• The Korean Journal of Physiology and Pharmacology
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• v.5 no.4
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• pp.315-321
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• 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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.140-140
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• 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
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• v.33 no.5
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• pp.396-401
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• 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
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• v.22 no.3
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• pp.217-224
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• 2004

Purpose: It is well known that the radiosensitivity of tumor cells can be significantly reduced under hypoxic conditions. Hypoxia-inducible factor-1 $\alpha$ (HIF-1 $\alpha$) plays a pivotal role in the essential adaptive responses to hypoxia. Therefore this study investigated the relationship between HIF-1 $\alpha$ expression and radiosensitivity. M Mouse hepatoma cell line hepafcic7 and HIF-1 $\beta$-deficient mutant cell line hepa1C4 were used to analyze the role of HIF-1 a. on radiosensitivity. These cells were exposed for 6 h to desferrioxamine (DFX) before radiation. HIF-1$\alpha$. expression was examined by Western blot. Apoptosis was assessed by DNA fragmentation, propidium iodide staining, and apoptotic cell death detection ELISA kit. Radiation sensitivity was determined using MTT assay. The radiobioiogical parameters, surviving fractions at 2 Gy and 8 Gy, and mean inactivation dose (MID) from the linear-quadratic model were used to assess radiation sensitivity in the statistical analyses. Results: The expression of HIF-1 $\alpha$. was Increased, whereas apoptosis was decreased, by radiation In the presence of DFX In hepal cl c7, but not In hepal C4. The radlosensitivity of hepal C4 cells was not significantly affected by DFX treatment. The radiosensitivlty of hepal cl c7 cells was significantly decreased in the presence of DFX Conclusion: The expression of HIF-1 w by hypoxia-mimic agent DFX reduced apoptosls and radiosensitlvity in mouse hepatoma cell line hepafclc7. These results suggested that HIF-1 u could be Induced by irradiation in hypoxic ceils of tumor masses, and that this mlght Increase radioresistance in hypoxic cells.

• The Journal of Korean Medicine
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• v.26 no.4
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• pp.1-11
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• 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
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• v.18 no.3
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• pp.139-143
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• 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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.114-114
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• 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
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• v.42 no.2
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• pp.123-127
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• 1999

Iron is an essential nutrient but potentially toxic element in human. To identify the effects of iron on the gene expression of mammalian cell, we have isolated several genes that are regulated by iron using the RNA differential display method. RNAs were isolated from HeLa cells treated with iron supplement or iron chelator. A total of 24 genes were isolated and of these, four genes were identified by DNA sequencing and northern blot.

• Toxicological Research
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• v.14 no.4
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• pp.541-545
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• 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
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• v.14 no.2
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• pp.399-414
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• 1997

There are several factors concerning to anemia in chronic renal failure patients. But when rHuEPO is used, most of these factors can be overcome, and the levels of hemoglobin are increased. However, about 10% of the renal failure patients represent rHuEPO-resistant anemia eventhough high dosage of rHuEPO. For these cases, desferrioxamine can be applied to correct rHuEPO resistnacy, and many mechanism of DFO are arguing. So we are going to know whether DFO can be applied to correct anemia of the such patients, how long its effect can be continued. The seven pateients as experimental group(DFO+EPO) who represent refractoriness to rHuEPO and the other seven patients as control group(EPO) were included. Experimental group had lower than 9 g/dL of hemoglobin levels despite high rHuEPO dosage (more than 4000U/Wk) and showed normocytic normochromic anemia. There were no definitve causes of anemia such as hemorrhage or iron deficiency. Control group patients had similar characteristics in age, mean dialysis duration but showed adequate response to rHuEPO. DFO was administered to experimental group for 8 weeks along with rHuEPO(the rHuEPO individual mean dosage had been determined by mean dosage of the previous 6 months. Total mean dosage; 123.5 U/Kg/Wk). After 8 weeks of DFO administration, the hemoglobin and rHuEPO dosage levels were checked for 15 consecutive months. It should be noted that the patients determined their own rHuEPO dosage levels according to hemoglobin levels and economic status. In conrol group, rHuEPO was administered by the same method used in experimental group without DFO through the same period. Fifteen months of observation period after DFO trial were divided as Time I(7 months after DFO trial) and Time II(8 months after Time I). The results are as follows: Before DFO trial, mean hemoglobin level of experimental group was 7.8 g/dL, which is similar level(p>0.05) to control group(mean Hb; 8.2 g/dL). But in experimental group, significantly(p<0.05) higher dosages of rHuEPO(mean; 123.5 U/Kg/Wk) than control group (mean; 41.6 U/Kg/Wk) had been used. It means resistancy to rHuEPO of experimental group. But after DFO trial, the hemoglobin levels of the experimental group were increased significantly(p<0.05), and these effect were continued to Time II.(Time I; mean 8.6g/dL, Time II; mean 8.6g/dL) The effects of DFO to hemoglobin were continued for 15 months after DFO trial with similar degree through Time I, Time II. Also, rHuEPO dosages used in the experimental group were decreased to similar levels of the control group after DFO trial and these effect were also continued for 15 months(Time I; mean 48.1 U/Kg/Wk. Time II; mean 51.8 U/Kg/Wk). In the same period, hemoglobin levels and rHuEPO dosages used in the control group were not changed significantly. Notibly, hemoglobin increment and rHuEPO usage decrement in experimental group were showed maxilly in the 1st month after DFO trial. That is, after the use of DFO, erythopoiesis was enhanced with a reduced rHuEPO dosage. So we think rHuEPO reisistancy can be overcome by DFO therapy. In conclusion, the DFO can improve the anemia caused by chronic renal failure at least over 1 year, and hence, can reduce the dosage of rHuEPO for anemia correction. Additional studies in order to determine the mechanism of DFO on erythropoiesis and careful attention to potential side effects of DFO will be needed.