• Food Science and Biotechnology
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• v.16 no.4
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• pp.584-589
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• 2007

The effect of water extract of adzuki beans on acetaminophen-altered lipid metabolism was examined in rats. Control group of rats was fed a basal diet, another group of rats was fed 0.5% acetaminophen (APAP group), and a third group of rats was fed 0.5% acetaminophen plus 5% adzuki bean extract (ABE group) for 4 weeks. Serum total and HDL cholesterol levels in the APAP group were significantly lower than those in the control and ABE groups. Hepatic cholesterol $7{\alpha}-hydroxylase$ and fatty acid synthase mRNA levels in the APAP and ABE groups were significantly higher and lower than in the control group, respectively. Hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase mRNA level in the APAP group was significantly lower than in the control group, whereas that in the ABE group was significantly higher than in the APAP group. These results indicate that adzuki bean extract may improve the acetaminophen-altered serum lipid metabolism in rats.

• Journal of Industrial and Engineering Chemistry
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• v.67
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• pp.301-311
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• 2018

In this study, the ion-gelation method was applied to fabricate novel Fe-carbon-bentonite-alginate beads ($Fe^0$/C-BABs). $Fe^0$/C-BABs could effectively control Fe release during persulfate (PS) activation in N-acetyl-p-aminophenol (APAP) oxidation. A novel two-stage approach that combined $Fe^0$/C-BABs and an oyster-shell-filled bed (OSFB) column was developed to address the low pH and high Fe concentration of the effluent of the traditional PS process. The application of the $Fe^0$/C-BABs and OSFB column regulated pH levels and Fe release during the advanced oxidation of APAP. The characteristics of $Fe^0$/C-BABs were also investigated through scanning electron microscopy, energy dispersive spectrometry, and Fourier transform infrared spectroscopy. The long-term operation performance of $Fe^0$/C-BABs in a continuous fixed-bed reactor under simultaneous PS and APAP feeding was also evaluated. The effects of initial PS concentration, pH, fixed-bed weight, in-flow rate, and dissolved oxygen (DO) were investigated. Under selected conditions, 86.3% efficiency was achieved during the first stage of APAP degradation (effluent pH of 3.05, Fe contents: $106.25mgL^{-1}$). Water quality improved after the effluent was passed through the OSFB column (effluent pH of 6.32, Fe contents: $21.43mgL^{-1}$). Moreover, this study analyzed the free radicals and intermediates produced during APAP degradation to identify the possible routes of APAP degradation.

• Molecular & Cellular Toxicology
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• v.2 no.4
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• pp.236-243
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• 2006

Microarray analysis of gene expression has become a powerful approach for exploring the biological effects of drugs, particularly at the stage of toxicology and safety assessment. Acetaminophen (APAP) has been known to induce necrosis in liver, but the molecular mechanism involved has not been fully understood. In this study, we investigated gene expression changes of APAP using microarray technology. APAP was orally administered with a single dose of 50 mg/kg or 500 mg/kg into ICR mice and the animals were sacrificed at 6, 24 and 72 h of APAP administration. Serum biochemical markers for liver toxicity were measured to estimate the maximal toxic time and hepatic gene expression was assessed using high-density oligonucleotide microarrays capable of determining the expression profile of >30,000 well-substantiated mouse genes. Significant alterations in gene expression were noted in the liver of APAP-administered mice. The most notable changes in APAP-administered mice were the expression of genes involved in apoptosis, cell cycle, and calcium signaling pathway, cystein metabolism, glutatione metabolism, and MAPK pathway. The majority of the genes upregulated included insulin-like growth factor binding protein 1, heme oxygenase 1, metallothionein 1, S100 calcium binding protein, caspase 4, and P21. The upregulation of apoptosis and cell cycle-related genes were paralleled to response to APAP. Most of the affected gene expressions were returned to control levels after 72 hr. In conclusion, we identified potential hepatotoxicity makers, and these expressions profiling lead to a better understanding of the molecular basis of APAP-induced hapatotoxicity.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.3
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• pp.350-355
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• 2010

The hepatoprotective effects of theanine on acetaminophen (APAP)-induced hepatotoxicity were investigated in vivo and in vitro. The effects of theanine on liver toxicity induced by APAP were assessed by blood biochemical and histopathological analyses. APAP treatment (400 mg/kg) caused severe liver injury in mice as indicated by their significantly elevated plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Pretreatment with theanine for 3 days attenuated the increase in ALT and AST when challenged with APAP. These protective effects of theanine against APAP-induced toxicity were consistent with the results from the histopathological examinations. We next examined the effects of theanine on the GSH concentration in liver plasma. The hepatic GSH level was significantly elevated in a dose-dependent manner by theanine treatment. The results suggest that the protective effects of theanine APAP-induced hapatotoxicity by antioxidative effect and GSH induction, implying that theanine should be considered a potential chemopreventive agent.

