• Toxicological Research
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• v.12 no.2
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• pp.251-258
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• 1996

Panax ginseng has been used for various diseases including hepatic disorders. The aim of the present study was to investigate the hepatoprotective effects of ethanol extract and saponin of Panax ginseng in thioacetamide-intoxicated rats and to compare with silymarin, a known hepatoprotective agent. Male Sprague-Dawley rats were given single intragastric administration of thioacetamide. Aqueous solutions of ethanol extract and saponin of Panax ginseng with or without silymarin were administered intragastrically daily for six days from four days before until one day after thioacetamide administration. At the end of the treatment, the rats were fasted overnight and sacrificed. As a result, thioacetamide caused significant increase in serum levels of AST, ALT, 5'-nucleotidase and bilirubin. Thioacetamide increased $Ca^++$ content but decreased protein content in liver tissue. These thioacetamide-induced biochemical changes were prevented both by ethanol extract of ginseng and silymarin, but not by ginseng saponin. Silymarin did not potentlate the effect of either ethanol extract or saponin of ginseng on these parameters. Thioacetamide-induced confluent necrosis was not protected by the test drugs. In conclusion, ethanol extract of ginseng protects the liver possibly by stabilizing the cell membrane and by inhibiting thioacetamide-induced $Ca^++$ increase in the hepatocytes, which was comparable to that of silymarin.

• The Korean Journal of Pharmacology
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• v.32 no.3
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• pp.399-406
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• 1996

Thioacetamide is a non-genotoxic carcinogen, a protein modifying agent. It causes nucleolar hypertrophy in short term treatment. In the present work, thioacetamide treated hepatocytes were observed in vivo and in vitro conditions. After 7 day treatment of rat liver with thioacetamide, the hepatocyte nucleoli were enlarged and their signalling molecules such as B23 and p38 MAPK were increased. When these hepatocytes were released by collagenases and were grown under the conditions of gene therapy grade tissue culture system, the enlarged nucleoli were further enlarged. The B23 content was again increased under in vitro conditions. From these experiments, it is clear that the hepatocytes possess approximately 100 fold flexibility of nucleolar capacity. It is suggested that thioacetamide enhances the ribosome genesis and exaggerates the nucleologenesis ability.

• YAKHAK HOEJI
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• v.23 no.1
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• pp.41-49
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• 1979

By intraperitoneal administration of thioacetamide to rats, acute liver injury was produced. In these rats, the level of serum GOT and GPT activities showed a remarkable increase and the principal histopathologic change was centrilobular hepatic necrosis. In this study, combined administration of silymarin with promethazine hydrochloride to the rats with acute liver injury which was produced by thioacetamide inhibited the increase of serum transaminase activities and protected the histopathologic change, showing comparatively more improved results than simple administration of silymarin alone. On the basis of these results, it is suggested that promethazine hydrochloride potentiates the effectiveness of silymarin in acute thioacetamide hepatotoxicity of rats.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05a
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• pp.73-73
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• 2002

Thioacetamide has been known to cause immune suppression. The object of the present study is to investigate the role of metabolic activation by flavin- containing monooxygenases (FMO) in thioacetamide-induced immune response. To determine whether the metabolites of thioacetamide produced by FMO causes the immunosuppression, methimazole (MMI), an FMO inhibitor, was used to block the FMO pathway.(omitted)

• Biomolecules & Therapeutics
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• v.22 no.2
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• pp.149-154
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• 2014

Effects of diallyl sulfide (DAS) on thioacetamide-induced hepatotoxicity and immunotoxicity were investigated. When male Sprague-Dawley rats were treated orally with 100, 200 and 400 mg/kg of DAS in corn oil for three consecutive days, the activity of cytochrome P450 (CYP) 2E1-selective p-nitrophenol hydroxylase was dose-dependently suppressed. In addition, the activities of CYP 2B-selective benzyloxyresorufin O-debenzylase and pentoxyresorufin O-depentylase were significantly induced by the treatment with DAS. Western immunoblotting analyses also indicated the suppression of CYP 2E1 protein and/or the induction of CYP 2B protein by DAS. To investigate a possible role of metabolic activation by CYP enzymes in thioacetamide-induced hepatotoxicity, rats were pre-treated with 400 mg/kg of DAS for 3 days, followed by a single intraperitoneal treatment with 100 and 200 mg/kg of thioacetamide in saline for 24 hr. The activities of serum alanine aminotransferase and aspartate aminotransferase significantly elevated by thioacetamide were protected in DAS-pretreated animals. Likewise, the suppressed antibody response to sheep erythrocytes by thioacetamide was protected by DAS pretreatment in female BALB/c mice. Taken together, our present results indicated that thioacetamide might be activated to its toxic metabolite(s) by CYP 2E1, not by CYP 2B, in rats and mice.

