• Title/Summary/Keyword: Depletion effect

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Differential Inhibition of $MPP^+$- or 6-Hydroxydopamine-induced Cell Viability Loss in PC12 Cells by Trifluoperazine and W-7

  • Lee, Chung-Soo
    • The Korean Journal of Physiology and Pharmacology
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    • v.9 no.4
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    • pp.247-253
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    • 2005
  • The present study assessed the effect of calmodulin antagonists trifluoperazine and W-7 against the cytotoxicity of $MPP^+$ and 6-bydroxydoparnine (6-OHDA) in relation to the mitochondrial dysfunction and cell death in PC12 cells. Trifluoperazine (an inhibitor of the mitochondrial permeability transition and calmodulin antagonist) and W-7 (a specific calmodulin antagonist) significantly attenuated the $MPP^+-induced$ cell viability loss in PC12 cells with a maximum inhibition at $0.5{\sim}1{\mu}M$; beyond these concentrations the inhibitory effect declined. Both compounds at this concentration range did not cause cell death significantly. In contrast to $MPP^+$, the trifluoperazine and W-7 did not depress the cytotoxic effect of 6-OHDA. Addition of trifluoperazine and W-7 inhibited the cytosolic accumulation of cytochrome c and caspase-3 activation in PC12 cells treated with $MPP^+$ and attenuated the formation of reactive oxygen species and the depletion of GSH, whereas both compounds did not reduce the effect of 6-OHDA. The results show that trifluoperazine and W-7 may attenuate the cytotoxicity of $MPP^+$ by inhibition of the mitochondrial permeability transition and calmodulin. Meanwhile, the cytotoxic effect of 6-OHDA seems to be mediated by the actions, which are different from $MPP^+$.

Antibacterial Effect of Amentoflavone and Its Synergistic Effect with Antibiotics

  • Hwang, Ji Hong;Choi, Hyemin;Woo, Eun-Rhan;Lee, Dong Gun
    • Journal of Microbiology and Biotechnology
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    • v.23 no.7
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    • pp.953-958
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    • 2013
  • Selaginella tamariscina is a traditional herb used in medicine. Phytochemical amentoflavone, a biflavonoid class of flavonoids, was isolated from the plant of Selaginella tamariscina. In this study, the antibacterial effects and combination effects of amentoflavone and conventional antibiotics such as ampicillin, cefotaxime, and chloramphenicol were investigated. These results showed that amentoflavone had a considerable antibacterial effect and synergistic interaction with antibiotics against various bacterial strains (fractional inhibitory concentration index ${\leq}$ 0.5), except for Streptococcus mutans. To study the mechanism(s) involved in the synergistic activities between amentoflavone and antibiotics, we detected hydroxyl radical formation using 3'-(p-hydroxyphenyl) fluorescein and measured the $NAD^+/NADH$ ratio by $NAD^+$ cycling assay. The results indicated that the formation of hydroxyl radical would be a cause of the synergistic effect and that this oxidative stress originated from a transient NADH depletion. This study suggests that amentoflavone synergizes with antibiotics and has potential as a therapeutic agent for antimicrobial chemotherapy.

The Effect of Salviae Radix on Oxidat-Inhibition of Phosphate Uptake in Renal Proximal Tubular Cells (단삼약침액(丹蔘藥鍼液)이 신장(腎臟) 근위세뇨관세포(近位細尿管細胞)에서 산화제(酸化劑)에 의한 인산(燐酸)의 이동억제(移動抑制)에 미치는 영향(影響))

