• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.297-307
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• 2003

In the present study, we investigated the protective effect of the Puerarie Radix water extract (PRE) against CCl₄-induced hepatotoxicity and the mechanism underlying these protective effects in the rats. The pretreatment of PRE has shown to possess a significant protective effect by lowering the serum alanine and aspartate aminoteansferase (AST and ALT) and alkaline phosphatase (ALP). This hepatoprotective action was confirmed by histological observation. In addition, the pretreatment of PRE prevented the elevation of hepatic malondialdehyde (MDA) formation and the depletion of reduced glutathione (GSH) content and catalase activity in the liver of CC1₄-injected rats. The PRE also displayed hydroxide radical scavenging activity in a dose-dependent manner (IC50 = 83.6 μg/ml), as assayed by electron spin resonance (ESR) spin-trapping technique. Moreover, the expression of cytochrome P450 2E1 (CYP2E1) mRNA, as measured by reverse transcriptase-polymerase chain reaction (RT-PCR), was significantly decreased in the liver of PRE-pretreated rats when compared with that in the liver of control group. Based on these results, it was suggested that the hepatoprotective effects of the PRE may be related to antioxidant effects and regulation of CYP2E1 gene expression.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.1
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• pp.91-100
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• 2003

In the present study, we investigated the protective effect of the Lycii Fructus water extracts (LFE) against CCl4-induced hepatotoxicity and the mechanism underlying these protective effects in the rats. The pretreatment of LFE has shown to possess a significant protective effect by lowering the serum alanine and aspartate aminoteansferase (AST and ALT) and alkaline phosphatase (ALP). This hepatoprotective action was confirmed by histological observation, In addition, the pretreatment of LFE prevented the elevation of hepatic malondialdehyde (MDA) formation and the depletion of reduced glutathione (GSH) content and catalase activity in the liver of CC1₄-injected rats. The LFE also displayed hydroxide radical scavenging activity in a dose-dependent manner (IC50 = 83.6 μg/ml), as assayed by electron spin resonance (ESR) spin-trapping technique. Moreover, the expression of cytochrome P450 2E1 (CYP2E1) mRNA, as measured by reverse transcriptase-polymerase chain reaction (RT-PCR), was significantly decreased in the liver of LFE-pretreated rats when compared with that in the liver of control group. Based on these results, it was suggested that the hepatoprotective effects of the LFE may be related to antioxidant effects and regulation of CYP2E1 gene expression.

• Biomedical Science Letters
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• v.15 no.1
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• pp.97-99
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• 2009

Geldanamycin is a benzoquinone ansamycin antibiotic that binds to cytosol HSP90 (Heat Shock Protein 90) and changes its biological function. HSP90 is involved in the intracellular important roles for the regulation of the cell cycle, cell growth, cell survival, apoptosis, angiogenesis and oncogenesis. To identify genes expressed during geldanamycin treatment against neurons of rats (PC12 cells), DNA microarray method was used. We have isolated 2 gene groups (up-or down-regulated genes) which are geldanamycin differentially expressed in neurons. Granzyme B is the gene most significantly increased among 204 up-regulated genes (more than 2 fold over-expression) and Chemokine (C-C motif) ligand 20 is the gene most dramatically decreased among 491 down-regulated genes (more than 2 fold down-expression). The gene increased expression of Cxc110, Cyp11a1, Gadd45a, Gja1, Gpx2, Ifua4, Inpp5e, Sox4, and Stip1 are involved stress-response gene, and Cryab, Dnaja1, Hspa1a, Hspa8, Hspca, Hspcb, Hspd1, Hspd1, and Hsph1 are strongly associated with protein folding. Cell cycle associated genes (Bc13, Brca2, Ccnf, Cdk2, Ddit3, Dusp6, E2f1, Illa, and Junb) and inflammatory response associated genes (Cc12, Cc120, Cxc12, Il23a, Nos2, Nppb, Tgfb1, Tlr2, and Tnt) are down-regulated more than 2 times by geldanamycin treatment. We found that geldanamycin is related to expression of many genes associated with stress response, protein folding, cell cycle, and inflammation by DNA microarray analysis. Further experimental molecular studies will be needed to figure out the exact biological function of various genes described above and the physiological change of neuronal cells by geldanamycin. The resulting data will give the one of the good clues for understanding of geldanamycin under molecular level in the neurons.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.6
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• pp.767-774
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• 2011

