• The Korean Journal of Physiology and Pharmacology
• /
• 제5권4호
• /
• pp.315-321
• /
• 2001

This study was aimed to evaluate the effects of quercetin and desferrioxamine on the development of the reflux esophagitis induced surgically, on gastric secretion and on lipid peroxidation which is a marker of oxidative stress. Omeprazole was used as a positive control drug. Omeprazole significantly and dose-dependently prevented the development of reflux esophagitis, but quercetin or desferrioxamine prevented only at high dose. Omeprazole significantly and dose-dependently inhibited the gastric acid secretion (gastric volume, pH and acid output), but quercetin or desferrioxamine did not inhibit. Malonyldialdehyde content, the end product of lipid peroxidation, increased significantly after the induction of reflux esophagitis. Omeprazole prevented lipid peroxidation. Quercetin and desferrioxamine inhibited the lipid peroxidation independent of their actions on gastric secretion. This result indicates that omeprazole confirmed preventing effect of rat reflux esophagitis, but quercetin and desferrioxamine inhibited esophagitis by reduction of lipid peroxidation irrespective of gastric acid secretion.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
• /
• pp.140-140
• /
• 1998

The aim of this study was to find out the effect of hypoxic condition on the regulation of cyplal gene expression. pcyplal-Luc construct was cloned and transfected into Hepa I cells. When Hepa-I cells containing pcyplal-Luc were treated by DFO (desferrioxamine) which is iron-chelating agent, the stimulatory effect of luciferase by TCDD was decreased. This inhibitory effect of desferrioxamine on the luciferase activity was dose dependent and abolished by concomitant treatment with N$\^$G/-nitro-ι-arginine. And when cobalt chloride which is known as a hypoxia inducing chemical was administrated, the stimulatory effect of luciferase by TCDD was also decreased. This inhibitory effect of cobalt chloride on the luciferase activity was dose dependent and abolished by concomitant treatment with N$\^$G/-nitro-ι-arginine. These data showed that hypoxic condition down regulates cyplal gene expression and this might be through nitric oxide action.

• BMB Reports
• /
• 제33권5호
• /
• pp.396-401
• /
• 2000

A differential display method is used to identify novel genes whose expression is affected by treatment with ferric ammonium citrate (FAC) or desferrioxamine (DFO), an iron chelating agent in the human hepatoblastoma cell line (HepG2). These chemicals are known to deplete or increase the intracellular concentration of iron, respectively. Initially, we isolated seventeen genes whose expressions are down- or up regulated by the treatment of the chemicals, as well as their four differentially expressed genes that are designated as clone-1, -2, -3, and -4. These are further characterized by cDNA sequencing and Northern blot analysis. Through the cDNA sequencing, as well as comparing them to genes published using the NCBI BLAST program, we identified the sequence of the clone-1 that is up-regulated by the treatment of DFO. It is identical to the human insulin-like growth factor binding protein-1 (IGFBP-1). This suggests that the IGFBP-1 gene in the HepG2 cell is up-regulated by an iron depletion condition. Also, the expression of the clone-3 and -4 is up-regulated by FAC treatment and their eDNA sequences are identical to the human ferritin-fight chain and human NADH-dehydrogenase, respectively. However, the sequence of the clone-2 has no significant homology to any other known gene. Therefore, we suggest that changes of the cellular iron level in the HepG2 cell affects the transcription of cellular genes. This includes human IGFBP-1, ferritin-fight chain, and NADH-dehydrogenase. Regulation of these gene expressions may have an important role in cellular functions that are related to cellular iron metabolism.

