• Nutrition Research and Practice
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• v.3 no.2
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• pp.95-101
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• 2009

It has been reported that dietary polyunsaturated fats (PUFA) increase liver injury in response to ethanol feeding. We tested the hypothesis that diets rich in linoleic acid (18:2n-6) would affect acute liver injury after acetaminophen injection and that protein restriction might exacerbate the liver injury. We examined effects of feeding diets with either 15% (wt/wt) corn oil or 14% beef tallow and 1% corn oil for six weeks with either 6 or 20 g/100 g protein on acute hepatotoxicity. After the feeding period, liver injury was induced by injecting either with 600 mg/kg body weight acetaminophen suspended in gum arabic-based vehicle, or with vehicle alone during fasting status. Samples of liver and plasma were taken for analyses of hepatic glutathione (GSH) levels and liver-specific enzymes [(Glutamate-pyruvate transaminase (GPT) and glutamate-oxaloacetate transaminase (GOT)], respectively. Whereas GSH level was significantly lower in only group fed 15% corn oil with 6 g/100 g protein among acetaminophen-treated groups, activities of GPT and GOT were significantly elevated in all groups except the one fed beef tallow with 20 g/100 g protein, suggesting low protein might exacerbate drug-induced hepatotoxicity. The feeding regimens changed the ratio of 18:2n-6 to oleic acid (18:1n-9) in total liver lipids approximately five-fold, and produced modest changes in arachidonic acid (20:4n-6). We conclude that diets with high 18:2n-6 promote acetaminophen-induced liver injury compared to diets with more saturated fatty acids (SFA). In addition, protein restriction appeared to exacerbate the liver injury.

• Molecular & Cellular Toxicology
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• v.4 no.4
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• pp.331-337
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• 2008

This study was conducted to quantitatively evaluate the recovery effects of herbal medicines on acetaminophen-induced hepatotoxicity. In the present study, the recovery effects of 251 herbal medicines on THLE-2 cells that had been damaged by acetaminophen were evaluated using an MTS assay. THLE-2 cells were cultured in 96-well plates and then pretreated with or without 60 ${\mu}M$ acetaminophen (${IC}_{50}$ value: 35.84) for 1 hr. Next, different herbal medicines were added to the wells, after which the cells were reincubated at $37^{\circ}C$ for 24 hr. After first round of screening, the candidate herbal medicines were selected based on a recovery rate of greater than 40% and their efficacy were then determined by dose response kinetic analysis. Among these extracts, 8 herbal medicines (Terminalia chebula, Pueraria lobata, Acronychia laurifolia, Lopatherum gracile, Oroxylum indicum, Cynanchum atratum, Senecio scandens, and Sophora flavescens) had a strong recovery effect on acetaminophen-induced damage in THLE-2 cells. Dose response non-linear regression analysis demonstrated that Senecio scandens showed the best recovery rate (98%), and that its ${EC}_{50}$ was 19.54 ng/mL. Additional studies of these herbal medicines should be conducted to determine if they possess novel therapeutic agents for the prevention or treatment of liver disorders.

• Journal of Pharmaceutical Investigation
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• v.36 no.3
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• pp.201-207
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• 2006

Acetaminophen (paracetamol), a para-aminophenol derivative, has analgesic and antipyretic properties and weak anti-inflammatory activity. The purpose of the present study was to evaluate the bioequivalence of two acetaminophen tablets, $Tylenol^{\circledR}$ ER (Janssen Korea Ltd.) and Tylicol ER (Hana Pharmaceutical Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of acetaminophen from the two acetaminophen formulations in vitro was tested using KP VIll Apparatus II method with pH 1.2 buffer solution. Twenty six healthy male subjects, $22.8{\pm}1.99$ years in age and $65.6{\pm}8.03$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single tablet containing 650 mg as acetaminophen was orally administered, blood samples were taken at predetermined time intervals and the concentrations of acetaminophen in serum were determined using HPLC with UV detector. The dissolution profiles of two formulations were similar in pH 1.2 buffer solution. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Tylenol^{\circledR}$ ER, were 2.84, 1.89 and -1.36% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., log $0.987{\sim}log$ 1.08 and log $0.944{\sim}log$ 1.17 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Tylicol ER tablet was bioequivalent to $Tylenol^{\circledR}$ ER tablet.

