• Journal of Ginseng Research
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• 제41권2호
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• pp.159-168
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• 2017

Background: Radiotherapy is one of the most important modalities in cancer treatment; however, normal tissue damage is a serious concern. Drug development for the protection or reduction of normal tissue damage is therefore a clinical issue. Herein, we evaluated the protective properties of Panax ginseng Meyer and its corresponding mechanisms. Methods: C56BL/6 mice were orally pretreated with P. ginseng water extract (PGE; 25 mg/kg, 50 mg/kg, or 100 mg/kg) or intraperitoneally injected melatonin (20 mg/kg) for 4 d consecutively, then exposed to 15-Gy X-ray radiation 1 h after the last administration. After 10 d of irradiation, the biological properties of hematoxicity, fat accumulation, histopathology, oxidative stress, antioxidant activity, pro-inflammatory cytokines, and apoptosis signals were examined in the hepatic tissue. Results: The irradiation markedly induced myelosuppression as determined by hematological analysis of the peripheral blood. Steatohepatitis was induced by X-ray irradiations, whereas pretreatment with PGE significantly attenuated it. Oxidative stress was drastically increased, whereas antioxidant components were depleted by irradiation. Irradiation also notably increased serum liver enzymes and hepatic protein levels of pro-inflammatory cytokines. Those alterations were markedly normalized by pretreatment with PGE. The degree of irradiation-induced hepatic tissue apoptosis was also attenuated by pretreatment with PGE, which was evidenced by a terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick-end labeling assay, western blotting, and gene expressions analysis, particularly of apoptotic molecules. Conclusion: We suggest that PGE could be applicable for use against radiation-induced liver injury, and its corresponding mechanisms involve the modulation of oxidative stress, inflammatory reactions, and apoptosis.

• 대한본초학회지
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• 제26권3호
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• pp.47-56
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• 2011

Objectives : This study investigated whether the water extract of Spatholobi Caulis (SCE) has the ability to protect hepatocyte against oxidative stress induced by tert-butylhydroperoxide (tBHP) in vitro and $CCl_4$ in vivo. Methods : In vitro, HepG2 cells pre-treated with Spatholobi Caulis water extract (1, 3, 10, $30{\mu}g$/ml) for 12h and further incubated with tBHP ($100{\mu}M$) for the next 12h. Cell viability was assessed by MTT assay. In vivo, rats were orally administrated with the aqueous extract of Spatholobi Caulis (SCE; 50, 100 mg/kg) for 4 days and then, injected with $CCl_4$ 1 mg/kg body weight to induce acute liver damage. Results : Treatment with SCE inhibited cell death induced by tBHP, as evidenced by alterations in the levels of the proteins associated with apoptosis:SCE prevented a decrease in $Bcl_2$, and cleavage of poly(ADP-ribose)polymerase and pro-caspase-3. Moreover, SCE inhibited the ability of tBHP to generate $H_2O_2$ production, thereby restoring GSH content. Moreover, SCE treatments in rats effectively decreased liver injuries induced by a single dose of $CCl_4$, as evidenced by decreases in hepatic degeneration and inflammation as well as plasma alanine aminotransferase and lactate dehydrogenase activities. Consistently, treatments of SCE also protected liver in rats stimulated by $CCl_4$, as indicated by restoration GSH and prevention of MDA in the liver. Conclusions : SCE has the ability 1) to protect hepatocyte against oxidative stress induced by tBHP and 2) to prevent $CCl_4$-inducible acute liver toxicity. Present findings may be informative not only in elucidating the pharmacological mechanism of Spatholobi Caulis, but in determining its potential application for oxidative cellular damage in the liver.