• Radiation Oncology Journal
• /
• 제22권3호
• /
• pp.217-224
• /
• 2004

목적: 저산소증은 방사선 감수성을 현저히 감소시키며, 이에 대한 적응 반응에서 hypoxia-inducible factor 1 $\alpha$(HIF-1 u$\alpha$가 중요한 역할을 하고 있다. HIF-1 $\alpha$의 발현과 방사선 감수성과의 상관 관계를 알아보고자 하였다. 대상 및 방법: 쥐의 간암 세포주인 hepalclc7 세포와 HIF-1 $\beta$가 결손되어 HIF-1 $\alpha$의 기능이 억제된 hepaIC4 세포를 사용했다 저산소 유사 물질인 desferrioxamine (DFX)을 전처치하고 6시간 뒤에 방사선조사를 하여 western blot으로 HIF-1 $\alpha$ 발현을 조사하였다. Apoptosis는 DNA 분절화, propidium iodide 핵염색, 그리고 apoptotic cell death detection ELISA kit를 이용하였다. MTT assay법으로 방사선 감수성을 측정하고 SF2$_{2}$ SF$_{8}$, 그리고 mean inactivation dose (MID)를 산출하여 통계적 분석을 하였다. 결과: Hepalclc7 세포에서는 DFX 전처치를 한 경우 방사선에 의해 HIF-1 $\alpha$의 발현이 증가했으나, hepalC4 세포 주에서는 변화가 없었다 Hepa1C4 세포의 방사선 감수성은 DFX처리에 따른 영향이 없었으나 hepalclc7 세포의 방사선 감수성은 DFX를 전처치했을 때 유의하게 감소하였다. 결론: 저산소 유사 물질인 DFX에 의해 유도된 HIF-1 $\alpha$가 쥐의 간암 세포주에서 apoptosis와 방사선 감수성을 감소시켰다 이러한 결과는 종괴내의 저산소 세포에서 방사선에 의해 HIF-1 $\alpha$가 유도되고 이로 인해 저산소 세포에서 방사선 감수성을 저하시키는 것으로 생각되었다.

• 대한한의학회지
• /
• 제26권4호
• /
• pp.1-11
• /
• 2005

This study was to investigate the effect of Danchunwhangagam(DCWGG) extract on the production of proinflammatory cytokines in peripheral blood mononuclear cells (PBMCs) from Cerebral infarction(CI) patients. Methods: We examined how the inhibition rate of tumor necrosis factor (TNF)-$\alpha$, interleukin(IL)-1$\alpha$, IL-1$\beta$, IL-6, and IL-8 productions in DCWGG pretreatment PBMCs culture supernatant in the lipopolysaccaride(LPS)- or desferrioxamine(DFX)treated cells compared to unstimulated cells. Results: DCWGG inhibited the productions of TNF-$\alpha$, IL-1$\alpha$, IL-1$\beta$, IL-6, and IL-8 induced by LPS in a dose-dependent manner. Conclusions: DCWGG might have regulatory effects on LPS or DFX-induced cytokine production, which might explain its beneficial effect in the treatment of CI.

• Environmental Engineering Research
• /
• 제18권3호
• /
• pp.139-143
• /
• 2013

This study was performed to examine the in vitro toxicities which are incurred due to the mobilization metals from standard reference material (SRM) 1648, fine ($PM_{2.5}$), and coarse ($PM_{10}$) particulate matter collected in Seoul metropolitan area. DNA single strand breaks of approximately 74% and 62% for $PM_{2.5}$ and for $PM_{10}$, respectively, were observed in the presence of chelator (EDTA or citrate)/reductant (ascorbate), as compared to the control by 2% without chelator or reductant. $PM_{2.5}$ induced about 40% more carbonyl formation with proteins in the presence of EDTA/ascorbate than $PM_{10}$. Therefore, more damage to biomolecules was incurred upon exposure to $PM_{2.5}$ than to $PM_{10}$. The treatment of a specific chelator, desferrioxamine, to the reaction mixture containing chelator plus reductant decreased the extent of damage to DNA to the level of the control, but did not substantially decrease the extent of damage to proteins. This suggests that different arrays of metals were involved in the oxidation of DNA and proteins.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
• /
• pp.114-114
• /
• 2001

