• Proceedings of the Korean Society of Toxicology Conference
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• 2005.05a
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• pp.108-108
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• 2005

• Biomolecules & Therapeutics
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• v.30 no.2
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• pp.126-136
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• 2022

Liver fibrosis is part of the wound healing process to help the liver recover from the injuries caused by various liver-damaging insults. However, liver fibrosis often progresses to life-threatening cirrhosis and hepatocellular carcinoma. To overcome the limitations of current in vivo liver fibrosis models for studying the pathophysiology of liver fibrosis and establishing effective treatment strategies, we developed a new mouse model of liver fibrosis using polyhexamethylene guanidine phosphate (PHMG-p), a humidifier sterilizer known to induce lung fibrosis in humans. Male C57/BL6 mice were intraperitoneally injected with PHMG-p (0.03% and 0.1%) twice a week for 5 weeks. Subsequently, liver tissues were examined histologically and RNA-sequencing was performed to evaluate the expression of key genes and pathways affected by PHMG-p. PHMG-p injection resulted in body weight loss of ~15% and worsening of physical condition. Necropsy revealed diffuse fibrotic lesions in the liver with no effect on the lungs. Histology, collagen staining, immunohistochemistry for smooth muscle actin and collagen, and polymerase chain reaction analysis of fibrotic genes revealed that PHMG-p induced liver fibrosis in the peri-central, peri-portal, and capsule regions. RNA-sequencing revealed that PHMG-p affected several pathways associated with human liver fibrosis, especially with upregulation of lumican and IRAK3, and downregulation of GSTp1 and GSTp2, which are closely involved in liver fibrosis pathogenesis. Collectively we demonstrated that the PHMG-p-induced liver fibrosis model can be employed to study human liver fibrosis.

• YAKHAK HOEJI
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• v.38 no.2
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• pp.166-173
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• 1994

Sex hormones not only regulate external sexual characteristics but several internal biochemical processes. It is well accepted that life-span of female is longer than that of male. Life-span is closely related with aging process in which free radicals are known to be involved. We investigated the effect of testosterone on free radical generating systems and lipid peroxidation based on the sexual difference. Lipid peroxide levels of male and female mouse were increased proportionately with age, especially in male mouse. Increase in enzyme activity of aldehyde oxidase with age was observed in male mouse, while no siginificant change in enzyme activity was found in female mouse. Enzyme activity of xanthine oxidase also showed similar results. It, however, was not significant statistically. Lipid peroxide level and xanthine oxidase type conversion ratio of male and female mouse liver homogenate incubated at $37^{\circ}C$, increased remarkably in proportion to incubation time, especially in male mouse. Lipid peroxide level and aldehyde oxidase activity were measured in normal male mouse, castrated mouse and testosterone treated-castrated mouse. Castrated mouse group showed decrease in lipid peroxide level and aldehyde oxidase activity compared with normal group. Treatment of castrated mouse with testosterone, however turned the level of lipid peroxide and aldehyde oxidase activity back to normal. From the above results, it might be concluded that testosteron could increase the activities of free radical generating enzymes which would result in the formation of lipid peroxide, consequently leading to aging.

• Journal of Photoscience
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• v.9 no.2
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• pp.415-417
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• 2002

Juvenile visceral steatosis (JVS) mouse is an animal model of the systemic camitine deficiency. JVS mice first develop fatty liver following cardiac hypertrophy. hyperammonemia, etc. To clarify the relationship between fatty liver and other symptoms. lipid hydroperoxides levels of peripheral oragans in JVS mice at 1 month were determined by the use of phosphine derivatives. We also report here a new method to quantitate the lipid components level in fatty liver of JVS mice.

• Archives of Pharmacal Research
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• v.19 no.6
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• pp.514-519
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• 1996

In order to understand the mechanism of action of flavonoids on the drug metabolizing enzyme, cytochrome P450IA1, this study was undertaken to examine the effect of chrysin, morin, myricetin and aminopyrine on the activities of ethoxyresorufin O-deethylase and benzo(.alpha.) pyrene hydroxylase in the liver. In the isolated perfused rat liver that was pretreated with 3-methylcholanthrene (3MC), chrysin, morin, myricetin and aminopyrine inhibited the activity of ethoxyresorufin O-deethylase with concentration dependent manner. The isolated liver perfusion with chrysin, morin, myricetin and aminopyrine showed inhibition on the induction of ethoxyresorufin O- deethylase by 3MC. And also, in mouse liver hepa I cells, 3MC-stimulated the benzo(.alpha.)pyrene hydroxylase activity which was inhibited by chrysin, morin, myricetin and aminopyrine. These results strongly suggested that hydoxylated flavonoids interfered not only the induction of cytochrome P45OIA1 enzymes by 3MC but also the interaction of substrates and enzyme.

