• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8271-8279
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• 2016

Background: Hepato-carcinogenesis is multifaceted in its molecular aspects. Among the interplaying agents are altered gap junctions, the proteasome/autophagy system, and mitochondria. The present experimental study was designed to outline the roles of these players and to investigate the tumor suppressive effects of curcumin with or without mesenchymal stem cells (MSCs) in hepatocellular carcinoma (HCC). Materials and Methods: Adult female albino rats were divided into normal controls and animals with HCC induced by diethyl-nitrosamine (DENA) and $CCl_4$. Additional groups treated after HCC induction were: Cur/HCC which received curcumin; MSCs/HCC which received MSCs; and Cur+MSCs/HCC which received both curcumin and MSCs. For all groups there were histopathological examination and assessment of gene expression of connexin43 (Cx43), ubiquitin ligase-E3 (UCP-3), the autophagy marker LC3 and coenzyme-Q10 (Mito.Q10) mRNA by real time, reverse transcription-polymerase chain reaction, along with measurement of LC3II/LC3I ratio for estimation of autophagosome formation in the rat liver tissue. In addition, the serum levels of ALT, AST and alpha fetoprotein (AFP), together with the proinflammatory cytokines $TNF{\alpha}$ and IL-6, were determined in all groups. Results: Histopathological examination of liver tissue from animals which received DENA-$CCl_4$ only revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules. Administration of curcumin, MSCs; each alone or combined into rats after induction of HCC improved the histopathological picture. This was accompanied by significant reduction in ${\alpha}$-fetoprotein together with proinflammatory cytokines and significant decrease of various liver enzymes, in addition to upregulation of Cx43, UCP-3, LC3 and Mito.Q10 mRNA. Conclusions: Improvement of Cx43 expression, nonapoptotic cell death and mitochondrial function can repress tumor growth in HCC. Administration of curcumin and/or MSCs have tumor suppressive effects as they can target these mechanisms. However, further research is still needed to verify their effectiveness.

• Journal of Nutrition and Health
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• v.1 no.1
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• pp.9-18
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• 1968

Dividing into six(6) experimental groups; Stock Diet(SD) Group, Rice Diet(RD) Group, Rice Diet supplemented with Barley(RD-BD) Group, Barley Diet(BD) Group, Rice Diet supplemented with Millet(RD-MD) Group, and Millet Diet(MD) Group, biochemical and nutritional effects of rice, barley, and millet on rats are studied. The grains used in this experiment are polished ones and purchased from market. Six(6) weaning male albino rats are housed into the individual cages in each group and fed with each experimental diet and water ad libitum for 21 weeks. The composition of the experimental diets are shown in Table 1. At the end of experiment, the appearences of rats are observed and the bloods are sampled by heart puncture method following ether anesthesia for determinations of serum protein and serum cholesterol. And the livers are sampled immediately right after heart after heart puncture for determinations of liver weight, liver nitrogen, liver fat, and liver glycogen. And also liver tissues are observed histologically. The result of growth experiment is shown in Table 2 and Figure 7. The results of blood analysis are shown in Table 3 and the results of liver analysis are shown in Table 4. And the histological observations of liver tissue are shown in Figures 1, 2, 3, 4, 5, and 6. According to the above results, it could be summarized as follows; 1) The normal appearences are observed at SD Group and BD Group. Alopecia is observed at RD, RD-­BD, RD-MD, and MD groups and the wet appearences of hair are observed at RD-MD and MD groups. The color of hair is changed to yellowish white at RD, RD-MD groups. The maximum growth inhibition, is observed at MD group and the growths of RD, RD-BD, BD, and RD-MD groups are significantly lower than that of SD group. The growth of RD group is lower than those of RD-BD and BD groups, though this difference is not significant. 2) At the blood analysis, the highest serum protein content is shown at SD group and the lowest serum protein is observed at MD group. The serum cholesterol contents are not significantly different among the six(6) experimental groups. 3) The highest liver weight is observed at SD group and the lowest weight is shown at MD group. However, oppositely the highest liver weight per 100 grams of body weight at MD group and the lowest liver weight per 100 grams of body weight at SD group are observed as shown in Table 6. 4) The differences of liver nitrogen contents of RD, RB-BD, BD, RD-MD, and MD Groups are not significant except SD group showing the highest content. 5) The significant highest content of liver fat is observed at RD group and the lowest content of liver fat is shown at SD group. And no significant differences in contents of liver glycogen are observed among the six(6) experimental groups. 6) No significant abnormal histological changes of liver tissue are observed at SD, RD-BD, and BD groups. However, the fat metamorphosis at peripheral zone of liver tissue is observed at RD Group and the some histological abnormal changes are observed at RD-MD and MD groups. According to the above summaries, the followings might be estimated and recommended; 1) The BD group shows histological normality of liver tissue, improvement of liver fat and liver nitrogen, normality of appearence, and better growth compared with RD Group. This could be indicated that barley is nutritionally and biochemically better than rice as the feeding diet on rat. And it might be considered that there might be the species speciality for nutritionary evaluation of food. 2) Recently, Marshall indicated that the high consumption of carbohydrate causes fatty liver and Kondo reported that the higher consumption of rice causes the more heart disease and the shorter life span. Considering these reports, the higher consumption of rice as a main dish in our country should be considered as an important national nutritional problem. And this might be improved by supplementing with barley or other grains to rice.

