• 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.

• Natural Product Sciences
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• v.15 no.2
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• pp.101-105
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• 2009

We previously reported that a novel cerebroside, LCC, isolated from the fruits of Lycium chinense (Solanaceae), significantly exerted hepatoprotective activity against both the carbon tetrachloride-induced and galactosamine-induced toxicities in primary cultures of rat hepatocytes. In the present study, we further attempted to determine the effect of LCC on hepatic fibrosis in animal model. Hepatic fibrosis was induced in rats by bile duct ligation/scission (BDL) for a period of 5 weeks. Treatment of BDL rats with LCC significantly reduced collagen deposition and the activities of serum alkaline phosphatase and ${\gamma}$-glutamyl transpeptidase. In addition, the LCC treatment of BDL rats significantly preserved the decreased hepatic glutathione as well as the activities of glutathione reductase and catalase in BDL rats. From the results, it can be speculated that LCC might exert antifibrotic activity in rats with BDL, in part, through the preservation of antioxidant enzymes and hepatic glutathione.

• The Journal of Internal Korean Medicine
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• v.19 no.1
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• pp.22-38
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• 1998

This study was to investigate the hepatoprotective and anticirrhotic effects of Ganyeumilhobang(GIE) on the acute and chronic liver injury induced by various agents. Chronic liver injury induced by dimethylnitrosamine(DMN) ; a new experimental model for cirrhosis and the intraperitoneal injection of dimethylnitrosamine in the rat. Acute liver njury induced by carbon tetrachloride$(CCl_4)$ and D-galactosamine ; a experimental model for acute liver injury, the administration of $CCl_4$ and the intraperitoneal injection of D-galactosamine in the rat. The development of fibrosis and acute liver injury by the three prescriptions were examined by the chemical analysis of AST, ALT, prothrombin time and hydroxyproline. The results obtained were as follows. 1. The increasing level of hydroxyproline volume induced by DMN in mice was decreased by the oral administration of GIB. 2. The degree of histological fibrosis and hepatic inflammatory cell infiltration induced by $CCl_4$ decreased by the oral administration of GIB. 3. The increase of senun AST and ALT of mice with acute liver damage induced by $CCl_4$ and D-galactosamine was inhibited by the administration of GIB. 4. The prolongation of prothrombin time(seconds) of mice acute liver damage induced by $CCl_4$ was shortened by the oral administration of GIB. 5. The liver of mice was hepatectomized partial1y after the oral administration of GIB. The mitotic index(% of nuclei), weight of liver, contents of protein, RNA and DNA synthesis of the liver tissue were increased by the oral administration of GIB.

• CELLMED
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• v.2 no.4
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• pp.34.1-34.5
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• 2012

The present study aimed to determine the hepatoprotective activity of the chloroform extract of D. linearis leaves (CEDL) using the paracetamol (PCM)- and carbon tetrachloride ($CCl_4$)-induced liver injury models in rats. The rats received $dH_2O$ (negative control), 200 mg/kg of silymarin (positive control) or CEDL (50, 250 and 500 mg/kg) orally once daily for 7 days and then were subjected to the hepatotoxic induction on the $7^{th}$ day. The samples (i.e. blood and liver) were collected and underwent biochemical and microscopical analysis, respectively. From the data obtained, both inducers caused significant (p < 0.05) increase in the levels of AST and ALT when compared to the control group, which were significantly (p < 0.05) reduced by CEDL in a generally dose-dependent manner. These biochemical findings were supported by the histopathological analysis and histological scoring. In conclusion, CEDL possesses potential hepatoprotective activity, which could be associated with its flavonoid and tannin contents with the mechanisms of hepatoprotection linked to either its antioxidant or anti-inflammtory/immunomodulating activities. Further in-depth studies are required to identify the responsible bioactive compound.

• 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.

