• Title/Summary/Keyword: Inhibition dose

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The Effect of Juglandis Semen Extract Solution on Oxidant-Induced Alteration of Glutamate Uptake in Rabbit Brain Synaptosome (호도약침액(胡桃藥鍼液)이 가토(家兎) 뇌(腦)의 Synaptosome에서 Oxidant에 의한 물질이동계(物質移動系)의 장애(障碍)에 미치는 영향(影響))

  • Kim Tae-Kook;Youn Hyoun-Min;Jang Kyung-Jeon;Song Choon-Ho;Ahn Chang-Beohm
    • Korean Journal of Acupuncture
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    • v.17 no.1
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    • pp.179-190
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    • 2000
  • This study was undertaken to determine whether Juglandis semen extract solution (JLS solution) exerts protective effect against oxidant-induced inhibition of glutamate uptake by synaptosomes. Synaptosome was prepared from rabbit brain cortex. Glutamate uptake increased by incubation time during 10 minutes, which was significantly inhibited by 1mM t-buthylhydroperoxide(t-BHP). JLS solution prevented t-BHP-induced inhibition of glutamate uptake in a dose-dependent manner. t-BHP reduced glutamate uptake in dose-dependent fashion, which was significantly prevented by 2% JLS solution. t-BHP(1mM) and $ascorbate/Fe^{2+}(50/1{\mu}M)$ increased lipid peroxidation in synaptosomes by 5-fold, and it was significantly prevented by 2% JLS solution. $HgCl_2(0.1mM)$ inhibited glutamate uptake and increased lipid peroxidation. These changes were prevented by 2% JLS solution. Synaptosomal Na-K-ATPase activity was inhibited by t-BHP(1mM) and $H_2O_2(50mM)$, which was prevented by 2% JLS solution. The results indicate that JLS solution prevents oxidant-induced inhibition of glutamate by synaptosomes, and this may result from inhibition of lipid peroxidation induced by oxidants.

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Hydrogen Peroxide-induced Alterations in Na+-phosphate Cotransport in Renal Epithelial Cells

  • Jung, Soon-Hee
    • Korean Journal of Clinical Laboratory Science
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    • v.41 no.2
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    • pp.83-92
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    • 2009
  • This study was undertaken to examine the effect of oxidants on membrane transport function in renal epithelial cells. Hydrogen peroxide ($H_2O_2$) was used as a model oxidant and the membrane transport function was evaluated by measuring $Na^+$-dependent phosphate ($Na^+$-Pi) uptake in opossum kidney (OK) cells. $H_2O_2$ inhibited $Na^+$-Pi uptake in a dose-dependent manner. The oxidant also caused loss of cell viability in a dose-dependent fashion. However, the extent of inhibition of the uptake was larger than that in cell viability. $H_2O_2$ inhibited $Na^+$-dependent uptake without any effect on $Na^+$-independent uptake. $H_2O_2$-induced inhibition of $Na^+$-Pi uptake was prevented completely by catalase, dimethylthiourea, and deferoxamine, suggesting involvement of hydroxyl radical generated by an iron-dependent mechanism. In contrast, antioxidants Trolox, N,N'-diphenyl-p-phenylenediamine, and butylated hydroxyanisole did not affect the $H_2O_2$ inhibition. Kinetic analysis indicated that $H_2O_2$ decreased Vmax of $Na^+$-Pi uptake with no change in the Km value. Phosphonoformic acid binding assay did not show any difference between control and $H_2O_2$-treated cells. $H_2O_2$ also did not cause degradation of $Na^+$-Pi transporter protein. Reduction in $Na^+$-Pi uptake by $H_2O_2$ was associated with ATP depletion and direct inhibition of $Na^+$-$K^+$-ATPase activity. These results indicate that the effect of $H_2O_2$ on membrane transport function in OK cells is associated with reduction in functional $Na^+$-pump activity. In addition, the inhibitory effect of $H_2O_2$ was not associated with lipid peroxidation.

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Effect of Benzalkonium Chloride on Biogas Potential of Pig Slurry (Benzalkonium Chloride가 돈슬러리의 바이오가스 생성에 미치는 영향)