• Journal of Nutrition and Health
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• v.16 no.1
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• pp.10-20
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• 1983

In order to establish tissue lipid status in animal on feeding of various dietary fat and oils, each group of rats was fed a semisynthetic diet containing 10%(w/w) mackerel oil (MO), eel oil (EO), soybean oil (SO), rapeseed oil (RO) or beef tallow (BT) for 1, 2 and 4 weeks, After each feeding period, levels of cholesterol, triglyceride and phospholipid were measured in serum. Fatty acid ${\leftarrow}$ composition was also investigated in serum and tissue lipids. Levels of total serum cholesterol were lower but HDL-cholesterol were higher in fish oil groups, which resulted in significantly higher ratio of HDL to total cholesterol in the fish oil groups. Fish oil groups, in general, also had lower levels of serum triglyceride and phospholipid than other groups, but S0 group maintained as low phospholipid levrl as fish oil groups. Fatty acid composition of dietary fat was reflected in all the tissues investigated but with varying degrees. Very long chain fatty acids, specific components exclusively found in fish oils were most well reflected in liver and relatively well in serum, whereas linoleic acid and erucic acid of SO and RO in the diet were better shown up in heart and adipose tissue. It attracted a particular attention that major proportions of long chain monoenoic acids $(C_{22:1})$ occurring both in MO and RO were detected separately in liver and heart plus adipose tissue, the result of which strongly indicates that there is a significant difference in metabolism between isomers $(C_{22:1}\;w\;11\;and\;C_{22:1}\;w\;9,\;respectively)$. It is suggested from this study that differences in lipid status as well as in the levels of serum lipids result from uniqueness in metabolism of each different fatty acid and give rise to distinguishable change in serum lipoprotein pattern, followed by diet with different fat sources.

• Applied Microscopy
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• v.25 no.4
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• pp.83-103
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• 1995

This experiment was carried out to investigate the effects of telluric acid on the histological and fine structural changes in the rat liver. Fischer 344 rats($150{\sim}200gm$) were used in this study as control and experimental groups. Telluric acid(5 mg/100 gm of body weight) suspensed in olive oil was given intraperitoneally to the animals of the experimental group and only olive oil to those of the control group. At the intervals of 3, 6 and 12 hours, 1, 2, 3, 5, 10, 20, 30 and 60 days after administration, the animals were sacrificed, and livers were obtained from the rats. For light microscopic examination of the liver, sections($5{\mu}m$) were stained with hematoxylineosin(H-E). For electron microscopic examination of the liver, sections were stained with uranyl acetate and lead citrate, finally examined with Zeiss EM 109 electron microscopes. The results obtained were as follows. 1. In the control group, round nucleus. well developed mitochondria, Golgi apparatus, rough endoplasmic reticulum(RER) and numerous glycogen particles were observed in the cytoplasm of the hepatocyte. In the cytoplasmic membranes of the hepatocyte, sinusoidal surface had numerous microvilli and cellular surface is combinated adjacent hepatocyte with desmosomes. The RER cisterns were dilated and zymogen granules were fewer than those of the dark cells. Kupffer cells with irregular nuclear membrane were observed. Fat storing cell and collagenous fiber bundle were observed in the Disse space. 2. Kupffer cell, inflammatory cells in the connective tissue of hepatic triad and lysosome were increased in the 3, 6, and 12 hour experimental group comparing with that of the control group. 3. In the 1 day experimental group, infiltration of inflammatory cells in interlobular connective tissue, dilatation of sinusoidal capillary and increasing of Kupffer cell were observed. Atropic change of hepatocyte and aggregation of glycogen particles in the cytoplasm of hepatocyte were observed. In this group, desmosome near bile canaliculi and collagenous fiber bundle in the Disse space were increased comparing with that of the 12 hours experimental group. In the 2 days experimental group, desmosome, lysosome, peroxisome and collagenous fiber bundle were increased comparing with that of the 1 day experimental group. Furthermore, lamellated bodies were also seen in the cytoplasm of the hepatocyte. 4. In 3 and 5 days experimental groups, transformations of hepatic cell cord and degeneration of the hepatocyte were markedly inclosed comparing with the all experimental groups. And damaged RER and mitochondria. collagenous fiber bundle were also inclosed comparing with that of the 2 days experimental group. Autophagosome and fat storing cells with large lipid droplets were also observed comparing with that of the 2 days experimental group. Tight junction and desmosome between the hepatocytes were separated. These degenerating changes were severe through the all experimental groups. 5. In the 10 and 20 days experimental groups, arrangement of hepatic cell cords and cell organelles of hepatocytes were similar to those of the control group. However, aggregation of glycogen particles, dilatation of sinusoidal capillary and infiltration of inflammatory cells remained. 6. In the 30 days experimental group, the tissue findings were similar to those of the control grout. But lamellated bodies in some hepatocytes and lysosome were remained in the cytoplasms of the Kupffer cells. In the 60 days experimental group, these all changes were recovered as the control group. In conclusion, telluric acid would directly induce the degenerative and necrotic changes on the hepatic tissue. However, these changes were perfectly recoverd in the 60 days experimental group as the control group.

