• Environmental Analysis Health and Toxicology
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• 제18권2호
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• pp.121-129
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• 2003

Pendimethalin [N-(1-ethyl-propyl)-2, 6-dinitro-3, 4-xylidine, $C_{13}$H$_{19}$N$_3$O$_4$, M.W. = 281.3, CAS No. 40481-42-1]는 제초제의 일종으로, 본 연구에서는 박테리아 복귀 돌연변이 시험과 포유동물 세포를 이용한 염색체 이상 시험 및 마우스를 이용한 in vivo 소핵 시험을 수행하여 pendimethalin의 유전독성을 평가하였다. 박테리아 복귀 돌연변이 시험에서 pendimethalin은 Salmonella thphimurium TA98, TA1537 균주의 경우, 대사 활성계 존재와 부재시,TA100의 경우는 대사 활성계 부재시에만 313∼5,000 $\mu\textrm{g}$/p1a1e의 범위에서 농도의존적인 돌연변이율의 증가를 보여주었고, TA1535의 경우에는 대사 활성계 존재시 약간의 돌연변이가 증가되는 것을 관찰할 수 있었다. 그러나 대사 활성계 부재시 TA1535와 대사 활성계 존재시 TA100균주의 경우에는 돌연변이 유발능을 관찰할 수 없었다. 한편 포유동물 세포인 Chinese hamster lung(CHL) fibroblast를 이용한 염색체 이상 시험에서 pendimethalin은 대사 활성계 존재 및 부재시 2.32∼9.28 $\mu\textrm{g}$/ml 농도에서 clastogenicity를 보이지 않았다. 또한 203∼810 mg/kg의 pendimethalin을 구강 투여한 마우스의 골수세포를 이용한 in vivo소핵 시험의 결과에서도 통계적으로 유의한 소핵 유발능을 관찰할 수 없었다.다.

• 식품과학과 산업
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• 제50권1호
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• pp.26-35
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• 2017

Obesity is a worldwide problem that is associated with metabolic disorders. Obesity is caused by the accumulation of an abnormal amount of body fat in adipose tissue. Adipose tissue is a major metabolic organ, and it has been classified as either white adipose tissue (WAT) or brown adipose tissue (BAT). WAT and BAT are characterized by different anatomical locations, morphological structures, functions, and gene expression patterns. WAT is mainly involved in the storage and mobilization of energy in the form of triglycerides. On the other hand, BAT specializes in dissipating energy as heat through uncoupling protein-1 (UCP-1)-mediated non-shivering thermogenesis. Novel type of brown-like adipocyte within WAT called beige/brite cells was recently discovered, and this transdifferentiation process is referred to as the "browning" or "britening" of WAT. Recently, Brown fat and/or browning of WAT have been highlights as a new therapeutic target for treatment of obesity and its related metabolic disorders. Here, we describe recent advances in the study of BAT and browning of WAT, focusing on proteomic approaches.

• Molecules and Cells
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• 제42권4호
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• pp.292-300
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• 2019

Immunometabolism, defined as the interaction of metabolic pathways with the immune system, influences the pathogenesis of metabolic diseases. Metformin and carbon monoxide (CO) are two pharmacological agents known to ameliorate metabolic disorders. There are notable similarities and differences in the reported effects of metformin and CO on immunometabolism. Metformin, an anti-diabetes drug, has positive effects on metabolism and can exert anti-inflammatory and anti-cancer effects via adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms. CO, an endogenous product of heme oxygenase-1 (HO-1), can exert anti-inflammatory and antioxidant effects at low concentration. CO can confer cytoprotection in metabolic disorders and cancer via selective activation of the protein kinase R-like endoplasmic reticulum (ER) kinase (PERK) pathway. Both metformin and CO can induce mitochondrial stress to produce a mild elevation of mitochondrial ROS (mtROS) by distinct mechanisms. Metformin inhibits complex I of the mitochondrial electron transport chain (ETC), while CO inhibits ETC complex IV. Both metformin and CO can differentially induce several protein factors, including fibroblast growth factor 21 (FGF21) and sestrin2 (SESN2), which maintain metabolic homeostasis; nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of the antioxidant response; and REDD1, which exhibits an anticancer effect. However, metformin and CO regulate these effects via different pathways. Metformin stimulates p53- and AMPK-dependent pathways whereas CO can selectively trigger the PERK-dependent signaling pathway. Although further studies are needed to identify the mechanistic differences between metformin and CO, pharmacological application of these agents may represent useful strategies to ameliorate metabolic diseases associated with altered immunometabolism.

• 동의생리병리학회지
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• 제28권2호
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• pp.195-199
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• 2014

Although the Herba Cirsii is known to posses beneficial health effects, the anti-diabetic effects and the mechanism of action have not been elucidated. In the present study we have shown that Herba Cirsii Extract (HCE) can stimulate glucose uptake in OP9 adipocytes. Unlike insulin, HCE did not stimulate the Ser473 phosphorylation and activation of Akt. The increasing effects of HCE on glucose uptake were inhibited by PD680509 and compound C pretreatment, which means that the glucose uptake effects by HCE were carried out by extracelluar signal-regulated kinase1/2(ERK1/2) and AMP-activated protein kinase (AMPK) activation. Further studies revealed that HCE stimulated glucose transport occurs through a mechanism involving ERK1/2 activation and AMPK activation.

