Ocular Manifestations of ß -Thalassemia Patients with the Use of Oral Iron Chelating Agents

Background: Ocular involvement in β-thalassemia major is very common. Iron chelators like Desferrioxamine and Deferiprone avoid systemic complications but chelate metals in retina. Objectives: 1.To study the relation of oral iron chelator (Deferiprone) on various ocular manifestations in β-thalassemia major patients. 2. To study the relation of serum ferritin with various ocular manifestations. Methods: 100β-thalassemia major patients out of those attending our thalassemia clinic were selected for the study as per our inclusion and exclusion criteria. They were divided into two major groups based on whether they were taking oral iron chelator (Deferiprone) or not. Detailed history, examination and investigations were done and recorded. Results: The study revealed that 52% of the patients had ocular involvement with 86.5% of them taking Deferiprone (p<0.0001), 13% had retinal pigment epithelium (RPE) degeneration with 92.3% of them on Deferiprone (p=0.003) and 18% had RPE mottling with 88.8% of them taking Deferiprone (p=0.001). Other ocular changes like lens opacity, disc hyperemia, best corrected visual acuity (BCVA) and venous tortuosity showed some difference between the two groups but that was insignificant. Further the study also showed that higher serum ferritin levels were significantly associated with ocular changes like decreased BCVA (p<0.001), RPE degeneration (p<0.001), RPE mottling (p<0.001) and venous tortuosity (p<0.025). Conclusion: Ocular changes in β-thalassemia major increases with greater duration of the disease and increased number of blood transfusions due to increased serum ferritin levels. Using iron chelators may reduce iron overload but they causechelator induced ocular involvement.

Current progress of iron metabolism and tumor development / 医学研究生学报

Iron is an essential nutrient that not only participates in cell oxidative phosphorylation, DNA synthesis and replication, but also regulates cancer associated genes through hypoxia-inducible factor (HIF).In the process of cancerization, cells change the way of iron metabolism resulting in a high consumption of iron.In this case, pathways of iron acquisition, efflux, storage and regulation are perturbed.Therefore, iron can significantly contribute to tumor growth, cell survival and metastasis.In this paper, we summarize the iron changes in cancer cells and the relationship between the changes and tumorigenesis.We also briefly state the potential problems of current clinical using iron chelating agents in oncotherapy.Targeting iron metabolic pathways may provide new tools for cancer prognosis and therapy.

Observation on the clinical effectiveness of deferasirox,deferiprone and desferrioxamine in the treatment of iron load in patients with thalassemia major / 中国综合临床

Objective To explore the clinical effectiveness of deferasirox, deferiprone and desferrioxamine in the treatment of iron overload in patients with thalassemia major.Methods Among the severe thalassemia patients with iron overload being diagnosis,treated and followed up in Guigang City People′s Hospital,fifty cases were tested by MRI T2 and were detected with cardiac and liver iron overload,the patients were selected and randomly divided into the deferoxamine treatment(DFO)group(18 case),deferiprone treatment(DFP)group(22 cases)and deferasirox treatment(DFX)group(10 case),The baseline data of the three groups were statistically analyzed.the serum ferritin(SF)value,the cardiac MRI T2 value and the liver MRI T2 value before and after treatment were measured.Results The patients completed the treatment,after 1 years of treatment,the serum SF value,cardiac and liver MRI T2 values of the patients were improved than those before the treatment(P<0.05); the differences in serum SF among the three groups were not statistically significant(F=3.089,P>0.05); the differences in liver MRI T2 value among the three groups were not statistically significant(F=0.131,P>0.05),There were significant differences in heart iron load MRI T2 values among the three groups((34.27 ± 6.30)ms vs.(23 ± 2.79)ms vs.(21.8 ± 2.20)ms,F=39.54,P<0.05) .Conclusion Deferoxamine,deferiprone and deferasirox can effectively alleviate the iron load in patients with thalassemia major.in terms of cardiac iron overload,the curative effects of deferiprone treatment in patients with thalassemia is superior than desferrioxamine and deferasirox treatment,it is worthy of clinical promotion.