Defatted green tea seed was extracted with 100% ethanol for 4 hr and then fractionated with petroleum ether, ethyl acetate and butanol. The ethanol and butanol extracts showed greater increases in antiproliferation potential against liver cancer cells than petroleum ether, ethyl acetate, $H_2O$, and hot water extracts did. Thus, this study was carried out to investigate the anti-proliferative actions of defatted green tea seed ethanol extract (DGTSE) in HepG2 cancer cells. The DGTSE contained catechins including EGC ($1039.1{\pm}15.2\;g/g$), tannic acid ($683.5{\pm}17.61\;{\mu}g/g$), EC ($62.4{\pm}5.00\;{\mu}g/g$), ECG ($24.4{\pm}7.81\;{\mu}g/g$), EGCG ($20.9{\pm}0.96\;{\mu}g/g$) and gallic acid ($2.4{\pm}0.68\;{\mu}g/g$), but caffeic acid was not detected when analyzed by HPLC. The anti-proliferation effect of DGTSE toward HepG2 cells was 83.13% when treated at $10\;{\mu}g$/mL, of DGTSE, offering an $IC_{50}$ of $6.58\;{\mu}g$/mL. DGTSE decreased CYP1A1 and CYP1A2 protein expressions in a dose-dependent manner. Quinone reductase and antioxidant response element (ARE)-luciferase activities were increased about 2.6 and 1.94-fold at a concentration of $20\;{\mu}g$/mL compared to a control group, respectively. Enhancement of phase II enzyme activity by DGTSE was shown to be mediated via interaction with ARE sequences in genes encoding the phase enzymes. DGTSE significantly (p<0.05) suppressed prostaglandin $E_2$ level, tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) protein expressions, and NF${\kappa}$B translocation, but did not affected nitric oxide production. From the above results, it is concluded that DGTSE may ameliorate tumor and inflammatory reactions through the elevation of phase II enzyme activities and suppression of NF${\kappa}$B translocation and TNF-${\alpha}$ protein expressions, which support the cancer cell anti-proliferative effects of DGTSE in HepG2 cells.

• Korean Journal of Clinical Pharmacy
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• v.21 no.1
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• pp.36-38
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• 2011

We report an unusual case of respiratory depression and prolonged apnea after the second dose of 100-mg intravenous tramadol. Due to continuous pain at foley catheter keep site, intravenous tramadol was administered to the patient. Soon after the second dose of tramadol injection, the patient became apneic. The patient did not respond to verbal command and started exhibiting oxygen desaturation. The patient was quickly treated with 100% oxygen, and it took 4 hours for the spontaneous respiration to return to regular. This case report demonstrates that even two doses of tramadol administered intravenously may manifest as sudden and prolonged apnea. Respiratory depression with tramadol has been reported in patients with impaired renal functions and Cytochrome P(CYP) 2D6 gene duplication.

• Journal of Plant Biotechnology
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• v.46 no.3
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• pp.189-204
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• 2019

In this study, we analyzed the changes in glucosinolate content and gene expression in TO1000DH3 and Early big seedling upon methyl jasmonate (MeJA) treatment. Analysis of glucosinolate contents after MeJA treatment at $200{\mu}M$ concentration showed that the total glucosinolate content increased by 1.3-1.5 fold in TO1000DH3 and 1.3-3.8 fold in Early big compared to those before treatment. Aliphatic glucosinolates, progoitrin and gluconapin, were detected only in TO1000DH3, and the changes in the content of neoglucobrassicin were the greatest at 48 hours after MeJA treatment in TO1000DH3 and Early big. The transcriptomic analysis showed that transcripts involved in stress or defense reactions, or those related to growth were specifically expressed in TO1000DH3, while transcripts related to nucleosides or ATP biosynthesis were specifically expressed in Early big. GO analysis on transcripts with more than two-fold change in expression upon MeJA treatment, corresponding to 12,020 transcripts in TO1000DH3 and 13,510 transcripts in Early big, showed that the expression of transcripts that react to stimulus and chemical increased in TO1000DH3 and Early big, while those related to single-organism and ribosome synthesis decreased. In particular, the expression increased for all transcripts related to indole glucosinolate biosynthesis, which is associated with increase in glucobrassicin and neoglucobrassicin contents. Upon MeJA treatment, the expression of AOP3 (Bo9g006220, Bo9g006240), TGG1 (Bo14804s010) increased only in TO1000DH3, while the expression of Dof1.1 (Bo5g008360), UGT74C1 (Bo4g177540), and GSL-OH (Bo4g173560, Bo4g173550, Bo4g173530) increased specifically in Early big.

