• Environmental Analysis Health and Toxicology
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• 제20권3호
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• pp.215-221
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• 2005

Environmental polycyclic aromatic hydrocarbones (PAHs), which are formed during incomplete combustion of fossil fuels, are widely distributed in our environment. Human exposure to PAHs may occur through smoking, polluted air, food consumption and occupational contact. Urinary naphthols, 1-and 2-naphthol, have been suggested as route -specific biomarkers for exposure to airborne PAHs. Cytochrome p450 2E1 (CYP2E1) is known to be a great importance for the metabolism of organic solvents, which is a precacinogens with small molecular weight. This study describes the metabolic differences between PstI and RsaI polymorphisms (c1 allele: PstI-. RsaI+ ; c2 allele: PstI+, RsaI-) of CYP2E1 5-flanking region by genetically modified HepG2 cells, which overexpress the polymorphic regions. The results of CAT assay and western blot in the c2 allele overexpressed cells have higher activities than the cl allele over-expressing cells. However, the metabolism of naphthalene to 2-naphthol has no difference due to the two genotypes. In this study, we established the CYP2E1 polymorphic allele transduced HepG2 cells to screen susceptibility -differences in PAH exposure. In conclusion, the CYP2E1 polymorphism may hardly induce susceptibility differences in PAH exposure monitoring with urinary naphthols.

• 한국식품영양과학회지
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• 제44권2호
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• pp.173-181
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• 2015

본 연구는 scopoletin 식이 보충이 알코올로 인해 유발되는 인슐린저항성과 항산화방어계에 미치는 영향을 구명하고자 하였다. 실험동물은 4주령의 수컷 SD계 흰쥐에게 총 열량의 36%에 해당하는 알코올을 액체식이 형태로 8주간 공급하였으며, scopoletin은 알코올 액체식이 리터당 0.01 g과 0.05 g 두 수준으로 첨가하였다. 정상군은 알코올대조군과 동량의 에너지를 섭취하도록 하였다. 8주간의 알코올 급여는 공복 시 혈당 변화를 일으키지 않았으나 혈청 인슐린 함량을 증가시켰으며, 이는 인슐린저항성과 내당능 장애를 유발하였다. 그러나 scopoletin 저농도와 고농도 급여군 모두 인슐린 함량, 인슐린저항성 지표 및 내당능을 효과적으로 개선하는 것으로 나타났다. 알코올대조군은 p-PI3K의 단백질 발현을 유의적으로 낮추어 glucokinase 유전자 발현과 활성을 억제한 반면, 당신생 효소인 glucose-6-phosphatase의 유전자 발현과 활성을 유의적으로 높였다. 그러나 scopoletin 급여에 의하여 이들 변화는 완화되었다. 다른 당신생 효소인 phosphoenolpyruvate carboxykinase의 유전자 발현과 활성에는 영향을 미치지 않았다. 또한 scopoletin 급여군 모두 간조직의 aldehyde dehydrogenase의 활성은 알코올 대조군에 비해 증가된 반면, cytochrome P450 2E1 활성은 억제되었다. 또한 알코올로 인하여 낮아진 간조직 중의 항산화 효소(superoxide dismutase, catalase와 glutathione peroxidase)의 유전자 발현과 활성을 높임으로써 과산화수소 및 지질과산화물의 함량을 낮추었다. 이와 같이 0.001%의 scopoletin 급여량에서도 당대사의 유전자 변화를 통하여 만성 알코올로 유도되는 인슐린저항성을 개선하였으며, 알코올대사계 활성 및 항산화방어계 효소의 유전자 발현을 증가함으로써 알코올로 인한 과산화수소와 지질과산화물 생성을 개선하는 것으로 나타났다.

• Preventive Nutrition and Food Science
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• 제19권4호
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• pp.268-273
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• 2014

The induction of detoxification enzymes by benzyl isothiocyanate (BITC) and its synthetic N-acetyl-L-cysteine (NAC) conjugate (NAC-BITC) was examined in Hepa1c1c7 murine hepatoma cells. BITC and NAC-BITC inhibited Hepa1c1c7 cell growth in a dose-dependent manner. Cell growth was 4.5~57.2% lower in Hepa1c1c7 cells treated with $0.1{\sim}1.0{\mu}M$ BITC than in control-treated Hepa1c1c7 cells. The NAC-BITC treatment had a similar inhibitory pattern on Hepa1c1c7 cell growth; $0.5{\mu}M$ and $10{\mu}M$ NAC-BITC decreased cell growth by 13.6% and 47.4%, respectively. Treatment of Hepa1c1c7 cells with $0.1{\sim}2.0{\mu}M$ BITC also elicited a dose-response effect on the induction of quinone reductase quinone reductase (QR) activity and QR mRNA expression. Treatment with $1{\mu}M$ and $2{\mu}M$ BITC caused 1.8- and 2.8-fold inductions of QR mRNA, respectively. By comparison, treatment with $1{\mu}M$ and $2{\mu}M$ NAC-BITC caused 1.6-and 1.9-fold inductions of QR mRNA, respectively. Cytochrome P450 (CYP) 1A1 and CYP2E1 induction were lower in $0.1{\sim}2{\mu}M$ BITC-treated cells than in control-treated cells. CYP2E1 activity was 1.2-fold greater in $0.1{\mu}M$ NAC-BITC-treated cells than in control-treated cells. However, the CYP2E1 activity of cells treated with higher concentrations (i.e., $1{\sim}2{\mu}M$) of NAC-BITC was similar to the activity of control-treated cells. Considering the potential of isothiocyanatesto prevent cancer, these results provide support for the use of BITC and NAC-BITC conjugates as chemopreventive agents.