Use of deferasirox, an iron chelator, to overcome imatinib resistance of chronic myeloid leukemia cells

BACKGROUND/AIMS: The treatment of chronic myeloid leukemia (CML) has achieved impressive success since the development of the Bcr-Abl tyrosine kinase inhibitor, imatinib mesylate. Nevertheless, resistance to imatinib has been observed, and a substantial number of patients need alternative treatment strategies. METHODS: We have evaluated the effects of deferasirox, an orally active iron chelator, and imatinib on K562 and KU812 human CML cell lines. Imatinib-resistant CML cell lines were created by exposing cells to gradually increasing concentrations of imatinib. RESULTS: Co-treatment of cells with deferasirox and imatinib induced a synergistic dose-dependent inhibition of proliferation of both CML cell lines. Cell cycle analysis showed an accumulation of cells in the subG1 phase. Western blot analysis of apoptotic proteins showed that co-treatment with deferasirox and imatinib induced an increased expression of apoptotic proteins. These tendencies were clearly identified in imatinib-resistant CML cell lines. The results also showed that co-treatment with deferasirox and imatinib reduced the expression of BcrAbl, phosphorylated Bcr-Abl, nuclear factor-kappaB (NF-kappaB) and beta-catenin. CONCLUSIONS: We observed synergistic effects of deferasirox and imatinib on both imatinib-resistant and imatinib-sensitive cell lines. These effects were due to induction of apoptosis and cell cycle arrest by down-regulated expression of NF-kappaB and beta-catenin levels. Based on these results, we suggest that a combination treatment of deferasirox and imatinib could be considered as an alternative treatment option for imatinib-resistant CML.

Disruption of iron homeostasis and relevant pharmacotherapies in Alzheimer's disease / 药学学报

Iron is the most abundant metal element to support the body's physiological activities and play crucial roles in the central nervous system. Iron homeostasis is under strict control in normal circumstances, and some diseases will occur once the homeostasis was disrupted. Numerous researches suggest that iron homeostasis disruptes in Alzheimer's disease (AD) and the homeostasis disruption interacts with AD's hallmarks. Dispute still exists on how iron plays a role in AD despite of the great number of researches. This article will focus on iron metabolism, normal function in the brain and recent therapies of AD based on iron chelation.

Anti-malarial effect of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one and green tea extract on erythrocyte-stage Plasmodium berghei in mice

Objective:To examine the efficacy of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) iron chelator and green tea extract (GTE) as anti-malarial activity in Plasmodium berghei (P. berghei ) infected mice. Methods:The CM1 (0–100 mg/kg/day) and GTE (0–100 mg (-)-epigallocatechin 3-gallate equivalent/kg/day) were orally administered to P. berghei infected mice for consecutive 4 days. Parasitized red blood cells (PRBC) were enumerated by using Giemsa staining microscopic method. Results: CM1 lowered percentage of PRBC in dose-dependent manner with an ED50 value of 56.91 mg/kg, when compared with pyrimethamine (PYR) (ED50=0.76 mg/kg). GTE treatment did not show any inhibition of the malaria parasite growth. In combined treatment, CM1 along with 0.6 mg/kg PYR significantly inhibited the growth of P. berghei in mice while GTE did not enhance the PYR anti-malarial activity. Conclusions: CM1 would be effective per se and synergize with PYR in inhibiting growth of murine malaria parasites, possibly by limiting iron supply from plasma transferrin and host PRBC cytoplasm, and chelating catalytic iron constitutive in parasites’ mitochondrial cytochromes and cytoplasmic ribonucleotide reductase. CM1 would be a promising adjuvant to enhance PYR anti-malarial activity and minimize the drug resistance.

Anti-malarial effect of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one and green tea extract on erythrocyte-stage Plasmodium berghei in mice

Objective: To examine the efficacy of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) iron chelator and green tea extract (GTE) as anti-malarial activity in Plasmodium berghei ( P. berghei) infected mice. Methods: The CM1 (0-100 mg/kg/day) and GTE (0-100 mg (-)-epigallocatechin 3-gallate equivalent/kg/day) were orally administered to P. berghei infected mice for consecutive 4 days. Parasitized red blood cells (PRBC) were enumerated by using Giemsa staining microscopic method. Results: CM1 lowered percentage of PRBC in dose-dependent manner with an ED

Combined treatment of 3-hydroxypyridine-4-one derivatives and green tea extract to induce hepcidin expression in iron-overloaded β-thalassemic mice

