• 한국식품영양학회지
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• 제9권3호
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• pp.294-298
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• 1996

By the 505 chromotest which utilized Escherichia bolt PQ 37, Korean medicinal plants had been screened to Investigate the antimutagenic effect to aflatoxin B1(AFBl). Ikmocho(IMC, Leonurus sibiricus L.) was extracted with hot water. The extract was not found to be mutagenic in the Salmonella mutation test with or without metabolic activation, and the extract was showed to possess the antimutagenic properties towards AFB1-induced metation. The mutagenicity of AFB1 was inhibited by methanol soluble fracstion (IMC-MS) in dose-dependent. However, water-soluble fraction exhibited comutagenic activity. The greatest inhibitory effect of IMC-MS on AFB1 mutagenicity occurred when IMC-MS was first incubated, AFB1 followed by a second incubation with the cells and 59 mixture. Also lower inhibition was occurred when S9 mixtures were first incubated, with IMC-MS followed by a second incubation with AFBI. The results of the sequential incubation study support the probability that one mechanism of inhibition could involve the formation of chemical complex between IMC-MS and AFB1 rather than deactivation of S9 enzyme.

• Toxicological Research
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• 제29권3호
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• pp.165-172
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• 2013

Acetaminophen (APAP) known as paracetamol is the main ingredient in Tylenol, which has analgesic and anti-pyretic properties. Inappropriate use of APAP causes major morbidity and mortality secondary to hepatic failure. Overdose of APAP depletes the hepatic glutathione (GSH) rapidly, and the metabolic intermediate leads to hepatocellular death. This article reviews the mechanisms of hepatotoxicity and provides an overview of current research studies. Pharmacokinetics including metabolism (activation and detoxification), subsequent transport (efflux)-facilitating excretion, and some other aspects related to toxicity are discussed. Nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated gene battery plays a critical role in the multiple steps associated with the mitigation of APAP toxicity. The role of Nrf2 as a protective target is described, and potential natural products inhibiting APAP toxicity are outlined. This review provides an update on the mechanism of APAP toxicity and highlights the beneficial role of Nrf2 and specific natural products in hepatoprotection.

• Toxicological Research
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• 제29권3호
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• pp.217-219
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• 2013

Hypertension is a serious health problem due to high frequency and concomitant other diseases including cardiovascular and renal dysfunction. Olmesartan cilexetil is a new antihypertensive drug associated with angiotensin II receptor antagonist. This study was conducted to evaluate the mutagenicity of olmesartan cilexetil by bacterial reverse mutation test using Salmonella typhimurium (TA100, TA1535, TA98, and TA1537) and Escherichia coli (WP2 uvrA). At the concentrations of 0, 62, 185, 556, 1667, and 5000 ${\mu}g$/plate, olmesartan cilexetil was negative in both Salmonella typhimurium and Escherichia coli regardless of presence or absence of metabolic activation system (S9 mix). These results demonstrate that olmesartan cilexetil does not induce bacterial reverse mutation.

• 한국연초학회지
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• 제9권2호
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• pp.87-93
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• 1987

The mutagenic activities of the pyrolyzates (300, 600, 750 and 85$0^{\circ}C$ ) of extracts from three saponeous expectorants (Platicodi Radix, Polygalae Radix and Asiasari Radix) and two nonalkaloidal antitussives (Lirionis Tuber and Codonopsis lanceolata Radix), medicinal plants, were studied in the Ames Salmonella/microsomes test system. The pyrolysates of Codonopsis lanceolata Radix and Asiasari Radix extracts at 85$0^{\circ}C$ were slightly mutagenic to tester strain TA98( frame shift ) and TA100(base-pair substitution) of Salmonella typhimurium, and the mutagens in these pyrolyzates required the metabolic activation by a liver microsomal fraction However, the extracts and pyrolyzates of all medicinal plants tasted except the above two results dud not show the significant increase in revertant colonies.