• IMMUNE NETWORK
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• 제23권1호
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• pp.9.1-9.15
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• 2023

Cancer immunotherapies continue to face numerous obstacles in the successful treatment of solid malignancies. While immunotherapy has emerged as an extremely effective treatment option for hematologic malignancies, it is largely ineffective against solid tumors due in part to metabolic challenges present in the tumor microenvironment (TME). Tumor-infiltrating CD8⁺ T cells face fierce competition with cancer cells for limited nutrients. The strong metabolic suppression in the TME often leads to impaired T-cell recruitment to the tumor site and hyporesponsive effector functions via T-cell exhaustion. Growing evidence suggests that mitochondria play a key role in CD8⁺ T-cell activation, migration, effector functions, and persistence in tumors. Therefore, targeting the mitochondrial metabolism of adoptively transferred T cells has the potential to greatly improve the effectiveness of cancer immunotherapies in treating solid malignancies.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Current Trends in Toxicological Sciences
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• pp.73-73
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• 2002

• Toxicological Research
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• 제24권4호
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• pp.263-271
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• 2008

Recently we reported that 2-bromopropane (2-BP) has maternal toxicity, embryotoxicity, and teratogenicity in Sprague-Dawley rats. The aims of this study are to examine the potential effects of 2-BP administration on pregnant dams and embryo-fetal development, and to investigate the effects of metabolic activation induced by phenobarbital (PB) on developmental toxicities of 2-BP. Pregnant rats received 1000 mg/kg/day subcutaneous 2-BP injections on gestational days (GD) 6 through 10 (Group II and Group IIII) or 11 through 15 (Group IV). Pregnant rats in Group III received an intraperitoneal PB injection once daily at 80 mg/kg/day on GD 3 through 5 for induction of the liver metabolic enzyme system. Control rats received vehicle injections only on GD 6 through 15. All dams underwent caesarean sections on GD 20 and their fetuses were examined for external, visceral, and skeletal abnormalities. Significant adverse effects on pregnant dams and embryo-fetal development were observed in all the treatment groups, and the maternal and embryo-fetal effects of 2-BP observed in Group II were higher than those seen in Group IV. Conversely, maternal and embryo-fetal developmental toxicities observed in Group III were comparable to those seen in Group II. These results suggest that the potential effects of 2-BP on pregnant dams and embryo-fetal development are more likely in the first half of organogenesis (days $6{\sim}10$ of pregnancy) than in the second half and that the metabolic activation induced by PB pre-treatment did not modify the developmental toxic effects of 2-BP in rats.

• 한국환경성돌연변이발암원학회지
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• 제22권3호
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• pp.149-156
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• 2002

The detection of many synthetic chemicals used in industry that may pose a genetic hazard in our environment is of great concern at present. Since these substances are not limited to the original products, and enter the environment, they have become widespread environmental pollutants, thus leading to a variety of chemicals that possibly threaten the public health. In this respect, to regulate and to evaluate the chemical hazard will be important to environment and human health. The clastogenicity of 18 synthetic chemicals was evaluated in Chinese hamster lung fibroblast cells in vitro. 4-Chloro-3,5-dimethyl phenol (CAS No. 88-04-0) induced chromosomal aberrations with significance at the concentration of 15.7 $\mu\textrm{g}$/$m\ell$ both in the presence and absence of metabolic activation system. Phenoxybenzene (CAS No. 101-84-8) which is one of the most cytotoxic chemical among 18 chemicals tested revealed no clastogenicity in the range of 0.11-0.43 $\mu\textrm{g}$/$m\ell$ both in the presence and absence of metabolic activation system. From the results of chromosomal aberration assay with 18 synthetic chemicals in Chinese hamster lung cells in vitro, 4-chloro-3,5-dimethyl phenol (CAS No. 88-04-0) revealed weak positive clastogenic results in this study.

• The Korean Journal of Physiology and Pharmacology
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• 제2권2호
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• pp.261-269
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• 1998

Concomitant administration of a single acute dose of ethanol (4 g/kg) protected mice from the hepatocellular injury observed upon administration of a large dose of acetaminophen (400 mg/kg). This was evidenced by the normal histological appearances of liver sections and by the lowered serum aminotransferase activities in mice treated with ethanol and acetaminophen together. In the mice treated with acetaminophen alone, along with the hepatic necrosis, the hepatic microsomal aminopyrine N-demethylase activity was decreased. However, co-administration of ethanol prevented this acetaminophen dependent inhibition on the microsomal mixed function oxidase activity. Pharmacokinetic studies indicated that the concentration of un-metabolized drug in the blood was increased in the ethanol treated mice. Furthermore, upon co-administration of ethanol, although the biliary levels of acetaminophen metabolites (glucuronide, sulfate and cysteine conjugates) were decreased, the level of unmetabolized acetaminophen was increased. Our findings suggest that co-administration of an acute dose of ethanol reduces the degree of hepatocellular necrosis produced by a large dose of acetaminophen and this ethanol dependent protection is, in major part, afforded by suppression of the hepatic microsomal mixed function oxidase activity catalyzing the metabolic activation of acetaminophen.

• Toxicological Research
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• 제21권1호
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• pp.71-75
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• 2005

Chrysin (5,7-dihydroxyflavone) is a flavonoid compound contained in many fruits, vegetables and honey. In our experiment, we investigated genotoxicity of chrysin using bacterial reverse mutation assay, chromosomal aberration test, in vivo micronucleus test. In bacterial reverse mutation assay, chrysin did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA102 with and without metabolic activation. In chromosome aberration test, chrysin did not also induce structural and numerical abberations regardless of metabolic activation in Chinese hamster lung fibroblast cells. In mouse micronucleus test, no significant increase in the occurrence of micronucleated polychromatic erythrocytes (MNPCE) was observed in ICR male mice orally administered with chrysin at the dose of 0.5, 1.0, 2.0 g/kg body weight. Taken together these results, chrysin has no mutagenic potential in our experiment.