• Nutrition Research and Practice
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• v.4 no.2
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• pp.93-98
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• 2010

Our previous study demonstrated that methanolic extract of Chrysanthemum zawadskii Herbich var. latilobum Kitamura (Compositae) has the potential to induce detoxifying enzymes such as NAD(P)H:(quinone acceptor) oxidoreductase 1 (EC 1.6.99.2) (NQO1, QR) and glutathione S-transferase (GST). In this study we further fractionated methanolic extract of Chrysanthemum zawadskii and investigated the detoxifying enzyme-inducing potential of each fraction. The fraction (CZ-6) shown the highest QR-inducing activity was found to contain (+)-(3S,4S,5R,8S)-(E)-8-acetoxy-4-hydroxy-3-isovaleroyloxy-2-(hexa-2,4-diynyliden)-1,6-dioxaspiro [4,5] decane and increased QR enzyme activity in a dose-dependent manner. Furthermore, CZ-6 fraction caused a dose-dependent enhancement of luciferase activity in HepG2-C8 cells generated by stably transfecting antioxidant response element-luciferase gene construct, suggesting that it induces antioxidant/detoxifying enzymes through antioxidant response element (ARE)-mediated transcriptional activation of the relevant genes. Although CZ-6 fraction failed to induce hepatic QR in mice over the control, it restored QR activity suppressed by $CCl_4$ treatment to the control level. Hepatic injury induced by $CCl_4$ was also slightly protected by pretreatment with CZ-6. In conclusion, although CZ-6 fractionated from methanolic extract of Chrysanthemum zawadskii did not cause a significant QR induction in mice organs such as liver, kidney, and stomach, it showed protective effect from liver damage caused by $CCl_4$.

• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.75-82
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• 1996

The hypothesis that calcium provoke $O_2^-$ formation by Kupffer cells and may contribute to carbon tetrachloride $(CCl_4)$ induced liver injury was studied in SD rats. In $CCl_4-treated$ animals, hepatic malonaldehyde (nmole/gm liver) and plasma ALT (IU/ml) levels elevated significantly from $119.63{\pm}13.00$ to $268.97{\pm}14.82$ and from $17.3{\pm}0.18$ to $806.08{\pm}37.63$, respectively, compared to those in controls. Activation of Kupffer cells with high dose of retinol (250,000 IU/kg/day, po, for 7 day) significantly enhanced ALT levels, while inactivation of Kupffer cells with gadolinium chloride (7.5 mg/kg/day, ip, for 2 day) attenuated the increase of serum ALT level following $CCl_4$ treatment. Diltiazem (10 mg/kg/day, ip for 2 day) given in combination with retinol led to a marked decrease in ALT levels compare to the level in rats treated only with retinol against $CCl_4$ treatment. In order to determine any alterations in cytochrome P450 activities, the P450 content and the CYP2E1 activity were measured and all $CCl_4-treated$ rats showed significantly lower levels compared to those in controls and vehicle-treated animals. There were significant increases in glutathione peroxidase in all $CCl_4-treated$ rats except diltiazem treated groups. No difference was found among untreated and vehicle-treated rats. It is concluded that Kupffer cells contribute to $CCl_4-induced$ liver injury and that calcium antagonist attenuated the increased $CCl_4-induced$ liver injury due to activation of Kupffer cells.

• Journal of Pharmacopuncture
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• v.2 no.1 s.2
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• pp.111-133
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• 1999

