• Journal of Life Science
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• v.24 no.7
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• pp.762-768
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• 2014

Diet exerts a major stress on the body and may affect gene expression and physiological functions. Understanding of cellular responses during starvation is necessary in developing strategies to reduce damage caused by diet. In this study, we isolated 10 genes (Comt, RGN, Scd1, Temt, Idi1, Fabp5, Car3, Cyp2c70, Pinx1, and Poldip3) that are down-regulated in starvation and are closely related to liver metabolism. Water supply during starvation had no effect on the induction of apoptosis, autophagy, and ERQC. The genes down-regulated by starvation were associated with many related pathways rather than limited to the liver homeostasis pathway. Water supply during starvation is important. However, maintaining NaCl homeostasis is more important. The results are thought to be closely related to gender-specific metabolism in starvation and NaCl.

• Environmental Analysis Health and Toxicology
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• v.25 no.3
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• pp.241-251
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• 2010

Crucian carp (Carassius auratus) has been used as the sentinel species for POPs (Persistent Organic Pollutants) monitoring in aquatic environment. However, there is little information for dioxin toxicity and especially, early life stage toxicity in crucian carp have been never carried out. In this study, we investigated several toxic effects for 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) in fertilized egg obtained by natural fertilization from crucian carp. The embryos at 3 h post-fertilization (hpf) were treated with 0.039, 0.156, 0.625, and 2.5 (${\mu}g/L$) TCDD by waterborne exposure for 60 minutes and changed with fresh water 2 times per day. Fertilized eggs started hatching at 51 hpf and TCDD exposed embryo showed decrease of hatching rate in a dose-dependent manner at 75 hpf. Pericardial edema was continuously observed in larvae exposed to TCDD from hatching start time (51 hpf), followed by the onset of mortality. In addition, AhR-related gene, CYP1A was clearly increased by TCDD in a dose dependent manner. These results indicated that fertilized eggs obtained from crucian carp have the TCDD related gene regulation and a distinct TCDD developmental toxicity syndrome by TCDD exposure. Therefore, we suggested that early life stage test in crucian carp could be used as test methods on dioxins toxicity.

• Biomolecules & Therapeutics
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• v.27 no.2
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• pp.134-144
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• 2019

The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased with the incidence of obesity; however, the underlying mechanisms are unknown. In this study, high-resolution metabolomics (HRM) along with transcriptomics were applied on animal models to draw a mechanistic insight of NAFLD. Wild type (WT) and catalase knockout (CKO) mice were fed with normal fat diet (NFD) or high fat diet (HFD) to identify the changes in metabolic and transcriptomic profiles caused by catalase gene deletion in correspondence with HFD. Integrated omics analysis revealed that cholic acid and $3{\beta}$, $7{\alpha}$-dihydroxy-5-cholestenoate along with cyp7b1 gene involved in primary bile acid biosynthesis were strongly affected by HFD. The analysis also showed that CKO significantly changed all-trans-5,6-epoxy-retinoic acid or all-trans-4-hydroxy-retinoic acid and all-trans-4-oxo-retinoic acid along with cyp3a41b gene in retinol metabolism, and ${\alpha}/{\gamma}$-linolenic acid, eicosapentaenoic acid and thromboxane A2 along with ptgs1 and tbxas1 genes in linolenic acid metabolism. Our results suggest that dysregulated primary bile acid biosynthesis may contribute to liver steatohepatitis, while up-regulated retinol metabolism and linolenic acid metabolism may have contributed to oxidative stress and inflammatory phenomena in our NAFLD model created using CKO mice fed with HFD.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.5
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• pp.716-721
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• 2016

This study investigated the effect of Bacillus subtilis (B. subtilis) natto on meat quality and skatole in TOPIGS pigs. Sixty TOPIGS pigs were randomly assigned to 3 groups (including 5 pens per group, with 4 pigs in each pen) and fed with basic diet (control group), basic diet plus 0.1% B. subtilis natto (B group), and basic diet plus 0.1% B. subtilis natto plus 0.1% B. coagulans (BB group), respectively. All pigs were sacrificed at 100 kg. Growth performance, meat quality, serum parameters and oxidation status in the three groups were assessed and compared. Most parameters regarding growth performance and meat quality were not significantly different among the three groups. However, compared with the control group, meat $pH_{24}$, fat and feces skatole and the content of Escherichia coli (E. Coli), Clostridium, $NH_3$-N were significantly reduced in the B and BB groups, while serum total cholesterol, high density lipoprotein, the levels of liver P450, CYP2A6, and CYP2E1, total antioxidant capability (T-AOC) and glutathione peroxidase and Lactobacilli in feces were significantly increased in the B and BB groups. Further, the combined supplementation of B. subtilis natto and B. coagulans showed more significant effects on the parameters above compared with B. subtilis, and Clostridium, and $NH_3$-N. Our results indicate that the supplementation of pig feed with B. subtilis natto significantly improves meat quality and flavor, while its combination with B. coagulans enhanced these effects.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.2
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• pp.207-213
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• 1999