Objective: To evaluate the efficacy of deferiprone (DFP), 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) or green tea extract (GTE) in enhancing expression of hepatic hepcidin1 (Hamp1) mRNA and relieving iron overload in β-globin knockout thalassemic mice. Methods: The β-globin knockout thalassemic mice were fed with a ferrocene-supplemented diet for 2 months and oral administration of deionized water, DFP (50 mg/kg), CM1 (50 mg/kg), GTE (50 mg epigallocatechin 3-gallate equivalent/kg), GTE along with DFP (50 mg/kg), and GTE along with CM1 (50 mg/kg) every day for 3 months. Levels of hepatic Hamp1 mRNA, plasma non-transferrin bound iron, plasma alanine aminotransferase activity and tissue iron content were determined. Results: All chelation treatments could reduce plasma non-transferrin bound iron concentrations. Additionally, hepatic Hamp1 mRNA expression was significantly up-regulated in the mice in a GTE + DFP combined treatment, correlating with a decrease in the plasma alanine aminotransferase activity and tissue iron deposition. Conclusions: The GTE + DFP treatment could ameliorate iron overload and liver oxidative damage in non-transfusion dependent β-thalassemic mice, by chelating toxic iron in plasma and tissues, and increasing hepcidin expression to inhibit duodenal iron absorption and iron release from hepatocytes and macrophages in the spleen. There is probably an advantage in giving GTE with DFP when treating patients with iron overload.

Iron-Chelating Property of Phytic Acid in Thalassaemia: An In vitro Study.

Aims: The aim of this study is to report an oral iron chelator phytic acid (PA), on blood samples from different types of thalassaemic patients of various age groups and physical conditions. Study Design: The In vitro iron chelating effect was evaluated by ferritin assay using ELISA. Methodology: Blood from the iron-overloaded 30 Thalassaemic patients of different age groups, body weights and heights were collected and the serum was separated. Patients without any history of blood transfusion and chelation therapy were taken as control group. The ELISA based ferritin assay was performed with standard phytic acid (40% water solution, Fluka), using Desferrioxamine (DFO) as control (0.5g Deferoxamine mesylate USP, Novartis, USA). The serum ferritin levels were recorded in two different conditions (treated with DFO and PA) at different time intervals (10, 30 and 60 min) by measuring absorbance at 450 nm. Results: The Kolmogorov-Smirnov test of patient samples in two different conditions showed that the ferritin concentration, treated by DFO and PA, was significantly decrease in PA treated group compared to DFO, when used in equivalent concentrations, at intervals of 10 min (P=0.760),30 min (P=0.537) and 60 min (P=0.055). Conclusion: The common iron chelators DFO or Deferiprone used as monotherapy may lead to transient and incomplete removal of iron, while PA showed a more complete and sustained removal of ferritin due to specific chemical binding at a wider pH range. However, further trial is required to establish its maintenance dose, comparative efficacy and mechanism of action.

Iron-chelating and anti-lipid peroxidation properties of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) in long-term iron loading β-thalassemic mice

<p><b>OBJECTIVE</b>To evaluate the iron-chelating properties and free-radical scavenging activities of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) treatment in chronic iron-loaded β-thalassemic (BKO) mice.</p><p><b>METHODS</b>The BKO mice were fed with a ferrocene-rich diet and were orally administered with CM1 [50 mg/(kg.day)] for 6 months. Blood levels of non-transferrin bound iron, labile plasma iron, ferritin (Ft) and malondialdehyde were determined.</p><p><b>RESULTS</b>The BKO mice were fed with an iron diet for 8 months which resulted in iron overload. Interestingly, the mice showed a decrease in the non-transferrin bound iron, labile plasma iron and malondialdehyde levels, but not the Ft levels after continuous CM1 treatment.</p><p><b>CONCLUSIONS</b>CM1 could be an effective oral iron chelator that can reduce iron overload and lipid peroxidation in chronic iron overload β-thalassemic mice.</p>

Iron-chelating and anti-lipid peroxidation properties of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) in long-term iron loading β-thalassemic mice

Objective: To evaluate the iron-chelating properties and free-radical scavenging activities of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) treatment in chronic iron-loaded β-thalassemic (BKO) mice. Methods: The BKO mice were fed with a ferrocene-rich diet and were orally administered with CM1 [50 mg/(kg.day)] for 6 months. Blood levels of non-transferrin bound iron, labile plasma iron, ferritin (Ft) and malondialdehyde were determined. Results: The BKO mice were fed with an iron diet for 8 months which resulted in iron overload. Interestingly, the mice showed a decrease in the non-transferrin bound iron, labile plasma iron and malondialdehyde levels, but not the Ft levels after continuous CM1 treatment. Conclusions: CM1 could be an effective oral iron chelator that can reduce iron overload and lipid peroxidation in chronic iron overload β-thalassemic mice.

