• 동의생리병리학회지
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• 제20권2호
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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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• 제3권3호
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• pp.229-232
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• 1995

In order to study if Glycyrrhizae Radix (GR) has protective effects on hepatotoxicity of acetaminophen in mouse, one of the species which are sensitive to acetaminophen-induced hepatotoxicity, effects of GR on liver weight to body weight ratio, serum alanine and aspartate transaminase (ALT and AST) activities, hepatic UDP-GT2 activity, and histopathologic changes were determined in acetaminophen-treated mice. Liver weight to body weight ratio and UDP-GT2 activity in mouse liver were not altered by GR. However, GR pretreatment lowered serum ALT and AST activities by 77% and 90% respectively, and diminished the degree of centrilobular necrosis caused by acetaminophen in liver as determined by histopathologic observation. These results suggest a possible protective effect of GR against the acetaminophen-induced hepatotoxicity in mice.

• 한국식품영양과학회지
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• 제26권6호
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• pp.1173-1180
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• 1997

Hepatotoxicity of caffeine and acetaminophen was investigated in this study. Special attention was paid to the effect of vitamins on the reduction of hepatotoxicity caused by the chemicals. Rat hepaocytes isolated by two-step perfusion method were cultured in two differents methods-suspension, monolayer cultures-, and exposed to caffeine and/or acetaminophen for 24hrs. Caffeine or acetaminophen exhibited no significant hepatotoxicity in terms of intracellular glutathione(GSH) level and lipid peroxidation(MDA), but GSH level was significantly decreased after administrated acetaminophen, and the toxicity caused by the chemicals showed a dose-dependent manner. The synergistic effect of caffeine and acetaminophen was observed when both caffeine and acetaminophen were supplemented to culture medium. At the concentration 1mM, caffeine enhanced the intracellular GSH depletion and MDA formation by 63% and 64%, respectively, compared to single supplementation of 10mM acetaminophen in culture medium. This hepatotoxicity induced membrane integrity loss was observed by lightmicroscope on the simultaneous administration of caffeine and acetaminophen in monolayer cultured hepatocytes. Co-supplementation of vitamins with caffeine/acetaminophen to culture medium results in the protection of hepatocytes from hepatotoxic attach by caffeine/acetaminophen. Especially, vitamin E was superior to vitamin C and $\beta$-carotene from the standpoints of GSH depletion and MDA formation. From this results, it has been speculated that vitamin E may play a role of antioxidant scavenging radicals produced from acetaminophen. Taken all together, in vitro culture system like monolayer culture of hepatocytes may be a useful tool for the evaluation of hepatotoxicity or protection ability of food ingredients.

• Journal of Pharmaceutical Investigation
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• 제25권4호
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• pp.313-322
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• 1995

The covalent conjugation of human recombinant superoxide dismutase (hrSOD) with trichloros-triazine activated polyethylene glycol (PEG) 5000 formed soluble conjugates with molecular weight of 92KD, which retained $90{\sim}98%$ of original activity with a markedly prolonged plasma half-life of enzyme activity. The effect of hrSOD-PEG conjugates on acetaminophen (ACP)-induced hepatotoxicity was tested in male rats which were pretreated with 3-methylcholanthrene. HrSOD-PEG conjugates inhibited the hepatotoxicity produced by ACP, on the other hand, native hrSOD had no protective effect. The above results indicated that oxygen radicals might participate in the mechanism of the ACP-induced hepatotoxicity and that polymer conjugated-protein drugs with prolonged half-lives could be employed as an effective therapeutic agent.

• Food Science and Biotechnology
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• 제15권5호
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• pp.752-755
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• 2006

This study was carried out to investigate the effects of ash tree leaf extract (ALE) on acetaminophen (APAP)-induced hepatotoxicity in mice. Hepatoprotective effects were detected by biochemical analysis of hepatic enzymes and histopathological examination of the liver. BALB/c mice were divided into three groups: 'normal' control mice, APAP-treated control mice, and mice pretreated with ALE and treated with APAP. A single dose of APAP markedly increased levels of plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Light micrographs of liver cells stained with hematoxylin and eosin showed that APAP induced severe centrilobular necrosis, degeneration, and infiltration by inflammatory cells. Moreover, APAP caused the numbers of TUNEL-positive hepatocytes to increase and caused glycogen content to decrease as observed by Periodic acid-Schiff stain. However, pretreatment with ALE for 7 days prior to the administration of APAP significantly decreased plasma levels of AST and ALT. Histological findings demonstrated that ALE pretreatment alleviated APAP-induced liver damage, and induced the regeneration of liver tissue and restoration of glycogen. These results indicate that ash tree leaf extract exerts a protective effect against APAP-hepatotoxicity induced injury.

