phosphate in the IRC and AJ groups were in normal ranges. Serum GOT and GPT activities were, however, higher in the 2.0AJ than Ovx group. These results suggest that the extracts of the Rubus coreanus Miq. and Atractylodes japonica Koidzumi at dietary levels as low as $0.1\%$ may be utilized as hypotriglyceridemic ingredients for functional foods.

• 한방재활의학과학회지
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• 제33권3호
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• pp.33-46
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• 2023

Objectives We investigated anti-obesity effects of Menthae Herba hydrosol in obese mice. Methods Animals were divided into four groups, and treatments were performed for 7 weeks. After the treatment, serum lipid profiles, weight and pathological morphology in liver, kidney, adipose tissue were measured. Also, hepatic protein and gene expression levels of lipid metabolism-related factors were analyzed. Results Body weight was decreased in P3% group. In P1% (group fed high-fat diet and 1% Menthae Herba hydrosol) and P3% (group fed high-fat diet and 3% Menthae Herba hydrosol) group, weight of white adipose tissue, serum levels of triglyceride and blood urea nitrogen were decreased, and weight of muscle was increased. Also, liver, kidney and epididymal adipocyte size were reduced in P1% and P3% group. Adenosine monophosphate-activated protein kinase was increased and sterol regulatory element binding protein-1c (SREBP-1c) was decreased in P3% group. mPeroxisome proliferator-activator receptor-γ, mMonocyte chemotactic protein-1 were decreased in P1% and P3% group. In P3% group, mSREBP-1c was decreased and mCarnitine palmitoyl transferase-1 was increased. And mUncoupling protein 1 in brown adipose tissue was increased. Conclusions These results suggest that Menthae Herba hydrosol has a worthy effect on anti-obesity.

• Journal of Yeungnam Medical Science
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• 제10권2호
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• pp.313-337
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• 1993

내독소에 의한 간 상해 때 Kupffer 세포의 역할과 작용 기전을 규명하기 위하여 내독소 (Escherichia coli 026 : B6 lipopolysaccharide)를 Sprague-Dawley rat에 체중 100g 당 1.5mg을 복강내에 투여하여 15분, 30분, 1시간, 2시간, 4시간, 8시간, 16시간, 24시간, 72시간, 120시간 후 Kupffer세포의 형태학적 변화를 광학 및 전자현미경적으로 관찰하여 다음과 같은 결과를 얻었다. 광학현미경적 소견으로는 내독소 투여 15분 후 부터 Kupffer 세포 수의 증가와 비대가 관찰되었으며 시간이 경과함에 따라 더욱 심해졌고, 동모양혈관내 호중구, 적혈구 및 섬유소의 침윤이 관찰되었다. 4시간 후에는 동모양혈관의 울혈과 확장이 관찰되었고 호중구외에도 호산구 및 림프구 등의 염증세포가 침윤되었다. 72시간 후 울혈은 감소되었고, 120시간 경과 후 Kupffer 세포의 수는 증가하였지만 형태학상 대조군과는 큰 차이는 없었다. 전자현미경적 소견으로는 내독소 투여 15분 후부터 Kupffer 세포에서는 포음소포의 증가와 일차 리소솜과 이차 리소솜의 수와 크기의 증가가 관찰되었으며 시간이 경과함에 따라 더욱 심해졌다. 진정염색질이 증가하였고 무과립형질내세망의 증가와 종창, 과립형질내세망의 종창, 골지복합체의 종창 및 폴리리보솜이 관찰되었다. 사립체의 종창, 전자밀도 저하 및 능선의 소실이 관찰되었고, 혈소판과 섬유소의 응집으로 인한 미소혈전이 동모양혈관내에서 관찰되었다. 72시간 후 Kupffer 세포의 이차리소솜이 감소되었으며, 120시간후 Kupffer 세포는 형태학적으로 대조군과 큰 차이는 없었다. 간세포는 1시간 후 지방변성이 보였고, 16시간 후에는 저산소성 공포 및 괴사가 관찰되었다. 이상의 성적을 종합하면 Kupffer 세포는 음세포작용에 의해 내독소를 탐식하고 진정염색질의 양의 증가와 세포소기관의 증가에 의해 활성화되어 리소솜의 형성을 증가시켜 내독소를 분해하고 해독화하여 간세포의 방어에 중요한 역할을 하며 내독소에 의한 간 상해는 간세포에 대한 직집적인 독성작용이라기 보다는 이러한 Kupffer 세포의 탐식과 분해하는 기능부전과 동모양혈관내 미소혈전 형성에 의한 허혈이 간 상해를 일으키는데 관여하였을 것으로 생각되었다.