These studies were carried out to investigate the effect of Herbal-acupuncture with Inzinsammultang extract on the recovery from liver injury of rats. The liver injury of rats induced with 0.3ml/ea carbon tetrachloride. The Herbal-acupunture with Inzinsam multang extract solution inserted into corresponding focus of Kansu(BL18) in rats. In this study, SD-Rats(Sprague-Dawley) were divided into 4 groups ; Normal group (None treated group), Control-group(The group not treated after $CCI_4$-intoxication), Treated group; Example I-group(Saline-injected groups after $CCl_4$-intoxication) and Example II-group(Inzinsammultang-injected groups after $CCl_4$-intoxication). Through histological observation, Example II-group sho-ws that liver injury is weaker than Control group.(p<0.05) Biochemical assays for each serum enzyme activities of AST, ALT and LDH, levels of albumin, ${\gamma}$-GT, TG, total cholesterol were performed. The results were summarized as follows 1. AST(Aspartate aminotransferase) activity in serum significantly decreased in the Inzinsammultang-injected groups after $CCl_4$-intoxication. Inzinsammultang-injected groups after $CCl_4$-intoxication showed significantly higher AST activities, compared with the Saline-injected groups after $CCl_4$-intoxication.(p<0.05) 2. ALT(Alanine aminotransferase) activity in serum significantly decreased in the Inzinsammultang-injected groups after $CCl_4$-intoxication. The Inzinsammultang-injected groups after $CCl_4$-intoxication showed significantly higher AST activities, compared with the Saline-injected groups after $CCl_4$-intoxication(p<0.05) 3. Level of Albumin in serum significantly increased in the Inzinsarnmultang-injected groups after $CCl_4$-intoxication. 4. LDH(Lactate dehydrogenase) activities in serum significantly decreased in the Inzinsammultang-injected groups after $CCl_4$-intoxication.(p<0.05) 5. ${\gamma}$-GT(Glutamyl transferase) in serum significantly decreased in the Inzinsammultang-injected groups after $CCl_4$-intoxication(p<0.05) 6. As for the TG(Triglyceride) levels in serum, Inzinsammultang-injected groups after $CCl_4$-intoxication is no significant differences compared with the Saline-injected groups after $CCl_4$-intoxication.(p<0.05) 7. Total cholesterol in serum significantly increased in the Inzinsarnmultang-injected groups after $CCl_4$-intoxication.(p<0.05) Those results indicate that the Inzinsammultang Herbal-acupuncture have significant effects on the liver injury induced by $CCl_4$. So it is expected that the Inzinsammultang Herbal-acupuncture can be used to cure inflammations and recover the functions of damaged liver cells.

• Journal of the East Asian Society of Dietary Life
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• v.4 no.1
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• pp.105-112
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• 1994

To evaluate the role of dietary earthworm flour in liver injury by CCl4 treatment, the rats were fed 5% earthworm flour supplemented diet for 53 days and control rats were fed standard diet without earthworm supplementation. Liver damage was induced both in earthworm flour supplemented diet and control groups by two intraperitoneal injections of CCl4 at the level of 0.1$m\ell$/100g body weight(50% in olive oil) at intervals of 16 hours the increasing rate of lover weight/body weight(%) and serum levels of alanine aminotransferase activity to the control group were higher in CCl4-treated rats fed earthworm flour supplemented diet than those fed standard diet. The decreasing rate of hepatic microsomal aniline hydroxylase activity was also higher in rats fed earthworm supplemented rats by the CCl4 treatment, Hepatic glutathione S-transferase activity was sinificantly higher in rats fed earthworm supplemented diet than those fed standard diet. It is concluded that a dietary earthworm flour argument the metabolic rate of CCl in rats.

• YAKHAK HOEJI
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• v.34 no.4
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• pp.267-276
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• 1990

To achieve a better understanding of antioxidant action manifested by malotilate, the dithiol malonates, we monitored the oxy radical-scavenging system against the chronic hepatic damage induced by $CCl_4$ alone or in combination with ethanol. Malotilate was given orally at a dose of 100 mg/kg/day and $CCl_4$ 1.5 ml/kg was injected subcutaneously twice a week for 4 weeks. In each group receiving ethanol, drinking water was replaced by 20% aqueous solution or glucose, isocaloric amounts of ethanol, as a control of ethanol was diluted in its drinking water. Each rat was killed as a starved state at 18 hours after the period of the experiment, four weeks. The results were summarized as follows: 1) Malotilate inhibited the rate of generation of superoxide radicals, the accumulation of lipoperoxides, and promoted the synthesis of glutathione in the liver. 2) Malotilate stimulated the enhancement of activity of superoxide dismutase in hepatic mitochondria. 3) Malotilate had no effects on the hepatic $H_2O_2$ contents. 4) Malotilate showed the increase of catalase activity in the liver poisoned with $CCl_4$, and also gave a tendency to increase it in the liver intoxicated with ethanol. Thus, our data suggested that the activation of hepatic antioxidant system in the presence of malotilate would play a role in protecting liver against the toxic effects of oxy radical and/or lipid peroxides under the hepatotoxic conditions induced by $CCl_4$ with or without ethanol. However, the effects of malotilate against the ethanol-induced hepatotoxicity appear to be insignificant.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.133.2-134
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• 2003

2-Methylaminoethyl-4, 4'-dimethoxy-5, 5', 6.6 -dimethylenedioxybiphenyl-2'-carboxy-2-carboxylate (DDB-S), a synthetic compound derived from DDB, has been known to protect liver against carbon tetrachloride-, D-galactosamine-, thioacetamide-, and prednisolone-induced hepatic injury in experimental animals. The metabolism of this compound has been assessed in rats by using liquid chromatography/electrospray tandem mass spectrometry (LC/MS/MS) method. (omitted)

