• 대한수의학회지
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• 제57권3호
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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.

• Toxicological Research
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• 제3권1호
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• pp.1-8
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• 1987

In vitro induction of cytochrome 450 associated monooxygenase activities by phenobarbital (PB) and 3-methylcholanthrene (MC) was investigated in primary cultures of adult rat hepatocytes. PB and MC were added to the culture 24 hr after the initial plating of hepatocytes. A signiftcant increase of the activities of 7-ethoxycoumarin 0-deethylase and aryl hydrocarbon hydroxylase were observed in MC and PB treated culture. MC caused about 500% induction of the initial oxidation rates of both enzymes in 48 hr. However the PB maintained both enzyme activities close to the level of freshly isolated hepatocytes. Biphenyl 4-hydroxylase and aminopyrine N-demethylase activities were also induced by MC and PB. But the level of induction was less than that occuring with 7-ethoxycoumarin 0-deethylase and aryl hydrocarbon hydroxylase. When aflatoxin $B_1$ was added to the hepatocyte cultures which have been treated with MC or PB, it caused a significant increase of the unscheduled DNA synthesis at higher dose of aflatoxin $B_1$ as compared to those of untreated control hepatocyte cultures. The results suggest that microsomal enzyme activities can be selectively controlled preferably in hepatocyte cultures by the in vitro induction method. This principle may be useful for studying the metabolism and other toxicological studies.

• Journal of Microbiology and Biotechnology
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• 제15권6호
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• pp.1310-1316
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• 2005

To evaluate the toxicological properties of human cytochrome P450 2E1 (CYP2E1) induced by ethanol and possible protective effects of various green tea catechins on alcohol-induced toxicity, transfected HepG2 cells that stably and constitutively express human CYP2E1 were established using the recombinant retroviral expression vector. Exposure of the CYP2E1-expressing HepG2 cells to high concentration of ethanol (200 mM) for 5 days resulted in a more than $50\%$ increase of cytotoxicity, assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction, lactate dehydrogenase (LDH) release, and reactive oxygen species (ROS) production, and loss of normal morphology, in comparison with HepG2 cells containing control vector. Treatment of the cells with various catechins increased cell viability by more than 2-fold. (-)-Epicatechin gallate and(-)-catechin gallate at the lowest concentration ($5\;{\mu}M$) attenuated cell death induced CYP2E1 by $60-65\%$. Therefore, the results showed that the catechins, including epimerized catechins, have strong protective effects against alcohol-induced CYP2E1 toxicity, and it is correlated with antioxidant effect.

• 대한의생명과학회지
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• 제18권1호
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• pp.1-9
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• 2012

Differentially expressed genes by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were identified in order to evaluate them as dioxin-sensitive markers and crucial signaling molecules to understand dioxin-induced toxic mechanisms in human bronchial cells. Gene expression profiling was analyzed by cDNA microarray and ten genes were selected for further study. They were cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1), S100 calcium binding protein A8 (calgranulin A), S100 calcium binding protein A9 (calgranulin B), aldehyde dehydrogenase 1 family, member A3 (ALDH6) and peroxiredoxin 5 (PRDX5) in up-regulated group. Among them, CYP1B1 was used as a hallmark for dioxin and sharply increased by TCDD exposure. Down-regulated genes were IK cytokine, interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), nuclease sensitive element binding protein 1 (NSEP1), protein tyrosine phosphatase type VI A, member 1 (PTP4A1), ras oncogene family 32 (RAB32). Although up-regulated 4 genes in microarray were coincided with northern hybridization, down-regulated 5 genes showed U-shaped expression pattern which is sharply decreased at lower doses and gradually increased at higher doses. These results introduce some of TCDD-responsive genes can be sensitive markers against TCDD exposure and used as signaling cues to understand toxicity initiated by TCDD inhalation in pulmonary tissues.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.149.1-149.1
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• 2003

We have previously shown that 2,4,3',5'-tetramethoxystilbene (TMS), a synthetic trans-stilbene analogue, is one of the most potently selective inhibitor of human cytochrome P450 1B1 in vitro and in vivo. In the present studies, the apoptotic effects of TMS were investigated in HL-60 cells. The effects of TMS on the proliferation of HL-60 cells were determined with MTT assay. TMS exhibited cytotoxicity with an $IC_50$ value of 37 nM. Cotreatment with TMS and etoposide, a well-known anticancer drug significantly enhanced the cytotoxicity. (omitted)

• Toxicological Research
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• 제4권1호
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• pp.13-22
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• 1988

The inhibitory effect of three polyacetylene compounds, panaxydol, panaxynol and panaxytriol isolated from Panax ginseng C.A. Meyer on $CCl_4$induced lipid peroxidation in vivo and in vitro hepatic microsomal lipid peroxidation induced by ADP-$Fe^{3+}$, NADPH and NADPH-cytochrome P-450 reductase were investigated. Their effects on lowering the lipid peroxide levels both in serum and liver and lowering the serum enzyme (GOT, GPT, LDH) activities without the $CCl_4$-induction were also determined. Male ICR mice were pretreated i.p. with polyacetylene compounds or DL-${\alpha}$-tocopherol before administration of $CCl_4$ i.p. and 20 hr after the administration of $CCl_4,$ serum and liver were analyzed. Hepatic microsome was isolated and used for the in vitro NADPH-dependent lipid peroxidation system. Except for panaxynol, treatment with polyacetylenes to control mice did not reduce the levels of lipid peroxides and serum enzyme activities. Panaxynol itself inhibited lipid peroxidation in the liver of normal mice. Polyacetylene compounds protected from the $CCl_4$-induced hepatic lipid peroxidation and lowered serum lipid peroxide levels. Polyacetylenes also inhibited the in virto hepatic microsomal lipid peroxidation in a dose-dependent manner. The results suggest that panaxydol, panaxynol and panaxytriol seem to be the antioxidant components which contribute the anti-aging activities of Panax ginseng C.A. Meyer.

