• Journal of Food Hygiene and Safety
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• v.9 no.2
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• pp.75-80
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• 1994

The effects of ursodeoxycholic acid (UDCA) were studied on the hepatotoxicity induced by several hepatotoxicants such as carbonte trachloride, thioacetamide and 1-naphthylisothiocyanate in ICR male mice. UDCA (50 mg/kg, 100 mg/kg) decreased the elevated serum bilirubin in carbon tetrachloride intoxicated mice, the elevated serum AST, alkaline phosphatase in thioacetamide intoxicated mice, the elevated serum AST and bilirubin in 1-naphthylisothiocyanate intoxicated mice.

• The Journal of Korean Medicine
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• v.15 no.2 s.28
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• pp.156-172
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• 1994

This study was performed to evaluate the effect of the Gamichunggantang on recovering from liver injury induced by d-galactosamine and ${\alpha}$-naphthylisothiocyanate. and following results were obtained. 1. The increases of the serum GOT. GPT activities in mice induced by d-galactosamine and ${\alpha}$-naphthylisothiocyanate were inhibited significantly by the administration of the Gamichunggantang. 2. The increases of the total cholesterol. triglyceride and blood urea nitrogen levels in mice induced by d-galactosamine and ${\alpha}$-naphthylisothiocyanate were significantly inhibited by the administration of the Gamichunggantang. 3. The increase of the ALP activity in mice following liver injury induced by d-galactosamine and ${\alpha}$-naphthylisothiocyanate were inhibited to an extend. but it was not significant. 4. It is considered that the efficacy of the Gamichunggantang on liver cell injury depends on its concentration rate.

• Korean Journal of Veterinary Research
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• v.35 no.3
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• pp.481-488
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• 1995

In oriental folk medicine, Artemisia messes-schmidiana var viridis(Compositae) has been used for jaundice, hepatitis, diuretic and liver cirrhosis etc. 1-naphthylisothiocyanate(ANIT) has been used for more than 20 years as a model compound to study mechanisms of intrahepatic cholestasis in laboratory animals as rat and mouse. Various biochemical and morphological changes including biliary epithelial and parenchymal cell necrosis occur in the liver of animals treated with ANIT. The purposes of present study are to examine pharmacological effects of Artemisia messes-schmidiana var viridis water extract(AMWE) on alterations of secretion volume and total bile acids level in bile juice, and that of serum AST, ALT, ALP, bilirubin, and glucose levels in rat. AMWE stimulated bile secretion and recovered ANIT-induced cholestasis. Bile acid concentrations increased to more than 60% compared with normal by ANIT, which were returned toward normal value with AMWE treatment. Serum AST and ALT activities were increased by ANIT and yet which were significantly decreased with AMWE treatment. In addition, this effect was apparent in AMWE pretreatment group. Serum glucose levels were increased with AMWE and ANIT, while were decreased compared with control in AMWE posttreatment group. Increased serum total bilirubin contents and ALP activities by ANIT were significantly decreased with AMWE posttreatment. In conclusion, AMWE exerted bile acid-independent choleresis effect and then improved to normal conditions ANIT-induced cholestatic syndromes. Also, AMWE have protective and regenerative effect of hepatocytes in rat.

• Journal of Veterinary Clinics
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• v.7 no.1
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• pp.381-390
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• 1990

In order to study the effects of administration of carbon tetrachloride(CCI$_4$) and 1-naphthylisothiocyanate(ANIT) on the liver of Korean black goats, some liver function tests and liver biopsy were done on 4 Korean black goats dosed with CCI$_4$(0.4m1/kg of body weight) in-traruminally and 4 Korean black goats dosed with ANIT(400mg/kg of body weight) by stomach tube. BSP Tl/2 and serum total bilirubin concentration in goats dosed with CCI$_4$ were increased gradually, reached to maximum value on 2nd and 1st day, respectively, and then began to decrease in normal range, gradually. In goats dosed with ANIT, BSP Tl/2 and serum total bilirubin concentration were increased rapidly, reached to maximum value on 0.5 and 1st day, respectively, and then returned to normal ragne, rapidly. Serum SDH, AST and GGT activities in goats dosed with CCI$_4$ were increased rapidly and reached to maximum value on 3rd, 1st and 2nd day, respectively. Thereafter, the serum enzyme activities began to decrease in normal range gradually. In goats dosed with ANIT, however, serum SDH, AST and GGT activities were not changed. The histopathologic changes in goats dosed with CCI$_4$ were lipidosis and centrilobular nee-rosis of the hepatic parenchyma. In goats dosed with ANIT, hyperplasia of bile duct epithelium was noticeable, but pathologic changes in liver parenchyma were not noticed. Conclusively, in Korean black goats dosed with CCI$_4$, main finding was necrosis of hepatic parenchyma. In Korean black goats dosed with ANIT, main finding was cholestasis.

