• YAKHAK HOEJI
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• v.36 no.1
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• pp.66-72
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• 1992

In order to test relationships between hepatotoxicity and transmethylation, activities of protein methylases and SAM (S-adenosyl-L-methionine)-synthetase were examined in liver tissues of rats treated with $CCl_4$. Also the concentrations of SAM and SAH were measured by HPLC in rat liver. The results are as follows. (1). Activities of protein methylases were not significantly changed in 24 hours after $CCl_4$ treatment. However, in 48 hours, activities of protein methylases were significantly increased in comparison with that of control. (2). Activity of SAM-synthetase was increased steadily in the time course after $CCl_4$ treatment. (3). S-adenosyl-L-methionine concentration of liver tissues in $CCl_4$-treated group was elevated in 24 hours, and then declined thereafter. But the SAH concentration was slightly decreased in the time course after $CCl_4$ treatment. These results indicate that SAM was very actively used in transmethylation reactions of $CCl_4$ damaged rat liver, suggesting the strong relationships between hepatotoxicity and transmethylation phenomena.

• Journal of The Korean Society of Clinical Toxicology
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• v.4 no.1
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• pp.73-77
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• 2006

Poisoning with mushroom containing amatoxin may be a real medical emergency and is characterized by long incubation time lag, gastrointestinal symptoms, hepatotoxic phase and sometimes death. We report a family of parents and two children who ingested wild mushroom and recovered from varying degrees of hepatotoxicity. After eating cooked wild mushroom and its soup, they all developed abdominal pain, vomiting and diarrhea 11 hours later, Their liver enzymes reached peak level between 48 and 72 hours after the ingestion. Among the family members, 5-year-old girl showed the most severe hepatic toxicity of AST/ALT 14,099/13,176 IU/L. They were all treated with supportive measures including repeated activated charcoal and penicillin G and recovered from the hepatotoxicity between 7 and 28 days after the ingestion. Being based on the shape and a typical course of the amatoxin poisoning, we presume that this wild mushroom belongs to Amanita virosa.

• Korean Journal of Pharmacognosy
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• v.30 no.1
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• pp.12-17
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• 1999

The youngkaechulgamtang (Y) composed of four herb drugs, including Hoelen (H). Cinnamomi Ramulus (C). Atractylodis Rhizoma Alba (A) and Glycyrrhizae Radix (G). In oriental medicine literatures, Youngkaechulgamtang is described to be effective in headache, inflammation, uremia, gastritis, diarrhea and hypertension. To estimate the clinical effectiveness of Youngkaechulgamtang, several pharmacological experiments were carried out. The results are summerized as follows; On acetaminophen-induced hepatotoxicity, C+A, Y-G, Y-H, MIX and Y showed the significant elevation of glutathione-S-transferase. But, C+A, Y-G, Y-H, MIX and Y showed the significant suppression of serum aminotransferases. On ANIT-induced cholestasis, U (Ursodesoxycholic acid 50 mg/kg)+$Y_l$ (760 mg/kg) showed the significant increase of bile juice volume. $Y_l,\;Y_2$ (1520 mg/kg), U, $U+Y_l$ showed the remarkable increase of cholic acid. U and $U+Y_l$ showed the significant decrease of total bilirubin. From these results, it is suggest that Y shows liver protective effect against various hepatic injury. Especially, Youngkaechulgamtang was more effective than mixture of 4 ingredients in the elevation of glutathione-S-transferase in acetaminophen-induced hepatotoxicity.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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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.

