• 대한한방내과학회지
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• 제31권2호
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• pp.346-355
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• 2010

Objectives : This study was performed in order to investigate the anti-fibrogenic effect of Acer tegmentosum Maxim. on r at hepatic stellate cell line T6. Materials and Methods : Hepatic stellate Cells (T6) were treated with various concentrations of distilled water Acer teg mentosum Maxim. extract for 24, 48, 72 hours. After the treatment, cell viability, proliferation, procollagen levels, mRNA of AS MA, MMP-2, collagen type 1a2 and IL-6 production were measured using MTT assay, BrdU assay, RT-PCR, procollagen typ e 1 C-peptide EIA kit and murine IL-6 ELISA development kit. Results : Cell viability of HSC-T6 decreased significantly in both 24 hours and 48 hours groups in a dose-dependant man ner. Proliferation of HSC also decreased in the same way. In the RT-PCR, mRNA expression of collagen type 1a2 and ASMA decreased in the groups which were treated with Acer tegmentosum Maxim. for 24 hours. The production of procollagen tended to decrease in a dose-dependant manner in the 24 hours treated group. IL-6 production increased under Acer tegmentosum trea tment in a dose-dependant manner in both 24 and 48 hours groups. Conclusion : These results show the possibility that Acer tegmentosum Maxim. can be an effective remedy for liver fibrosi s and liver cirrhosis.

• Toxicological Research
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• 제26권1호
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• pp.29-35
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• 2010

The present study was conducted to investigate the antimutagenic potential of the methanolic extract from the leaves of sweet potato (Ipomea batatas, IB) with the SOS chromotest (umu test) and Salmonella typhimurium TA 98 and TA 100. The anticarcinogenic effects were also studied by calculation of the $IC_{50}$ on human cancer cell lines and investigating the function of gap junction in rat liver epithelial cells. The IB extract inhibited dose-dependently the ${\beta}$-galactosidase activity induced spontaneously at concentration of more than 200 mg/ml in S. typhimurium TA 1535/pSK 1002, and decreased significantly (p < 0.01) the ${\beta}$-galactosidase activities induced by mutagen 6-chloro-9-[3-(2-chloroethylamino)proylamino]-2-methoxyacridine dihydrochloride (ICR) at dose of more than 0.4 mg/0.1 ml. The IB extract showed no effect on the spontaneous reversions of S. typhimurium TA 98 and 100 but benzo(${\alpha}$)pyrene (BaP)-stimulated reversions were decreased dose-dependently (p < 0.01) at the concentration of more than 100 mg/ml. The $IC_{50}$ value of stomach cancer cells was lower than that of normal rat liver epithelial cells, but the values of colon and uterine cancer cell lines were similar to those of normal rat liver epithelial cells. The transfer of dye through gap junctions was not affected by treatment of the IB extracts at any concentration during treatment periods. The simultaneously treatment of IB extract and 12-O-tetradecanoylphorbol-13-acetate (TPA) effectively prevented the inhibition of dye transfer induced by TPA 1 hour after treatment at all exposed concentrations. The number of gap junctions was significantly (p < 0.01) increased by the treatment with IB extract at concentrations of more than 40 ${\mu}g$/ml. The inhibition of the expression of gap junction proteins by TPA (0.01 ${\mu}g$/ml) was recovered dose dependently by the simultaneous treatment of IB extracts. Our data suggest that Ipomea batatas has antimutagenic and anticarcionogenic activity in vitro.