• 한국환경성돌연변이발암원학회지
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• 제16권2호
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• pp.97-102
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• 1996

In this study, we have quantified genotype frequency of the cytochrome P450 (P450) 2E1 which codes for the P450 enzyme primarily responsible for the metabolic activation of carcinogenic nitrosamines and low molecular organic solvents, in Korean population by using PCR and RFLP at two sites previously associated with some cancers; a PstI and RsaI RFLP in the transcriptional regulatory region of the human P450 2E1 gene. The genotype frequencies of homozygous wild type (PstI site-absent) and heterozygous mutant type (PstI site-present) in PstI RFLP were 0.70 and 030, respectively. The homozygous mutant type in Pstl RFLP was not observed in Korean population. The genotype frequencies of homozygous wild type (RsaI site-present), heterozygous mutant type (RsaI site-absent), and homozygous mutant type in RsaI RFLP were 0.71, 0.26, and 0.03, respectively.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.36-41
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• 1996

Drugs mean not only medicines but also poisons, pesticides, food additives, cosmetics, cleaning agents, environmental pollutants and so on, which are normally considered foreign to the body, It is important to know what happens to these drugs when they get into the body. In the past the metabolic changes of drugs had been referred to as “detoxication mechanism”, but since there are many instances in which drugs are converted in the body to more active substances. Thus, metabolism of drugs is responsible for activation and inactivation of the drugs in the body. The major reactions in drug metabolism are oxidation, reduction, hydrolysis and conjugation. Of these four areas, most of the attention had been focused on the oxidation. Therefore, in contract of ample literatures on drug-oxidizing enzymes, there were relatively few reports on drug-reducing enzymes. In recent years, however, the reduction has received an increasing interest due to its pharmacological or toxicological significance. The present lecture is organized keeping with a focus on drug-reducing enzymes which have been explored by us and by other groups.

• Natural Product Sciences
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• 제10권5호
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• pp.197-206
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• 2004

Cytochrome P4501A2 (CYP1A2) is responsible for the metabolic activation of a number of aromatic amines and amides to mutagenic and carcinogenic moieties. Considerable variations in the level of CYP1A2 expression in humans have been reported. Thus, the level of human CYP1A2 may determine an individuals susceptibility to these chemicals. Given its importance, the molecular mechanisms of CYP1A2 regulation have been studied by many groups. Direct interactions between transcription factors with the promoters of the gene represent one of the primary means by which the expression of CYP1A2 is controlled. In this review, several important cis elements, transcription factors and the effects of deacetylation/methylation of promoter regions that play an important role in the induction by PAHs as well as constitutive expression of human CYP1A2 are discussed.

• 한국동물생명공학회지
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• 제35권2호
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• pp.113-118
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• 2020

Hepatic stellate cells (HSCs) play essential roles in normal and pathophysiological function in liver. In steady state, HSCs contribute to retinoid storage, immune tolerance, and extracellular matrix (ECM) homeostasis. Upon liver injury, they become activated and lead to morphological and functional changes. Studies have demonstrated that activation of HSCs by various stimuli such as toxins, microbial infection, or metabolic overload can promote the fibrotic changes in liver by production of ECM. Herein, we provide current knowledge about the basic characteristics of HSCs and the mechanism by which they are activated.

• 한국식품영양과학회지
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• 제19권2호
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• pp.156-162
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• 1990

Antimutagenic effect of doenjag (Korean fermented soy paste) on mutagenesis induced by aflatoxin B1 (AFB1) in Salmonella typhimurium strains TA98 and TA100 was studied. AFB1 revealed maximum mutagenicity at dose level of 1 $\mu$g/plate with metabolic activation system in both strains. Strong antiutagenic activity toward AFB1 was completely inhibited at the level of 50% of the doenjang extract. At the same concentration 64-66% and 39-53% of the AFB1 induced mutageneses were blocked when the methanol extracts of raw and cooked soybeans were added in the system respectively Raw soybeans showed higher ihhibition rate to the mutagenicity than cooked soybeans but the fermented soybeans(doenjang) was the most effective (p<0.05) Other soybean fermented foods such as commercial doenjang natto and miso were also exhibited some antimutagenic activities however the traditional doenjang was the most effective and then commercial doenjang. Natto and miso were less effective.

• 한국환경성돌연변이발암원학회지
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• 제15권2호
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• pp.81-87
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• 1995

The clastogenic activity of capsaicin, a major pungent and irritating constituent of hot chili pepper, was evaluated in cultured human lymphocytes. Capsaicin (125, 250, and 500 $\mu$M) caused cytogenetic damage as determined by increased frequency of chromosome/chromatid aberrations compared to the solvent control. The mitotic indices were also decreased in a concentration-related manner in capsaicin-treated cells. Moreover, capsaicin suppressed [$^3$]thymidine incorporation into lymphocytes. The clastogenicity and cytotoxicity of capsaicin towards human lymphocytes were evident without an external metabolic activation system. Taken together, these findings suggest that capsaicin is a genotoxic agent and may thus represent a potential health hazard in humans.