• Biomolecules & Therapeutics
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• v.4 no.1
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• pp.89-96
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• 1996

The effect of Cimicifuga heracleifolia on CC1$_4$-induced hepatotoxicity was investigated. Cimicifuga heracleifolia has been used to diaphoresis, antipyretics and detoxification in oriental remedy. We examined the effect of Cimicifuga heracleifolia methanol extract by blood chemical analysis and histopathologic examination. ALT and AST were decreased by 38% and 67% in pretreatment group of Cimicifuga heracleifolia compared to CC1$_4$control group respectively. There were significant changes neither in total protein, albumin, triglyceride and cholesterol nor in BUN and creatinine. In histopathologic examination, there were severe necrosis and hemorrhage with infiltration of inflammatory cells around the central vein, zone 3 in the liver of CC1$_4$ treated rat. Ballooning degeneration of hepatocytes were frequently noted in the periphery of the hemorrhagic necrosis. In Cimicifuga heracleifolia pretreatment group, we observed mild degree of ballooning degeneration and inflammatory cell infiltration. No gross necrosis was observed. We measured malondialdehyde (MDA) formation by TBA method. It showed that the formation of MDA in Cimicifuga heracleifolia pretreatment group was decreased compared to the $CCl_4$control group. We got the result of the effect of Cimicifuga heracleifolia on CC1$_4$-induced hepatotoxicity by decreasing serum ALT and AST. It seems that the decrease of lipid peroxidation is related to the recovery effect.

• The Journal of Korean Medicine
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• v.32 no.4
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• pp.48-67
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• 2011

Objectives: There has been a lot of controversy about whether Korean traditional medicines cause drug-induced hepatotoxicity or not. However, this controversy has not been examined from a scientific approach, especially in terms of toxicology. Thus, this article for traditional Korean medicine-induced hepatotoxicity was reviewed on a basis of toxicological assessment. Methods: Toxicological assessments were carried out in a view of reactive intermediates formation from biotransformation in animals based on cytochrome P450 activity inducing oxidative stress, and case reports in world-wide. Results and Conclusions: Several herbal materials used for traditional Korean medicines were identified as possible agents causing drug-induced hepatotoxicity. Most of these agents seem to produce toxic reactive intermediates caused by cytochrome P450. Oxidative stress followed by cytochrome P450 activation could also be a reason for herb-induced hepatotoxicity. Plausible prevention of herb-induced hepatotoxicity was suggested.

• Biomolecules & Therapeutics
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• v.3 no.3
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• pp.223-228
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• 1995

In an attempt to define the effects of biphenyldimethyl dicarboxylate (DDB) on the lipid peroxidation and oxygen free radical scavenging enzymes activities in mercuric chloride-induced hepatotoxic rats, we studied malondialdehyde (MDA) level and the activities of catalase and superoxide dismutase (SOD) in liver of the rats at 24 hr after the injection of mercuric chloride. Sprague-Dalwey albino rats were injected subcutaneously with mercuric chloride (5 mg/kg) only and mercuric chloride (5 mg/kg) plus. DDB (200 mg/kg/day, p.o) is administered for 4 days prior to 3 days from the injection of mercuric chloride. The group treated with mercuric chloride showed significantly higher MDA level and lower catalase and SOD activities as compared with that of control group. The group treated with mercuric chloride plus DDB showed significantly lower MDA level and catalase activity and higher SOD activity as compared with that of mercuric chloride-treated group. These results suggest that the excessive oxygen free radicals resulting from the depression of superoxide dismutase activity is an important determinant in the pathogenesis of mercuric chloride-induced hepatotoxicity and DDB has antioxidant effects.

• Biomolecules & Therapeutics
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• v.4 no.4
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• pp.428-436
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• 1996

The protective effect of Carthamus tinctorius L. Semen on the carbon tetrachloride induced liver damaged rats were studied. First, methanol extract was prepared and the extract was fractionated with hexane, $CHCl_3$, BuOH and $H_2O$ respectively. Animals were divided into 6 groups and each group was treated with each fraction respectively. To investigate the hepato-protective effect of Carthamus tinctorius L. Semen AST, ALT, albumin, TP, cholesterol, TG, creatinine and total bilirubin values were measured in each treated group and compared with those of control group. GST activity was increased in BuOH group compared with the control group. In malondialdehyde levels, all fractions was decreased compared with the control group. In histopathologic examination, hexane and $H_2O$ fractions of Carthamus tinctorius L. Semen observed mild degree of ballooning degeneration. The results show the protective effect of Hexane,$CHCl_3$, BuOH and $H_2O$ fractions on hepatotoxicity of $CHl_4$ by decreasing ALT, AST, bilirubin, cholesterol, TG and BUN. It seems that the decrease of MDA are related to the recovery effect. The protective effects of Carthamus tinctorius L. Semen fractions in hepatotoxic pathogenesis by $CHl_4$ was suggested in blood chemistry analysis and histopathologic examination.