• 대한한방내과학회지
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• 제32권4호
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• pp.550-564
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• 2011

Objectives : Oxidative stress seems to play a major role in mechanisms by which ethanol causes liver injury. Previous studies have shown that treatment with Yinjinchunggan-tang (Yinchenqinggan-tang, YJCGT) has protective effects on alcoholic liver disease. The aim of this study was to investigate the protective effects of YJCGT on alcohol-induced oxidative stress. Materials and Methods : In vitro, we evaluated the inhibitory activities of YJCHT on DPPH(1,1-diphenyl-2-picryl-hydrazyl), xanthine oxidase, trypsin, and hyaluronidase. In a cell culture model, we measured cell viability and proliferation, and the activities of superoxide dismutase (SOD), and catalase (CAT) after YJCGT treatment in C34 and E47 cell lines, and HepG2 cells transfected with/ without cytochrome P450IIE1 (CYP2E1) gene. In vivo, we estimated serum level of hepatic biochemical markers, and alcohol concentration in the blood. Results : YJCGT showed significant free radical scavenging activity against DPPH and xanthine oxidase and decreased hyaluronidase activity effectively in vitro. YJCGT also increased cell viability, and proliferation in C34 and in E47 cell lines, and increased activities of superoxide dismutase, and catalase in C34 and in E47 cell lines. YJCGT reduced serum AST, LDH, and total cholesterol level in some of the results, and reduced blood alcohol concentration in vivo, as well. Conclusions : This study suggests that YJCGT has protective effects on oxidative stress by inhibiting alcohol-induced suppression of antioxidant enzyme activities.

• Biomolecules & Therapeutics
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• 제1권1호
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• pp.50-57
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• 1993

This study characterized the effect of liver injury produced by hepatotoxicants on the biliary and urinary excretion of acetaminophen(AA) metabolites. Liver damage was produced in male S.-D. rats, 24 hr after dosing with carbon tetrachloride(4CCl_4,$ 0.75 mι/kg, ip) or thioacetamide(TA, 200 mg/kg, ip), or 16 hr after administration of cadmium chloride(4CdCl_2,$ 3.9 mg/kg, iv). Liver damage without renal injury was confirmed by measuring serum enzymes, creatinine and BUN levels as well as by histopathological examination. AA and its metabolites were measured for 3 hr by HPLC in rats injected iv with 1 mmo1/kg of AA. The excreted amounts of AA-glucuronide into bile were reduced to 60~70% of control rats by hepatotoxicants, but did not change urinary excretion of AA-glucuronide and AA-sulfate. Treatments with $CCl_4,\; CdCl_2$ and TA decreased the total (biliary plus urinary) excretion of thioethers of AA(30~50% of control), suggesting that these toxicants decrease cytochrome P-450-mediated toxification of AA. However, treatments of $CdCl_2$and TA markedly enhanced the excretion of AA-mercapturate into urine. Thus, 4CdCl_2$ and TA not only influence the formation of AA-glutathione, but may also alter the excretory routes (i.e. bile and urine) for the elimination of AA-metabolite.

• 동의생리병리학회지
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• 제17권2호
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• pp.297-307
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• 2003

In the present study, we investigated the protective effect of the Puerarie Radix water extract (PRE) against CCl₄-induced hepatotoxicity and the mechanism underlying these protective effects in the rats. The pretreatment of PRE has shown to possess a significant protective effect by lowering the serum alanine and aspartate aminoteansferase (AST and ALT) and alkaline phosphatase (ALP). This hepatoprotective action was confirmed by histological observation. In addition, the pretreatment of PRE prevented the elevation of hepatic malondialdehyde (MDA) formation and the depletion of reduced glutathione (GSH) content and catalase activity in the liver of CC1₄-injected rats. The PRE also displayed hydroxide radical scavenging activity in a dose-dependent manner (IC50 = 83.6 μg/ml), as assayed by electron spin resonance (ESR) spin-trapping technique. Moreover, the expression of cytochrome P450 2E1 (CYP2E1) mRNA, as measured by reverse transcriptase-polymerase chain reaction (RT-PCR), was significantly decreased in the liver of PRE-pretreated rats when compared with that in the liver of control group. Based on these results, it was suggested that the hepatoprotective effects of the PRE may be related to antioxidant effects and regulation of CYP2E1 gene expression.