• Toxicological Research
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• v.28 no.3
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• pp.165-172
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• 2012

Raphanus sativus (Cruciferaceae), commonly known as radish is widely available throughout the world. From antiquity it has been used in folk medicine as a natural drug against many toxicants. The present study was designed to evaluate the hepatoprotective activity of radish (Raphanus sativus) enzyme extract (REE) in vitro and in vivo test. The $IC_{50}$ values of REE in human liver derived HepG2 cells was over 5,000 ${\mu}g/ml$ in tested maximum concentration. The effect of REE to protect tacrine-induced cytotoxicity in HepG2 cells was evaluated by MTT assay. REE showed their hepatoprotective activities on tacrine-induced cytotoxicity and the $EC_{50}$ value was 1,250 ${\mu}g/ml$. Silymarin, an antihepatotoxic agent used as a positive control exhibited 59.7% hepatoprotective activity at 100 ${\mu}g/ml$. Moreover, we tested the effect of REE on carbon tetrachloride ($CCl_4$)-induced liver toxicity in rats. REE at dose of 50 and 100 mg/kg and silymarin at dose of 50 mg/kg were orally administered to $CCl_4$-treated rats. The results showed that REE and silymarin significantly reduced the elevated levels of serum enzyme markers induced by $CCl_4$. The biochemical data were supported by evaluation with liver histopathology. These findings suggest that REE, can significantly diminish hepatic damage by toxic agent such as tacrine or $CCl_4$.

• Korean Journal of Pharmacognosy
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• v.33 no.1 s.128
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• pp.5-12
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• 2002

This study was performed to evaluate hepatoprotective effect of Daewhang-whangryunhaedok-Tang(DWT) on liver injured rats induced by $CCl_4$ and the acute oral toxicity of it in mice. The activities of serum transaminase(ALT/AST), alkaline phosphatase(ALP) and lactic dehydrogenase (LDH), the levels of serum total cholesterol(TC) and triglyceride(TG), change of liver enlargement, and inhibitory activities of lipid peroxidation, catalase and glutathione-S-transferase(GST) in liver microsome were determined in hepatotoxic rats induced by $CCl_4$ DWT DWT was significantly reduced the serum ALT, AST, ALP, LDH, TC and TG levels. And, the increase of lipid peroxidation, decrease of catalase and GST activities in the liver microsome of $CCl_4$-intoxicated rat were significantly improved by the treatment of DWT. Male and female mice were administered maximum dosages of 5,000 mg/kg b.w. of DWT. After single oral administration of DWT to mice, we observed them daily for 2 weeks. DWT did not induce any toxic signs in the mortalities, clinical signs, body weight changes, and gross necropsy findings of mice. Based on these results, it is concluded that DWT may have the hepatoprotective effect on $CCl_4$ induced hepatotoxicity in rats. Also, DWT may have no side effect and its $LD_{50}$ value may be over 5,000 mg/kg b.w. in mice.

• Natural Product Sciences
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• v.9 no.1
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• pp.13-17
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• 2003

The hepatoprotective effect of the ethanolic extract of Coccinia indica fruits in rats treated with carbon tetrachloride. In hepatotoxic rats, liver damage was studied by assessing parameters such as aspartate aminotransferase (AST), alanine aminotransferase (AlT), alkaline phosphatase (AIP) and gamma glutamyl transpeptidase (GGT) in serum, and concentrations of total proteins, total lipids, phospholipids, triglycerides and cholesterol in both serum and liver. The effect of co-administration of ethanolic extract on the above parameters was further investigated. Histopathological study of the liver in experimental animals was also undertaken. Hepatic damage as evidenced by a rise in the levels of AST, AIT, AIP and GGT in serum, and also changes observed in other biochemical parameters In serum and liver showed a tendency to attain near normalcy in animals co-administered with the extract. The normal values for AST (IU/L), AIP (IU/I), protein (g/100 ml) and total lipids (mg/100 ml) in serum (i.e.,20.24, 70.04, 5.72 and 135.54 respectively) were found to alter towards values 32.61, 127.11, 3.83 and 265.91 in hepatotoxic rats. These parameters Attained near normal values (I.e.,22.82, 79.30, 5.22 and 151.24 for AST, AIP protein and total lipids respectively) in ethanolic extract co-administered rats. Profound steatosis, ballooning degeneration and nodule formation observed in the hepatic architecture of $CCl_4$ treated rats were found to acquire near-normalcy in drug co-administered rats, thus corroborating the biochemical observations. Thus the study substantiates the hepatoprotective potential of ethanolic extract of Coccinia indica fruits.

