• Proceedings of the Ginseng society Conference
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• 1990.06a
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• pp.58-64
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• 1990

The effects of ginseng saponins, G-Rbl and G-Rc on the rat liver LDH A-gene transcnptional activity was investigated during pro-replicative phase of rat liver after partial hepatectomy. Changes in LDH A-mRNA levels in regenerating rat liver after intraperitoneal administrations of G-Rbl of G-Rc were tested by slot blot hybridization methods. The results showed that G-Rbl (1 mg/100g B.W) and G-Rc (1 ma/100g B.W) caused marked increases of LDH A-mRNA contents by respectively 1.9- and 1.5-fold in rat liver at 5·hours after partial hepatectomy. Dose dependent effect of G-Rbl and G-Rc (1-25 mg/100g B.W) on the LDH A-mRNA levels on regenerating rat liver were also analyzed. The maximal in- creases of liver LDH A-mRNA levels were observed with the doses of 1 mg for G-Rbl and 5 mg for G-Rc However, when the administration doses of G-Kbl and G-Rc were increased to 20 mg, G-Rbl caused a marked decrease of LDH A-mRNA level to 61% of those in sham-operated rat liver In contrast, G-Rc slightly decreased the liver LDH A-mRNA contents by 30% as compared to those of the maximum value but still maintained 22% higher LDH A-mRNA levels then those of sham-operated rate liver. On the basis of these experimental results, we conclude that ginseng saponin, G-Rb 1 and G·Rc have stimulatory effect at the lower concentration (1 mg/100g B.W) and inhibitory effect at the higher concentration (20 moi loos 5.W) on the LDH A-gene transcription during regeneration of rat liver, Additionally we also investigated the stimulatory effects of ginsenosides on the protein and DNA synthetic activities in hepatocyte primary cell cultures isolated from regenerating rat liver. Both of G·Rc and -Re increased the synthetic rates of hepatocytes proteins and DNA at the administration doses of 50 ug and 100 ug/3 ml/dish respectively representing 1.3-1.6 fold increases. From these results we postulate that G-Rc and -Re may have a mitogen enhancer activity for the hepatocyte proliferation during rat liver regeneration period. Keywords Inductive effects of ginsenosides, G-Rb, -Rc, and -Re, rat LDH A-gene transcription, the sin thetic rate of proteins and DNA in regeneration rat liver.

• Toxicological Research
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• v.22 no.4
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• pp.323-328
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• 2006

Global gene expression profile was analyzed by microarray analysis of rat liver RNA after acute acetaminophen (APAP) administration. A single dose of 1g/kg body weight of APAP was given orally, and the liver samples were obtained after 24, 48 h, and 2 weeks. Histopathologic and biochemical studies enabled the classification of the APAP effect into injury (24 and 48 h) and regeneration (2 weeks) stages. The expression levels of 4900 clones on a custom rat gene microarray were analyzed and 484 clones were differentially expressed with more than a 1.625-fold difference(which equals 0.7 in log2 scale) at one or more time points. Two hundred ninety seven clones were classified as injury-specific clones, while 149 clones as regeneration-specific ones. Characteristic gene expression profiles could be associated with APAP-induced gene expression changes in lipid metabolism, stress response, and protein metabolism. We established a global gene expression profile utilizing microarray analysis in rat liver upon acute APAP administration with a full chronological profile that not only covers injury stage but also later point of regeneration stage.

• Biomedical Science Letters
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• v.11 no.1
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• pp.45-49
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• 2005

The change of catechol-O-methyltransferase (COMT) activity during regeneration of rat liver was studied. Cytosolic, mitochondrial and microsomal COMTs activities were estimated in regenerating rat livers over a period of ten days after $70\%$ (median and left lateral lobes) partial hepatectomy. The values of Km and Vmax in the hepatic enzymes were also measured. The activities of cytosolic and microsomal COMTs in regenerating rat liver after partial hepatectomy were found to be significantly increased between the second and the third day. Whereas the mitochondrial COMT activity did not change. The Vmax values of the cytosolic and microsomal COMTs in the regenerating rat liver were significantly increased at the second day after partial hepatectomy, however, the Km values of the above hepatic enzymes did not vary in all the experimental groups. Therefore, the results suggest that the biosynthesis of COMT was increased during the regeneration of rat liver.