To examine individual variation in drug metabolism catalyzed by flavin-containing monooxygenase (FMO), 179 Korean volunteers' urinary molar concentration ratio of theobromine (TB) and caffeine (CA) was determined. Their urine was collected for 1 hr (between 4 and 5 hrs) after they drank a cup of coffee containing 115 mg CA and analyzed by an HPLC system. The lowest TB/CA ratio obtained was 0.40, the highest ratio was 15.17 (38-fold difference), and the median ratio for all subjects was 1.87. The mean was 2.66 with 2.36 S.D.. In 134 nonsmokers, the mean ratio was $2.35{\pm}1.93,$ that of 51 males was $2.30{\pm}2.26$ and 83 females was $2.37{\pm}1.85,$ respectively. There was no significant gender difference in the obtained TB/CA ratio (Mann-Whitney test; p=0.518). There were no smokers among the 83 female volunteers. In the remaining 96 male subjects, the ratio obtained in 51 nonsmokers was $2.30{\pm}2.06$ and that of 45 smokers was $3.62{\pm}3.19.$ This indicated that the TB/CA ratio was increased significantly in smokers (p=0.007). However, when the TB/CA ratios (FMO activity) obtained in all 179 Korean volunteers are compared with the urinary concentration ratios of paraxanthine (PX) plus 1,7-dimethylurate (17U) to CA (CYP1A2 activity), there was a weak but significant correlation (Pearson's correlation coefficient test; $r^2=0.28,$ p＜0.0001). This indicates that, although the urinary TB/CA ratio mostly represents FMO activity, minor contribution by CYP1A2 activity cannot be ignored. In conclusion, the FMO activity measured by taking the urinary TB/CA ratio from normal healthy Korean volunteers shows marked individual variations without significant gender differences and the increased TB/CA ratio observed in cigarette smokers may have been caused by the increased CYP1A2 activity.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.10a
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• pp.153-155
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• 1995

To investigate the mechanism of the regulation of cytochrome P450IAl, the 5'-flanking region of a trout cytochrome P4501Al was cloned into the CAT basic expression vector at HindⅢ site. This trout Cytochrome P450IAl upstream DNA containing CAT construct was transfected into Hepa-1 cells .3MC treatment to hepa I cells transfected with trout P450IAl-CAT construct increased CAT protein and mRNA by 2.81 fold when it was compared with that of control. This increase CAT protein and mRNA was decreased by concomitantly treated flavonoids and aminopyrine. The level of CAT protein was 29.2-58.0% of 3MC stimulated CAT protein.

• Toxicological Research
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• v.17
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• pp.127-133
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• 2001

Together with cytochrome P450 (CYP), flavin-containing monooxygenase (FMO) present in liver microsomes oxidizes various endogenous and exogenous chemicals. In an effort to determine the human FMO activity, we have developed two non-invasive urine analysis methods using caffeine (CA) and ranitidine (RA) as the probe compounds. As the production of theobromine (TB) and ranitidine N-oxide (RANO) from CA and RA is catalyzed primarily by the hepatic FMO, we have assigned the urinary molar ratios of TB/CA and RA/RANO as the in vivo FMO activity. In 200 age-matched Korean volunteers, the obtained TB/CA ratio ranged from 0.4 to 15.2 (38-fold difference) and the RA/RANO ratio from 5.7 to 27.2 (4.8-fold). The FMO activity of 20's, determined by caffeine metabolism, was the highest (2.5$\pm$l.9) and those of 30's, 40's, 50's, 60's and 70's were 40%, 50%, 24%, 39% and 36% of the 20's, respectively. Intake of grapefruit juice, known to contain flavonoids, inhibited the in vivo FMO (TB/CA) activity by 79%. Addition of the flavonoids like naringin, quercitrin and kaempferol, present in grapefruit juice, to the in vitro microso-mal FMO assay, thiobenzamide S-oxidation, produced 75%, 70% and 60% inhibition, respectively. Obtained Ki values of quercitrin, kaempferol and naringin on the in vitro FMO activity were 6.2, 12.0 and 13.9 $\mu\textrm{M}$, respectively. This suggested that the dose of drug should need to be adjusted to suit the individual FMO activities when the drugs metabolized by FMO are given to patients. As the intake of grapefruit juice has been identified to inhibit the FMO as well as CYP3A4 and lA2 activities, patients taking drugs metabolized by these enzymes should not drink grapefruit juice as the carrier.