• 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

• Korean Journal of Clinical Laboratory Science
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• v.49 no.2
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• pp.88-98
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• 2017

To prevent toxicity from both robax platinum (methocarbamol, ibuprofen) and robaxacet (methocarbomol, acetaminophen), separately, we used stretches and naproxen as a non-steroidal anti-inflammatory drug (NSAID) to compare each effectiveness. This study used the United States Forces Korea Prescription form (Annex A-Over-The-Counter Prescription) and Alice Rich's Pain scale with robax platinum, robaxacet including narproxen. The IBM SPSS statics version 24 was used to calculate the data. The combined methocarbamol 500 mg, acetaminophen 325 mg tablet, and ibuprofen 200 mg (or naproxen) tablet can work as well as the combined methocarbamol 500 mg tablet with acetaminophen 325 mg tablet with stretches. Both methods were successful in managing pain. The drug combination of methocarbamol 500 mg, acetaminophen 325 mg and ibuprofen 200 mg tablets yielded similar benefits as the methocarbamol 500 mg and acetaminophen 325 mg tablets paired with physical stretching exercises regarding managing overall pain.

• Journal of The Korean Society of Clinical Toxicology
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• v.16 no.2
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• pp.141-148
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• 2018

Purpose: The Korean government approved selected nonprescription drugs (Over-The-Counter drug; OTC drug) to be distributed in convenience stores from 15. Nov. 2012. This study examined the changes in the incidence and the clinical outcome of acute pharmaceutical drug poisoning after the deregulation of OTC drug sales. Methods: This study analyzed the data of Emergency Department based Injury In-depth Injury Surveillance (EDIIS), Korea Centers for Disease Control and Prevention, from 2011 to 2014. The following items were examined: age, gender, intention, alcohol association, pharmaceutical drugs resulting acute poisoning, the clinical outcomes in emergency department, and the admission rate of intensive care unit (ICU). This is a retrospective cross section observational study. Results: A total of 10,162 patients were subject to pharmaceutical drug poisoning. Acute poisoning by acetaminophen and other drugs were 1,015 (10.0%) and 9,147 (90.0%) patients, respectively. After the deregulation of OTC drug sales, acute poisoning by other drugs increased from 4,385 to 4,762 patients but acute poisoning by acetaminophen decreased from 538 to 477 patients (p<0.05). The rate of admission of acetaminophen poisoning increased from 36.1% (194/538) to 46.8% (223/477). The admission rate to the ICU by acetaminophen poisoning increased from 4.6% (25/538) to 11.3% (54/477) after the deregulation of OTC drug sales (p<0.05). Conclusion: Since the deregulation of OTC drugs sales, pharmaceutical drug poisoning has increased but acetaminophen poisoning has decreased. The rate of hospitalization and ICU admission by pharmaceutical drug poisoning with or without acetaminophen has also increased.

• Journal of The Korean Society of Clinical Toxicology
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• v.18 no.2
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• pp.78-84
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• 2020

Purpose: In acute acetaminophen poisoning, the administration of N-acetylcysteine (NAC) can effectively treat the main complications, such as kidney injury and liver failure. In the current situation, measurements of the acetaminophen concentration are not checked in the usual medical facilities. Therefore, this study examined the factors of determining the administration of NAC in addition to the stated amount of intake. Methods: The medical records of patients who visited Ajou University Hospital emergency center with acetaminophen poisoning from January 2015 to December 2019 were reviewed retrospectively. One hundred and seventy-nine patients were initially included. Among these patients, 82 patients were finally selected according to the inclusion criteria in the study. The inclusion criteria were as follows: patients who were 15 years of age or older; those whose ingested dose, ingested time, and body weight were clearly identified; and patients whose acetaminophen sampling time was within 24 hours. Patients were divided into two groups: NAC administered vs. non-NAC administered. The following variables were compared in these two groups: ingested dose, ingested dose per body weight, hospital arrival time after ingestion, suicide attempt history, psychiatric disease history, classification of toxic/non-toxic groups, duration of hospitalization, and laboratory results. Results: Univariate analysis revealed the ingested dose per body weight, hospital arrival time after ingestion, suicide attempt history, and psychiatric disease history to be the determining factors in administering NAC. Logistic regression analysis confirmed that the ingested dose per body weight was the only significant factor leading to an NAC treatment decision. (Odds ratio=1.039, 95% Confidential interval=1.009-1.070, p=0.009) Conclusion: The ingested dose per body weight was the only determining factor for administering NAC in patients with acute acetaminophen poisoning. On the other hand, additional criteria or indicators for the NAC administration decision will be necessary considering the inaccuracy of the ingested dose per body weight and the efficiency of NAC administration.

