• Applied Microscopy
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• v.29 no.3
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• pp.363-376
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• 1999

This study aims to demonstrate the effect of chitosan oligosaccharide on the ultrastructural changes in the mouse liver toxicated by carbon tetrachloride $(CCl_4)$. A healthy male ICR mouse that weighted $27{\pm}2gm$ was used for experiment. The experimental group was divided into three groups; the group A; the pretreated group with chitosan oligosaccharide, the group B; the simultaneous group, the group C; treated only the $CCl_4$. The group A was simultaneously treated with chitosan oligosaccharide and $CCl_4$ after pretreated with chitosan oligosaccharide for 7 days. The group B injected $CCl_4$ and chitosan oligosaccharide to the intraperitoneal. The group C injected with only $CCl_4$ to the intraperitoneal. The results were as follow: In the group A, the nuclear membrane and the mitochondria were observed almost normal in shapes at overall the time. Some lamellae of the RER (rough endoplasmic reticulum) destructed until 48 hours but ribosome attached. The destructed lamellae reformed at 72 hours but the smooth membrane vesicles not observed. The lysosomes observed at 72 hours. At 96 hours, all organelles showed in normal shapes. In the group B, changes of nuclear membranes were relatively lighter than group C. Mitochondria observed normal shape through the time. Parts of RER reformed the lamellae, other parts dilated inner cavity. And lipid droplet observed around the 24 hours. Glycogen and lysosome observed 48 hours and 72 hours, respectively. In the group C, nuclear membrane was irregular and nuclear cytoplasm condensed through the time. The lamellae of RER destructed from 24 to 96 hours. Smooth membrane vesicles observed in the cytoplasm at 48 ours. Mitochondria was less effected by toxic. And from the 24 hours, the variable sizes of lipid droplets observed in tile cytoplasm. These results suggest that chitosan oligosaccharide attenuates the toxic effect of the carbon tetrachloride in the mouse liver.

• BMB Reports
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• v.36 no.5
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• pp.450-455
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• 2003

Antioxidant enzymes are scavenger reactive-oxygen intermediates and are involved in many cellular defense systems. We previously reported that a crude extract of Garnoderma lucidum, a medicinally potent mushroom, profoundly increased the catalase gene expression and enzyme activities in mouse livers (Park et al., J. Biochem. Mol. Biol. 34. 144-149, 2001). In this study, we elucidated the detailed mechanism whereby G. lucidum stimulates the catalase activity and expression. The major active fraction was isolated from G. lucidum and methyl linoleate was considered the most major component of the fraction. In order to determine whether methyl linoleate increases mRNA and protein synthesis of catalase, Northern and Western blot analyses were performed in vivo with methyl linoleate-treated mouse liver homogenate after feeding methyl linoleate to the mice. Northern and Western blot analyses of the crude liver homogenates in the mice that were administered methyl linoleate revealed that the expression catalase was significantly increased when compared to the untreated controls. In addition, the catalase protein levels and enzymatic activities increased in the mouse liver homogenates. These results suggest that methyl linoleate that is produced by G. lucidum stimulates the catalase expression at the transcription level.

• Molecular & Cellular Toxicology
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• v.3 no.3
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• pp.177-184
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• 2007

As a possible feasibility of the extrapolation between in vivo and in vitro systems, we investigated the global gene expression from both mouse liver and mouse hepatic cell line treated with hepatotoxic chemical, acetaminophen (APAP), and compared between in vivo and in vitro genomic profiles. For in vivo study, mice were orally treated with APAP and sacrificed at 6 and 24 h. For in vitro study, APAP were administered to a mouse hepatic cell line, BNL CL.2 and sampling was carried out at 6 and 24 h. Hepatotoxicity was assessed by analyzing hepatic enzymes and histopathological examination (in vivo) or lactate dehydrogenase (LDH) assay and morphological examination (in vitro). Global gene expression was assessed using microarray. In high dose APAPtreated group, there was centrilobular necrosis (in vivo) and cellular toxicity with the elevation of LDH (in vitro) at 24 h. Statistical analysis of global gene expression identified that there were similar numbers of altered genes found between in vivo and in vitro at each time points. Pathway analysis identified glutathione metabolism pathway as common pathways for hepatotoxicty caused by APAP. Our results suggest it may be feasible to develop toxicogenomics biomarkers or profiles by comparing in vivo and in vitro genomic profiles specific to this hepatotoxic chemical for application to prediction of liver toxicity.