• The Journal of Internal Korean Medicine
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• v.32 no.2
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• pp.153-169
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• 2011

Objectives : This study was performed to investigate the anti-fibrogenic effect and the effect on cell growth and apoptosis in YJCGT, YJCGT YSO and YJCGT YSCO on thioacetamide-induced rat liver tissue and the immortalized human hepatic cell line LX2. Materials and Methods : LX2 cells were treated with various concentrations (0, 50, 150, 300 ug/ml) of YJCGT, Y+YSO, and Y+YSCO extract for 24, 48 and 72 hours. After the treatment, cell viability was measured by using MTT assay. Caspase inhibitor assay, and cell viability were determined by a colorimetric assay with PMS/MTS solution. Rat liver fibrosis was induced by intraperitoneal thioacetamide injection 150 mg/kg 3 times a week for 5 weeks. After the treatment, body weight, liver & spleen weights, liver function test, the complete blood cell count and the change of portal pressure were studied. After YJCGT, Y+YSO, and Y+YSCO treatment, percentages of collagen in thioacetamide-induced rat liver tissue were measured. Results : The viability of the LX2 cell decreased in a dose- and time-dependent manner. Exposure of LX2 cells to YJCGT, YJCGT+YSO and YJCGT+YSCO induced caspase-3 activation, but co-treatment of YJCGT, YJCGT+YSO and YJCGT+YSCO with the pan-caspase inhibitor Z-VAD-FMK, and the caspase-3 inhibitor Z-DEVE-FMK, blocked apoptosis. There was no difference in rat body weight between the thioacetamide only group and the YJCGT, YJCGT+YSO and YJCGT+YSCO groups. In the YJCGT, YJCGT YSO and YJCGT YSCO groups, the serum level of GPT significantly went down compared with the thioacetamide only group. In the YJCGT, Y+YSO, Y+YSCO groups, white blood cell elevated by thioacetamide injection decreased but RBC, Hgb, and Hct increased. In the Y+YSO group, the portal pressure elevated by thioacetamide injection significantly decreased. In the histological finding, thioacetamide injections caused severe fibrosis, but YJCGT, Y+YSO, and Y+YSCO treatment significantly reduced the amounts of hepatic collagens. Conclusions : YJCGT, Y+YSO, and Y+YSCO inhibit the growth of LX2 cells by inducing apoptosis through caspase activity. YJCGT, Y+YSO, and Y+YSCO have beneficial effects on the treatment of cirrhotic patients as well as patients with chronic hepatitis.

• 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.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.05a
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• pp.121-121
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• 2001

Thioacetamide has been known to cause immune suppression. In this report we studied the role of metabolic activation by flavin-containing monooxygenase in the thioacetamide-induced immune response. To determine whether the metabolites of thioacetamide produced by flavin-containing monooxygenase result in the immunosuppression, methimazole, a flavin-containing monooxygenase inhibitor, was used to block the flavin-containing monooxygenase pathway.(omitted)

• Archives of Pharmacal Research
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• v.27 no.7
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• pp.781-789
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• 2004

The effect of 1,8-cineole on cytochrome P450 (CYP) expression was investigated in male Sprague Dawley rats and female BALB/c mice. When rats were treated orally with 200, 400 and 800 mg/kg of 1,8-cineole for 3 consecutive days, the liver microsomal activities of benzy-loxyresorufin- and pentoxyresorufin-D-dealkylases and erythromycin N-demethylase were dose-dependently induced. The Western immunoblotting analyses clearly indicated the induction of CYP 2B1/2 and CYP 3A1/2 proteins by 1,8-cineole. At the doses employed, 1,8-cineole did not cause toxicity, including hepatotoxicity. Subsequently, 1,8-cineole was applied to study the role of metabolic activation in thioacetamide-induced hepatotoxicity and/or immunotoxicity in animal models. To investigate a possible role of metabolic activation by CYP enzymes in thioacetamide-induced hepatotoxicity, rats were pre-treated with 800 mg/kg of 1,8-cineole for 3 days, followed by a single intraperitoneal treatment with 50 and 100 mg/kg of thioacetamide in saline. 24 h later, thioacetamide-induced hepatotoxicity was significantly potentiated by the pretreatment with 1,8-cineole. When female BALB/c mice were pretreated with 800 mg/kg of 1,8-cineole for 3 days, followed by a single intraperitoneal treatment with 100 mg/kg of thioace-tamide, the antibody response to sheep red blood cells was significantly potentiated. In addition, the liver microsomal activities of CYP 2B enzymes were significantly induced by 1,8-cineole as in rats. Taken together, our results indicated that 1,8-cineole might be a useful CYP modulator in investigating the possible role of metabolic activation in chemical-induced hepato-toxicity and immunotoxicity.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2008.04a
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• pp.168-168
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• 2008