• 대한약침학회지
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• 제10권1호통권22호
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• pp.101-107
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• 2007

Objectives : This study was aimed at investigating liver protection mechanism of Cultivated Ginseng and Cultivated Wild Ginseng of Korean and Chinese by inducing liver toxicity through $CCl_4$ and t-BHP in mice and evaluated serological findings. Methods : Experiment groups was categorized into untreated normal group, treated control group, and orally administered Cultivated Ginseng and Cultivated Wild Ginseng of Korean and Chinese experimental groups. At the termination of experiment, gross examination of the liver as well as Total bilirubin, AST, and ALT contents in the serum were evaluated. Results : 1. In the $CCl_4$ induced acute hepatotoxicity test, total bilirubin, AST and ALT didn't show significant differences between the control and experimental groups. 2. In the t-BHP induced acute hepatotoxicity test, total bilirubin, AST and ALT didn't show significant differences between the control and experimental groups. Conclusion : Taken together, Cultivated Ginseng and Cultivated Wild Ginseng of Korean and Chinese cannot be effectively used for recovering the liver functions in acute hepatotoxicity tests using $CCl_4$ and t-BHP. Further researches, for example treated long period, must be tried to verify the efficacies.

• 약학회지
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• 제42권6호
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• pp.598-606
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• 1998

The liver expresses a considerable amount of nitric oxide (NO) upon induction with cytokines or/and endotoxin. The NO synthesized by inducible NO synthase (NOS) of the liver see ms to play a role in various hepatic physiological processes. Here we investigate the effects of NO on acetaminophen (AA)-induced liver injury. The treatment of S-nitros-N-acetyl penicillamine (SNAP, exogenous NO donor) at the dose of 0.1mM decreased AA-induced hepatotoxicity suggesting the possibility of NO to play a role in protection from the hepatotoxicity induced by AA. On the other hand, the excessive NO produced by NO donor (SNAP: 0.5, 2.5, 6.25mM) has been shown to cause a concentration dependent hepatotoxicity, and such damages was decreased by Superoxide and increased by superoxide dismutase, indicating that the hepatotoxicity induced by excessive NO depends on balancing between NO and superoxide. Taken together, the results indicate that NO has biphasic effects on hepatotoxicity.

• 한국콘텐츠학회논문지
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• 제15권8호
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• pp.389-396
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• 2015

간 섬유화는 임상에서 흔히 접하는 질환으로, 간세포 염증 및 괴사가 수년간 지속 및 반복되는 질환으로 간경변이 진행된다. 따라서, 만성 간질환 환자에서 간경변 및 간세포암으로의 진행을 막음으로써 간경변의 합병증 및 간세포암에 의한 사망률 및 유병률을 감소시키는 것이 주요한 임상 과제라 할 수 있다. 이에 본 연구에서는 미만성 간질환 환자에게서 초음파 영상, 혈액검사, 간탄력도와의 상관관계를 수치화 하고자 하였다. 본 연구에서는 P사의 초음파 진단기 (IU-22)로 영상을 획득한 환자와 Fibrosccan을 시행 받은 141명을 대상으로 시행하였고, 혈액 검사는 초음파 영상과 간섬유 스캔을 시행한 시점의 검사 결과로 기초자료를 획득하였다. 각 자료에 대한 통계 분석은 집단 간 차이 검증을 위해 일원분산분석(One-way, ANOVA)을 시행하여 검증하였다. 탄성 초음파의 수치는 정상, 만성간질환, 간경변 순으로 증가하였다. 판독 결과에 따라 ALT, Albumin은 대상군 간 통계학적 차이를 보이지 않았으며, 나이, AST, ALP, Bilirubin, PLT, PT, kPa에서 초음파 판독 결과에 따라서 차이가 있고, 통계적으로 유의(p<0.05)하였다. 그리고 다른 연구에서 만성 간질환 탄성 초음파 수치값이 12.5kPa 이상이라고만 제시하였으나, 본 연구에서는 질환별 평균 kPa임계값을 제시하여, 정량적으로 진단이 가능하게 수치화를 하였다. 또한, 진단결과의 상관관계를 제시하여 질환별 만성 간질환 환자의 진단에 일차적인 도구로 사용될 수 있으리라 사료된다.

