• 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.

• 약학회지
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• 제40권5호
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• pp.574-581
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• 1996

The study was initiated to elucidate the protective mechanism by examining in vivo effect of some marine natural products, Styela plicata, Ecklonia stolonifera and Pachymeniopsis elliptica on acetaminophen-induced lipid peroxidation. The methanol extract of S. plicata prevented acetaminophen (800mg/kg, i.p.)-induced hepatotoxicity in rats as evidenced by the decreased formation of lipid peroxide. But the methanol extracts of E. stolonifera and P. elliptica were not affected on the formation of lipid peroxidation. The activities of cytochrome P-450, animopyrine N-demethylase and aniline hydroxylase were not changed by the treatment with S. plicata in comparison with acetaminophen-teated group. In acetaminophen-treated control rats, the glutathione S-transferase activity was decreased markably. However. in S. plicata pretreated group, the effect caused by acetaminophen was markably reduced. A-cetaminophen decreased the level of hepatic, glutathione, which was restored to same degree by S. plicata pretreatment. And activity of ${\gamma}$-glutamylcystein synthetase was not changed by S. plicata pretreatment, but the activity of glutathione reductase was increased significantly.

• Environmental Analysis Health and Toxicology
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• 제27권
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• pp.11.1-11.8
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• 2012

Objectives: Hepatotoxicity of acetaminophen has been widely studied. However, the adverse effects on the heart have not been sufficiently evaluated. This study was performed to investigate cytotoxicity and alterations of gene expression in cultured cardiomyocytes ($H_9C_2$ cells) after exposure to acetaminophen. Methods: $H_9C_2$ cells were incubated in a 10 mM concentration of acetaminophen for the designated times (6, 12, and 24 hours), and cytotoxicity was determined by the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Alteration of gene expression was observed by microarray analysis, and RT-PCR was performed for the three representative oxidative stress-related genes at 24 hours after treatment. Results: It revealed that acetaminophen was toxic to cardiomyocytes, and numerous critical genes were affected. Induced genes included those associated with oxidative stress, DNA damage, and apoptosis. Repressed genes included those associated with cell proliferation, myocardial contraction, and cell shape control. Conclusions: These findings provide the evidences of acetaminophen-induced cytotoxicity and changes in gene expression in cultured cardiomyocytes of $H_9C_2$ cells.

• 대한한의학방제학회지
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• 제12권2호
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• pp.139-154
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• 2004

Acetaminophen은 세계적으로 널리 사용되는 해열 진통제이지만, 또한 과용 및 남용, 알코올 중독과 같은 여러 원인에 의해 간독성을 유발할 수 있는 약물이다. 이러한 acetaminophen의 간독성은 CYP에 의해 생성되는 대사산물인 NAPQI와 활성산소에 의해 유발되는 것으로 알려져 있다. 본 연구에서 5주된 수컷 백서에 acetaminophen (500 mg/kg)을 투여하기 전에 대시호탕 (500 mg/kg)를 일주일간 투여하였다. 이후 GOT, GPT, GST 그리고, 조직사진으로 대시호탕의 간보호작용을 측정하였다. 또한 대시호탕의 간보호작용 기전을 항산화작용과 CYP 2E1 발현조절을 통한 NAPQI 생성억제의 두 가지 면에서 측정하였다. GOT, GPT 그리고 조직사진에서 나타난 결과들은 대시호탕이 고용량의 acetaminophen에 대한 간보호작용이 있음을 증명할 수 있었다. 또한 LPO와 catalase, 그리고 GSH 실험에서 나타난 결과들을 통해 대시호탕이 항산화작용이 있음을 알 수 있었다. 그리고 GSH, GST, RT-PCR, western blot 실험에서 대시호탕이 CYP 2E1의 발현을 조절하여 NAPQI 생성을 억제한다는 것도 알 수 있었다. 이상의 결과들을 바탕으로 대시호탕은 항산화작용에 의한 활성산소 제거력과 CYP 2E1의 발현조절을 통한 NAPQI 생성억제로 고용량 acetaminophen에 의해 유도된 간손상에 대해 유의성 있는 보호작용을 한다는 것을 알 수 있었다.

• 약학회지
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• 제52권4호
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• pp.316-321
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• 2008

The hepatoprotection by the methanol extract of Oenanthe javanica DC (water dropwort) (OJME) was investigated in Sprague Dawley rats with inducing liver damage by acetaminophen. After OJME administration for 1 week, the increase of hepatic lipid peroxide level by acetaminophen-induced hepatotoxicity was significantly reduced. In case of phase I microsomal enzyme systems including cytochrome P-450, aminopyrine N-demethylase and aniline hydroxylase, any significant differences between in control and in OJME-pretreated group was observed after acetaminophen treatment. However, the pretreatment of OJME maintained the hepatic glutathione level and the activity of liver cytosolic glutathione S-transferase, which was significantly decreased by the acetaminophen intoxication. Among the glutathione-generating system, glutathione reductase was more responsible for its biosynthesis rather than ${\gamma}-glutamylcystein$ synthetase. OJME itself showed the strong inhibition activity on DPPH radical generation. In conclusion, OJME administration maintains the liver glutathione pool and hepatic glutathione S-transferase activity, in addition with its high anti-oxidative capability, to show hepatoprotective effect from acetaminophen intoxication.

