• Proceedings of the Korean Society of Toxicology Conference
• /
• 2001.10a
• /
• pp.195-195
• /
• 2001

The inhibitory potentials of TCAs (imipramine, desipramine, amitriptyline, and nortriptyline) on phenytoin p-hydroxylation and probe metabolic pathways of each CYP isoforms were evaluated from incubation studies of human liver microsomes and cDNA-expressed cytochrome P450s in vitro in order to understand the mechanism of drug interaction between TCAs and phenytoin, a substrate of CYP2C9 and CYP2C19. (omitted)

• Parasites, Hosts and Diseases
• /
• v.49 no.1
• /
• pp.45-49
• /
• 2011

Chemotherapy of clonorchiasis with praziquantel (PZQ) is effective but about 15% of treated cases have been reported uncured. The present study investigated correlation of single nucleotide polymorphisms (SNPs) of the cytochrome P450 gene, CYP3A5 and cure of clonorchiasis. A total of 346 egg passing residents were subjected and treated by 3 doses of 25 mg/kg PZQ. Reexamination recognized 33 (9.5%) uncured and 313 cured. Numbers of eggs per gram of feces (EPGs) before treatment were significantly lower in the cured group than in the uncured group ($2,011.2{\pm}3,600.0$ vs $4,998.5{\pm}7,012.0$, P<0.001). DNAs of the subjects were screened for SNPs at 7 locations of CYP3A5 using PCR. In the uncured group, the SNP frequencies at g.-20555G > A and g.27526C > T of CYP3A5 were 15.2% and 9.1% while those were 3.8% and 1.0%, respectively, in the cured group. The cure rate was Significantly lower in the cases with SNP at g.27526C > T and EPGs ${\geq}$ 1,000. In conclusion, EPGs and SNPs of CYP3A5 are factors which influence cure of clonorchiasis by PZQ therapy. It is strongly suggested to recommend 2-day medication for individuals with high EPGs ${\geq}$ 1,000.

• Herbal Formula Science
• /
• v.30 no.1
• /
• pp.1-9
• /
• 2022

Objectives : This study investigated the protective effect of Ojeok-san (OJS) on cellular damage induced by oxidative stress and whether it induces changes in CYP450 expression. Methods : To investigate the protective effect, we used cells stimulated by oxidative stress caused by the combination treatment of AA+iron. Changes in CYP450 expression were detected by immunoblotting analysis using Huh7 cells. Results : We observed that OJS altered the expression of CYP1A2, CYP3A4, CYP2C19, CYP2D6, and CYP2E1. OJS increased cell viability against AA+iron-induced oxidative stress and inhibited mitochondrial dysfunction. OJS increased phosphorylation of LKB1, phosphorylation of AMPK, and phosphorylation of ACC, which are related to the LKB1-AMPK pathway. In addition, phosphorylation of LATS1 and phosphorylation of YAP, which are related to the Hippo-YAP pathway, were increased. Conclusions : Our results show that OJS has 1) the ability to protect hepatocytes against oxidative stress, and 2) the potential to induce changes in CYP450.

• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.88.1-88.1
• /
• 2003

CJ-11668 is a new potent and selective COX-2 inhibitor (IC$\sub$50/ COX-2 65nM; COX-l/COX-2 ratio 770). The pharmacokinetic profile of CJ-11668 (20 mg/kg, p.o.) in the rat was characterized by high bioavailability (90%) and long plasma half-life (11.7 hr) with low clearance (0.4 L/hr/kg). In the dog, the PK profiles (2 mg/kg, p.o.) also showed long plasma half-life (l7.9hr) with low clearance (0.5 L/hr/kg), and the bioavalability of 60%. The inhibition of CJ-11668 infive different cytochrome P450 isozymes (1A2, 2C9, 2C19, 2D6 and 3A4) was determined in vitro and had observed no significant effect. (omitted)