• Journal of radiological science and technology
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• v.39 no.3
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• pp.451-459
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• 2016

The development of radioprotector is being actively conducted in order to reduce the damage from over radiation exposure at radiation accident or radiation therapy. So this study was confirmed for radiation protective effects using the Cynanchi wilfordii Radix that has been known to be effective for antioxidant activity, anti-cancer, immune enhancing effects. The method of this study was administered orally Cynanchi wilfordii Radix ethanol extracts to Sprague Dawley Rat(SD Rat) for 14 days once a day, while measuring changed blood cell, spleen index, liver and uterus tissue along the change in time of 1, 4, 7 and 21 days after X-ray beam of 7 Gy irradiation. As the result of the experiment, the experimental group's rats which are administered with Cynanchi Wilfordii Radix ethanol extracts showed a rapid recovery in white blood cell count(p < 0.05) and spleen index(p < 0.05). In addition, condensation of nuclei, cytoplasmic swelling, and inflammatory cell infiltration in experimental group's liver cell was decreased more than in irradiation group's component. Further, experimental group's Uterine gland decreased the apoptosis more than irradiation group's components did. It is expected that Cynanchi Wilfordii Radix extracts will be useful as a new radioprotector. With above in mind, this paper may provide appropriate implications with the field of emergency management such as radiation accident.

• The Korean Journal of Zoology
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• v.12 no.2
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• pp.50-56
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• 1969

The present investigation involves a comparative study of enzymatic activities in various animals. The levels of the liver protein of rat (22.0$\pm$0.01mg/ml and pigeon (22.0$\pm$ 0.16) are twice as high as that of crucian carp (13.0$\pm$ 0.09)(p < 0.01). Generally, the specific acitivity (3.77 $\pm$0.18 unit/mg) of rat glutamic pyruvic transaminase (GPT) is highest, pigeon intermediate (1.93 $\pm$0.01), and crucian carp lowest (0.71$\pm$0.07). On the other hand, the specific activity (8.23$\pm$0.09 unit/mg)of rat glutamic oxaloacetic transaminase (GOT) is highest, pigeon intermediate (3.95$\pm$0.09), and crucian carp lowest (0.92$\pm$0.01) (p < 0.01). Ratios of GOT activity to GPT activity appear no remarkable difference from the levels of various animals. Specific activity of glutamic dehydrogenase(GDH) in pigeon tissue exceeds those of rat and crucian carp. In liver, rat GOT specific activity is greater than crucian carp and pigeon. On the other hand, pigeon GDH specific activity is greater than those of rat and crucian carp. This wouls seem to be in accord with protein metabolic intensity. The patterns for GDH isozyme were remarkably appeared in various animals. Glutamic dehydrogenase isozymes gave different electrophoretic mobilities in various animals. It is interesting that crucian carp, pigeon, and rat would show this difference, which may be indicative of an evolutional pattern. The fact that livers in various animals show quite different enzyme activities would suggest the existence of such a general phylogenetic relationship.