• Journal of Ginseng Research
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• v.14 no.2
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• pp.200-206
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• 1990

The effects of ginseng saponins, SRbl and G-Rc on the rat liver LDH A-gene transcriptional activity was investigated during prereplicative phase of rat liver after partial hepatectomy. Changes in LDH A-mRNA levels in regenerating rat liver after intraperitoneal administrations of G-Rbl or 'G-Rc were tested by slot blot hybridization methods. The results showed that G-Rbl (1 mg/100g B.W) and G-Rc (1 mg/100g B.W) caused marked increases of LDH A-mRNA contents by respectively 1.9- and 1.5-fold in rat liver at 5-hours after partial hepatectomy Dose dependent elect of G-Rbl and G-Rc (1-25 mg/ 100g B.W) on the LDH A-mRNA levels on regenerating rat liver were also analyzed. The maximal increases of liver LDH A-mRNA levels were observed with the doses of 1 mg for G-Rbl and 5 mg for G-Rc. However, when the administration doses of G-Rbl and G-Rc were increased to 20 mg, G-Rbl caused a marked decrease of LDH A-mRNA level to 61% of those in sham-operated rat liver. In contrast, G-Rc slightly decreased the liver LDH A-mRNA contents by 30% as compared to those of the maximum value but still maintained 22% higher LDH A-mRNA levels then those of sham-operated rate liver. On the basis of these experimental results, we conclude that ginseng saponin, G-Rbl and G-Rc have stimulatory effect at the lower concentration (1 mg/ 100g B.W) and inhibitory effect at the higher concentration (20 mg/ 100g B.W) on the LDH A-gene transcription during regeneration of rat liver. Additionally we also investigated the stimulatory effects of ginsenosides on the protein and DNA sinthetic activities in hepatocyte primary cell cultures isolated from regenerating rat liver. Both of G-Rc and -Re increased the synthetic rates of hepatocytes proteins and DNA at the administration doses of 50 us and 100 $\mu\textrm{g}$/3 ml/dish respectively representing 1.3-1.6 fold increases. From these results we postulate that G-Rc and -Re may have a mitogen ehincer activity for the hepatocyte proliferation during rat liver regeneration period.

• YAKHAK HOEJI
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• v.32 no.4
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• pp.239-244
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• 1988

Transcriptional rate of lactate dehydrogenase A-gene(LDH-A) during the prereplicative phase of regenerating rat liver was determined by in vitro run-off transcription assay. The results show that the transcription rate of LDH A-gene increases between 12 hours and 15 hours peaking at 13 hours after partial hepatectomy of rat liver. The increased rate of LDH A-gene transcription was interfered after DL-propranolol treatment intraperitoneally injected twice at 1 hour and 8 hours after partial hepatectomy indicating that the transcriptional control of LDH A-gene expression may be mediated by beta adrenergic receptor and cAMP as a second messenger. And also was it shown that the temporally increased rate of LDH A-gene transcription was maximum one hour after the second cAMP-surge which is known to play an important role for the initiation of DNA replication during regeneration of rat liver. And the transcriptional rate of LDH A-gene was decreased to the basal level at the time period when the hepatocytes proliferate rapidly suggesting that the induced LDH Aisozyme may be required for the initiation of DNA replication during regeneration of rat liver. These data may be supporting for the hypothesis suggesting that the induced LDH A-isozyme during the pre-replicative phase of regenerating rat liver may play bifunctional roles as a glycolytic enzyme and a helix destablizing protein as well.

• Applied Microscopy
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• v.18 no.2
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• pp.205-217
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• 1988

An ultrastructural study of hepatocyte proliferation in the regenerating rat liver has been made by means of the partial hepatectomy. And electron microscopic histochemistry of hepatocyte in the regenerating rat liver is studied through alkaline phosphatase reaction. The results are as follows: 1. When the regeneration of rat liver is induced by the partial hepatectomy, the prominent ultrastructural characteristics of hepatocyte are changes of the distribution of chromatin in nucleus, increase of the number of mitochondria and decrease of the size of them, development of rough endoplasmic reticulum, and transient decrease of glycogen granules in cytoplasm. 2. Alkaline phosphatase reaction products are appeared in the nucleus or rough endoplasmic reticulum of hepatocyte during the initial regeneration of liver as 24, 48 and 72 hour groups after partial hepatectomy. And these positive reaction are mainly increased in cytoplasm and plasma membrane of hepatocytes during 1, 2 and 3 week groups after partial hepatectomy. As 4 weeks passed after partial hepatectomy, these positive reaction is located in the sinusoidal epithelial cells or erythrocytes. With above results, we concluded that alkaline phosphatase was synthesized in the rough endoplasmic reticulum bounded ribosomes of regenerating hepatocyte, was transported to the plasma membrane of them, and then was transported in blood by the way sinusoidel epithelial cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.13 no.4
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• pp.451-458
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• 1984

The effects of branched chain amino acids added to a diet on changes in the body weight with or without liver, moist and dry liver weight, protein, DNA, $^3H-thymidine$ incorporation into DNA, ana mitotic index of regenerating liver were studied in partial hepatectomized rat. Experimental diet was a 14.63% casein diet supplemented with 1.49% L-leucine, 0.90% L-isoleucine and 0.98% L-Valine, and control diet was an 18.0% casein. In both diets, 2.54% nitrogen were included. Rats fed experimental diet were significantly increased body weight with or without liver 7 days, and regenerated weight of dry liver and an index of liver regeneration 5 days after partial hepatectomy. Mitotic index, contents of protein and DNA increased in regenerating liver after partial hepatectomy was higher in experimental diet group. This results suggest that branched chain amino acids have an benefitial effect on whole body as well as liver regeneration after partial hepatectomy in rat.