  • Lee, Ho-Dong;Youn, Hyoun-Min;Jang, Kyung-Jeon;Song, Choon-Ho;Ahn, Chang-Beohm
    • Journal of Acupuncture Research
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    • v.17 no.3
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    • pp.208-218
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    • 2000
  • This study was undertaken to determine if Salviae Radix (SR) exerts protective effect against oxidant-induced inhibition of phosphate uptake in renal proximal tubular cells. Membrane transport function and cell death were evaluated by measuring phosphate uptake and trypan blue exclusion, respectively, in opossum kidney (OK) cells, an established proximal tubular cell line. $H_2O_2$ was used as a model oxidant. $H_2O_2$ inhibited the phosphate uptake in a dose-dependent manner over the concentration range of 0.1-0.5 mM. Similar fashion was observed in cell death. However, the phosphate uptake was more vulnerable to $H_2O_2$ than cell death, suggesting that $H_2O_2$-induced inhibition of phosphate uptake is not totally attributed to cell death. Decreasedphosphate uptake was associated with ATP depletion and inhibition of $Na^+$-pump activity as determined by direct inhibition of $N^+-K^+$-ATPase activity. When cells were treated with $H_2O_2$ in the presence of 0.05% SR, the inhibition of phosphate uptake and cell death induced by $H_2O_2$ was significantly attenuated. SR restored ATP depletion and decreased $Na^+-K^+$-ATPase activity, and this is likely responsible for the protective effect of SR on decreased phosphate uptake. The protective effect of SR was similar to the $H_2O_2$ scavenger catalase. SR reacts directly with $H_2O_2$ to reduce the effective concentration of the oxidant. The iron chelator deferoxamine prevented the inhibition of phosphate uptake and cell death induced by $H_2O_2$, suggesting that $H_2O_2$-induced cell injury is resulted from an iron-dependent mechanism. These results indicate that SR exerts the protective effect against $H_2O_2$-induced inhibition of phosphate uptake by reacting directly with $H_2O_2$ like the $H_2O_2$scavenger enzyme catalase, in OK cells. However, the underlying mechanism remains to be explored.

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Protective Effect of DA-9601, an Extract of Artemisiae Herba, against Naproxen-induced Gastric Damage in Arthritic Rats

  • Oh, Tae-Young;Ryu, Byong-Kweon;Ko, Jun-Il;Ahn, Byoung-Ok;Kim, Soon-Hoe;Kim, Won-Bae;Lee, Eun-Bang;Jin, Joo-Hyun;Hahm, Ki-Baik
    • Archives of Pharmacal Research
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    • v.20 no.5
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    • pp.414-419
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    • 1997
  • Gastrointestinal irritation is the most frequent adverse effect in patients chronically taking nonsteroidal antiinflammatory drugs (NSAIDs) for the treatment of arthritic conditions. Gastroprotective effect of DA-9601, a new antiulcer agent from Artemisiae Herba extract, against NSAID was evaluated in a rat model of arthritis that is similar in many aspects to human rheumatoid arthritis. Daily oral dosing of naproxen (30 mg/kg), one of the most commonly used NSAID, induced apparent gastric lesions as well as a significant decrease in mucosal prostagiandin $E_2;(PGE_2)$ and prostagiandin F_${1{\alpha}}$$(PGF_{1{\alpha}})$ levels. Coadministration of DA-9601 prevents naproxen-induced mucosal injury and depletion of prostaglandins, in a dose-related manner. DA-9601 did not alter the antiinflammatory or analgesic effect of naproxen. The present results suggest that DA-9601 may be useful as a mucoprotectant against NSAIDs in clinical practice.

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Protective Effect of R. palmatum on 1-Methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP)-induced Neurotoxicity in Mice (생쥐의 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-유도 신경독성에 대한 대황의 보호효과)

  • 이형철;김대근;조원준;황석연;이영구;김명동;전병훈
    • YAKHAK HOEJI
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    • v.46 no.6
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    • pp.433-440
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    • 2002
  • The protective efficacy of Rheum palmatum water extract on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism was studied in C57BL/6 mice. In order to demonstrate neuroprotective effect of R. palmatum extract, animals were administered intraperitoneally with the water extract (100 or 200 mg/kg/day) for 14 days, and MPTP (10 mg/kg/day) was injected subcutaneously into the mice for the first 6 consecutive days from the beginning 1 hr before R. palmatum extract treatment. All animals were measured the several neurobiochemical markers such as dopamine level and monoamine oxidase B (MAO-B) activity in various regions of brain. The treatment of mice with R. palmatum extract was confirmed recovery effect on MAO-B activity in the cerebellum and the cerebral cortex. R. palmatum extract was attenuated the MPTP-induced depletion of substantia nigra dopamine. The contents of MDA, a marker of lipid peroxidation, in brain tissues (cerebellum and cerebral cortex mitochondria) were decreased significantly by R. palmatum extract. These results suggest that R. palmatum water extract plays an effective role in attenuating MPTP-induced neurotoxicity in mice. This protective effect of R. palmatum might be estimated the result from the inhibitory activity on monoamine oxidase B and the enhancement of antioxidant activity.