• Biomolecules & Therapeutics
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• v.25 no.2
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• pp.112-121
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• 2017

Drug-induced liver injury (DILI) is the serious and fatal drug-associated adverse effect, but its incidence is very low and individual variation in severity is substantial. Acetaminophen (APAP)-induced liver injury accounts for >50% of reported DILI cases but little is known for the cause of individual variations in the severity. Intrinsic genetic variation is considered a key element but the identity of the genes was not well-established. Here, pre-biopsy method and microarray technique was applied to uncover the key genes for APAP-induced liver injury in mice, and a cause and effect experiment employing quantitative real-time PCR was conducted to confirm the correlation between the uncovered genes and APAP-induced hepatotoxicity. We identified the innately and differentially expressed genes of mice susceptible to APAP-induced hepatotoxicity in the pre-biopsied liver tissue before APAP treatment through microarray analysis of the global gene expression profiles (Affymetrix $GeneChip^{(R)}$ Mouse Gene 1.0 ST for 28,853 genes). Expression of 16 genes including Gdap10, Lpl, Gabra3 and Ccrn4l were significantly different (t-test: FDR <10%) more than 1.5 fold in the susceptible animals than resistant. To confirm the association with the susceptibility to APAP-induced hepatotoxicity, another set of animals were measured for the expression level of selected 4 genes (higher two and lower two genes) in the liver pre-biopsy and their sensitivity to APAP-induced hepatotoxicity was evaluated by post hoc. Notably, the expressions of Gabra3 and Lpl were significantly correlated with the severity of liver injury (p<0.05) demonstrating that these genes may be linked to the susceptibility to APAP-induced hepatotoxicity.

• Journal of Biomedical Engineering Research
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• v.40 no.4
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• pp.132-136
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• 2019

This study proposes an auto-titrating algorithm for auto-titrating positive airway pressure (APAP). The process of the proposed algorithm is as follows. First, sleep apnea-hypopnea and snoring events were detected using nasal pressure. Second, APAP base pressure and SDB events were used for automatic titration of optimal pressure. And, auto-titrating algorithm is built into M3 (MEK-ICS CO. Ltd., Republic of Korea) for evaluation. The detection results of SDB showed mean sensitivity (Sen.) and positive predictive value (PPV.) of 85.7% and 87.8%, respectively. The mean pressure and apnea-hypopnea index (AHI) of auto-titrating algorithm showed $13.0{\pm}5.2cmH_2O$ and $3.0{\pm}2.4$ events/h, respectively. And, paired t-test was conducted to verify whether the performance of our algorithm has no significant difference with AutoSet S9 (p>0.05). These results represent better or comparable outcomes compared to those of previous APAP devices.

• Journal of Pharmacopuncture
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• v.22 no.4
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• pp.239-247
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• 2019

Objectives: Allium jesdianum (Aj) is a medicinal plant that has highlighted pharmacological features. In this study, the effects of Aj extract were examined on acetaminophen (APAP)-induced hepatic failure in rats. Methods: Methanolic fraction of hydro-alcoholic extract of Aj was obtained by silica gel column chromatography method. Animals were randomly divided into four groups each containing six rats and treated by gavage as follows: the first and second groups received normal saline, the third and fourth groups were received with 50 and 100 mg/kg of Aj extract, respectively. After two consecutive weeks, the groups 2-4 were given a single dose of APAP (2 g/kg). After 48 hours, blood and liver samples were collected for biochemical and histological examinations. Results: The findings of the study demonstrated that APAP caused a significant increase in ALT (P < 0.001), AST (P < 0.001), LDH (P < 0.001), ALP (P < 0.001) serum levels, hepatic lipid peroxidation (LPO; P < 0.001) and nitric oxide (NO; P < 0.001). In this regard, APAP led to the depletion of the total antioxidant capacity (TAC; P < 0.001), glutathione and total thiol groups (TTGs; P < 0.001), and structural change in the liver. In the Aj extract groups, a considerable improvement was found in the hepatic function alongside the histopathologic changes. Conclusion: This investigation indicated that the influential effects of Aj extract in APAP-induced hepatic failure might depend on its effect on improving oxidant/antioxidant balance in hepatic tissue.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.4
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• pp.707-713
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• 2002