• Korean Journal of Clinical Laboratory Science
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• v.44 no.4
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• pp.229-238
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• 2012

Cyclooxygenase(COX-2) is an inducible enzyme that catalyzes the synthesis of prostaglandins (PGs) from arachidonic acid. Over-expression of COX-2 has been reported to be associated with progressive hepatic fibrosis in chronic hepatic C infection and rat liver fibrosis induced by carbon tetrachloride($CCl_4$). Recently, it is well known that mast cell products can stimulate the proliferation of hepatic stellate cells and key players in liver fibrosis. But little is known regarding their role in $CCl_4$-induced liver fibrosis in rat. Our aim was to investigate the relation between COX-2 expression and mast cells during liver fibrosis after $CCl_4$ treatment. Thirty Wistar rats were divided into five groups (non-treated 0, 2, 4, 6 and 8-week after $CCl_4$-treatment). Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry were used to assess the expression of ${\alpha}$-smooth muscle actin (${\alpha}$-SMA), collagen-1 and COX-2 in liver tissue from $CCl_4$-treated rats. The density of collagen and mast cells were determined using a computerized image analysis system in liver sections stained with picrosirius red and toluidine blue, respectively. The expression levels of ${\alpha}$-SMA, collagen-1 and COX-2 mRNA were significantly higher at 2 wk in $CCl_4$-treated groups than non-treated group. The number of mast cells in liver tissues increased gradually from 2 wk to 6 wk depending on the fibrosis severity but decreased abruptly at 8 wk. The significant increase of collagen-1 and ${\alpha}$-SMA mRNA expression in $CCl_4$-treated rats was continued until 6 wk while the COX-2 mRNA was significantly decreased at 8 wk. These results suggest that increased mast cells are closely associated with COX-2 over-expression during hepatic fibrogenesis of $CCl_4$-treated rats.

• Journal of Environmental Impact Assessment
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• v.9 no.3
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• pp.203-214
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• 2000

Health risk assessment is applied to streamlining LCA(Life Cycle Assessment) using Monte carlo simulation for probabilistic/stochastic exposure and risk distribution analysis caused by data variability and uncertainty. A case study was carried out to find benefits of this application. BTC(Benzene, Trichloroethylene, Carbon tetrachloride mixture alias) personal exposure cases were assumed as production worker(in workplace), manager(in office) and business man(outdoor). These cases were different from occupational retention time and exposure concentration for BTC consumption pattern. The result of cancer risk in these 3 scenario cases were estimated as $1.72E-4{\pm}1.2E+0$(production worker; case A), $9.62E-5{\pm}1.44E-5$(manger; case B), $6.90E-5{\pm}1.16E+0$(business man; case C), respectively. Portions of over acceptable risk 1.00E-4(assumed standard) were 99.85%, 38.89% and 0.61%, respectively. Estimated BTC risk was log-normal pattern, but some of distributions did not have any formal patterns. Except first impact factor(BTC emission quantity), sensitivity analysis showed that main effective factor was retention time in their occupational exposure sites. This case study is a good example to cover that LCA with probabilistic risk analysis tool can supply various significant information such as statistical distribution including personal/environmental exposure level, daily time activity pattern and individual susceptibility. Further research is needed for investigating real data of these input variables and personal exposure concentration and application of this study methodology.