• The Journal of Korean Medicine
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• v.31 no.5
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• pp.124-135
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• 2010

Background and Objective: Atherosclerosis is a diffuse, systemic disease that affects the coronary, cerebral, and peripheral arterial trees. Clopidogrel is widely used antiplatelet agent and its efficacy has been proven in cardiac and extracardiac vascular diseases, but it has several side effects. Therefore we investigated whether Sopunghwalhyeoltang, which is widely used for treating the blood stasis syndrome in traditional medicine, could decrease the side effect of antiplatelets and have a synergic effect. Methods & Materials: Male $ApoE^{(-/-)}$ mice were randomly divided into three different experimental groups, non-treated group (Control group), clopidogrel-treated group (CP group) and clopidogrel with Sopunghwalhyeol-tang treated group (CPS group). The control group was fed with only an atherogenic diet, the CP group an atherogenic diet plus clopidogrel 25mg/kg and the CPS group an atherogenic diet plus clopidogrel 25mg/kg with Sopunghwalhyeol-tang 100 mg/kg. We investigated plasma lipids with liver function test, and performed a histological investigation of liver and abdominal aorta. Results: 1. Photomicrographs of liver and abdominal aorta tissue showed lower histological injury and lipid accumulation in the CP and CPS groups than those in the Control group. 2. In the CPS group, plasma triglyceride level was significantly lower than in the Control and CP groups. 3. In the CPS group, the plasma aspartate aminotransferase (AST) level was significantly lower than in the CP group. Conclusions: The above results shows that a combined treatment of Sopunghwalhyeol-tang and clopidogrel have a synergic effect through inhibiting vessel injury and decrease the side effects of clopidogrel alone.

• YAKHAK HOEJI
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• v.40 no.4
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• pp.442-448
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• 1996

Mitomycin C(MMC) has been used as an anticancer drug and behaves as an alkylating agent forming covalent cross-link between complementary strands of double strand DNA. The purpose of this research was to determine number of DNA adducts, formed in vivo by Mitomycin C, in mouse organs. DNAs from liver, lung, brain and pancreas were isolated and used for $^{32}P$-postlabelling. The labeled nucleotides were separated by 2D-TLC and subjected to autoradiography. Numbers of MMC-DNA adducts were 9,9,5,4 in liver, pancreas, lung and brain, respectively.

• Reproductive and Developmental Biology
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• v.35 no.4
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• pp.415-420
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• 2011

The experimental manipulation of protooncogenes and their gene products is a valuable research tool for the study of human neoplasia. In this study, the recently identified human cervical cancer protooncogene (HccR-2) was expressed in transgenic mice under the control of the tetracycline regulatory system. Mice expressing the HccR-2 transgene showed an altered myeloid development characterized by an increased percentage of mature and band-form neutrophils in the peripheral blood, liver and spleen. This phenotype is similar to human chronic neutrophilic leukemia (CNL) in many ways, which is a rare chronic myeloproliferative disorder (CMD) that presents as a sustained leukocytosis of mature neutrophils with a few or no circulating immature granulocytes, an absence of peripheral blood monocytosis, basophilia, or eosinophilia, and an infiltration of neutrophils into the liver, spleen and kidney. Thus, the HccR-2 transgenic mouse model is imperative not only for investigating the biological properties of the HccR-2 protooncogene in vivo, but also for analyzing the mechanisms involved in the progression of CNL.