Sobrecarga de hierro en enfermedades hematológicas y no hematológicas: una bomba de tiempo / Iron overload in hematological and no hematological disease: a time bomb

La sobrecarga de hierro es una complicación frecuente en un número importante de enfermedades hematológicas que cursan con anemia y requieren transfusiones sanguíneas como parte de su terapia. Entre ellas se destacan la talasemia, la drepanocitosis, los síndromes mielodisplásicos, la anemia de Blackfan-Diamond, la anemia de Fanconi y la deficiencia de piruvato quinasa, La sobrecarga de hieroo tambiún se presenta en otras enfermedades tales como la hemocromatosis hereditaria, la hepatitis viral, el síndrome metabólico y determinados trastornos neurovegetativos. El diagnóstico de sobrecarga suele hacerse mediante la determinación del hierro sérico no unido a la transferrina, la ferritina sérica y un aumento de la concentración hepática de hierro. Las consecuencias más importantes del efecto tóxico de un exceso de hierro son las disfunciones cardíacas y endocrinas, debidas al efecto oxidante del hierro sobre las membranas celulares, con el consiguiente daño celular. Tales alteraciones contribuyen al incremento de la morbilidad y la mortalidad en estos pacientes. El tratamiento consiste básicamente en el usode agentes quelantes de hierro que facilitan la excreción del exceso del metal y reducen su efecto tóxico, Entre tales agentes se cuentan la deferrioxamina (de uso intravenoso). y móa recientemente el deferiprone (ambos de uso orak)

Iron overload is a frequent complication in patients with hematological diseases which develop anemía and require blood transfusion as a therapeutic measure. Thalassemia, drepanocytosis, myelodisplastic syndromes, Blackfan-Diamond anemia, Franconi anemia and pyruvate kinase deficiency are the most common of these diseases. Iron overload is the hallmark of hereditary hemochromatosis, and also complicates diseases such as viral hepatitis, the metabolic syndrome, and certain neurovegetative disfunctions. The diagnosis of iron overload is commonly established through the evaluation of serum iron, transferrin saturation, serum ferritin and liver iron concentration. Cardiac and endocrine dysfunctions are the most important consequences of the toxic efffect of iron accumulation; these are due to the oxidixing effect of iron upon the cellular membranes, followed by cellular damage. Such alterations contribute to the increased morbility and mortality rates in these patients. The treatment of iron overload is based mainly on the use of iron chelators which facilitate the excretion of iron excess and reduce its toxic effect. Deferrioxamine (for intravenous use), and more recently deferiprone and deferasirox (both for oral administration) are the drugs of choice

Promise of Neurorestoration and Mitochondrial Biogenesis in Parkinson's Disease with Multi Target Drugs: An Alternative to Stem Cell Therapy

There is an unmet need in progressive neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. The present therapeutics for these diseases at best is symptomatic and is not able to delay disease or possess disease modifying activity. Thus an approach to drug design should be made to slow or halt progressive course of a neurological disorder by interfering with a disease-specific pathogenetic process. This would entail the ability of the drug to protect neurons by blocking the common pathway for neuronal injury and cell death and the ability to promote regeneration of neurons and restoration of neuronal function. We have now developed a number of multi target drugs which possess neuroprotective, and neurorestorative activity as well as being able to active PGC-1alpha (peroxisome proliferator-activated receptor gamma coactivator-1alpha), SIRT1 (NAD-dependent deacetylase protein) and NTF (mitochondrial transcription factor) that are intimately associated with mitochondrial biogenesis.

In vitro Studies of Iron Chelation Activity of Purified Active Ingredients Extracted from Triticum aestivum Linn. (Wheat Grass).