• BMB Reports
• /
• v.40 no.2
• /
• pp.247-260
• /
• 2007

Cinnamate 4-hydroxylase (C4H) is a key enzyme of phenylpropanoid pathway, which synthesizes numerous secondary metabolites to participate in development and adaption. Two C4H isoforms, the 2192-bp BnC4H-1 and 2108-bp BnC4H-2, were cloned from oilseed rape (Brassica napus). They both have two introns and a 1518-bp open reading frame encoding a 505-amino-acid polypeptide. BnC4H-1 is 57.73 kDa with an isoelectric point of 9.11, while 57.75 kDa and 9.13 for BnC4H-2. They share only 80.6% identities on nucleotide level but 96.6% identities and 98.4% positives on protein level. Showing highest homologies to Arabidopsis thaliana C4H, they possess a conserved p450 domain and all P450-featured motifs, and are identical to typical C4Hs at substrate-recognition sites and active site residues. They are most probably associated with endoplasmic reticulum by one or both of the N- and C-terminal transmembrane helices. Phosphorylation may be a necessary post-translational modification. Their secondary structures are dominated by alpha helices and random coils. Most helices locate in the central region, while extended strands mainly distribute before and after this region. Southern blot indicated about 9 or more C4H paralogs in B. napus. In hypocotyl, cotyledon, stem, flower, bud, young- and middle-stage seed, they are co-dominantly expressed. In root and old seed, BnC4H-2 is dominant over BnC4H-1, with a reverse trend in leaf and pericarp. Paralogous C4H numbers in Brassicaceae genomes and possible roles of conserved motifs in 5' UTR and the 2nd intron are discussed.

• Biomolecules & Therapeutics
• /
• v.25 no.3
• /
• pp.288-295
• /
• 2017

The incidence of polypharmacy-which can result in drug-drug interactions-has increased in recent years. Drug-metabolizing enzymes and drug transporters are important polypharmacy modulators. In this study, the effects of bosentan and rifampin on the expression and activities of organic anion-transporting peptide (OATP) and cytochrome P450 (CYP450) 2C9 and CYP3A4 were investigated in vitro. HEK293 cells and primary human hepatocytes overexpressing the target genes were treated with bosentan and various concentrations of rifampin, which decreased the uptake activities of OATP transporters in a dose-dependent manner. In primary human hepatocytes, CYP2C9 and CYP3A4 gene expression and activities decreased upon treatment with $20{\mu}M$ $bosentan+200{\mu}M$ rifampin. Rifampin also reduced gene expression of OATP1B1, OATP1B3, and OATP2B1 transporter, and inhibited bosentan influx in human hepatocytes at increasing concentrations. These results confirm rifampin- and bosentan-induced interactions between OATP transporters and CYP450.

• Korean Journal of Ichthyology
• /
• v.18 no.3
• /
• pp.202-208
• /
• 2006

An experiment was conducted to investigate the effects of three water temperatures (15, 20 and $25^{\circ}C$) in combination with three salinities (0, 15 and 30 psu) on the oxygen consumption rate of juvenile spotted sea bass, Lateolabrax maculatus (mean body weight $5.5{\pm}0.3g$). The oxygen consumption rates of L. maculatus were measured in triplicate for 24 hours using a continuous flow-through respirometer. Water temperature resulted in significant differences in the mean oxygen consumption rate of L. maculatus (p<0.001), but salinity and combinations of salinity and water temperature did not have (p>0.05). The oxygen consumption increased with increasing water temperatures in all experimental salinity regimes (p<001). Mean oxygen consumption rates at 15, 20 and $25^{\circ}C$ ranged 328.8~342.3, 433.9~441.0 and 651.5~659.9 mg $O_2\;kg^{-1}\;h^{-1}$, respectively. $Q_{10}$ values did not vary with salinity, bud varied with water temperature. $Q_{10}$ values ranged 1.63~1.75 between 15 and $20^{\circ}C$, 2.24~2.26 between 20 and $25^{\circ}C$, and 1.92~1.98 over the full temperature range. The energy loss by metabolic cost increased with increasing water temperatures in all experimental salinity regimes (p<0.001) Mean energy loss rates at 15, 20 and $25^{\circ}C$ ranged 224.6~233.8, 296.3~301.2 and $444.9{\sim}450.7kJ\;kg^{-1}\;d^{-1}$, respectively. These data suggest that the culture of juvenile spotted sea bass is possible without energy loss by salinity difference in freshwater as well as seawater after salinity acclimation. Thus, this result has an application for culture management and bioenergetic model for growth of this species.

