• 약학회지
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• 제56권2호
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• pp.99-107
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• 2012

The protective effect of AI-1367 (Alnus japonica extract) on liver injury was investigated. Primary rat hepatocyte intoxication was induced by tert-butyl hydroperoxide (tBH), carbon tetrachloride ($CCl_4$), or D-glactosamine (D-GalN). Liver injury was induced by $CCl_4$, D-GalN or MCD (methionine choline deficient)-diet in mouse. The cellular leakage of lactate dehyrogenase and cell viability followed by the treatment of hepatotoxicants were significantly improved by AI-1367 treatment at a concentration range of 5~50 ${\mu}g/ml$ for tBH, 5~50 ${\mu}g/ml$ for D-GalN, and 5~100 ${\mu}g/ml$ for $CCl_4$, respectively. Treatment with AI-1367 (20, 10, 5 mg/kg, p.o.) on liver injury induced by subcutaneous injection of $CCl_4$ or D-GalN reduced significantly the levels of aspartate transaminase and alanine transaminase in serum. Histological observations revealed that fatty acid changes, hepatocyte necrosis and inflammatory cell infiltration in $CCl_4$ (D-GalN)-induced liver injury was improved by administration of AI-1367. AI-1367 treatment (10, 5, 2.5 mg/kg, p.o.) also significantly recovered the body weight change and serum levels of aspartate transaminase, alanine transaminase and triglyceride in liver injury induced by MCD diet. From these results, AI-1367 shows protective effects against tBH, $CCl_4$, D-GalN, or MCD diet-induced hepatotoxicity in vitro or in vivo.

• Toxicological Research
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• 제8권2호
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• pp.265-272
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• 1992

Effects of repeated physical exercise on the carbon tetrachloride ($CCl_4$) hepatotoxicity were examined in adult female rats. Rats were introduced into a cylindrical rotating cage and forced to exercise for 1 hr each day, 6days/week, for 5 consecutive weeks at a speed starting from 10m/min, increased by 1m/min per day until the speed reached 27m/min. Significantly less body weight gain was observed in the exercise group suggesting that physical fitness had been induced in these animals. Eighteen hours following termination of the last exercise bout rats were treated with $CCl_4$(2 mmol/kg.ip). The $CCl_4$-induced heptotoxicity was significantly potentiated in the repeated exercise group compared to the resting sedentary animals as determined by changes in serum sorbitol dehydrogenase (SDH), glutamic oxaloacetic transaminase(GOT), glutamic pyruvic transaminase (GPT), and glucose-6-phosphatase(G-6-Pase) activities when measured 24hrs following the $CCl_4$ treatment. Hepatic drug metabolizing activity was determined in order to elucidate the underlying mechanism of potentiating action of the $CCl_4$ hepatotoxicity induced by repeated physical exercise. Repeated exercise increased the hepatic microsomal cytochrome P-450 contents and aminopyrine N-demethylase activity. The results suggest that the potentiation of $CCl_4$ hepatotoxicity by repeated exercise is associated with induction of the mixed function oxidase (MFO) enzyme system mediating the metabolism of $CCl_4$ to its active metabolite(s).

• Nutrition Research and Practice
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• 제2권2호
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• pp.134-137
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• 2008

Atherosclerosis is characterized by a chronic inflammatory disease, and chemokines play an important role in both initiation and progression of atherosclerosis development. Leukotactin-1 (Lkn-1/CCLl5), a new member of the human CC chemokine family, is a potent chemoattractant for leukocytes. Our previous study has demonstrated that Lkn-1/CCL15 plays a role in the initiation of atherosclerosis, however, little is currently known whether Lkn-1/CCL15 is associated with the progression of atherosclerosis. Matrix metalloproteinases (MMPs) in human coronary atherosclerotic lesions playa crucial role in the progression of atherosclerosis by altering the vulnerability of plaque rupture. In the present study, we examined whether Lkn-1/CCLl5 modulates MMP-9 release, which is a prevalent form expressed by activated macrophages and foam cells. Human THP-1 monocytic cells and/or human peripheral blood monocytes (PBMC) were treated with phorbol myristate acetate to induce their differentiation into macrophages. Foam cells were prepared by the treatment of THP-1 macrophages with human oxidized LDL. The macrophages and foam cells were treated with Lkn-1/CCL15, and the levels of MMP-9 release were measured by Gelatin Zymography. Lkn-1/CCL15 significantly enhanced the levels of MMP-9 protein secretion from THP-1 monocytic cells-derived macrophages, human PBMC-derived macrophages, as well as macrophage-derived foam cell in a dose dependent manner. Our data suggest that the action of Lkn-1/CCL15 on macrophages and foam cells to release MMP-9 may contribute to plaque destabilization in the progression of atherosclerosis.

