• Biomolecules & Therapeutics
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• v.17 no.4
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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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• v.23 no.5
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• pp.381-386
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• 2008

Lipophilic ammonia is toxic gas and can easily diffuse across cell membranes. Excess ammonia is implicated in the pathogenesis of several metabolic disorders including hepatic encephalopathy and may result in the death. The purpose of this study was to clarify the inhibition effect of metronidazole on liver cell damage due to ammonia in human Hep G2 cell and rat hepatocytes. The effects of metronidazole were studied in ammonium chloride treated human Hep G2 cell (75 mM) and rat hepatocyte (100 mM) following $0.1{\mu}M$ metronidazole treatment. In MTZ+AC group, cell viabilities increased prominently and LDH activities decreased over 25% than AC group. Furthermore, ammonia level according to ammonium chloride treatment reduced over 30% and lipid peroxidation as an index of cell membrane damage decreased more than twice. By comparison with control, catalase activity showed more than 30% reduction in AC group while less than 10% reduction in MTZ+AC group, respectively. In addition, MTZ+AC group showed the similar cell structure as control in cell morphology study by using light microscope, and represented fluorescent intensity decrement compared with AC group in fluorescent microscopic study with avidin-TRITC fluorescent dye. And cleaved PARP expression due to ammonia reduced twofold or more in MTZ+AC group. As the results suggest, metronidazole may protect the liver cell by inhibiting cell damages due to ammonia and be used for an effective antagonist of ammonia in hyperammonemia.

• Toxicological Research
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• v.29 no.3
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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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.14 no.1
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• pp.27-32
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• 1985

For the purpose of investigating the influence of pollen load un alcohol metabolism in rat, we analyzed quantitatively amino acids of pollen load, and investigated the changes of hepatic alcohol dehydrogenase(ADH) activity and hepatocyte morphology in rat administrated various concentrations of alcohol and various amounts of pollen load. 18 species of amino acids including phenylalanine in the sunflower pollen load were quantitatively analyzed, and it was found that the amount of phenylalanine, leucine, threonine, lysine are especially higher than that of the other amino acids. The liver ADH activity of experimental animals decreased with the proportion of ethanol concentration much more in ethanol administrated group than in control group, while increased in pollen load mixed with ethanol administrated group, but didn't increased as much as that in control group. In any case the less the degree of ethanol concentration was administrated, the higher the liver ADH activity increased. There was fat infiltration in the hepatocyte of ethanol administrated animals, and remarkably little fat infiltration in that of animals administrated pollen load mixed with ethanol.

• Korean Journal of Veterinary Pathology
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• v.6 no.1
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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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• v.9 no.4
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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.

• Journal of Korean Medicine Rehabilitation
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• v.33 no.3
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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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• v.10 no.2
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• pp.313-337
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• 1993

The aim of this study was to clarify the role of Kupffer cells in the mechanism of endotoxin-induced liver injury. The study on fine structure of Kupffer cells was performed after the injection of endotoxin. The endotoxin(Escherichia coli lipopolysaccharide 026 : B6. 1.5mg/100 g of body weight) was intraperitoneally injected in Sprague-Dewley rats. Animals were sacrificed at 1/4, 1/2, 1, 2, 4, 8, 16, 24, 72 and 120 hours after the injection of endotoxin. Livers were extirpated and processed to be examined by light and electron microscopy. The results obtained were summerized as follows: Early changes observed in liver after endotoxin injection included the increased number and hypertrophy of Kupffer cells, infiltration of neutrophils and presence of fibrin thrombi within the sinusoids. The continuous increase of the Kupffer cells in number with hypertrophy, congestion and infiltration of inflammatory cells within the sinusoids were observed. Hepatocytes showed fatty change and occasional necrosis. At 72 hours the congestion decreased. At 120 hours the number of Kupffer cells was increased, but the morphology of Kupffer cells became similar to that of the control group. The numbers and sizes of primary and secondary lysosomes and amount of euchromatin of Kupffer cells increased. Swellings and increase in number of mitochondria, Golgi complex, smooth endoplasmic reticulum, rough endoplasmic reticulum were evident. Microthrombi were present within the sinusoids. The swelling of rough endoplasmic reticulum and mitochondria, decrease of glycogen particles, fatty change, hypoxic vacuoles, pyknotic nuclei and occasional necrosis were observed in hepatocytes. At 72 hours the number of secondary lysosomes in Kupffer cells decreased. At 120 hours the morphology of Kupffer cells became similar to that of the control group. According to these results, it was postulated that the endotoxin was initially taken up by pinocytosis into Kupffer cells and degraded in secondary lysosomes of activated Kupffer cells. Kupffer cells may play an important role in the defense mechanism of liver during endotoxemia. The dysfunction of Kupffer cells and ischemia by sinusoidal microthrombi may cause liver injury.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.4
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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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• v.32 no.10
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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.