• Advances in Traditional Medicine
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• v.2 no.2
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• pp.94-100
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• 2002

Liver cirrhosis is characterized by hyperaccumulation of fibrous tissue components and is commonly observed in latter or terminal states of chronic hepatic diseases. In this study, the antifibrotic effects of GLM001 on liver cirrhosis were examined in bile duct ligated rats and patients with hepatic diseases. GLM001 (250 mg/kg rat weight/ day) was administrated to cirrhotic rats for 4 weeks and to humans for 14 weeks. Bile duct ligated rats significantly increased liver collagen content and biochemical markers of hepatic injury. Liver histology showed collagen fiber deposition was increased and the normal architecture was lost with large zones of necrosis being observed frequently. GLM001 administrated rats showed significantly decreased liver collagen content, and accumulation of collagen fiber in histological analysis. Patients, who were treated with GLM001, showed decreases in biochemical markers of hepatic diseases. These results demonstrate the usefulness of GLM001 as an antifibrotic agent for liver cirrhosis.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.5
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• pp.443-454
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• 2021

Purpose: Due to the increasing prevalence of obesity worldwide, non-alcoholic fatty liver disease (NAFLD) has reached epidemic dimensions over time. NAFLD is the most common cause of childhood chronic liver disease. There is a relationship between NAFLD and oxidative stress. This study aims to investigate the changes in thiol/disulfide homeostasis parameters to determine the oxidant/antioxidant balance in obese rats with diet-induced NAFLD and healthy rats. Methods: Twelve Wistar albino rats were used in this study. Experimentally produced NAFLD obese rats (n=6) and healthy rats were compared. Experimental NAFLD model was created with a special fatty liver diet (Altromin^® C1063, Fatty Liver Diet, Exclusivet, Lage, Germany). The biochemical and histopathological features of the groups, as well as serum thiol/disulfide homeostasis parameters, were analyzed and compared. Results: In the experimentally induced NAFLD rat model, they gained more weight than the control group. Steatosis (at least grade 2) occurred in all rats fed with special fatty liver diet for 12 weeks. Histopathologically, no high-grade inflammation was observed in rats with experimental NAFLD after feeding a diet for 12 weeks. Results revealed that aspartate transaminase and alanine transaminase levels were high, albumin levels were low, oxidant stress parameters increased, and antioxidant thiol groups decreased. Conclusion: Experimental NAFLD is characterized by increased oxidant stress accompanying fatty tissue in the liver. Analysis of thiol/disulfide homeostasis parameters in NAFLD can be used in further studies to develop effective treatment options.

• The Journal of Internal Korean Medicine
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• v.1 no.1
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• pp.70-77
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• 1976

The Sam Mool Injin extract is occasionally used as a kind of remedies for the treatment of hepatic discomfort in herb medicine. The study for the effect on the hepatic parenchymal cells, especially regenerating activity and even its toxicity have. little been done and only a very few pharmacological properties have been reported. So, an experimental study for the morphologic changes in the acute carbon tetrachloride poisoning of wister rat by administration of its extract has been performed. Male Wister rat weighing around 200gm were used in this experiment. Results were as follows; 1) In the $Ccl_4$ 0.3c.c 7day group, there is noted considerable increase of regenerating activity in the experimental group compared with non-extract treated group, in half of them. 2) Remaining all of the experimental group do not show significant difference of regenerating activity compared with control group. 3) In the group treated with Sam Mool Injin extract alone, there was noted some considerable increase of nonspecific leukocytic infiltrations compared with saline control group. This can be considered as a possibility of hepatic tissue reaction on the Sam Mool Injin extract.

• YAKHAK HOEJI
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• v.40 no.1
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• pp.52-58
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• 1996

Solvent fractions were prepared from traditional herbal drugs which of methanol extracts inhibited $CCl_4$-induced cytotoxicity in primary cultured rat hepatocytes and c ontinuously assayed their effects. Ethylacetate and n-buthanol fractions from Cibotii Rhizoma and chloroform fraction from Gelatina Nigra inhibited the release of LDH and GPT from $CCl_4$-treated hepatocytes, respectively. Water fraction (WAR) among solvent fractions from Astragali Radix showed the most potent inhibitory effect on the release of GOT or GPT by treatment with $CCl_4$. All of solvent fractions prepared from Eucommiae Cortex had no effect on $CCl_4$-induced cytotoxicity. Chloroform and ethylacetate fractions from Rehmanniae Radix Preparata increased the release of GPT from $CCl_4$-treated hepatocytes. n-Hexan, chloroform or ethylacetate fraction from 5 herbal drugs increased the release of LDH, GOT or GPT from normal hepatocytes at the dose of 1.Omg/ml. Administration of WAR suppressed the elevation of GOT, ALP activities and MDA contents in the serum as well as in the liver tissue of $CCl_4$-intoxicated rats. Based on these results, isolation of antihepatotoxic substances from WAR is under the process.