• Toxicological Research
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• v.24 no.3
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• pp.195-199
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• 2008

It has been reported that hepatic microsomal cytochrome P450(CYP) 2E1 is responsible for the metabolism of chlorzoxazone(CZX) to 6-hydroxychlorzoxazone. The present study was undertaken to assess the possible interaction of rutaecarpine, an alkaloid originally isolated from the unripe fruit of Evodia rutaecarpa, with CZX. Male Spraque-Dawley rats were administered with 80 mg/kg/day of oral rutaecarpine for three consecutive days. Twenty four hr after the pre-treatment with rutaecarpine, the rats were treated with 20 mg/kg of intravenous CZX. Rat hepatic microsomes isolated from rutaecarpine-treated rats showed greater(50% increase) activity of p-nitrophenol hydroxylase(a marker of CYP2E1) when compared with the control rats. Compared with control rats, the AUC of CZX was significantly smaller(84% decrease) possibly due to significantly faster CL(646% increase) in rats pretreated with rutaecarpine. This could be, at least partially, due to induction of CYP2E1 by rutaecarpine.

• Korean Journal of Environmental Biology
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• v.24 no.2 s.62
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• pp.195-200
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• 2006

The response of hepatic mixed function oxygenase (MFO) system was investigated in olive flounder exposed to formalin. Hepatic microsome of olive flounder incubated in vitro with formalin demonstrated the induction of cytochrome P450 (CYP), ethoxyresorufin deethylase (EROD), cytochrome P450 reductase (P450R) and cytochrome b5 reductase (b5R) activity. In addition, olive flounder was exposed to 100, 300 and 500 ppm of formalin for 1 h and then transferred to a flow-through type of 1000 L aquarium. Hepatic MFO enzyme activity was determined for 72 h. As the result, hepatic CYP, P450R and EROD activities increased following exposure of formalin, but b5R and GST showed no significant change. These results imply that CYP and P450R can be considered as main hepatic enzymes involving in detoxification of formalin.

• YAKHAK HOEJI
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• v.34 no.2
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• pp.69-79
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• 1990

The aim of this experiment is to observe the toxicity of cypermethrin[S, R- -cyano-3-phenoxybenzyl-(1R, 1s, cis, trans)-2,2-dimethyl-3-(2,2-dichlorovinyl) cyclopropane carboxylate]and to investigate the synergistic effect of piperonyl butoxide on the cypermethrin toxicity. In cypermethrin (CYP) treated group, the biochemical parameters such as ALT, LDH, glucose in serum were remarkably elevated. The content of cytochrome P-450 and activity of NADPH-cytochrome c reductase in renal microsomal fraction were increased but those in hepatic microsomal fraction were not significantly increased. The activity of aniline hydroxylase and ATPase in liver were decreased. In the case of CYP plus piperonyl butoxide (PB) treated group, AST, ALT, LDH and glucose were more increased. Cytochrome P-450 and NADPH-cytochrome c reductase in liver and kidney were supressed and aniline hydroxylase and ATPase in liver were more decreased. Especially, in the case of CYP plus PB 100 mg/kg treated group, hepatic TBA value was increased but activity of glucose-6-phosphatase was remarkably depressed.

• Journal of Life Science
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• v.28 no.2
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• pp.176-186
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• 2018

In this study, the total polyphenol contents, antioxidant activities and anti-proliferation effects of HepG2 cell lines in organic slovent fractions obtained from the main methanolic extract of P. yezoensis were analyzed. The polyphenol content of the $CHCl_3$ fraction was $10.3{\mu}g/mg$, slightly less than $13.08{\mu}g/mg$ of the water fraction, but $ED_{50}$ estimated by measuring DPPH free radical scavenging activity exhibited the highest $16.96{\mu}g/ml$ in the $CHCl_3$ fraction. The proliferation effects of $CHCl_3$ and EtOAc fraction toward HepG2 cells inhibited in a dose-dependent manner, showed 90% inhibition when treated for 24 hr at $900{\mu}g/ml$ of $CHCl_3$ fraction. Meanwhile gene expression patterns in HepG2 cells treated $50{\mu}g/ml$ of $CHCl_3$ fraction were identified with microarray analysis. Concerning the efficacy of P. yezoensis, gene ontology analysis explored the genes associated with response to molecule of bacterial origin, vitamin D metabolic process, and response to nutrient. Thus IL6R, CYP1A1 were selected as significant genes based on expression patterns of HepG2 cells, and pathway analysis indicates that ARNT might be considered as a upstream regulator. Also, expression analysis of IL6R and CYP1A1, activity of upstream regulator ARNT in HepG2 cells was confirmed based on Western blotting analysis at the protein level after being treated with 50 and $100{\mu}g/ml$ of $CHCl_3$ fraction.