• Applied Microscopy
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• v.30 no.4
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• pp.327-335
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• 2000

The aim of this study was to discover whether Yukmijihwangtang which was added Plygalae Radix, Acori graminei Rhizoma, has antioxidant effects on aged senescence-accelerated mouse (SAM) P8. The control group used 12 months old SAM P8 and the experimental group was treated with Yukmijihwangtang extracts from 8 to 12 months old. In the liver, the MnSOD of the control group were approximately 11% higher than that of the experimental group treated with herbal extracts, but CuZnSOD activities of the experimental group were approximately 20% higher than that of the control group. The catalase activities of the experimental group was approximately 67% higher than that of the control group. The hepatocytes, in the control group compared with the experimental group, contained the dilated cisternae of rough endoplasmic reticulum and the abnormal mitochondira which had electron-dense matrix and indistinguishable cristae. The inner cavity of the smooth endoplasmic reticulum were slightly dilated, and a number of vacuoles and transitional vesicles occured in of the hepatocytes of the control group. These results suggest that the herbal extract has an antioxidant effects on the liver of SAM P8.

• Applied Microscopy
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• v.32 no.3
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• pp.231-246
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• 2002

This study was carried out to investigate the effect of squalene (SQ) on the mouse hepatotoxicity induced by cadmium. ICR male mouse weighting about 30 gm were injected $CdCl_2$ (5.0 mg/kg) and SQ (180 mg/kg) into intraperitoneal. At the 1, 2, 3, 4, 5, 6, 7 days, livers were treated with superoxide dismutase (SOD) activity and transmission electron microscopical method and then observed with electron microscope. The results obtained were summarized as follows: SOD activity in the liver, Group A was higher than in normal. Group B was lower than in Group A. In the histological observation, nucleus of Group A showed irregular shape. Inner cavity of mitochondria swellen and development of cristae weakened. Swelling of Lamellae of rough endoplasmic reticulum (RER) showed. Nucleus of group B showed normal shape. Typical lamellae of RER were observed. These results described above treatment of SQ decreased the hepatotoxicity of the $CdCl_2$ and SOD activity in the mouse liver, and then it suggests SQ may be effective for the recovery of hepatic cell.

• Reproductive and Developmental Biology
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• v.38 no.3
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• pp.99-105
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• 2014

In this study, to further understand the mechanism of animal growth and to develop a miniature transgenic animal model, we constructed and tested tetracycline-inducible RNAi system using shRNA targeting the mRNA of mouse insulin-like growth factor (mIGF-1) or mouse growth hormone receptor (mGHR) gene. Quantitative real-time PCR analysis of mouse liver cell (Hepa1c1c7) cells transfected with these vectors showed 85% or 90% of expression inhibition effect of IGF-1 or GHR, respectively. In ELISA analysis, the protein level of IGF-1 in the cells expressing the shRNA targeting IGF-1 mRNA was reduced to 26% of non-transformed control cells. Unexpectedly, in case of using shRNA targeting GHR, the IGF-1 protein level was decreased to 75% of control cells. Further experiments are needed to explain the lower interference effect of GHR shRNA in IGF-1 protein. Accumulated knowledge of this approach could be applicable to a variety of related biological area including gene function study, gene therapy, development of miniature animals, etc.

• Biomedical Science Letters
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• v.6 no.1
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• pp.45-53
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• 2000

The anti-oxidative effects of Korean red ginseng extracts (total saponine, water extracts, alcohol extracts, lipophilic extracts), which were administered with the concentration of 200 mg/kg BW, were investigated after the injection of paraquat (1,1-dimethyl-4,4-bipyrimidinium dichloride: PQ) with dosage of 100 mg/kg BW on the peritoneal cavity to 6 weeks of 23~26 gm ICR male mice. The accumulation of hydrogen peroxide ($H_2O$$_2$) on the liver of mouse was lowered only in alcohol extract-treated group (p<0.05). The activity of glutathione peroxidase increased in the mouse treated with lipophilic ginseng extracts. And GSSG level was lowered in all groups, and this might be due to the paraquat ions that might prevent the reaction of GSSG into GSH. But we cannot find any relation between glutathione oxide-reductase activity on Korean ginseng extracts. Finally, the lipid peroxidation (MDA) level was lowest (p<0.01) in the group of mouse treated with water extracts of ginseng.

• International Journal of Industrial Entomology and Biomaterials
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• v.2 no.1
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• pp.15-18
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• 2001

Silk fibroin (SF) derided from the domestic silk worm, bombyx mori, is the natural protein and widely used as bio-functional materials as well as apparels. We studied the livers protective effect of SF from alcohol-induced hepatotoxicity in the alcohol preference mouse. To increase more absorption of SF in experimental animals, molecular weight of SF was lowered by 2N of HCI aqueous solution at 10$0^{\circ}C$ for 48 hrs. SF was added to liquid diet with alcohol and fed to the alcohol preference mice for 4 weeks. To assess the liver function, the concentration of alanine aminotransferase (AlT), aspartate aminotransferase (AST) and cholesterol present in either blood or liver tissue were measured. As compared with non-SF treated groups the SF-treated showed significantly low concentrations of ALT, AST, cholesterol and triacylglycerol values, respectively. Histopathological examination revealed that the extent of hepatocyte injury in the SF-treated group was reduced when it was compared with non SF-treated group. These results suggest that SF may have liver protective effects against alcohol-induced hepatotoxicity.