• 대한약리학회지
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• 제17권1호
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• pp.33-39
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• 1981

In this paper, the influences of adrenergic neuronal blockades of different mode: guanethidine and ${\alpha}$-methyl-para-tyrosine on the changes induced by carbon tetrachloride $(CCl_4)$ of hepatic total lipid, glycogen, and lipid peroxide contents and serum lactic dehydrogenase activity were investigated in male mice. The results obtained were summarized as follows: 1) The hepatic total lipid and lipid peroxide contents and serum lactic dehydrogenase activity were markedly increased by $CCl_4$, but hepatic glycogen content were decreased. 2) The hepatic total lipid and lipid peroxide contents and serum lactic dehydrogenase activity were not significantly changed by guanethidine(20mg/kg) or ${\alpha}$-methyl-para-tyrosine (5 mg/kg) injection. 3) The increase of hepatic total lipid induced by $CCl_4$ was inhibited by the pretreatment of guanethidine or ${\alpha}$-methyl-para-tyrosine, and the increase of hepatic lipid peroxide content induced by $CCl_4$ was slightly inhibited by them. But the decrease of hepatic glycogen content and the increase of serum lactic dehydrogenase activity induced by $CCl_4$ were not affected by them.

• 생약학회지
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• 제34권2호통권133호
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• pp.166-171
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• 2003

The hepatoprotective effects of Liriopis tuber on carbon tetrachloride $(CCl_4)$ intoxicated rats were studied. The water extract prepared from Liriopis tuber were administrated to the pretreatment group orally once a day for successive 7 days, followed by treatment with $CCl_4$ on the seventh day. The post treatment group was treated with $CCl_4$ and then the water extract was administrated. The activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), lactate dehydrogenase (LDH), and contents of total cholesterol and triglyceride in pretreatment rats serum were significantly decreased compared to the only $CCl_4$ treated rats. The level of high density lipoprotein (HDL) cholesterol was considerably increased compared to the only $CCl_4$ treated rats. In the pretreatment group with the water extract of Liriopis tuber tissue destruction was not observed in light microscopic investigation, compared to the only $CCl_4$ treated rats. These results suggest that Liriopis tuber have potent hepatoprotective effect against carbon tetrachloride intoxicated rats.

• 동의생리병리학회지
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• 제20권2호
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• pp.410-413
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• 2006

This study was done to investigate the protective effects of Iljungbogan-Tang on acute hepatotoxicity of rats induced by $CCL_4$ and acetaminophen. The subject animals were divided into 3 groups : control group(administrated 0.5% carboxymethyl cellulose), sample group(30, 100, 300, 600mg/kg administrated), positive control group (administrated silymarine), Acute hepatotoxicity of rats were induced by $CCL_4$ and acetaminophen, and the serum transaminase(AST, ALT) were measured for enzyme activities. The inhibitory effects on the serum AST activities were noted in sample group(100, 300, 600mg/kg administrated) on hepatotoxicity of rats induced by $CCL_4$. The inhibitory effects on the serum AST, ALT activities were noted in sample group(30mg/kg administrated) on hepatotoxicity of rats induced by acetaminophen. The inhibitory effects on the serum AST activities were noted in sample group(600mg/kg single dose administrated) on hepatotoxicity of rats induced by acetaminophen. It is considered that Iljungbogan-Tang has protective effects against hepatotoxicity in rats induced by $CCL_4$ and acetaminophen. So it is required to study about the actions of mutual relation of medicines and patho-mechanism through experiment.