• Environmental Analysis Health and Toxicology
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• v.31
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• pp.10.1-10.8
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• 2016

Objectives Aromatase inhibitors that block estrogen synthesis are a proven first-line hormonal therapy for postmenopausal breast cancer. Although it is known that standardized extract of Ginkgo biloba (EGb761) induces anti-carcinogenic effects like the aromatase inhibitors, the effects of EGb761 on steroidogenesis have not been studied yet. Therefore, the effects of EGb761 on steroidogenesis and aromatase activity was studied using a H295R cell model, which was a good in vitro model to predict effects on human adrenal steroidogenesis. Methods Cortisol, aldosterone, testosterone, and $17{\beta}$-estradiol were evaluated in the H295R cells by competitive enzyme-linked immunospecific assay after exposure to EGb761. Real-time polymerase chain reaction were performed to evaluate effects on critical genes in steroid hormone production, specifically cytochrome P450 (CYP11/ 17/19/21) and the hydroxysteroid dehydrogenases ($3{\beta}$-HSD2 and $17{\beta}$-HSD1/4). Finally, aromatase activities were measured with a tritiated water-release assay and by western blotting analysis. Results H295R cells exposed to EGb761 (10 and $100{\mu}g/mL$) showed a significant decrease in $17{\beta}$-estradiol and testosterone, but no change in aldosterone or cortisol. Genes (CYP19 and $17{\beta}$-HSD1) related to the estrogen steroidogenesis were significantly decreased by EGb761. EGb761 treatment of H295R cells resulted in a significant decrease of aromatase activity as measured by the direct and indirect assays. The coding sequence/Exon PII of CYP19 gene transcript and protein level of CYP19 were significantly decreased by EGb761. Conclusions These results suggest that EGb761 could regulate steroidogenesis-related genes such as CYP19 and $17{\beta}$-HSD1, and lead to a decrease in $17{\beta}$-estradiol and testosterone. The present study provides good information on potential therapeutic effects of EGb761 on estrogen dependent breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3345-3349
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• 2013

Background: Susceptibility to lung cancer has been shown to be modulated by inheritance of polymorphic genes encoding cytochrome P450 1A1 (CYP1A1) and glutathione S transferases (GSTM1 and GSTT1), which are involved in the bioactivation and detoxification of environmental toxins. This might be a factor in the variation in lung cancer incidence with ethnicity. Materials and Methods: We conducted a case-control study of 218 northern Indian lung cancer patients along with 238 healthy controls, to assess any association between CYP1A1, GSTM1 and GSTT1 polymorphisms, either separately or in combination, with the likelihood of development of Lung cancer in our population. Results: We observed a significant difference in the GSTT1 null deletion frequency in this population when compared with other populations (OR=1.87, 95%CI: 1.25-2.80-0.73, P=0.002). However, GSTM1 null genotype was found associated with lung cancer in the non-smoking subgroup. (P=0.170). Conclusions: Our study showed the GSTT1 null polymorphism to be associated with smoking-induced lung cancer and the GSTM1 null polymorphism to have a link with non-smoking related lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.78 no.2
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• pp.99-105
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• 2015

Background: Aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, binds to a wide variety of synthetic and naturally occurring compounds. AhR is involved in the regulation of inflammatory response during acute and chronic respiratory diseases. We investigated whether nuclear receptor coactivator 7 (NCOA7) could regulate transcriptional levels of AhR target genes and inflammatory cytokines in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated human bronchial epithelial cells. This study was based on our previous study that NCOA7 was differentially expressed between normal and chronic obstructive pulmonary disease lung tissues. Methods: BEAS-2B and A549 cells grown under serum-free conditions were treated with or without TCDD (0.15 nM and 6.5 nM) for 24 hours after transfection of pCMV-NCOA7 isoform 4. Expression levels of cytochrome P4501A1 (CYP1A1), IL-6, and IL-8 were measured by quantitative real-time polymerase chain reaction. Results: The transcriptional activities of CYP1A1 and inflammatory cytokines were strongly induced by TCDD treatment in both BEAS-2B and A549 cell lines. The NCOA7 isoform 4 oppositely regulated the transcriptional activities of CYP1A1 and inflammatory cytokines between BEAS-2B and A549 cell lines. Conclusion: Our results suggest that NCOA7 could act as a regulator in the TCDD-AhR signaling pathway with dual roles in normal and abnormal physiological conditions.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.3
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• pp.342-347
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• 2013