• 대한한의학방제학회지
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• 제11권1호
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• pp.129-149
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• 2003

Liver is an important target of the toxicity of drugs, xenobiotics and oxidative stress. Acetaminophen pverdose causes acute liver injury in both humans and animals. This study was performed to observe the effect of sachunwhan and its component groups on recovery of hepatoxicity in acetaminophen treated rats. The experimental group was divided into 4 groups: sachungwhan(SC), samultang group(SC-1: 當歸, 川芎), chungyul group(SC-2: 龍膽草, 大黃, 梔子), and haepyo group(SC-3:羌活, 防風). Under the same condition Normal group was fed basal diet and water; Control group was injected acetaminophen and fed basal diet for 2 weeks; Experimental groups were injected acetaminophen and fed each extracts for 2 weeks respectively. The results were obtained as follows: 1. In the study on antioxidative defense system in vivo, SC reduced the amount of lipid peroxide in both serum and liver and showed activity on antioxidative enzymes such as catalase, glutathion. Other groups had effect only on glutathion. 2. In the study on hepatotoxicity(GOT, GPT, ${\gamma}$-GTP, ALP, LDH, Bilirubin), SC had a significant effect on recovery of hepatoxicity in acetaminophen treated rats. Other groups had no effect except SC-1 having effect on ${\gamma}$-GTP. As results shown, only Sachungwhan(SC) has significant effects on recovery of hepatoxicity and antioxidative defense system in vivo. These results suggest that Sachungwhan(SC) made antioxidative defense system active and it seemed to be very important to its effect on recovery of hepatoxicity. In the other hand, Component groups had no effect on recoverv of hepatoxicity and antioxidative defense system in vivo. This was thought that component drugs' cooperative synergy effect would be important to Sachungwhan(SC)'s effects mentioned in this paper.

• 대한한의학방제학회지
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• 제9권1호
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• pp.355-366
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• 2001

Objectives : Oldenlandiae Diffusae herba has been used as a natural drug for tumor, inflammation and liver disease in traditional medicine. This study was performed in order to investigate the antioxidative effects of Oldenlandiae Diffusae herba methanol extract(ODHM) on acetaminophen induced acute liver injury in mice. Methods : In order to investigate the protective effect of ODHM on acute hepatic injury in vivo, ICR mice were pretreated with ODHM, and then treated with acetaminophen(500mg/kg). And the levels of LPO and glutathione(GSH), antioxidative enzyme activities were measured. The levels of LPO were measured by TBA method. And catalase activity was measured as the decrease in hydrogen peroxide absorbance at 240nm on spectrophotometer using 30mM hydrogen peroxide. Superoxide dismutase(SOD) was assayed by recording the inhibition of nitro blue tetrazolium reduction with xanthine and xanthine oxidase. Glutathione peroxidase(GPX) activity was determined by the modified coupled assay developed by Paglia and Lawrence. The reaction was started by addition of 2.2mM hydrogen peroxide as substrate. The change in absorbance at 340nm was measured for 1min on spectrophotometer. Glutathione-S-transferase(GST) activity was assayed with CDNB as substrate and enzyme activity of GST towards the glutathione conjugation of CDNB. And Total SH and GSH levels were measured. Results : In vivo study, LPO levels of acetaminophen treatment group were significantly higher than other groups. This increased level was significantly reduced by ODHM pretreatment. The acetaminophen treatment resulted in a decrease of catalase, GPX, SOD and GST activities. By contrast, ODHM pretreatment markedly increased compare to those of untreated groups. Total SH and GSH levels were reduced by of acetaminophen treatment, and ODHM pretreatment significantly increased GSH levels.

• 동의생리병리학회지
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• 제22권6호
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• pp.1495-1499
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• 2008

The purpose of this study is to investigate the effect of water extract from Artemisiae Argi Folium (WAAF) on hydrogen peroxide production within mouse macrophage Raw 264.7 Cells treated with gallic acid, EtOH, LPS, and acetaminophen. WAAF (0${\sim}$400 ug/mL) was treated with gallic acid, EtOH, LPS, acetaminophen. And the intracellular productions of hydrogen peroxide were measured by dihydrorhodamine 123 (DHR) assay. WAAF showed the restoration of the intracellular productions of hydrogen peroxide which were reduced by gallic acid, EtOH, LPS, and acetaminophen in Raw 264.7 Cells. WAAF could be supposed to have the immunological activity related with macrophage's oxidative burst.

• Journal of Pharmaceutical Investigation
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• 제14권4호
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• pp.156-160
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• 1984

The pharmacokinetics of acetaminophen administered intravenously(20mg/kg) was investigated in the rabbits of carbon tetrachloride induced hepatic failure. The blood level, the total AUC and the biological half life of acetaminophen were increased significantly in hepatic failure rabbits compared with those of normal rabbits. The urinary excretion and the overall elimination rate of acetaminophen were decreased significantly in hepatic failure rabbits. There was significant relationship between GOT value and AUC or biological half life of acetaminophen.

• IMMUNE NETWORK
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• 제16권4호
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• pp.256-260
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• 2016

An association between drug treatment for viral infections and severe cutaneous adverse reactions has been noted. We investigated six patients diagnosed with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) after being prescribed acetaminophen for suspected viral illnesses. Multiplex analysis was performed to measure cytokine levels in sera before and after treatment. IL-2Ra levels significantly decreased during the convalescence phase. Although acetaminophen is relatively safe, the drug can trigger SJS/TEN in patients with suspected viral infections. T-cells and monocytes may be key components of the link between viral infection and acetaminophen-induced SJS/TEN.