• The Journal of Korean Medicine
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• v.17 no.2 s.32
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• pp.214-226
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• 1996

In an attempt to evaluate the effect of high and low concentration of Injinsaryungsan and high and low concentration of Sosihotang on cholestatic liver injery induced by $ANIT({\alpha}-naphthylisothiocyanate)$, biochemical changes in serum transaminase(GOT, GPT), alkaline phosphate, lactate dehydrogenase, total cholesterol, triglyceride, total-bilirubine were studied and the following results were obtained. 1. High concentration of Injinsaryungsan(2.2g／Kg) inhibited significantly the activity increases of GOT, GPT, ALP, LDH, TC, TG, T-Bilirubine induced by $ANIT({\alpha}-naphthylisothiocyanate)$. 2. Low concentration of Injinsaryungsan(1.1g／Kg) inhibited the activity increases of ALP, LDH, TC, TG with statistical significance, while inhibited the activity increase of GOT ,but with no statistical significance. 3. High concentration of Sosihotang(2.4g／Kg) inhibited the activity increases of LDH, TG, TC with statistical significance while inhibited the activity increases of GOT, GPT, ALP, T-bilirubine with no significance. 4. Low concentration of Sosihotang(1.2g／Kg) inhibited the activity increase of TG, while inhibited the activity increase of ALP, TC with no statistical sig-nificance, but didn't inhibite the activity increases of GOT, GPT, LDH, T-Bil. These results suggest that Injinsaryungsan has more significant effect on the liver injury induced by $ANIT({\alpha}-naphthylisothiocyanate)$ compared with Sosihotang and so can be applicable clinically to virus hepatitis and cholestatic liver injury. Further study will be required to evaluate the effect of Sosibotang on cholangitis and cholecystitis.

• Korean Journal of Veterinary Research
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• v.35 no.3
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• pp.489-496
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• 1995

Artemisia messes-schmidiana var viridis(Compositae) has been used for jaundice, hepatitis, diuretic and liver cirrhosis etc. 1-naphthylisothiocyanate(ANIT) has been used as a model compound to study mechanisms of intrahepatic cholestasis in laboratory animals as rat and mouse. The purposes of present study are to examine pharmacological effects of Artemisia messes-schmidiana var viridis water extract(AMWE) on alterations of triacylglycerol, cholesterol, protein, albumin and A/G ratio levels in serum, of histopathological appearances of liver, and that of hepatic microsomal cytochrome P-450 contents. Increased serum triacylglycerol levels by ANIT were significantly decreased with AMWE. However, AMWE posttreatment aggravated ANIT-induced cholesterol increase. Serum total protein and albumin contents, and A/G ratio were decreased in all ANIT-treated groups, and there were increased compared with control by AMWE posttreatment. Hepatic microsomal cytochrome P-450 contents were decreased in either AMWE and ANIT treatment, which greatly increased with AMWE pretreatment. On the other hand, in histological findings, our results shown that ANIT induced increase of lipid droplets and widening of sinusoidal capillary and these phenomena were disappeared with AMWE treatment. In conclusion, AMWE have choleresis effect. Also, AMWE improved lipid metabolism, protection and regeneration of hepatocytes in ANIT-induced cholestasis.