Objective: Seven to eight days germinated plants of Triticum aestivum (wheat grass) are a rich source of vitamin A, C, calcium, magnesium, phosphorus, potassium, sodium, sulphur, cobalt, zinc and protein. Traditionally the aqueous extract of T. aestivum was reported to be used as a health tonic in folk and ayurvedic medicine. We previously reported that aqueous extract of T. aestivum was found to reduce the blood transfusion requirement in iron overloaded Thalassemia and Myelodysplastic syndrome patients. Our objective was to extract and purify active ingredients from wheat grass and study their mode of action in stabilizing hemoglobin level in those patients. Design and Method: Active ingredients of wheat grass were extracted and purified by cation exchange column chromatography followed by High Performance Liquid Chromatography. In vitro experiments with phenylhydrazine treated red blood cell hemolysate were carried out before and after treatment of purified fraction of T. aestivum to study iron chelating activity. Result: Purified fraction of T. aestivum treated red blood cell showed significant inhibition of free reactive iron production and formation of thio-barbituric acid reactive substances when compared to desferrioxamine treated hemolysate. Conclusion: Iron chelating activity of purified fraction of T. aestivum, an inexpensive, easily available source, is very promising for further clinical trial and development of oral iron chelator drug for Thalassemia, Myelodysplastic syndrome and other iron overloaded diseases.

Iron overloading and brain injury following intracerbral hemorrhage / 国际脑血管病杂志

Intracerebral hemorrhage (ICH) is a common nervous system disease, its mortality and disability are very high. However, the mechanisms of brain injury after ICH have not yet been fully explained. "[he latest studies have suggested that iron overloading plays an important role in the brain injury after ICH. This article reviews the advances in research on the distribution and function of iron in the brain, the mechanisms of brain injury caused by iron overloading after ICH as well as the use of iron chelator.

The Damage Mechanisms of Iron Ion in Intracerebral Hemorrhage and the Neuroprotective Effects of Iron Chelator / 国际脑血管病杂志

A series of pathophysiologic changes in brain tissues will occur after intracerebral hemorrhage, including the enlargement of hematoma, metabolism abnormality in perihematoma tissues, and formation of cerebral edema. Recent researches have demonstrated that iron ions play an important role in the secondary brain injury after intracerebral hemorrhage. Iron chelator can block iron-induced injury process by specifically binding iron ions. This article reviews the changes of iron metabolism, iron-related mechanisms of brain injury, and the neuroprotective effect of iron chelator.

Iron chelator inducesMIP-3alpha/CCL20 in human intestinal epithelial cells: implication for triggeringmucosal adaptive immunity

A previous report by this laboratory demonstrated that bacterial iron chelator (siderophore) triggers inflammatory signals, including the production of CXC chemokine IL-8, in human intestinal epithelial cells (IECs). Microarray-based gene expression profiling revealed that iron chelator also induces macrophage inflammatory protein 3 alpha (MIP-3alpha)/ CC chemokine-ligand 20 (CCL20). As CCL20 is chemotactic for the cells involved in host adaptive immunity, this suggests that iron chelator may stimulate IECs to have the capacity to link mucosal innate and adaptive immunity. The basal medium from iron chelator deferoxamine (DFO)-treated HT-29 monolayers was as chemotactic as recombinant human CCL20 at equivalent concentrations to attract CCR6+ cells. The increase of CCL20 protein secretion appeared to correspond to that of CCL20 mRNA levels, as determined by real-time quantitative RT-PCR. The efficacy of DFO at inducing CCL20 mRNA was also observed in human PBMCs and in THP-1 cells, but not in human umbilical vein endothelial cells. Interestingly, unlike other proinflammatory cytokines, such as TNF-alpha and IL-1beta, a time-dependent experiment revealed that DFO slowly induces CCL20, suggesting a novel mechanism of action. A pharmacologic study also revealed that multiple signaling pathways are differentially involved in CCL20 production by DFO, while some of those pathways are not involved in TNF-alpha-induced CCL20 production. Collectively, these results demonstrate that, in addition to some bacterial products known to induce host adaptive immune responses, direct chelation of host iron by infected bacteria may also contribute to the initiation of host adaptive immunity in the intestinal mucosa.