• Korean Journal of Veterinary Research
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• v.57 no.3
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• pp.147-154
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• 2017

The present study was performed to evaluate the hangover relieving effect of germinated buckwheat (GB) and Sanghwang mushroom mycelium cultured in GB (SGB). Both GB and SGB showed 1,1-diphenyl-2-picrylhydrazyl radical scavenging activities and significantly increased (p < 0.001) aldehyde dehydrogenase (ALDH) activities; up to 140% increase at concentrations of $16{\mu}L/mL$. Locomotor activity test results from alcohol-SGB and alcohol-GB groups showed improved motor activities over that of the alcohol-water group at 90 min post-administration. Both alcohol-GB and alcohol-SGB groups had significantly reduced (p < 0.001) alcohol ($40.02{\pm}33.38{\mu}g/mL$, $66.01{\pm}22.04{\mu}g/mL$, respectively) and aldehyde ($5.72{\pm}0.47{\mu}g/mL$, $6.72{\pm}1.70{\mu}g/mL$, respectively) concentrations in blood compared to those in the alcohol-water group ($199.75{\pm}33.83{\mu}g/mL$, $50.43{\pm}13.88{\mu}g/mL$, respectively) at 90 min post-administration. Based on cDNA microarray analysis, expressions of ALDH genes ALDH1a7 and ALDH18a1 and cytochrome P450 (CY450) gene CYP4a30b were upregulated in the alcohol-GB and alcohol-SGB groups compared to levels in the control group. Overall, the results suggest that both GB and SGB have hangover relieving effects by reducing blood acetaldehyde levels. The molecular mechanisms may involve ALDH activation and upregulated expression of alcohol metabolism-related genes such as ALDH and CYP450.

• Journal of Pharmaceutical Investigation
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• v.36 no.3
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• pp.157-160
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• 2006

This study investigated the effect of clarithromycin on the pharmacokinetics of ambroxol in rats. The pharmacokinetic parameters of ambroxol in rats were determined after the oral administration of ambroxol (12 mg/kg) in the presence or absence of clarithromycin (5 or 10 mg/kg). Compared with the control (given ambroxol alone), coadministration of clarithromycin significantly (p<0.05 at 5 mg/kg; p<0.01 at 10 mg/kg) increased the area under the plasma concentration-time curve (AUC), peak plasma concentrations $(C_{max})$ and absorption rate constant $(K_a)$ of ambroxol. Clarithromycin increased the AUC of ambroxol in a dose dependent manner within the dose range of 5 to 10 mg/kg. The absolute bioavailability (AB%) of ambroxol in the presence of clarithromycin was significantly higher than that of the control (p<0.05 at 5 mg/kg; p<0.01 at 10 mg/kg), and the relative bioavailability (RB%) of ambroxol with clarithromycin was increased by 1.32-to 1.71-fold. However, there were no significant changes in time to reach peak concentration $(T_{max})$ and terminal half-life $(T_{1/2})$ of ambroxol in the presence of clarithromycin. Coadministration of clarithromycin enhanced the bioavailability of ambroxol, which may be due to the inhibition of intestinal and hepatic metabolism of ambroxol by CYP 3A4. Further studies for the potential drug interaction are necessary since ambroxol is often administrated concomitantly with clarithromycin in humans.

• Korean journal of applied entomology
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• v.40 no.4
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• pp.337-344
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• 2001

The house fly (Musca domestica L.) strains were derived from the Yumenoshima III strain by selecting with cypermethrin and methomyl for 19 and 16 generations, respectively. The resulting strains, cypermethrin resistance strain (Cyp-R19) and methomyl resistance strain (Met-R16), showed high level of resistance by 12906 and 51 times, respectively, comparing with the susceptible SRS strain. The Cyp-R19 strain was resistant to synthetic pyrethroids such as deltamethrin, esfenvalerate, fenpropathrin, $\beta$-cyfluthrin, showing > 11000, 1231, 103, 292 times higher $LD_{50}$ values than the SRS strain, respectively. It was also resistant to 3 organophosphates and 2 carbamates such as fenitrothion, profenofos, pyridaphenthion, benfuracarb, methomyl, showing resistance ratios fo 51, 17, 49, 39 and 62 comparing to SRS strain. The Met-R16 strain was resistant to synthetic carbamate benfuracarb, showing 6 times higher $LD_{50}$ value than SRS strain. It was also resistant to 4 organophosphates such as acephate, fenitrothion, profenofos and pyridaphenthion, showing > 40, 103, 19, 60 times higher $LD_{50}$ value. It was also resistant to 5 pyrethroids and a pyrrole such as cypermethrin, deltamethrin, esfenvalerate, fenpropathrin, $\beta$-cyfluthrin and chlorfenapyr, showing 3030, 249, 4063, 34, 330 and 86 times higher $LD_{50}$ values than the SRS strain. Cyp-R14 strain which was selected for 14 generations by cypermethrin and developed 11014 times higher resistance to the SRS strain was used in the dominance and linkage group analysis. Cypermethrin resistance inheritance was incompletely dominant in house fly as judged by the reciprocal cross between the resistant and susceptible strains. The linkage group analysis for the major factors responsible for this resistance was carried out by the$ F_1$male-backcross method, using susceptible multi-chromosomal marker aabys strain. The major factors for cypermethrin resistance were located on the 1st, the 3rd and the 4th chromosomes, and the effect of the 3rd chromosome was most prominent.