Since hypoxia-inducible factor-lalpha (HIF-lalpha) and the arylhydrocarbon receptor (AhR) shared the AhR nuclear translocator (Arnt) for hypoxia- and AhR-mediated signaling, respectively, it was possible to establish the hypothesis that hypoxia could regulate Cyplal expression. In order to understand the mechanism of Cyplal gene expression, we demonstrated here that hypoxic agents such as cobalt chloride, desferrioxarnine, and picolinic acid reduced the TCDD induced Cyplal promoter activity based on the determination of luciferase activity in Hepa I cells transfected with pmCypla1-Luc. Also cobalt chloride inhibited the TCDD stimulated Cyplal mRNA level as well as EROD activities in both Hepa I and MCF-7 cells. Hypoxic agents such as cobalt chloride, picolinic acid, and desferrioxamine showed inhibition of luciferase activity that was induced by lnM TCDD treatment with dose dependent manner. Concomitant treatment of 150${\mu}$M ferrous sulfate with 1∼100${\mu}$M desferrioxarnine or 1∼100${\mu}$M picolinic acid recovered from the hypoxic agents-inhibited luciferase activity that was stimulated by TCDD. Reciprocally, the hypoxic agents down regulated TCDD induced Cyplal mRNA level and CYP1A1 enzyme activity in Hepa I cells.

• Applied Biological Chemistry
• /
• 제42권2호
• /
• pp.123-127
• /
• 1999

철은 사람에게 필수적인 영양소일 뿐 아니라 해로운 요소로도 작용한다. 이러한 철에 의해 진핵생물체에서 발현이 조절되는 유전자들을 밝히기 위해 철이 첨가되거나, 제거된 조건에서 배양된 HeLa세포로부터 RNA differential display 방법을 이용하여 발현 또는 억제되는 유전자들을 선별하였다. 모두 24개의 유전자가 선별되었으며, 염기배열 확인과 northern blot의 발현 확인과정을 거쳐 4개의 유전자들이 철에 의해 영향을 받는 것으로 확인되었다.

• Toxicological Research
• /
• 제14권4호
• /
• pp.541-545
• /
• 1998

This experiment carried out to compare the protective effects of some antioxidants to hydroxyl radicals in embryonic mouse whole brain tissue culture. The ICR mouse whole brain (13 embryonic day) was cultured in hydroxyl radical system in which radicals were generated by 20 mU / ml glucose oxidase (GO). In this experiment, to make ferrous iron from ferric iron, iron as an accelerator, and ascorbic acid as a reductant were used. For comparison of the protective effects to hydroxyl radicals, antioxidants such as desferrioxamine (DFX), laccase. water or ethanol extracts from Rhus Vemiciflua Stokes (RVS), and $\alpha$-tocopherol were used, because they relate to metal ion. The results of this experiment showed that all antioxidants protected effectively the cytotoxicity from hydroxyl radicals in the brain cultures. More than 70% of cell viabilities among different antioxidants was at 1 mM DFX, 1.43 $\mu\textrm{m}$ laccase, 12.5 $\mu\textrm{m}$ water extract, 12.5 $\mu\textrm{m}$ ethanol extract and 50 $\mu\textrm{m}$ $\alpha$-tocopherol individually, compared with 20 mU/ml GO alone. In comparison to the antioxidative activities of antioxidants, laccase and extracts from RVS showed strong antioxidative effects even at low concentration.