• Journal of Life Science
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• v.6 no.3
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• pp.159-164
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• 1996

Effects of 1% dietary orotic acid on triglyceride metabolism were examined in SD-rats and Kud: ddY mice. When rats were fed semisynthetic diet containing 1% orotic acid and n-6 polyunsaturated fatty acid (linoleic acid), the hepared diet. In contrast to rats which respond to orotic acid consumption with increases in hepatic triglyceride content, mice did not so respond. The rats-limiting step in triglyceride synthesis is catalyzed by the enzyme phosphatic acid phosphohydrolase (EC3.1.3.4) which is present in the liver cytosol and microsomes of rats fed oroic acid diet. This finding suggests that the activity of this enzyme may play a tole in the fatty liver formation in rats.

• YAKHAK HOEJI
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• v.49 no.6
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• pp.505-510
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• 2005

Allylthio group of allicin and other organosulfur compounds which are isolated from garlic is considered as a pharmacophore, a key structure component of the molecule which is responsible biological activities. In the foregoing studies various 3-allylthio -6- alkoxypyridazine derivatives (K- compounds ) and 3-allylthio -6- alkylthiopyridazine derivatives(Thio-K-compounds) were synthesized and their biological activities were tested in vivo. They showed good hepatoprotective activities on the carbon tetrachloride-treated mouse and aflatoxin Bl-treated rat and chemopreventive activities on bepatocarcinoma cells in rat as expected. Now 3-allylthio-6-heterocyclylalkylaminopyridazine derivatives that the oxygen atom at 6-Position of 3-allylthio-6-alkoxypyridazine is replaced by nitrogen (N) were synthesiz ed and their activities were tested in vitro against SK-Hep-1 human liver cancer cells. They showed good chemopreventive activities on hepatocarcinoma cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.27 no.5
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• pp.968-972
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• 1998

Allium tuberosum Rotter(Liliaceae) is a perennial herb of which leaves are used for food. Leek has been reported to have pharmacological effects including alleviations of abdominal pain, diarrhea, hematemesis, snakebite, and asthma. To investigate the effect of dietary leek supplementation on the drug-metaboizing enzymes, quinone reductase(QR) and arylhydrocarbon hydroxylase(AHH) activities in the liver, stomach, small intestine and lung, and on the plasma testosterone and dihydrosterone hormone levels, mice were fed 2% and 5% leek diets for 8 weeks. Quinone reductase, an anticarcinogenic enzyme, was significantly induced in stomach, small intestine, and lung but slightly lowered in hepatic tissue in the experimental groups compared to control group. Arylhydrocarbon hydroxylase activity, involved in bioactivation of procarcinogens, was significantly decreased in liver and lung. Leek feeding led to the reduction in the plasma level of dihydrotestosterone which is associated with the incidence of prostate cancer. These findings support the potential chemopreventive activity of leek supplementation.

• The Korean Journal of Malacology
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• v.8 no.1
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• pp.52-60
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• 1992

Clams were collected from mouth part of Mangeong Gang(river) of which heavy metals were heavily contaminated. Scapharca subcrenata, one of the clams, were fed to mice for 1-2 months with regular food stuffs. Eventhough difference of body weight was recognized between the experimental group and normal diat group, accumulation of heavy metals examined, cadmium was found 1.16 $\mu\textrm{g}$/gm in liver, 3.31 $\mu\textrm{g}$/gm in kidney and 0.21 $\mu\textrm{g}$/gm in blood of experimental group at 60th day, whereas 0.14 $\mu\textrm{g}$/gm, 0.35$\mu\textrm{g}$/gm and 0$\mu\textrm{g}$/gm respectively in normal diet group ate tje same period. No specific histo pathological finding was found in brain and kidney, although slighr fatty change and focal necrosis were found in liver tissues of the experimental group in second month.