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.251.2-251.2
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• 2002

2-Methylaminoethyl- 4,4' -dimethoxy- 5, 5',6,6' -dimethylenedioxybiphenyl- 2' -carboxy- 2-carboxylate (DDB-S) is a synthetic compound derived from DDB. which is protects liver against carbon tetrachloride-, D-galactosamine-, thioacetamine-, and prednisolone- induced hepatic injury in experimental animals. We assessed the use of liquid chromatography/electrospray iontrap tandem mass spectrometry (LC/MS/MS) method to identify and quantify in vivo metabolites and to measure excretion. (omitted)

• Journal of Radiation Industry
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• v.7 no.1
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• pp.81-85
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• 2013

This study was conducted to investigate the effect of fermented blackberry drinks (BD) on carbon tetrachloride ($CCl_4$)-induced liver injury in rats. Male Sprague-Dawley rats were randomly divided into four groups with 6 rats per group: control, $CCl_4$, $CCl_4$ plus BD $3ml\;kg^{-1}$, and $CCl_4$ plus BD $6ml\;kg^{-1}$. We found that the levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly increased and the activity of antioxidant enzyme glutathione peroxidase (GPx) in the liver was decreased in rats treated with $CCl_4$ alone when compared with the control group. However, the administration of BD attenuated the levels of serum AST and ALT in $CCl_4$-treated rats. Moreover, the administration of BD significantly increased the activity of GPx in $CCl_4$-treated rat livers. Taken together, these results suggest that BD could protect the liver from $CCl_4$-induced hepatic damage.

• Journal of the Korean Society of Food Science and Nutrition
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• v.26 no.1
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• pp.137-143
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• 1997

This study was carried out to investigate the effect of godulbaegi leaf extracts on detoxication of liver injury in $CCl_4$-treated rats. We divided normal group(5) and $CCl_4$-treated group and then $CCl_4$- treated group was divided into 6 groups; only $CCl_4$-treated group(CS), aqueous extract pretreated group (CSA), n-butanol extract pretreated group(CSB), Tween 80 pretreated group(CT), n-hexane extract pretreated group(CTH) and ethyl acetate extract pretreated group(CTE). The ratio of liver weight per body weight and the activity of GPT in hexane extract group(CTH) were lowest, similar to the results of S. Godulbaegi n-hexane extract(IS) groups intoxicated by $CCl_4$ had lower values of MDA than CS and CT which are control groups. Histological finding of liver tissue revealed less of necrosis in IS extracts groups than in control groups(CS, CT). From these results, IS extracts could predominently prevent hepat-otoxicity of rats. Especially, hexane extract was effective on the detoxication of liver injury among the other extracts.

• Korean Journal of Clinical Laboratory Science
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• v.43 no.4
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• pp.194-204
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• 2011

This study was carried out to compare the histopathological differences of liver lesions in carbon tetrachloride ($CCI_4$), dimethylnitrosamine (DMN), thioacetamide (TAA) and bile duct ligation (BDL)-induced rats. $CCl_4$, DMN and TAA were administered intraperitoneally and conducted bile duct ligation for 4 weeks to induce hepatic fibrosis. Indices of liver cell injury (steatosis, hydropic degeneration, bile duct hyperplasia, hemorrhage & hemosiderin deposition), the extent of liver fibrosis (fibrotic area) and the rate of regeneration (number of PCNA-positive cells) were investigated in each group. Liver tissues were stained with hematoxylin-eosin (HE), sirius red, prussian blue and immunostained with ${\alpha}$-smooth muscle actin (${\alpha}$-SMA), transforming growth factor-${\beta}1$ (TGF-${\beta}1$), proliferative cell nuclear antigen (PCNA), and quantified using a computerized image analysis system. Liver cell steatosis was significantly increased in $CCl_4$ and TAA groups, and hydropic degeneration and bile duct hyperplasia were significantly increased in TAA and BDL groups when compared with that in normal control, respectively. Fibrosis area was significantly increased in all four groups, especially in $CCl_4$ group. Correlation between ${\alpha}$-SMA and TGF-${\beta}1$ expressions in four groups was good. Hemorrhage area in liver parenchyma was significantly increased in DMN group only when compared with that in normal control, while hemosiderin deposition area was significantly increased in TAA and BDL groups as well as DMN group. The Number of PCNA-positive cells was significantly increased in all four groups, especially in TAA group. These results indicate that the duration and methods of hepatotoxic drug treatment are very important factors to make plans for animal experimentation on the induction of hepatic fibrogenesis in rats.