• Korean Journal of Pharmacognosy
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• v.31 no.3
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• pp.351-356
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• 2000

The hepatoprotective effects of bergenin and its derivative, acetylbergenin, were evaluated against D-galactosamine-induced liver damage in rats. Bergenin is a C-glucoside of 4-O-methyl gallic acid that has been isolated from the cortex of Mallotus japonicus (Euphorbiaceae). Acetylbergenin was synthesized from acetylation of bergenin to increase lipophilic and physiological activities. Bergenin (50, 100 and 200 mg/kg) and acetylbergenin (25, 50 and 100 mg/kg) were administered orally once daily for successive 5 days after the injection of galactosamine (400 mg/kg, i.p.), respectively. The substantially elevated serum enzyme activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase and ${\gamma}-glutamyltransferase$ due to galactosamine treatment were dose-dependently restored towards normalization by post-treatment with bergenin and acetylbergenin. Bergenin and acetylbergenin also significantly prevented the elevation of hepatic malondialdehyde formation and depletion of reduced glutathione content induced by galactosamine in a dose-dependent manner. In addition, the decreased activities of glutathione S-transferase and glutathione reductase were restored towards normalization. These results suggest that effects of bergenin and acetylbergenin may be related to complex mechanisms that involve prevention of lipid peroxidation and preservation of hepatic glutathione. The results of this study clearly indicate that bergenin and acetylbergenin have potent hepatotherapeutic action against galactosamine-induced hepatotoxicity in rats, and lipophilic acetylbergenin is more active in the antihepatotoxic effects against galactosamine than much less lipophilic bergenin.

• Biomolecules & Therapeutics
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• v.8 no.4
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• pp.293-298
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• 2000

Bergenin is a C-glucoside of 4-O-methyl gallic acid that has been isolated from the cortex of Mallotus japonicus (Euphorbiaceae). Acetylbergenin was synthesized by acetylation from bergenin to increase lipophilic and physiological activities. The therapeutic effects of bergenin and acetylbergenin were evaluated against carbon tetrachloride ($CCl_4$)-induced hepatotoxicity in rats. Bergenin and acetylbergenin were administered orally once daily for successive 5 days, after the intraperitoneal injection of a mixture 0.5 m1/kg of $CCl_4$ in olive oil (1:1). The substantially elevated serum enzymatic activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase and ${\gamma}$-glutamyltransferase induced by $CCl_4$ were restored towards normalization by posttreatment with bergenin and acetylbergenin. Bergenin and acetylbergenin also significantly prevented the elevation of hepatic malondialdehyde formation and depletion of glutathione content induced by $CCl_4$ in a dose dependent fashion. In addition, the decreased activities of glutathione S-transferase and glutathione reductase were restored towards normalization. These results suggest that therapeutic effects of bergenin and acetylbergenin may be related complex mechanisms that involve prevention of lipid peroxidation and preservation of hepatic GSH. The results of this study clearly indicate that bergenin and acetylbergenin have potent hepatothrapeutic action against $CCl_4$-induced hepatotoxicity in rats. In addition, acetylbergenin 50 mgHg showed almost the same levels of hepatoprotective activity as those of bergenin 100 mgAg, indicating the fact that lipophilic acetylbergenin is more effective in the hepatoprotective action against $CCl_4$ than bergenin.