• Asian-Australasian Journal of Animal Sciences
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• 제23권12호
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• pp.1557-1565
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• 2010

Methyl paraben (MP), which is used as a preservative in pharmaceutical and cosmetic (shampoo) products, foods and beverages, enters into the aquatic environment and can pose a potential fish health hazard. In this experiment, effects of MP were evaluated in adult male common carp (Cyprinus carpio) by exposing them to fractions (1/$143^{rd}$ to 1/29th) of the $LC_{50}$ dose with every change of water for 28 days. Vitellogenin induction, metabolic enzymes, somatic indices and bioaccumulation were studied at weekly intervals. The $96^{th}$ h $LC_{50}$ of MP in fingerlings was 120 mg/L. Compared to the control, except for increases (p<0.01) in alkaline phosphatase (EC 3.1.3.1), alanine aminotransferase (EC 2.6.1.2) and liver size, there were decreases (p<0.01) in activity of acid phosphatase (EC 3.1.3.2), aspartate aminotransferase (EC 2.6.1.1), and testiculosomatic index following exposure to any dose of MP. Vitellogenin induction was significantly higher (p<0.01) in exposed than unexposed (control) fish. The bioaccumulation of MP in testis, liver, brain, gills and muscle tissues of fish increased significantly (p<0.01) with increase of dose from 0.84 ppm to 1.68 ppm. Dose and duration of exposure (p<0.01) indicated that an exposure period of 1 to 2 weeks was sufficient to cause changes in the quantifiable parameters studied. Fish exposed to 4.2 ppm MP became lethargic after the $26^{th}$ d. Histologically, degeneration, vacuolization and focal necrotic changes in liver and fibrosis-like changes in testicular tissue were noted.

• Biomolecules & Therapeutics
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• 제16권1호
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• pp.46-53
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• 2008

The preventive hypolipidemic effect of the aqueous extracts of Picrorrhiza Rhizoma (PR) was observed in a high fat diet (HFD) feeding hyperlipidemic mouse with their hepatoprotective effects. PR extracts (50, 100 and 200mg/kg) were orally dosed once a day for 12 weeks initiated with HFD supply, and changes on body weight and gains, liver weight, serum aspartate transferase (AST) and alanine transferase (ALT) levels were monitored with serum low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride and total cholesterol levels. The efficacy of test articles was compared to that of 10mg/kg of simvastatin (SIMVA). Dramatic decrease of both absolute and relative liver weight was dose-dependently observed in all PR extract dosing groups as compared with HFD control group. The serum AST and ALT levels were dose-dependently decreased in PR extract dosing groups. The serum LDL, triglyceride and total cholesterol levels were dose-dependently decreased in PR extract dosing groups compared to that of HFD control group. The serum HDL levels were slightly but dose-dependently increased in PR extract dosing groups as compared with control group. The efficacy on the serum lipid levels of PR extracts was slighter than that of SIMVA. Based on these results, it is concluded that water extract of PR has a relatively good favorable preventive effects on the HFD inducing hyperlipidemia and hepatopathy.

• 대한한방종양학회지
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• 제8권1호
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• pp.9-21
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• 2002

Object The effect of Banhasasim-tang extracts on the hepatic, splenic toxicity and induced by Doxorubicin administration(Three injection protocol) were monitored using male ICR mice. Method The changes of body weigh, organ weights of liver and spleen were observed with blood GOT and GPT level. Results 1. Increase of absolute and relative liver weight observed in Doxorubicin treatment group were dose-dependently inhibited by Banhasasim-tang extracts. In addition, the degrees of liver congestion and necrotic spot were significantly and dose-dependently decreased after Banhasasim-tang extracts dosing groups compared to that of Doxorubicin treatment group. It is also demonstrated that elevated serum GOT and GPT levels in Doxorubicin treatment group were significantly decreased in Banhasasim-tang extracts dosing groups. 2. Decrease of absolute and relative spleen weight observed in Doxorubicin treatment group were dose dependently inhibited by Banhasasim-tang extracts. In addition, the degrees of splenic atrophy were significantly and dose-dependently decreased after Banhasasim-tang extracts dosing groups compared to that of Doxorubicin treatment group.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Current Trends in Toxicological Sciences
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• pp.137-137
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• 2002