Astragali radix (AR) is one of the oldest and mast frequently used crude drug for traditional medicine in many Asian countries. This study designed to investigate the hepatoprotective effects of the aqueous extracted AR (ARE) against acetaminophen (APAP)-induced hepatic damage in ICR mice. APAP at the dose of 450 mg/kg i.p produced liver damage in ICR mice. Serum enzyme activities of alanine aminotransferase, aspartate aminotransferase and sorbitol dehydrogenese was dramatically decreased up to control level by pretreatment of ARE. However, hepatic glutathione level did not show a significant change between the tested groups. We also investigated TNF α mRNA gene expression on APAP-induced liver damage by RT-PCR. APAP dramatically induced TNF α mRNA gene expression in ICR mice. Pretreatment of mice with ARE led to a marked decrease of TNF α mRNA gene expression. These data indicate that 1) ARE has clearly revealed a hepatoprotective effect against APAP-induced hepatic damage in ICR mice, and 2) the protective effect of ARE may be, in part, associated with the regulation of TNF α mRNA gene expression.

• BMB Reports
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• v.52 no.3
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• pp.190-195
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• 2019

Acetaminophen (APAP) overdose can cause hepatotoxicity by inducing mitochondrial damage and subsequent necrosis in hepatocytes. Sirtuin2 (Sirt2) is an $NAD^+$-dependent deacetylase that regulates several biological processes, including hepatic gluconeogenesis, as well as inflammatory pathways. We show that APAP decreases the expression of Sirt2. Moreover, the ablation of Sirt2 attenuates APAP-induced liver injuries, such as oxidative stress and mitochondrial damage in hepatocytes. We found that Sirt2 deficiency alleviates the APAP-mediated endoplasmic reticulum (ER) stress and phosphorylation of the p70 ribosomal S6 kinase 1 (S6K1). Moreover, Sirt2 interacts with and deacetylates S6K1, followed by S6K1 phosphorylation induction. This study elucidates the molecular mechanisms underlying the protective role of Sirt2 inactivation in APAP-induced liver injuries.

• Korean Architects
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• s.589
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• pp.126-141
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• 2018

안양공공예술프로젝트(APAP)는 한국에서 가장 성공적인 공공예술사업으로 손꼽힌다. 낙후된 유원지와 중소 도시 도심에 예술조형물로 활력을 불어넣고, 우수한 국내외 작가들이 자발적으로 참여해 도시의 격을 높여 시민의 자산으로 정착됐다는 평가를 받는다. 서울시의 도시 게릴라 프로젝트나 광주 비엔날레의 도심 조형물 설치 작업인 '폴리 프로젝트'가 벤츠마킹한 대상이 되기도 했다. APAP는 2005년 만안구 안양유원지를 정비해 예술공원으로 조성하는 것으로 시작돼 2007년에는 이를 도시공원화 작업으로 확대하며 평촌 일대에 공공조형물이 조성됐다. 2010년에는 골목 안으로 들어가 주민들과 함께 공동체 복원을 위한 프로젝트로 진행됐다. 특히 안양예술공원 안에 있는 안양 파빌리온(구 알바로 시자 홀)은 포르투갈 출신의 세계적인 건축사 알바로 시자(1992년 프리츠커상 수상)가 설계한 작품이다.(그는 이 작품에 이어 파주출판단지에 '미메시스 아트 뮤지엄'을 만든다.) 당연히 안양시 차원에서 추진된 공공예술사업에는 건축사 등 많은 전문가들이 참여했다. 최승원 건축사는 "지방건축발전에 기회가 오면 건축사가 적극 자문하여야 지방다운 건축이 살아나고 꽃피울 수 있다"고 강조한다. APAP 초창기부터 참여해 역할을 해온 최승원 건축사에게 안양예술공원으로 보는 지역건축에 대해 들어봤다.