• Bulletin of the Korean Chemical Society
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• v.32 no.4
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• pp.1341-1345
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• 2011

A novel ruthenium(II) complex, [$RuCl_2(DMSO)_2$(PhenTPy)] has been synthesized by the condensation of $RuCl_2(DMSO)_4$ with (1-(1,10-phenanthrolinyl)-2,5-di(2-thienyl)-1H-pyrrole)[PhenTPy] in $CHCl_3$ solution. The [$RuCl_2(DMSO)_2$(PhenTPy)] complex modified electrode was fabricated through the electropolymerization of the monomer in a 0.1 M tetrabutylammonium perchlorate (TBAP)/$CH_2Cl_2$ solution, to take advantage of the electronic communication between metal ion center by the conjugated backbone. The UV-visible spectroscopy (UV), mass spectrometry (MS), and cyclic voltammetry (CV) were employed to characterize the [$RuCl_2(DMSO)_2$(PhenTPy)] complex and its polymer (poly-Ru(II)Phen complex). The poly-Ru(II)Phen complex modified electrode exhibited an electrocatalytic activity to the oxidation of acetaminophen and the catalytic property was used for the analysis of acetaminophen at the concentration range between 0.09 and 0.01 mM in a phosphate buffer solution (pH 7.0).

• Herbal Formula Science
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• v.11 no.2
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• pp.135-146
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• 2003

Objectives : Wolguk-whan has been used as a prescription of natural drug for the treatment of stress digestive system disease. Recently, we reported that Wolguk-whan methnol extract (WGWM) exerted a significant protective effect against oxidative damage to the liver of ICR mice. This study was purposed to investigate the effects of Wolguk-whan water extract (WGWW) on liver injury induced by oxidative stress. Methods : In order to investigate the effects of WGWW on acute liver injury, ICR mice were pretreated with WGWW for 6days, starved for 24hrs, and administerated acetamirtophen(500mg/kg, i.p.). In the liver homogenates, lipid peroxide and glutathione(GSH) levels were measured. In addition, activities of hepatic enzyme, such as catalase, glutathione peroxidase(GSH-Px), glutathione S-transferase(GST) were measured in the hepatic mitochondrial and cytosolic fractions. Results : In vivo administeration of WGWW showed effective inhibition of acetaminophen induced lipid peroxidation, and showed elevations of GSH level, catalase, GSH-Px, GST activities. Conclusions : These results suggested that WGWW might suppress the formation of oxidative metabolites, and prevent acetaminophen induced hepatotoxicity.

• Microbiology and Biotechnology Letters
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• v.26 no.5
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• pp.413-419
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• 1998

Aryl acylamidase [EC 3.5.1.13] present in an acetaminophen-assimilating Pseudomonas sp. has been purified to a homogeneity using series of ammonium sulfate fractionation, DEAE-Sephacel anion exchange, Phenyl-Sepharose CL-4B hydrophobic, and Sephadex G-100 gel-permeation chromatography. The molecular weight, which was estimated by gel-permeation filtration and sodium dodecyl sulfate polyacylamide gel electrophoresis, was about 57 kDa and 56 kDa, respectively, indicating that this enzyme is a monomeric protein. The optimum pH was 10.5 and the optimum temperature was 40$^{\circ}C$. After incubation of the enzyme at 50$^{\circ}C$ for 30 min, residual activity of the enzyme was 34% compared to its original activity. The Km values for acetaminophen and 4'-nitroactanilide were 0.10 mM and 0.11 mM, respectively.