In this study, we investigated changes in the organosulfur compounds of garlic (by fermentation with lactic acid bacteria) and the effects of these fermented garlic extracts on alcohol-induced cytotoxicity in CYP2E1-transfected HepG2 cells. Lactobacillus plantarum has the highest growth rate in a garlic medium and the S-allyl-L-cysteine (SAC) in fermented garlic extracts with Lactobacillus plantarum and Pediococcus pentosaceus were significantly higher compared to other lactic acid bacteria strains (p<0.05). The SAC, S-ethyl cysteine (SEC) and S-methyl cysteine (SMC) in garlic extracts were all increased by fermentation with lactic acid bacteria. However, alliin in the fermented garlic extracts with lactic acid bacteria strains was lower than the original garlic extract and the contents of cycloalliin in the garlic extracts did not change with fermentation (p<0.05). The electron donating ability of the fermented garlic extracts increased with dose. The electron donating ability of the fermented garlic extract with L. plantarum and P. pentosaceus was over 90% efficient at 5 mg/g. The fermented garlic extracts (with lactic acid bacteria) and garlic extract were not influenced, up to $100{\mu}g/mL$, in CYPE1-transfected HepG2 cells. The CYPE1-transfected HepG2 cell viabilities were 92.60% and 92.23% when treated with both alcohol (200 mM) and fermented garlic extract ($100{\mu}g/mL$) with lactic acid bacteria respectively, for 6 days.

• Archives of Pharmacal Research
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• v.25 no.5
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• pp.664-668
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• 2002

KR-31543,(2S,3R,4S)-6-amino-4-[N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amino]-3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-2H-1-benzopyran is a new neuroprotetive agent for ischemia-reperfusion damage. The in vitro and in vivo metabolism of KR-31543 in rats has been studied by LC-electrospray mass spectrometry. Rat liver microsomal incubation of KR-31543 in the presence of NADPH resulted in the formation of a metabolite M1. M1 was identified as N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amine on the basis of LC-MS/MS analysis with the synthesized authentic standard. Rat CYP3A1 and 3A2 are the major CYP isozymes involved in the formation of M1.

• Journal of Korean Medicine for Obesity Research
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• v.4 no.1
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• pp.139-160
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• 2004

The obesity is detrimental to the health of people living in affluent societies. Individual differences in energy metabolism are caused primarily by single nucleotide polymorphisms(SNPs), some of which promote the development of obesity-related type 2 diabetes mellitus. Type 2 diabetes mellitus is a common multifactorial genetic syndrome, which is determined by several different genes and environmental factors. In this review, five major conclusions are reached: (1)To be clinically significant, SNPs must be relevant, prevalent, modifiable, and measurable. (2)Differences in SNPs may have been caused by famine, ultraviolet light, alcohol, climate, agricultural revolution. livestock, lactase persistence, and westernized lifestyle. (3)Candidate obesity genes of calorie intake restriction are SIM 1, MC3R, MC4R, AGRP, CART, CCK, CNTFR, DRD2, Ghrelin, 5-HT receptor, NPY, PON and those of energy metabolism are LEP, LEPR, UCP1, UCP2, UCP3, B2AR, B3AR, PGC-1, Androgen receptor and those of fat mobilization are AGT, ACE, ADA, APM1, Apolipoproteins, PPAR, FABP, FOXC2, GCGR, $11-{\beta}HSDI$, LDLR, Hormonal sensitive lipase, Perilipin, $TNF-{\alpha}$, $TNF-{\beta}$ (4)Candidate obesity genes in the eastern are NPY, LEP, LEPR, UCP1, UCP2, UCP3, B2AR, B3AR, ACE, APM1, PPAR, and FABP. (5)Candidate obesity genes in type 2 diabetes mellitus are MC3R, MC4R, B2AR, B3AR, ADA, APM1, PPAR, FABP, FOXC2, PC1, PC2, ABCC8, CAPN10, CYP19, CYP7, ENPP1, GCK, GYS1, IGF, IL-6, Insulin receptor, IRS, and LPL. The discovery of SNPs will lead to a greater understanding of the pathogenesis of obesity and to better diagnostics, treatment, and eventually prevention.