• The Korean Journal of Physiology and Pharmacology
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• 제20권1호
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• pp.15-23
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• 2016

Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure. The study aimed to investigate the protective effect of carnosic acid (CA) on APAP-induced acute hepatotoxicity and its underlying mechanism in mice. To induce hepatotoxicity, APAP solution (400 mg/kg) was administered into mice by intraperitoneal injection. Histological analysis revealed that CA treatment significantly ameliorated APAP-induced hepatic necrosis. The levels of both alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were reduced by CA treatment. Moreover, CA treatment significantly inhibited APAP-induced hepatocytes necrosis and lactate dehydrogenase (LDH) releasing. Western blot analysis showed that CA abrogated APAP-induced cleaved caspase-3, Bax and phosphorylated JNK protein expression. Further results showed that CA treatment markedly inhibited APAP-induced pro-inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and MCP-1 mRNA expression and the levels of phosphorylated $I{\kappa}B{\alpha}$ and p65 protein in the liver. In addition, CA treatment reduced APAP- induced hepatic malondialdehyde (MDA) contents and reactive oxygen species (ROS) accumulation. Conversely, hepatic glutathione (GSH) level was increased by administration of CA in APAP-treated mice. Mechanistically, CA facilitated Nrf2 translocation into nuclear through blocking the interaction between Nrf2 and Keap1, which, in turn, upregulated anti-oxidant genes mRNA expression. Taken together, our results indicate that CA facilitates Nrf2 nuclear translocation, causing induction of Nrf2-dependent genes, which contributes to protection from acetaminophen hepatotoxicity.

• Toxicological Research
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• 제3권2호
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• pp.121-128
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• 1987

Protective effect of scoparone against the acetaminophen inducible hepatic toxicity in mice was investigated. Scoparone (5mg/kg) was administered intraperitoneally to mice daily for 5 days. Scoparone pretreatment before the administration of acetaminophen has blocked subsequent increases in liver to body weight ratio. When biological changes were measured, scoparone protects against acetaminophen inducible hepatotoxicity in mice as evidenced by the decreased formation of lipid peroxide, lowered serum transaminase activity and the decreased level of serum acetaminophen. In conjuction with the results of Huh (Arch. Pharm. Res. 10, 165(1987)), these results suggest that the most likely mechanism for the observed protective effects of scoparone against the acetaminophen-induced hepatotoxicity is the induction of hepatic microsomal UDP-glucuronyltransferase activity.

• 대한한의학회지
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• 제23권3호
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• pp.33-42
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• 2002

Objective : This study was performed to investigate the activity of Whagan-Jeon (huaganjian) in protection against acetaminophen (AAP)-induced hepatotoxicity and the possible mechanisms in vivo. Methods : The following were performed : Serum ALT, depletion of hepatic glutathione (GSH) levels, the microsomal p. nitrophenol hydroxylation activity, microsomal aniline hydroxylation activity, genomic DNA fragmentation and its reversal, hepatic glutathione-S-transferase (GST) activity, and hepatic NAD(P)H:quinone oxidoreductase (QR) activity Results : Whagan-Jeon (huaganjian) protected against AAP-inducedhepatotoxicity by the increase of GSH levels, inhibition of P450 2E1-specific metabolic activities, attenuation of hepatic DNA damage, and induction of GST and QR activities in vivo. Conclusions : In conclusion, Whagan-Jeon (huaganjian) was effective in protection against AAP-induced hepatoxicity.

• 생약학회지
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• 제36권2호통권141호
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• pp.81-87
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• 2005

The effects of the DWP-04 [DDB:selenium yeast:glutathione (31.1 : 6.8 : 62.1 (w/w%)] on acetaminophen detoxification enzyme system were studied in rats. Treatment with DWP-04 was prevented againt acetaminophen-induiced hepatotoxicity in rat as evidenced by the decreased formation of lipid peroxide. Effect of DWP-04 on the activities of free radical-generating enzymes, free radical scavenging enzymes and glutathione-related enzymes as well as detoxification mechanism of DWP-04 against acetaminophen-treated was investigated in rat. Activities of cytochrome p450, cytochrome b5, aminopyrine demethylase and aniline hydroxylase as free radical-generating enzymes activities were decreased by the treatment with DWP-04 against acetaminophen treated. Although acetaminophen-induced hepatotoxicity results in the significantly decrease in the level of hepatic glutathione and activities of glutathine S-transferase, quinone reductase, glutathione reductase and ${\gamma}-glutamyl-$cysteine synthetase, these decreasing effects were markedly lowered in the DWP-04-treated rat. Therefore, it was concluded that the mechanism for the observed preventive effect of DWP-04 against the acetaminophen-induced hepatotoxicity was associated with the decreased activities in the free radical-generating enzyme system.

• 생약학회지
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• 제30권1호
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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.