• Animal cells and systems
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• v.5 no.3
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• pp.263-266
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• 2001

Metallothionein (MT) is induced in the regenerating rat liver. We have investigated expression of MT gene by RT PCR as well as specific localization of MT by immunocytochemistry in regenerating rat liver after partial hepatectomy (PH). MT mRNA level started to increase from 1 h and reached the peak at 8 h after PH. The level decreased gradually by 24 h, and became similar to that of control group. In the immunocytochemical study, in all groups treated with primary antibody, immunogold particles indicating the presence of MT were evenly distributed throughout both cytoplasm and nucleus of the rat hepatocytes. Within the nucleus, the gold particles appeared to be intensely localized in the areas of euchromatin and nucleolus. Within the cytoplasm, gold particles did not seem to adhere to mitochondria or Iysosomes, but were freely distributed. However, rough endoplasmic reticulum was the obvious compartment on which the gold particles were localized. Time course of MT immunoreactivity revealed that distribution of gold particles in hepatocytes increased gradually by 24 h, and decreased at 48 h after PH. Briefly, PH resulted in the sharpest increase in the expression of MT mRNA at 8 h and in the immunoreactivity of MT at 24 h, respectively. It is suggested that the increase of MT mRNA expression, the intensity of immunoreactivity and the specific localization of MT may be associated with the compensatory cell proliferation followed by PH.

• Korean Journal of Veterinary Research
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• v.44 no.2
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• pp.185-193
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• 2004

The effects of membrane lipid peroxidation and retinyl palmitate on rat liver microsomal functions were investigated in vitro. Rat liver homogenates exposed to oxygen tension for 0, 3, 6, 9 or12 hours and lipid peroxidation levels were evaluated by the measurements of fluorescence intensity, malondialdehyde (MDA) and retinyl palmitate. The fluorescence intensity of homogenates and microsomes were elevated and retinyl palmitate concentrations were decreased. But the concentration of MDA was not affected to exposure time. Therefore, fluorescence intensity and retinyl palmitate concentration were used to analyze the correlation between lipid peroxidation and microsomal functions. To investigate the liver microsomal functions, the microsome was isolated from rat liver homogenates exposed to oxygen. The concentration of cytochrome P450 and the activity of NADPH-cytochrome P450 reductase in liver microsomes were gradually decreased with increasing the exposure time. The correlation between fluorescence intensity of microsomes showed a very high inverse correlation of -0.97 and -0.93, respectively. The decrease of cytochrome P450 concentration was due to the regeneration of cytochrome P450 to cytochrome P420. Also, the activities of cytochrome P450-dependent aminopyrine demethylase and benzpyrene hydroxylase of liver microsomes were gradually decreased with increasing the exposure time. The correlation with fluorescence intensity of microsome showed a high inverse correlation of -0.97 and -0.91, respectively. The retinyl palmitate concentrations of rat liver homogenates were decreased with increasing the exposure time. The decrease of retinyl palmitate concentration was followed by a low concentration of cytochrome P450 and activity of NADPH-cytochrome P450 reductase. The correlation indicated high direct correlation of 0.92 and 0.93, respectively. The decrease of retinyl palmitate concentration was also accompanied by the reduction of aminopyrine demethylase and benzpyrene hydroxylase activities. The correlation was analyzed a high direct correlation of 0.90 and 0.85, respectively. In conclusion, these studies have shown that the membrane lipid peroxidation of rat liver microsome proportionally decreased microsomal enzyme activities in vitro experiments.

• Archives of Pharmacal Research
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• v.20 no.3
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• pp.239-246
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• 1997

In the present study, liver regeneration rate (%) was increased up to 70% 3 days after partial hepatectomy (PH). Nitric oxide synthase (NOS) activity in liver tissue as well as serum nitrite/ nitrate content had no timed response, revealing no significant difference between shamoperated and partially hepatectomized rat liver. Contents of free methylarginines in liver tissue were increased biphasically in a time-dependent manner after PH. However, those in serum did not exhibit the same patterns as in liver. Taken together, the results suggest that $N^{G}$-monomethyl-L-arginine (MMA) and $ N^{G}, N^{G}$-dimethylarginine (DMA) play a role in inhibiting nitric oxide (NO) synthesis in regenerating rat liver because the increase of their contents was synchronized with NOS expression.