Biologically Based Dose-Response (BBDR) models were developed using biomarkers for cancer risk assessment. To establish the relationship among biomarkers, exposure dose and tumor response, biomarkers in the lung, liver, stomach or blood were measured after a single or continuous administration of selected carcinogen (; BaP) in mice or rats.(omitted)

• Molecular & Cellular Toxicology
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• 제1권4호
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• pp.268-274
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• 2005

Bromobenzene (BB) is well known hepatotoxicant. Also, BB is an industrial solvent that arouses toxicity predominantly in the liver where it causes centrilobular necrosis. BB is subjected to Cytochrome P450 mediated epoxidation followed by either conjugation with glutathione, enzymatic hydrolysis or further oxidation. In this study, we focused on BB-induced gene expression at non-hepatotoxic dose. Mice were exposed to two levels of BB, sampled at 24 h, and hepatic gene expression levels were determined to evaluate dose dependent changes. When examining the toxic dose of BB treated group in other previous studies, genes related to heat shock protein, oxidative stress, and drug metabolism are expressed. Compared to these results, our study, in which non-toxic dose of BB was administrated, showed similar patterns as the toxic conditions above. The purpose of the study was to select genes that showed changes in relation to the differing dose through confirmation of the difference within transcriptomic boundaries, but those that are not detected by the existing classic toxicology tools in non-hepatotoxic dose.

• 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.

• 동의생리병리학회지
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• 제18권2호
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• pp.413-418
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• 2004

Objectives : Cirsii Japonici Herba (CJH) is one of medicinal plants that has been frequently used for styptic purposes in Asian countries. In order to evaluate a hepatoprotective effects of CJH in the liver fibrotic diseases, the present study investigated how CJH improves a hepatic function in the dimethylnitrosamine(DMN) treated rat. Methods : CJH were orally administered to rats that has been treated with DMN. Subsequently, the amount of blood L-asparate aminotransferase (AST), L-alanine aminotransferase (ALT), and hydroxyproline were quantitated. Several histopathological markers for examining the degree of hepatic fibrosis were investigated by H-E and Masson-Trichrome staining. Results: DMN treatment caused a increase of relative liver weight to the body at 14 days after DMN induction, Administration of CJH with 100mg/kg and 1,000mg/kg dose decreased significantly the AST level elevated by DMN injection(p<0.01). But ALT level was not improved. The hydroxyproline level was reduced by a simultaneous treatment of CJH with DMN for 7 days, but not recovered completely to its normal value, CJH administration improved conspicuously the DMN-induced histopathological changes of liver such as granuloma, but cell necrosis and fibrosis were not improved with CJH 1,000mg/kg dose. Conclusion: These results indicate that CJH has protective effect on liver injury and can inhibit liver fibrosis Induced by DMN in rats.

• Journal of Acupuncture Research
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• 제22권5호
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• pp.151-160
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• 2005

Objectives : This study was undertaken to examine whether Juglandis Semen herbal acupuncture (JGA) exerts protective effect against oxidant-induced cell injury in rabbit liver. Methods : The cell damage was estimated by measuring lactate dehydrogenase (LDH) release, and lipid peroxidation was estimated by measuring malondialdehyde (MDA) in rabbit liver slices. Results : t-Butylhydroperoxide (tBHP) caused an increase in LDH release and lipid peroxidation in a dose-dependent manner over concentrations of 0.5-2 mM, which were prevented by addition of 0.05% JGA. The protective effect of JGA was dose-dependent in concentration range of 0.005 to 0.1%. The concentrations of 0.005 and 0.1% JGA completely prevented the LDH release and lipid peroxidation by 1 mM tBHP. When liver tissues were exposed to 1 mM tBHP, alanine aminotransferase (ALT) activity in the medium was significantly increased, which was prevented by 0.05% JGA. tBHP (2 mM) decreased GSH content and the effect was prevented by 0.05% JGA. Conclusion : These results suggest that JGA exerts protective effect against oxidant-induced cell injury by antioxidant action resulting from enhancement of GSH content in the liver.