Effect of Baicalein on t-Butylhydroperoxide-Induced Cell Injury in Renal Tubular Epithelial Cells

  • Soon-Bee Jung
    • Biomedical Science Letters
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    • v.9 no.4
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    • pp.189-193
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    • 2003
  • This study was undertaken to investigate the effect of baicalein, a major flavone component of Scutellaria balicalensis Georgi, on oxidant-induced cell injury in renal epithelial cells. Opossum kidney cells, an established proximal tubular epithelial cells, were used as a cell model of renal epithelial cells and t-butylhydroperoxide (tBHP) as an oxidant drug model. Cell viability was measured by MTT assay and lipid peroxidation was estimated by measuring the content of malondialdehyde, a product of lipid peroxidation. Exposure of cells to tBHP caused cell death and its effect was dose-dependent over concentration range of 0.1~1.0 mM. When cells were exposed to tBHP in the presence of various concentrations (0.1~10 $\mu$M) of baicalein, tBHP-induced cell death was prevented with a manner dependent of baicalein concentration. tBHP induced A TP depletion, which was significantly prevented by baicalein. Similarly, tBHP-induced DNA damage was prevented by baicalein. tBHP produced a marked increase in lipid peroxidation and its effect was completely inhibited by baicalein. These results indue ate that tBHP induces cell injury through a lipid peroxidation-dependent mechanism in renal epithelial cells, and baicalein prevented oxidant-induced cell injury via antioxidant action inhibiting lipid peroxidation. In addition, these results suggest that baicalein may be a candidate for development of drugs which are effective in preventing and treating renal diseases.

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Protective Effects of Houttuynia cordata Thunb on Carbon Tetrachloride-induced Hepatotoxicity in Rats (어성초 분획물이 사염화탄소로 유발된 흰쥐의 간손상에 대한 보호효과)

  • Kim, Ok-Kyung
    • Korean Journal of Pharmacognosy
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    • v.33 no.4 s.131
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    • pp.324-331
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    • 2002
  • This study was performed to investigate the protective effect of Houttuynia cordata Thunb on hepatotoxicity in carbon tetrachloride$(CCI_4)$ intoxicated rats. The examined effects hexane, chloroform, butanol and water fractions prepared from the Houttuynia cordata Thunb methanol exlract and rats were administrated with those orally once a day for successive 6 days, fellowed by treaoent with $CCl_4$ on the sixth day. After 6 days, the activities of aminotransferase, alkalinephosphatase, ${\gamma}-glutamyl$ transpeptidase, lactate dehydrogenase and contents of triglyceride, hepatic lipid peroxide in butanol fraction pretreated rats were significantly decreased compared to the only $CCl_4$ treated rats, also depletion glutathione content induced by treatment with $CCl_4$ was prevented by butanol fraction pretreated rats. In addition, activities of hepatic superoxide dismutase, catalase, glutathione peroxidase in butanol fiaction pretreated rats were significantly decreased compared to the only $CCl_4$ treated rats, but the activity of hepatic glutathione-S-transferase was not significantly effect. These results suggest that butanol fiuction of Houttuynia cordata Thunb methanol extract have potent hepatoprotective effect against carbon tetrachloride intoxicated rats.

Effect of Pyunggangaeuljihyul-tang (Pinggankaiyuzhixue-tang) on Toxic Agent Induced Liver Cell Damage (평간개울지혈탕이 독성약물에 의한 간조직 손상에 미치는 영향)

  • 오세광;김원일;김우환
    • The Journal of Korean Medicine
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    • v.24 no.3
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    • pp.96-107
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    • 2003
  • Objective : This study was undertaken to determine if Pyunggangaeuljihyul-tang (Pinggankaiyuzhixue-tang, PG) has a protective effect against cell injury induced by various toxic agents in rabbit liver, Methods : Cell injury in vitro was estimated by measuring lactate dehydrogenase (LDH), and that in vivo was estimated by measuring alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in serum. Lipid peroxidation was examined by measuring malondialdehyde, a product of lipid per oxidation. Results : PG prevented the LDH release by $CCl_4$, mercury, menadione, and tert-butyl hydroperoxide treatment in vitro in liver slices. The extent of protection by 2% PG was similar to that of $10{\mu\textrm{M}}$ N,N'-diphenyl-p-phenylenedianline, a potent antioxidant, in tert-butyl hydroperoxide-induced LDH release. PG also prevented lipid peroxidation and depletion of cellular ATP induced by Hg. Hg causes motphological changes including cell necrosis and its effect was significantly prevented by PG. When rats were treated intraperitoneatly with 0.5 ml/kg of $CCl_4$, serum alanine aminotransferase and aspartate aminotransferase activities were increased compared with the control, which was significantly inhibited by pretreatment of PG. PG also prevented reduction in GSH and lipid peroxidation induced by $CCl_4$ Conclusion : These results suggest that PG exerts aprotective effect against various toxic agents by its antioxidant action in liver tissues. Thus, PG may be used in prevention and treatment of drug-induced liver cell injury. However, the precise mechanisms of PG protection remain to be determined.