• Asian-Australasian Journal of Animal Sciences
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• 제33권4호
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• pp.605-614
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• 2020

Objective: This study was conducted to determine the effects of stale maize on growth performance, immunity, intestinal morphology, and antioxidant capacity in broilers. Methods: A total of 800 one-day-old male Arbor Acres broilers (45.4±0.5 g) were blocked based on body weight, and then allocated randomly to 2 treatments with 20 cages per treatment and 20 broilers per cage in this 6-week experiment. Dietary treatments included a basal diet and diets with 100% of control maize replaced by stale maize. Results: The content of fat acidity value was higher (p<0.05) while the starch, activities of catalase and peroxidase were lower (p<0.05) than the control maize. Feeding stale maize diets reduced (p<0.05) average daily feed intake (ADFI) throughout the experiment, feed conversion ratio (FCR) during d 0 to 21 and the whole experiment as well as relative weight of liver, spleen, bursa of Fabricius and thymus (p<0.05) on d 21. Feeding stale maize diets decreased jejunum villus height (VH) and VH/crypt depth (CD) (p<0.05) on d 21 and 42 as well as ileum VH/CD on d 42. The levels of immunoglobulin G, acid α-naphthylacetate esterase positive ratios and lymphocyte proliferation on d 21 and 42 as well as lysozyme activity and avian influenza antibody H₅N₁ titer on d 21 decreased (p<0.05) by the stale maize. Feeding stale maize diets reduced (p<0.05) serum interferon-γ, tumor necrosis factor-α, interleukin-2 on d 21 and interleukin-6 on d 21 and 42. Broilers fed stale maize diets had lower levels of (p<0.05) total antioxidative capacity on d 42, superoxide dismutase and glutathione peroxidase on d 21 and 42, but higher (p<0.05) levels of malondialdehyde on d 21 and 42. Conclusion: Feeding 100% stale maize decreased ADFI and FCR, caused adverse effects on immunity and antioxidant function and altered intestinal morphology in broilers.

• Asian-Australasian Journal of Animal Sciences
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• 제32권10호
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• pp.1540-1547
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• 2019

Objective: This study was conducted to evaluate the effects of tannins and cellulase on growth performance, nutrient digestibility, blood profiles, intestinal morphology, and carcass characteristics in Hu sheep. Methods: A total of 48 three-month-old meat Hu sheep ($25.05{\pm}0.9kg$) were blocked based on body weight, and randomly allotted to 4 treatments with 3 replicates of 4 sheep each. The experiment lasted for 80 d, and dietary treatments were as follows: i) CON, control diet; ii) TAN, CON+0.1% tannins; iii) CEL, CON+0.1% cellulase; iv) TAN+CEL, CON+0.1% tannins and 0.1% cellulase. Results: Compared with CON, CEL, and TAN+CEL had greater (p<0.05) final body weight (FBW) and average daily gain but lower (p<0.05) feed conversion ratio, while FBW of TAN+CEL was lower (p<0.05) than that of CEL. The apparent total tract digestibility (ATTD) of dry matter in TAN, CEL, and TAN+CEL groups were higher (p<0.05) than that in CON. CEL and TAN+CEL groups had greater (p<0.05) ATTD of crude fiber compared with TAN and CON, while TAN group had lower (p<0.05) ATTD of crude protein than other treatments. TAN, CEL, and TAN+CEL groups increased (p<0.05) serum globulin and alkaline phosphatase but decreased (p<0.05) albumin/globulin. Serum total protein was greatest for TAN+CEL, intermediate for TAN and CEL and least for CON (p<0.05). TAN+CEL group increased (p<0.05) dressing percentage compared with CON, while the backfat thickness of CEL was lower (p<0.05) than that of CON. The villus height of jejunum and ileum in CEL and TAN+CEL groups were greater (p<0.05) than that in CON, and the crypt depth and villus height: crypt depth of jejunum were increased (p<0.05) in TAN, CEL, and TAN+CEL groups. Conclusion: The addition of tannins and cellulase together promoted nutrient digestion, liver protein synthesis and intestinal development and thus improved growth performance and carcass characteristics.