• 동의생리병리학회지
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• 제17권1호
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• pp.91-100
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• 2003

In the present study, we investigated the protective effect of the Lycii Fructus water extracts (LFE) against CCl4-induced hepatotoxicity and the mechanism underlying these protective effects in the rats. The pretreatment of LFE has shown to possess a significant protective effect by lowering the serum alanine and aspartate aminoteansferase (AST and ALT) and alkaline phosphatase (ALP). This hepatoprotective action was confirmed by histological observation, In addition, the pretreatment of LFE prevented the elevation of hepatic malondialdehyde (MDA) formation and the depletion of reduced glutathione (GSH) content and catalase activity in the liver of CC1₄-injected rats. The LFE also displayed hydroxide radical scavenging activity in a dose-dependent manner (IC50 = 83.6 μg/ml), as assayed by electron spin resonance (ESR) spin-trapping technique. Moreover, the expression of cytochrome P450 2E1 (CYP2E1) mRNA, as measured by reverse transcriptase-polymerase chain reaction (RT-PCR), was significantly decreased in the liver of LFE-pretreated rats when compared with that in the liver of control group. Based on these results, it was suggested that the hepatoprotective effects of the LFE may be related to antioxidant effects and regulation of CYP2E1 gene expression.

• 한국축산식품학회지
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• 제42권6호
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• pp.1046-1060
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• 2022

This study aimed to investigate the effects of the metabolites of Latilactobacillus curvatus BYB3 and indole-activated aryl hydrocarbon receptor (AhR) to increase the tight junction (TJ) proteins in an in vitro model of intestinal inflammation. In a Western blot assay, the metabolites of L. curvatus BYB3 reduced the TJ demage in lipoploysaccharide (LPS) stimulated-Caco-2 cells. This reduction was a result of upregulating the expression of TJ-associated proteins and suppressing the nuclear factor-κB signaling. Immunofluorescence images consistently revealed that LPS disrupted and reduced the expression of TJ proteins, while the metabolites of L. curvatus BYB3 and indole reversed these alterations. The protective effects of L. curvatus BYB3 were observed on the intestinal barrier function when measuring transepithelial electrical resistance. Using high-performance liquid chromatography analysis the metabolites, the indole-3-latic acid and indole-3-acetamide concentrations were found to be 1.73±0.27 mg/L and 0.51±0.39 mg/L, respectively. These findings indicate that the metabolites of L. curvatus BYB3 have increasing mRNA expressions of cytochrome P450 1A1 (CYP1A1) and AhR, and may thus be applicable for therapy of various inflammatory gut diseases as postbiotics.

• BMB Reports
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• 제41권1호
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• pp.68-71
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• 2008

Flavones are synthesized from flavanones through the action of flavone synthases (FNSs). There are two FNSs, FNS I and II. FNS I is a soluble dioxygenase present in members of the Apiaceae family and FNS II is a membrane bound cytochrome P450 enzyme that has been identified in numerous plant species. In this study, we cloned OsFNS I-1 from rice by RTPCR, expressed it in E. coli, and purified the recombinant protein. By NMR analysis, we found that OsFNS I-1 converted the flavanone (2S)-naringenin into the flavone, apigenin. Moreover, we found that the cofactors oxoglutarate, $FeSO_4$, ascorbate and catalase are required for this reaction. OsFNS I-1 encodes a flavone synthase I. This is the first type I FNS I found outside of the Apiaceae family.

• Safety and Health at Work
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• 제2권2호
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• pp.97-104
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• 2011

N,N-Dimethylformamide (DMF) is globally used as an organic solvent in the production of synthetic leather and resins because of its low volatility, making it an attractive industrial material. Despite its excellent property as a chemical solvent, utilization of DMF is somewhat controversial nowadays due to its hazardous effects on exposed workers in work places. Many toxification cases are being reported globally and the number of cases of liver damage is still increasing in developing countries. On account of this, a series of epidemiologic surveys are being conducted to understand the degrees of liver damage caused by DMF exposure. Furthermore, many investigations have been performed to clarify the mechanism of DMF-induced liver toxicity using both human and experimental animal models. This review summarizes the current occupational cases reported on liver damage from workers exposed to DMF in industrial work places and the research results that account for DMF-induced liver failure and possible carcinogenesis. The findings reviewed here show the synergistic toxicity of DMF exposure with other toxicants, which might occur through complicated but distinct mechanisms, which may extend our knowledge for establishing risk assessments of DMF exposure in industrial work places.