• 약학회지
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• 제35권2호
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• pp.99-110
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• 1991

This study was initiated to investigate the effects of organic germanium on cadmium and mercury intoxication. The effect was determined by the metallothionein induction in liver and kidney. Male rats (Sprague-Dawley) were treated with CdCI$_{2}$ (2mg/kg), HgCI$_{2}$ (1 mg/kg) and organic germanium (GE-132) (100 mg/kg) in single and in combination via intraperitoneal injection or intragastric administration every other days for 17 days. Experimental animals were sacrificed after 7, 12 and 17 days treatment. The serum transaminase activities (SGOT, SGPT), concentration of metal and metallothionein, metal-binding capacity of metallothionein in liver and kidney were determined and pathomorphological observations were undertaken. The combined treatment of GE-132 and CdCI$_{2}$ significantly decreased the increment of serum transaminase activities in rats treated with CdCI$_{2}$ only, but the combined treatment of GE-132 and HgCI$_{2}$ did not affect to activities of transaminases induced by mercury only. The concentration of metals (Cd and Hg) except Ge in the liver and kidney of rats increased with the time of treatment. Mercury concentration in kidney of rat treated with HgCI$_{2}$ only was significantly higher than the combined treatment of GE-132 and HgCI$_{2}$. The combined treatment of GE-132 and CdCI$_{2}$ significantly increased the concentration of metallothionein in liver compared to the CdCI$_{2}$ only, although the concentration of cadmium in liver were not significantly different between two groups. This indicates that GE-132 decreased toxicity of cadmium in liver by promoting metallothionein induction. There were no significant differences in metallothionein concentration in liver and kidney of rats between the combined treatment of GE-132 and HgCI$_{2}$ and HgCI$_{2}$ only. Metal-binding capacity of metallothionein varied with each time intervals in liver and kidney of metals treated rats except the liver of the combined treatment of GE-132 and CdCI$_{2}$. This finding explains the concentration of metallothionein in liver keeps abreast with the concention of metal. Furthermore, the combined treatment of GE-132and CdCl$_{2}$ revealed pathologically less changes in liver tissue than CdCl$_{2}$ only; the damages of liver cell, such as lobular necrosis and portal inflammation, were relieved and appeared more later. From the above results, organic germanium is considered to have some beneficial effect on the protection of liver from the cadmium intoxication.

• 환경생물
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• 제22권3호
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• pp.405-410
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• 2004

The effect of treatment with Citrus junos fractions (citron 3W, citron 3H, citron 4W and citron 4H) upon rat hepatocytes exposed to alcohol was investigated. We compared the serum biochemistry of rats administered both alcohol and Citrus junos fractions to control rats treated with alcohol alone. The effects of Alanine amino transferase (ALT) were significantly lower in the citron 3H extract group compared with the negative control group (p<0.05) and other experimental groups were not significantly low but a little low compared to negative control group. The levels of triglyceride (TG) were significantly low in all experimental groups compared with negative control group. Especially triglyceride level of citron 3H was lowest near to normal control group. The concentration of total cholesterol was significantly high in negative groups compared with normal control group but in all experimental groups, the concentration of total cholesterol was similar to that of negative control group. Total cholesterol of the citron 4W group was somewhat low compared with negative control group. In contrast, activities of alcohol dehydrogenase (ADH) were significantly higher in all experimental groups compared with the negative control (p<0.05) group. These data suggest that Citrus junos fractions may represents an excellent candidate for protection of rat hepatocytes from alcohol-mediated damage.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.993-1001
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• 2016