• Preventive Nutrition and Food Science
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• 제3권4호
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• pp.351-355
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• 1998

The purpose of this study was to investigate the effect of protein and dietary fiber levels on the activities of ehanol metabilizing enzymes of the brain in acute and chronic ethanol-treated rats. Male Sprague-Dwley rats were fed on diets containing two levels of protein(7%, 20%)) with two levels of fiber(5%, 105) for 5 weeks. Rats were orally administered 40% (v/v) ethanol(5g/body weight) 90 min before decapitation in the acute ethanol-treated groups and 25% (v/v) ethanol (5g/kg body weight) once a day for 5 weeks in the chronic ethnol-treated groups. Cytosilic alcohol dehydrogenase (ADH) activities were higher than those of mitochondrial ADH. The ADH activities were increased by 20% protein and %% fiber levels in the diet in two fractions , but were decreased by chronic ethanol treatment. Mitochondrial aldehyde dehydrogenase (ALDH) activities did not change by ethanol treatment but were increased by the 20% protein level. However, cytosilic ALDH activities were decreased by chronic ethanol treatment at the 5% fiber level and did not change with protein levels. Both ALDH activities were higher in the 10% fiber groups than the 5% fiber groups. Cytochrome P-450 contents were significantly increased in the chronic ethanol-treated groups but xanthine oxidase (XO) activities did not change. P-450 contents and XO activities were significantly decreased in both the low protein and fiber groups.

• Parasites, Hosts and Diseases
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• 제49권1호
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• pp.45-49
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• 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.

• 한국임상약학회지
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• 제23권3호
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• pp.206-212
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• 2013

Purpose: The aim of this study was to investigate the effect of nimodipine on the pharmacokinetics of warfarin after oral and intravenous administration of warfarin in rats. Methods: Warfarin was administered orally (0.2 mg/kg) or intravenously (0.05 mg/kg) without or with oral administration of nimodipine (0.5 or 2 mg/kg) in rats. The effect of nimodipine on the P-glycoprotein as well as cytochrome P450 (CYP) 3A4 activity was also evaluated. Results: Nimodipine inhibited CYP3A4 enzyme activity with 50% inhibition concentration ($IC_{50}$) of $10.2{\mu}M$. Compared to those animals in the oral control group (warfarin without nimodipine), the area under the plasma concentration-time curve (AUC) of warfarin was significantly greater (0.5 mg/kg, P<0.05; 2 mg/kg, P<0.01) by 31.3-57.6%, and the peak plasma concentration ($C_{max}$) was significantly higher (2 mg/kg, P<0.05) by 29.4% after oral administration of warfarin with nimodipine, respectively. Consequently, the relative bioavailability of warfarin increased by 1.31- to 1.58-fold and the absolute bioavailability of warfarin with nimodipine was significantly greater by 64.1-76.9% compared to that in the control group (48.7%). In contrast, nimodipine had no effect on any pharmacokinetic parameters of warfarin given intravenously. Conclusion: Therefore, the enhanced oral bioavailability of warfarin may be due to inhibition of CYP 3A4-mediated metabolism rather than P-glycoprotein-mediated efflux by nimodipine.

• Biomolecules & Therapeutics
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• 제19권3호
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• pp.364-370
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• 2011

The purpose of this study was to investigate the effects of curcumin on the pharmacokinetics of loratadine in rats. The effect of curcumin on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 activity was evaluated. Pharmacokinetic parameters of loratadine were also determined after oral and intravenous administration in the presence or absence of curcumin. Curcumin inhibited CYP3A4 activity with an IC50 value of 2.71 ${\mu}M$ and the relative cellular uptake of rhodamine-123 was comparable. Compared to the oral control group, curcumin significantly increased the area under the plasma concentration-time curve and the peak plasma concentration by 39.4-66.7% and 34.2-61.5%. Curcumin also significantly increased the absolute bioavailability of loratadine by 40.0-66.1% compared to the oral control group. Consequently, the relative bioavailability of loratadine was increased by 1.39- to 1.67-fold. In contrast, curcumin had no effect on any pharmacokinetic parameters of loratadine given intravenously, implying that the enhanced oral bioavailability may be mainly due to increased intestinal absorption caused via P-gp and CYP3A4 inhibition by curcumin rather than to reduced renal and hepatic elimination of loratadine. Curcumin enhanced the oral bioavailability of loratadine in this study. The enhanced bioavailability of loratadine might be mainly attributed to enhanced absorption in the gastrointestinal tract via the inhibition of P-gp and reduced fi rst-pass metabolism of loratadine via the inhibition of the CYP3A subfamily in the small intestine and/or in the liver by curcumin.