  • Park, H. R.;Choi, H. L.;Suresh, Arumuganainar
    • Journal of the Korea Organic Resources Recycling Association
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    • v.19 no.3
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    • pp.63-72
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    • 2011
  • Benzalkonium chloride is most widely used in S. Korea as a disinfectant in livestock husbandry. Inhibition of biogas potentials were investigated with three different doses of benzalkonium chloride in swine slurry. The system was operated at batch mode. The inhibition rates were 10%, 30~40% and >70% at the dose of 10ppm, 40ppm and 80ppm, respectively assuming it was zero percent in case of no dose. Enzymatic activities were analyzed to determine the enzymatic type which was inhibited by benzalkonium chloride. The acid phosphatase, alkaline phosphatase and protease were shown negatively correlated with biogas potential. Correlation of ${\alpha}$-glucosidase and biogas potentials was observed not high (p<0.01, r=-0.426) while benzalkonium chloride (r=-0.853, p<0.01) and acid phosphatase (p<0.01) with biogas potentials were significantly and negatively correlated. The effect of benzalkonium chloride on Escherichia coli were also evaluated by disc diffusion method. As increase of benzalkonium concentration, inhibition zone of anaerobic bacteria was extended. It revealed that benzalkonium chloride significantly deteriorated biogas potential through inhibition of acetogenic bacteria.

Experimental Study of Fraction of Citri Reticulatae Viride Pericarpium extract on the Brain Damage in Cerebral Ischemia (청파활성분획이 허혈성 뇌손상에 미치는 실험적 연구)

  • Rho Young Ho;Jeong Hyun Woo;Lee Won Suk
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.16 no.5
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    • pp.893-898
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    • 2002
  • Citri Reticulatae Viride Pericarpium extract(CRVP) have been used in oriental medicine for many centuries as a therapeutic agent for smoothing the liver and regulating the circulation of qi, and promoting digestion and removing stagnated food. The effects of CRVP on the inhibition of brain damage in cerebral ischemia is not known. Therefore, this Study was designed to investigate the cerebral protective effects of CRVP on the transient cerebral ischemia using modern techniques, and further to provide the possibility of scientification of oriental medicine. The size of cerebral infarct size was measured by morphometry, and brain edema was measured by morphometry and brain water content determination. The results were a$ follows ; 1. Water fraction of CRVP was reduced infect area of rats brain slices which were subjected to a transient cerebral ischemia in a dose-dependent manner. 2. Methylene chloride fraction and hexane fraction of CRVP was significantly reduced infarct area of rats brain slices which were subjected to a transient cerebral ischemia in a dose-dependent manner. 3. Methylene chloride fraction and hexane fraction of CRVP was significantly reduced infarct volume of rats brain which was subjected to a transient cerebral ischemia in a dose-dependent manner. 4. Methylene Chloride fraction and hexane fraction of CRVP was significantly decreased brain edema induced by a transient cerebral ischemia in a dose-dependent manner. 5. Methylene chloride fraction and hexane fraction of CRVP was significantly decreased brain water content of rats which were subjected to a transient cerebral ischemia. It is suggested that CRVP has an anti-ischemic effect through the inhibition of brain damage in a transient cerebral ischemia, and that in future further development of main effective constituent in CRVP can provide a novel therapeutic strategy for cerebral ischemia.

Inhibition of Cell Proliferation and Induction of Apoptosis by Diallyl Disulfide in Human Colon Cancer Cell lines (사람 대장암 세포주에서 Diallyl Disulfide의 세포증식억제 및 Apoptosis 유도 효과)

  • Kim Tae Myoung;Ryu Jae Myun;Kwon Hyun Jung;Woo Koan Sik;Jeong Heon Sang;Hong Jin Tae;Kim Dae Joong
    • Toxicological Research
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    • v.21 no.4
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    • pp.355-360
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    • 2005
  • Epidemiological and laboratory studies provide insight into the anti-carcinogenic potential of garlic and its constituent compounds. Garlic is appealing as an anti-carcinogenic agent due to its ability to induce apoptosis in vitro. Diallyl disulfide (DADS) is one of the major components of garlic that used to determine inhibition of cell proliferation and induced apoptosis in human colon cell lines. In this study, human colorectal cancer cell lines (LOVO, HCT-116, SW-480) were exposed to DADS. The inhibitory effects of DADS dose level more than $50\;{\mu}M$ in the cell viability of all cell lines. Cell growth activity inhibits of human colon cancer cell lines. The inhibitory effects of DADS dose level more than $25\~50\;{\mu}M$ in the cell growth using MTT assay. We found that DADS may have the apoptosis action (chromatin condensation, DNA fragmentation) using DAPI staining and increased the expression of caspase-3 at the dose level more than $100\;{\mu}M$, decreased the expression level of $\beta-catenin$ at dose dependent in the western blotting. We suggest that DADS may have a potential candidate as cancer chemopreventive agents.