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Effect of Scutellaria baicalensis Georgi Extract on Oxidant-Induced Inhibition of Organic Cation in Rabbit Renal Cortical Slices (황금약침액(黃芩藥鍼液)이 가토(家兎)의 신피질절편(腎皮質切片)에서 Oxidant로 유발된 유기양이온의 이동장애에 미치는 영향(影響))

  • Son, In-suk;Cho, Tae-sung;Kwon, Hae-yon;Jo, Mi-hyeong;Youn, Hyoun-min;Jang, Kyung-jeon;Song, Choon-ho;Abn, Chang-beohm
    • Journal of Acupuncture Research
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    • v.19 no.2
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    • pp.211-220
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    • 2002
  • Objective : This study was undertaken to determine whether Scutellaria baicalensis Georgi extract (SbG) 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 tetraethylammonium (TEA) uptake in rabbit renal cortical slices. The slices were treated with 0.2 mM tBHP for 60 min at $37^{\circ}C$. tBl-IP caused an inhibition in TEA uptake by renal cortical slices. Such an effect was accompanied by depressed Na+-K+-ATPase activity and ATP depletion. Result : SbG prevented tBHP-induced inhibition of TEA uptake in a dose-dependent manner at the concentration ranges of 0.05-0.1%. SbG also prevented H2O2-induced reduction in TEA uptake. tBHP-induced inhibition of Na+-K+-ATPase activity and ATP depletion were significantly prevented by 0.05% SbG. Oxidants increased LDH release, which was blocked by SbG. Oxidants 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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The Changes of UV-B Radiation at the Surface due to Stratospheric Aerosols (성층권 에어로졸에 의한 지표면 UV-B 복사량 변동)

  • Jai-Ho Oh;Joon-Hee Jung;Jeong-Woo Kim
    • International Union of Geodesy and Geophysics Korean Journal of Geophysical Research
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    • v.21 no.1
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    • pp.31-46
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    • 1993
  • A radiative transfer model with two-stream/delta-Eddington approximation has been developed to calculate the vertical distributions of atmospheric heating rates and radiative fluxes. The performance of the model has been evaluated by comparison with the results of ICRCCM (Intercomparison of radiative codes in climate models). It has been demonstrated that the presented model has a capability to calculate the solar radiation not only accurately but also economically. The characteristics of ultraviolet-B radiation (UV-B; 280-320nm) are examined by comparison of relation between the flux at the top of atmosphere and that at the surface. The relation of UV-B is quadratic due to the strong ozone absorption in this band. Also, the dependence of the UV-B radiation on the stratospheric ozone depletion and stratospheric aerosol haze due to volcanic eruption on the stratospheric ozone depletion and stratospheric aerosol haze due to volcanic eruption has been tested with various solar zenith angles. The surface UV-B increases as the solar zenith angle increases. The existence of stratospheric aerosols causes an increase in the planetary albedo due to the aerosols' backscattering. The planetary albedo with aerosol's effect has been increases as the solar zenith angle is not sensitive. It may be caused by the fact that the aerosols' scattering effect becomes saturated with the relatively long path length in a large solar zenith angle. Finally, the regional impact of stratospheric aerosols due to volcanic eruption on the intensity of UV-B radiation at the surface has been estimated. A direct effect is that the flux is diminished at the low latitudes, while it is enhanced in the high latitudes by the aerosols' photon trap or twilight effect. In the high latitudes, both aerosols' scattering and ozone absorption have strong and opposite impacts to the surface UV-B radiation is located at the mid-latitudes during spring season in both hemispheres.

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