• Environmental Analysis Health and Toxicology
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• v.21 no.3 s.54
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• pp.291-299
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• 2006

The experiments investigated whether early exposure to testosterone propionate (TP) during prepuberty alters testis development in Sprague-Dawley male rats. We performed Hershberger assay using the stimulated weanling male rats by OECD protocols, cDNA microarray, and Western blot. TP was subcutaneously injected to uncastrated Sprague-Dawley male rat of 22 days old for 10 consecutive days at doses of 0.4, 0.8, 1.0, 1.2, 1.6 mg/kg per day. At necropsy, the following tissues were removed and weighed: combined testes, epididymides (Epi), Cowper's glands (COW), levator am, and bulbocavernosus muscles (LABC), seminal vesicles, together with coagulating gland (SV) and ventral prostate (VP). We found that TP increased the weights of Epi, VP, SV, COW, and LABC, while testis was decreased in a dose-dependent manner. In cDNA microarray analysis of testis, there were significant reductions in the expression of cytochrome P450 11A (CYP11A), the rate-limiting enzyme of steroidogenesis. Taken together these results, TP exposure before puberty in male rats may produce the delay in testis development by inhibiting the CYP11A gene expression.

• 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.

• BMB Reports
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• v.45 no.6
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• pp.331-336
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• 2012

The retinoid-related orphan nuclear receptor gamma ($ROR{\gamma}$) plays critical roles in regulation of development, immunity and metabolism. As transcription factor usually forms a protein complex to function, thus capturing and dissecting of the $ROR{\gamma}$ protein complex will be helpful for exploring the mechanisms underlying those functions. After construction of the recombinant tandem affinity purification (TAP) plasmid, pMSCVpuro $ROR{\gamma}$-CTAP(SG), the nuclear localization of $ROR{\gamma}$-CTAP(SG) fusion protein was verified. Following isolation of $ROR{\gamma}$ protein complex by TAP strategy, seven candidate interacting proteins were identified. Finally, the heat shock protein 90 (HSP90) and receptor-interacting protein 140 (RIP140) were confirmed to interplay with $ROR{\gamma}$ by co-immunoprecipitation. Interference of HSP90 or/and RIP140 genes resulted in dramatically decreased expression of CYP2C8 gene, the $ROR{\gamma}$ target gene. Data from this study demonstrate that HSP90 and RIP140 proteins interact with $ROR{\gamma}$ protein in a complex format and function as co-activators in the $ROR{\gamma}$-mediated regulatory processes of HepG2 cells.

• Journal of Animal Science and Technology
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• v.63 no.6
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• pp.1247-1264
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• 2021

Anabolic steroids are frequently used to increase the growth rate of meat-producing animals. Exposure to an anabolic-androgenic steroid, nandrolone decanoate (ND), is associated with expressional reduction of testicular steroidogenic enzymes. However, the effect of withdrawal of ND exposure on the expression of these testicular molecules has not been thoroughly explored. The current research investigated expression changes of testicular steroidogenic enzymes in rats at several recovery periods (2, 6, and 12 weeks) after the stop of ND treatment with different doses (2 and 10 mg/kg body weight) for 12 weeks. Body and testis weights were recorded, and transcript levels of molecules were determined by quantitative real-time polymerase chain reaction (PCR). The immunohistochemistry was used to examine the changes of immuno-intensities of molecules. At 6 and 12 weeks of the recovery period, the 10 mg/kg ND-treated rats were lighter than other experimental groups. The interstitial compartment vanished by ND treatment filled up as the recovery period became longer. The expression of steroidogenic acute regulatory protein was returned to the control level at 12 weeks of the recovery period. Expression levels of cytochrome P450 side-chain cleavage and 17a-hydroxylase were increased in 2 mg/kg ND-treated group at 6 weeks of the recovery period, and transcript levels of these molecules in 2 and 10 mg/kg ND-treated groups at 12 weeks of the recovery period were significantly lower than the control. Expression levels of 3β-hydroxysteroid dehydrogenase (HSD) type I and 17β-HSD type 3 in 2 mg/kg ND-treated group were comparable with those of control at 12 weeks of the recovery period, but not in 10 mg/kg ND-treated group. Expression of cytochrome P450 aromatase (Cyp19) was reverted to the control level at 2 weeks of the recovery period. Except for Cyp19, there was a visible increase of immuno-staining intensity of other testicular steroidogenic enzymes in the Leydig cells as the recovery period progressed. This research has demonstrated that the cease of ND administration could restore the expression of testicular steroidogenic enzymes close to the normal level. Nevertheless, a relatively long recovery period, compared to the ND-exposure period would be required to retrieve normal expression levels of testicular steroidogenic enzymes.