Antimutagenic and Anticarcinogenic Effect of Methanol Extracts of Sweetpotato (Ipomea batata) Leaves

  • Kang, Hwan-Goo;Jeong, Sang-Hee;Cho, Joon-Hyoung
    • Toxicological Research
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    • v.26 no.1
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    • pp.29-35
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    • 2010
  • The present study was conducted to investigate the antimutagenic potential of the methanolic extract from the leaves of sweet potato (Ipomea batatas, IB) with the SOS chromotest (umu test) and Salmonella typhimurium TA 98 and TA 100. The anticarcinogenic effects were also studied by calculation of the $IC_{50}$ on human cancer cell lines and investigating the function of gap junction in rat liver epithelial cells. The IB extract inhibited dose-dependently the ${\beta}$-galactosidase activity induced spontaneously at concentration of more than 200 mg/ml in S. typhimurium TA 1535/pSK 1002, and decreased significantly (p < 0.01) the ${\beta}$-galactosidase activities induced by mutagen 6-chloro-9-[3-(2-chloroethylamino)proylamino]-2-methoxyacridine dihydrochloride (ICR) at dose of more than 0.4 mg/0.1 ml. The IB extract showed no effect on the spontaneous reversions of S. typhimurium TA 98 and 100 but benzo(${\alpha}$)pyrene (BaP)-stimulated reversions were decreased dose-dependently (p < 0.01) at the concentration of more than 100 mg/ml. The $IC_{50}$ value of stomach cancer cells was lower than that of normal rat liver epithelial cells, but the values of colon and uterine cancer cell lines were similar to those of normal rat liver epithelial cells. The transfer of dye through gap junctions was not affected by treatment of the IB extracts at any concentration during treatment periods. The simultaneously treatment of IB extract and 12-O-tetradecanoylphorbol-13-acetate (TPA) effectively prevented the inhibition of dye transfer induced by TPA 1 hour after treatment at all exposed concentrations. The number of gap junctions was significantly (p < 0.01) increased by the treatment with IB extract at concentrations of more than 40 ${\mu}g$/ml. The inhibition of the expression of gap junction proteins by TPA (0.01 ${\mu}g$/ml) was recovered dose dependently by the simultaneous treatment of IB extracts. Our data suggest that Ipomea batatas has antimutagenic and anticarcionogenic activity in vitro.

Effects of Gamioncheong-decoction Water-extract on Anti-inflammation, Anti-oxidation and Skin Whitening (가미온청음(加味溫淸飮) 추출물이 항염증, 항산화 및 미백에 미치는 효과)

  • Choi, You Jin;Roh, Jeong Du
    • Journal of Acupuncture Research
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    • v.32 no.3
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    • pp.117-126
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    • 2015
  • Objectives : This study was an analysis of the anti-inflammatory, anti-oxidative and skin whitening properties of Gamioncheong-decoctione(GMOCD) extract. Methods : GMOCD(96 g) and 2 L of distilled water were heated at $100^{\circ}C$ for four hours and then concentrated, frozen, freeze-dried, dissolved in distilled water and filtered. The following analysis was completed: cell cytotoxic effect using MTT assay, oxidative products of NO by griess assay, concentration of prostaglandin $E_2(PGE_2)$ by commercially competitive enzyme immunoassay, and cytokines($IL-1{\beta}$, IL-6 and TNF-${\alpha}$) by Bio-Plex$^{(R)}$ Suspension Array System's Bio-Plex Pro$^{TM}$ mouse cytokine, chemokine, and growth factor assay. Anti-oxidative effect was measured using the DPPH method and skin whitening effect using tyrosinase inhibition assay. Results : GMOCD water-extract did not show any toxicity at all doses and cell viability was more than 90 % at all doses. GMOCD water-extract significantly inhibited NO production at doses of 100, 200, $400{\mu}g/ml$, significantly inhibited $PGE_2$ production at doses of 200 and $400{\mu}g/ml$ and reduced the LPS-induced IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ production in a dose-dependent manner. $IL-1{\beta}$ production was significantly reduced at a dose of $400{\mu}g/ml$ and IL-6 production was significantly reduced at doses of 200 and $400{\mu}g/ml$. DPPH free radical scavenging capability had a skin whitening effect rate of more than 50%. Tyrosinase inhibition activity was apparent in a dose-dependent manner. Conclusions : This study suggests that GMOCD water-extract suppressed NO and $PGE_2$ production and inhibited cytokines($IL-1{\beta}$, IL-6 and TNF-${\alpha}$). GMOCD also improved DPPH free radical scavenging capability. GMOCD water-extract increased tyrosinase inhibitory activity in a dose-dependent manner but this was not a statistically significant result.