• Journal of Yeungnam Medical Science
• /
• 제14권2호
• /
• pp.399-414
• /
• 1997

신 부전 환자에게 발생하는 빈혈의 원인은 여러 가지가 있다. 그러나 rHuEPO를 투여할 시 이러한 요인들을 극복하고 빈혈을 교정할 수가 있다. 하지만 약 10%의 환자들에서는 고용량의 rHuEPO에도 불구하고 rHuEPO 저항성 빈혈을 나타낸다. 이러한 경우 DFO는 이러한 저항성을 극복할 수 있다고 하며, 이에 대한 기전은 아직 논란이 많다. 따라서 저자들은 DFO를 투여시 나타나는 여러 인자들을 고려해보고 기존의 보고보다 장기적인 관찰을 통하여 이러한 환자에게서 DFO가 빈혈을 교정할 수 있을지 여부를 알아보고 DFO가 rHuEPO 저항성 빈혈을 극복하는 기전을 추측해보고자 하였다. 영남대학교 의과대학 부속병원 투석실에서 투석을 시행하는 만성 신부전 환자 중 rHuEPO의 효과에 저항성을 나타내는 7명의 환자가 실험군(DFO+EPO)으로 정해지고, 다른 7명이 대조군으로 선정되었다. 실험군은 주당 4000 U의 고용량의 rHuEPO에도 불구하고 혈색소치가 9 g/dL이하 이며 출혈이나 철결핍성 빈혈같은 뚜렷한 원인 없이 정구성 정색소성 빈혈을 나타낸 환자들이었으며 대조군은 나이, 평균 투석 기간에 있어서 대조군과 차이를 보이지 않으며 rHuEPO에 비교적 적절한 반응을 보이는 환자들이었다. DFO는 8주간 rHuEPO와 함께 투여 되어 졌고 rHuEPO의 사용 용량은 지난 6개월의 평균 용량과 같게 투여 되었다(평균 사용 용량은 123.5 U/Kg/Wk). 8주간 DFO가 투여된 후 15 개월간 혈색소치와 rHuEPO 사용 용량을 추적하였다. 이 15개월간은 각 개인의 혈색소치와 경제 사정에 의해 rHuEPO의 용량이 결정지어 졌다. 대조군에서는 같은 기간 실험군에서와 같은 방법으로 rHuEPO가 투여되어 졌으나 DFO는 사용되지 않았다. DFO가 투여된 15 개월의 추적기간은 Time I(DFO투여후 7개월간)과 Time II(Time I 이후 8개월간)으로 나누었다. 성적은 다음과 같다: DFO 투여 전, 실험군의 평균 혈색소치는 대조군과(평균 8.2 g/dL) 같은 정도의(p>0.05) 수준인 7.8 g/dL 이었다. 하지만 rHuEPO의 사용 용량은 평균 123.5 U/Kg/Wk으로서 대조군의 그것(평균 41.6 U/Kg/Wk)보다 의미있게 많은(p<0.05) 용량을 사용하여 rHuEPO에 대한 저항성을 나타내었다. 하지만 DFO사용후 실험군에서 혈색소치는 의미있게 상승되었고(p<0.05) 이것은 Time II에 이르기까지 지속되었다(Time I; 평균 8.6 g/dL, Time II; 평균 8.6 g/dL). 즉, 혈색소치에 대한 DFO의 효과는 투여 후 15 개월간 Time I, Time II의 시기에 걸쳐 균등한 정도로 지속되었다. 또한 실험군에서 rHuEPO의 사용 용량은 DFO투여후 대조군과 유사한 수준으로 감소하였고 이것도 마찬가지로 15개월간 지속되었다(Time I; 평균 48.1 U/Kg/Wk. Time II; 평균 51.8 R/Kg/Wk. 한편, 같은 기간 대조군에서의 혈색소치와 rHuEPO사용 용량의 변화는 없었다. 특히, 실험군에서 혈색소치의 증가와 rHuEPO의 사용 용량의 감소는 DFO투여 후 1개월동안에 극대점을 이루었다. 즉, DFO 사용 후 감소된 rHuEPO사용 용량으로도 조혈 작용을 증강시킬 수 있었고 따라서 DFO를 사용함으로써 rHuEPO의 저항상을 극복할 수 있으리라고 생각된다. 보다 대규모의 실험과 잠재적으로 위험한 DFO의 부작용을 최소화 할 수 있는 적절한 용량과 투여 방법에 대한 연구가 더 필요하다고 사료된다.