• 동의생리병리학회지
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• 제24권3호
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• pp.439-445
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• 2010

Pretreatment with Taraxacum Mongolicum H(TMH) prior to the administration of on $CCl_4$ significantly prevented the increased serum enzymatic activity of aminotransferase(ALT, AST), gamma-glutamyl transpeptidase(GGT) and bilirubin concentration in dose-dependent manner. In addition, pretreatment with TMH also significantly restored the elevation of hepatic malondialdehyde formation and the depletion of reduced glutathione content in the liver $CCl_4$-intoxicated rats. The restoration of microsomal aniline hydroxylase and aminopyrine N-demethylase activities indicated the improvement in functional status of endoplasmic reticulum. $CCl_4$-induced hepatotoxicity was also essentially prevented, as indicated by a liver histopathologic study. TMH showed antioxidant effects in $FeCl_2$-ascorbate-induced lipid peroxidation in rat liver homogenate and in superoxide radical scavenging activity. Our results suggest that the protective effect of TMH against $CCl_4$-induced hepatotoxicity possibly involve mechanisms related to its ability to block p450-mediated $CCl_4$ bioactivation and free radical scavenging effects.

• 동국한의학연구소논문집
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• 제5권
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• pp.53-77
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• 1996

The purpose of this study is to observe the effect of Sayeuksan on serum reaction in $CCl^4$ treated rats. In this study the experimental rats divided four group (Control group, $CCl^4$ group, sayeuksan group, and shiho, kamcho group) Under the same condition control group were administered water, sample group were administered Sayeuksan for 8days. and then, both $CCl_4$ group and sample group were injeccted to abdomen with $CCl_4$ for 1days. The change of GOT GPT ${\gamma}$-GTP ALP LDH activity in blood serum. The obtained results are summarised as follows : 1. In the change of GOT GPT contents, as compared with control group sample group was significantly decreased. 2. In the change of ${\gamma}$-GTP contents as compared with control group, sample group was significantly decreased. 3. In the change of ALP contents, as compared with control group, sample group was significantly decreased. 4. In the change of LDH contents, as compared with contol group, sample group was significantly decreased.

• 동의생리병리학회지
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• 제16권4호
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• pp.684-692
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• 2002

Cordyceps militaris has been known as a Chinese traditional medicine for the treatment of tuberculosis, asthma, kidney disease, debility and fatigue etc. This study was attempted to investigate the therapeutic effect of C. militaris extract on the cytotoxic activity of HepG2, human hepatocellular carcinoma cells and the liver damage induced by carbon tetrachloride in SD rats. C. militaris extracts inhibited significantly the proliferation of HepG2 cells in vitro. Carbon tetrachloride(CCl₄) caused a significant an increase in liver weight, serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) activity, alkaline phosphatase(ALP), serum thiobarbituric acid reactive substances (TBARS), microsomal TBARS, and decrease in microsomal detoxification enzymes (cytochrome P-450, P-450 reductase, cytochrome b5, b5 reductase). TBARS and ALP in serum pretreated with C. militaris extracts (300mg/kg/day, 600mg/kg/day) was significantly reduced compared to control group(CCl₄). Cytochrome b5 and b5 reductase activities were significantly increased in CM300 (300 mg/kg/day) and CM600 group(600 mg/kg/day), and cytochrome P-450 reductase was significantly increased in CM300 group. Pretreatment (100, 300, and 600 mg/kg/day for 7 days) of C. militaris with CCl₄ was significantly inhibited the accumulation microsomal TBARS and the significantly increased in the cytochrome P-450 activity. These results suggested that C. militaris (300mg/kg/day for 7 days) has appreciable therapeutic effect on CCl₄ induced hepatotoxicity.

• Biomolecules & Therapeutics
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• 제19권1호
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• pp.52-58
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• 2011

The inhibitory effect of Chung-Jang-Hwan (C-mix) consisted of Geranium nepalense subsp. thunbergii, Saururus chinensis, and Rubus coreanus were investigated in dextran sulfate sodium (DSS)-induced colitic mice by microarray analysis. Treatment with Cmix improved colitic symptoms, including colon shortening and myeloperoxidase activity. Treatment with DSS alone upregulated the expression levels of inflammation-related genes, including IL-$1\beta$, IL-6, CCL2, CCL4, CCL5, CCL7, CCL8, CCL24, CXCL1, CXCL2, CXCL5, CXCL9 and CXCL10, and other colitis-related genes such as COX-2, PAP, MMP family, S100a8, S100a9 and DEFA1 in mice. However, treatment with C-mix inhibited the expression levels of inflammation-associated genes induced by DSS. The increased expression levels of COX-2 and IL-$1\beta$, representative inflammatory genes, were confirmed by a quantitative realtime polymerase chain reaction analysis. These results indicate that C-mix may ameliorate colitis by the inhibitory regulation of inflammation-associated genes.