• Molecular & Cellular Toxicology
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• v.2 no.1
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• pp.48-53
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• 2006

[ ${\alpha}-Naphthylisothiocyanate$ ] (ANIT) induces intrahepatic cholestasis, involving damage to biliary epitheial cells. This study investigates hepatic gene expression and histopathological alterations in response to ANIT treatment in order to elucidate early time response of ANIT-induced hepatotoxicity. ANIT was treated with single dose (3, 6, and 60 mg/kg) in corn oil by oral gavage. Serum biochemical and histopathological observation were performed for evaluation of hepatotoxicity level. Affymetrix oligo DNA chips were used for gene expression profile by ANIT-induced hetpatoxicity. Hepatic enzyme levels (ALT, AST, and ALP) were increased in 24 hr high dose group. In microscopic observations, moderate hepatocellular necrosis, were confirmed 24 hr high dose groups. We found that gene expression patterns were dependent on time and dose. Our selected genes were related inflammation and immunomodulation. In this study, ANIT-induced hepatotoxicity was involved in acute phase responses and provides evidence for role of neutrophil could be mechanism associated with ANIT-mediated hepatotoxicity.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.214.1-214.1
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• 2003

Metabonomic analysis using Liquid Chromatography-Mass Spectrometry (LC-MS) was employed to test the feasibility to predict chemical-induced toxicity. Time-dependent metabolic variations were evaluated in rats treated with the model hepatotoxin, ${\alpha}$- naphthylisothiocyanate (ANIT). Urine samples of ANIT treated group and control group were collected up to 7 days postdose. Urine samples were analyzed by gradient HPLC combined with electrospray mass spectrometry. The chromatographic results were data-reduced and analyzed using principal component analysis to show the time dependent biochemical variations induced by ANIT toxicity. (omitted)

• YAKHAK HOEJI
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• v.44 no.1
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• pp.87-94
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• 2000

In order to investigate the hepatoprotective constituents, Melonis Pedicellus was systematically extracted and fractionated with n-hexane, ethyl acetate, butanol and water Treatment of rats with ethyl acetate fraction reduced hepatic injuries induced by $\alpha$-naphthylisothiocyanate or D-galactosamine, whereas the components in water fraction showed protective effect only against D-galactosamine-induced hepatitis in rats. Two cucurbitacins and three sterols were isolated from ethylacetate fraction and their chemical structures were identified as cucurbitacin B, isocucurbitacin B, $\alpha$-spinasterol, stigmast-7-en-3-ol and stigmast-7-en-3-ol-0-$\beta$-D-glucopyranoside. Cucurbitacin B at the dose of 1 mg/kg (p.o.) signifcantly increased in bile flow in rats with ANIT-induced cholestasis. Isocucurbitacin B at 5 mg/hg (p.o.) showed signilicant protective effects against ANIT-induced cholestasis. These results showed that cucurbitacin B and isocucurbitacin B from Melonis Pedicellus may have hepatoprotective effect in rats with experimental cholestasis.

• Korean Journal of Pharmacognosy
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• v.34 no.1 s.132
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• pp.45-54
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• 2003

We have conducted to characterize the physico-chemical change and pharmacological transformation of traditional herbal medicines by means of processing. Processed Gardeniae Fructus was prepared by heating of fruit of Gardenia jasminoides(GF) for $30{\sim}50\;minute$ in the roster designed for herb processing. The contents of drying loss, water extract, diluted ethanol extract, ether extract and geniposide in non-processed GF and processed GF were examined. The contents of drying loss, water extract and geniposide in processed GF showed a decrease as compared with those of non-processed GF, however the contents of dilute ethanol and ether extract showed a increase as compared with those of non-processed GF. The rate of decrease/increase of those index were in proportion to heating time. And, biological activities of methanol extract of non-processed GF and processed GF were investigated. DPPH scavenging effects and inhibitory effect of xanthine oxidate and hemolysis of processed GF exhibited more effective than those of non-processed GF in vitro. Accelerating effect of large intestinal transport and purgative action of non- processed GF were discriminated by processing of GF. Methanol extracts of non-pro- cessed GF and processed GF showed the protective effects against the hepatotoxicity induced by ${\alpha}-naphthylisothiocyanate$ in rats. These results suggested that the transformation of biological activities of GF by means of processing may be due to the physico-chemical change of the constituents in GF by heating.