• Journal of Life Science
• /
• v.9 no.3
• /
• pp.268-275
• /
• 1999

Rhodopseudomonas sp. was immobilized in three supports(agar, k-carrageenan, and PVA) in order to remove nitrate in wastewater coming from fish farm. Among them 3% agar was the most suitable support when denitrification rate and bead durability were tested. Optimum bead size was 4mm-diameter when the substrate transfer into the bead and shear stress for bead were considered, and optimum cell loading was 25mg dry $cells/cm^2$gel gel. Ethanol was the best as a carbon source, and optimum C:N ratio, temperature and pH were 1.5:1, $31^{\circ}C$,, and 6, respectively. Under these conditions the maximum denitrification rate in synthetic wastewater was $$345{\MU}{\ell};N_2/Cm^3 gel{\cdot}hr;and that in modified MYC medium was 450{\MU}{\ell}};N_2/Cm^3 gel{\cdot}hr $$.

• Journal of the Korean Crystal Growth and Crystal Technology
• /
• v.9 no.6
• /
• pp.542-546
• /
• 1999

InP single crystal, III-V binary compound semiconductor, was grown by VGF(vertical gradient freeze) method using quartz ampoule and its electrical optical properties were investigated. Phosphorous powders were put in the bottom of quartz ampoule and Indium metal charged in conical quartz crucible what was attached at the upper side position inside the quartz ampoule. It was vacuous under the pressure of $10^5$Torr and sealed up. Indium metal was melted at $1070^{\circ}C$ and InP composition was formed by diffusion of phosphorous sublimated at $450^{\circ}C$ into Indium melt. By cooling the InP composition melt ($2^{\circ}C$~$5^{\circ}C$/hr of cooling rate) in range of $1070^{\circ}C$~$900^{\circ}C$, InP crystal was grown. The grown InP single crystals were investigated by X-ray analysis and polarized optical microscopy. Electrical properties were measured by Van der Pauw method. At the cooling method. At the cooling rate of $2^{\circ}C$/hr, growth direction of ingot was [111] and the quality of ingot was better at the upper side of ingot than the lower side. It was found that the InP crystals were n-type semiconductor and the carrier concentration, electron mobility and relative resistivity were $10^{15}$~$10^{16}/\textrm{cm}^3$ , $2\times 10^3$~$3\times 10^4{\textrm}{cm}^2$/Vsec and$2\times 10^{-1}$~$2\times 10^{-3}$/ Wcm in the range of 150K~300K, respectively.

• Biomolecules & Therapeutics
• /
• v.17 no.3
• /
• pp.311-317
• /
• 2009

Ginkgo biloba (G. biloba) extract is a widely used phytomedicine for the oral treatment of peripheral vascular disease. Cilostazol is a synthetic antiplatelet and vasodilating agent for the treatment of intermittent claudication resulting from peripheral arterial disease. It is likely to use concomitantly G. biloba extract and cilostazol for the treatment of peripheral arterial disease, which raises a concern of increasing their adverse effects of herbal-drug interactions. To clarify any possible herbal-drug interaction between G. biloba extract and cilostazol, the effect of the G. biloba extract on the pharmacokinetics of cilostazol was investigated. As cilostazol is known to be eliminated mainly by cytochrome P450 (CYP)-mediated metabolism, we investigated the effects of G. biloba extract on the human CYP enzyme activities and the effect of G. biloba extract on the pharmacokinetics of cilostazol after co-administration of the two agents to male beagle dogs. The G. biloba extract inhibited more or less CYP2C8, CYP2C9, and CYP2C19 enzyme activities in the in vitro microsomal study with $IC_{50}$ values of 30.8, 60.5, and $25.2{\mu}g/ml$, respectively. In the pharmacokinetic study, co-administration with the G. biloba extract had no significant effect on the pharmacokinetics of cilostazol in dogs, although CYP2C has been reported to be responsible for the metabolism of cilostazol. In conclusion, these results suggest that there may not be a pharmacokinetic interaction between G. biloba extract and cilostazol.