Low-dose metronomic doxorubicin inhibits mobilization and differentiation of endothelial progenitor cells through REDD1-mediated VEGFR-2 downregulation

  • Park, Minsik;Kim, Ji Yoon;Kim, Joohwan;Lee, Jeong-Hyung;Kwon, Young-Guen;Kim, Young-Myeong
    • BMB Reports
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    • v.54 no.9
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    • pp.470-475
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    • 2021
  • Low-dose metronomic chemotherapy has been introduced as a less toxic and effective strategy to inhibit tumor angiogenesis, but its anti-angiogenic mechanism on endothelial progenitor cells (EPCs) has not been fully elucidated. Here, we investigated the functional role of regulated in development and DNA damage response 1 (REDD1), an endogenous inhibitor of mTORC1, in low-dose doxorubicin (DOX)-mediated dysregulation of EPC functions. DOX treatment induced REDD1 expression in bone marrow mononuclear cells (BMMNCs) and subsequently reduced mTORC1-dependent translation of endothelial growth factor (VEGF) receptor (Vegfr)-2 mRNA, but not that of the mRNA transcripts for Vegfr-1, epidermal growth factor receptor, and insulin-like growth factor-1 receptor. This selective event was a risk factor for the inhibition of BMMNC differentiation into EPCs and their angiogenic responses to VEGF-A, but was not observed in Redd1-deficient BMMNCs. Low-dose metronomic DOX treatment reduced the mobilization of circulating EPCs in B16 melanoma-bearing wild-type but not Redd1-deficient mice. However, REDD1 overexpression inhibited the differentiation and mobilization of EPCs in both wild-type and Redd1-deficient mice. These data suggest that REDD1 is crucial for metronomic DOX-mediated EPC dysfunction through the translational repression of Vegfr-2 transcript, providing REDD1 as a potential therapeutic target for the inhibition of tumor angiogenesis and tumor progression.

Bacterial Reverse Mutation Test of CP pharmacopunture (세균을 이용한 CP 약침의 복귀돌연변이 시험)

  • Hwang, Ji Hye;Ku, Jaseung;Jung, Chul
    • The Journal of Korean Medicine
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    • v.41 no.3
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    • pp.55-65
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    • 2020
  • Objectives: This study aimed to evaluate the toxicity of CP pharmacopunture using bacterial reverse mutation test. Methods: To determine the mutagenic potential of CP pharmacopunture, histidine requiring Salmonella typhimurium (TA98, TA100, TA1535, and TA1537) and tryptophan requiring Escherichia coli (WP2uvrA, pKM101) strains were used. The negative (normal saline solution) and positive (Sodium azide, 2-Nitrofluorene, 2-Aminoanthracene, 9-Aminoacridine, and 4-Nitroquinoline N-oxide) control groups were used. To determine the dose levels of the main study, a dose range-finding study was conducted. Results: As a results of the dose range-finding study, the growth inhibition by CP pharmacopunture was not evident at any dose levels in the absence and presence of metabolic activation. As a results of the main study, the mean number of revertant colonies was less than twice when compared to the negative control values at all dose levels of the CP pharmacopuncture in the presence and absence of metabolic activation, showing no dose-related increase. In the positive control group, the number of revertant colonies was markedly increased by more than twice when compared to the negative control group. Conclusion: According to the results of this study, CP pharmacopunture did not show any signs of mutagenic potential.

Beneficial Effect of Scutellaria Balicalensis Georgi Extract ont-Buthylhydroperoxide-Induced Inhibition of Organic Cation in Rabbit Renal Cortical Slices (황금약침액(黃芩藥鍼液)이 토끼의 신장절편에서 t-BHP로 유발된 유기양이온의 이동장애에 미치는 영향(影響))

  • Jo, Mee-hyeong;Jang, Kyung-jeon
    • Journal of Acupuncture Research
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    • v.18 no.4
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    • pp.143-151
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    • 2001
  • Objective : This study was undertaken to determine whether Scutellaria balicalensis Georgi (SbG) extract exerts the protective effect against oxidant-induced alterations in organic cation transport in the renal proximal tubule. Methods : Organic cation transport was estimated by examining alterations in tetraethylammon - ium(TEA) uptake in rabbit renal cortical slices. The slices were treated with 0.2 mM tBHP for 60 min at $37^{\circ}C$. tBHP caused an inhibition in TEA uptake by renal cortical slices. Such an effect was accompanied by depressed Na+-K+-ATPase activity and ATP depletion. tBHP also induced a significant increase in LDH release. Results : SbG prevented tBHP-induced inhibition of TEA uptake in a dose-dependent manner at the concentration ranges of 0.05-0.1%. tBHP-induced inhibition of Na+-K+-ATPase activity and ATP depletion were significantly prevented by 0.05% SbG. tBHP-induced LDH release also was blocked by SbG. tBHP caused a significant increase in lipid peroxidation and its effect was prevented by SbG. Conclusion : These results suggest that SbG prevents oxidant-induced alterations in organic cation transport in rabbit renal cortical slices. Such protective effects of SbG may be attributed to inhibition of peroxidation of membrane lipid.

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