Type 2 diabetes mellitus patients are at increased risk of many forms of malignancies, especially of the pancreas, colon and hepatocellular cancer. Unfortunately, little is known of the possible interaction between antidiabetic drugs and anticancer agents. The present study investigates the influence of metformin (MET) and sitagliptin (SITA) on the in vitro anticancer activity of the microtubule depolymerization inhibitor agent epothilone A (EpoA). Hepatocellular liver carcinoma cell line (HepG2) viability and apoptosis were determined by the MTT test and by double staining with PO-PRO-1 and 7-aminoactinomycin D, respectively, after treatment with EpoA, metformin or sitagliptin. The levels of nuclear factor NF-${\kappa}B$ and p53 were evaluated in the presence and absence of inhibitors. While EpoA and MET inhibited HepG2 cell proliferation, SITA did not. EpoA and SITA induced higher p53 levels than MET. All tested drugs increased the level of NF-${\kappa}B$. Only MET enhanced the proapoptotic effect of EpoA. The EpoA+MET combination evoked the highest cytotoxic effect on HepG2 cells and led to apoptosis independent of p53, decreasing the level of NF-${\kappa}B$. These findings support the link between NF-${\kappa}B$ and p53 in the modulation of apoptotic effects in HepG2 cells treated by EpoA. Our studies indicate that the combination of EpoA and MET applied in subtoxic doses has a stronger cytotoxic effect on liver cancer cells than each of the compounds alone. The therapeutic advantages of the combination of EpoA with MET may be valuable in the treatment of patients with diabetes mellitus type 2 (T2DM) and liver cancer.

• Food Science and Biotechnology
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• 제17권1호
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• pp.203-207
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• 2008

The present study aimed at assessing the protective effect of water extract from fruit body of the Grifola frondosa (GFW) on carbon tetrachloride ($CCl_4$)-induced hepatotoxicity. Rats orally administered with GFW 0.5, 1.0, 2.0 g/kg for 14 days were treated with $CCl_4$ to induce hepatotoxicity. Pretreatment with GFW remarkably prevented the elevation of serum AST, ALT, ALP, LDH, $\gamma$-GTP, and liver lipid peroxides in $CCl_4$-treated rat and GFW administration in liver injured rats by $CCl_4$ showed significant (p<0.05) protection of liver as evidenced from normal serum enzymes and malondialdehyde (MDA) levels. In the ultrastructural changes, administration of $CCl_4$-induced damage of hepatocytes with vacuolation, a highly damaged endoplasmic reticulum, and degenerating nuclei. However, pre-administration with GFW preserved normal ultrastructure of hepatocytes. These results suggest that GFW had an effect to inhibit $CCl_4$-induced liver injury in rat, and that it could be used as an effective hepatoprotective agent against chemical-induced liver damage.

• 대한수의학회지
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• 제47권3호
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• pp.265-271
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• 2007

This study investigated the protective effects of ethylene glycol-bis(${\beta}$-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), an extracellular calcium chelator, and ethylenediaminetetraacetic acid (EDTA), which chelates calcium and most metal ions, against carbon tetrachloride ($CCl_4$)-induced acute hepatotoxicity in mice. Mice were treated with EGTA or EDTA at a dose of 20 (low) or 100 mg/kg (high) subcutaneously 1h before $CCl_4$ administration. The mice were fasted and sacrificed 18h after $CCl_4$ treatment. Blood samples were collected from the carotid artery by decapitation under light ether anesthesia. Serum alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), and cholesterol levels were measured. Malondialdehyde (MDA) production was determined as an index of lipid peroxidation in the liver. The liver, kidneys, and spleen were weighed. We also evaluated the histopathological changes in the liver in each group. The relative weights of the liver were significantly higher in the $CCl_4$-treatment group than in the normal group, except in the high-EDTA treatment group. EGTA and EDTA treatment caused a significant decrease in serum ALP, ALT, and AST levels. Of all of the doses of EGTA and EDTA tested, the high-EDTA dose resulted in the most remarkable inhibitory action. The protective effect in the high-EDTA-treatment group was confirmed histopathologically. The low-EGTA-treatment group showed a significant decrease in serum TG and cholesterol levels. Liver MDA levels were significantly decreased in the EGTA (20 mg/kg) and EDTA (20, 100 mg/kg) groups. These results suggest that EDTA, which chelates both calcium and metal ions, confers better protection in $CCl_4$-induced acute liver damage than does EGTA, a calcium chelator.