Iron Chelator Induces MIP-3alpha/CCL20 in Human Intestinal Epithelial Cells: Implication for Triggering Mucosal Adaptive Immunity / 체질인류학회지

A previous report by this laboratory demonstrated that bacterial iron chelator (siderophore) triggers inflammatory signals, including the production of CXC chemokie IL-8, in human intestinal epithelial cells(IECs). Microarray-based gene expression profiling revealed that iron chelator also induces CC chemokie MIP-3alpha/CCL20. As CCL20 is chemotactic for the cells involved in host adaptive immunity, this suggests that iron chelator may stimulate IECs to have the capacity to link mucosal innate and adaptive immunity. The basal medium from iron chelator deferoxamine (DFO)-treated HT-29 monolayers was as chemotactic as rhCCL20 at equivalent concentrations to attract CCR6+cells. The increase of CCL20 protein secretion appeared to correspond to that of CCL20 mRNA levels, as determined by real-time quantitative RT-PCR. The efficacy of DFO at inducing CCL20 mRNA was also observed in human Peripheral Blood Mononuclear Cells (PBMCs) and in THP-1 cells, but not in Human Umbillical Vein Endothelial Cells (HUVECs). Interestingly, unlike other proinflammatory cytokines, such as TNF-alpha and IL-1beta, a time-dependent experiment revealed that DFO slowly induces CCL20, suggesting a novel mechanism of action. A pharmacologic study also revealed that multiple signaling pathways are differentially involved in CCL20 production by DFO, while some of those pathways are not involved in TNF-alpha-induced CCL20 production. Collectively, these results demonstrate that, in addition to some bacterial products known to induce host adaptive immune responses, direct chelation of host iron by infected bacteria may also contribute to the initiation of host adaptive immunity in the intestinal mucosa.

Role of Hydroxyl Radicals and Lipid Peroxidation in Cisplatin-induced Acute Renal Failure in Rabbits / 대한신장학회잡지

PURPOSE: This study was undertaken to determine whether lipid peroxidation induced by hydroxyl radicals play a critical role in cisplatin(cis-diamminedichloroplatinum II)-induced acute renal failure. METHODS: Animals received cisplatin at a single i.p. dose of 5 mg/kg, and changes in renal function were measured at 48 hr after cisplatin injection. RESULTS: Cisplatin caused an increase in serum creatinine level, which was accompanied by reduction in GFR. The fractional excretion of Na(+), glucose, and inorganic phosphate was increased in animals treated with cisplatin alone. Cisplatin treatment in vivo inhibited PAH uptake by renal cortical slices and Na(+)-K(+)-ATPase activity in microsomal fraction. Lipid peroxidation was increased in cisplatin-treated kidneys. When animals received the antioxidant N,N'-diphenyl-p-phenylenediamine(DPPD), the iron chelator deferoxamine, and hydroxyl radical scavengers dimethylthiourea and sodium benzoate before cisplatin injection, alterations in renal function and lipid peroxidation induced by cisplatin were significantly prevented. Exposure of renal cortical slices to cisplatin in vitro caused an increase in LDH release and lipid peroxidation, which were completely prevented by DPPD and deferoxamine. By contrast, hydroxyl radical scavengers(dimethylthiourea and thiourea) did not prevent cisplatin-induced LDH release despite they inhibited cisplatin-induced lipid peroxidation. CONCLUSION: These results suggest that the lipid peroxidation resulting from generation of hydroxyl radicals may play a role in cisplatin-induced acute renal failure. In addition, the protective effects of hydroxyl radical scavengers in vivo studies are different from the results obtained from in vitro studies using renal cortical slices.

Effect of Allopurinol on Methylmercuric Chloride in Cultured O1igodendrocytes / 체질인류학회지

In order to examine the neurotoxic mechanism of oxygen radicals on cultured bovine oligodendrocytes, cytoxic effect of oxygen radicals was examined when cultures were treated with various concentrations of xanthine oxidase (XO) and hypoxanthine (HX) in culture medium. In addition, the neuroprotective effect of iron-chelators against the neurotoxicity induced by oxygen radicals was evaluated by MTT assay. Cell viability was remarkably decreased in a time-dependent manner after exposure of cultured bovine oligodendrocytes to 20mU/ml XO and 0.1mM HX for 4 hours. In the neuroprotective effect of iron-chelators on oxidant-induced neurotoxicity, tetrakis (2-pyridylmethyl)ethylenediamine (TPEN) blocked the neurotoxicity induced by oxygen radicals, while DFX was not effective in blocking oxidant-induced neurotoxicity in these cultures. These results suggest that oxygen radicals are toxic in cultured bovine oligodendrocytes, and also selective iron-chelators such as TPEN are effective in blocking the neurotoxicity induced by oxygen radicals.