Iron overload in myelodysplastic syndrome (MDS) results from multiple RBC-transfusions and inappropriate increased iron absoption associated with ineffective erythropoiesis. Data from hereditary iron-loading anemias i...Iron overload in myelodysplastic syndrome (MDS) results from multiple RBC-transfusions and inappropriate increased iron absoption associated with ineffective erythropoiesis. Data from hereditary iron-loading anemias indicate long-term consequences of iron toxicity are preventable and potentially reversible by effective iron-chelation therapy (ICT). There is increasing interest in using ICT in persons with MDS because of the recent introduction of orally effective iron-chelators which are suitable for older persons, (1-4). Ideally, evidence supporting the benefit of ICT in MDS should be evidenced-based, especially data from randomized trials showing better survival and, in exceptional cases, improved heart function . Such data are lacking. Nevertheless, it is possible to rely on the extensive data from trials of ICT in persons with thalassemia and to use well-defined predictors of increased risks of life-threatening complications to identify persons with MDS most likely to benefit from iron-chelating therapy.展开更多
Objective:To evaluate the iron—chelating properties and free—radical scavenging activities of1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methyIpyridin—4-one(CM1) treatment in chronic iron-loaded β-thalassemic(BKO) mice....Objective:To evaluate the iron—chelating properties and free—radical scavenging activities of1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methyIpyridin—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 hound 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.展开更多
Iron is one of the necessary metal elements in the human body.There are numerous factors that control the balance of iron metabolism,and its storage and transportation mechanisms are intricate.As one of the most energ...Iron is one of the necessary metal elements in the human body.There are numerous factors that control the balance of iron metabolism,and its storage and transportation mechanisms are intricate.As one of the most energyintensive tissues in the body,the retina is susceptible to iron imbalance.The occurrence of iron overload in the retina leads to the generation of a significant quantity of reactive oxygen species.This will aggravate local oxidative stress and inflammatory reactions and even lead to ferroptosis,eventually resulting in retinal dysfunction.The blood-retinaretinal barrier is eventually harmed by oxidative stress and elevated inflammation,which are characteristics of retinal vascular disorders.The pathophysiology of retinal vascular disorders may be significantly influenced by iron.Recently,iron-chelating agents have been found to have antioxidative and anti-inflammatory actions in addition to iron chelating.Therefore,iron neutralization is considered to be a new and potentially useful therapeutic strategy.This article reviews the iron overload in retinal vascular diseases and discusses the therapeutic potential of iron-chelating agents.展开更多
AIM To evaluate the inhibitory effects of deferasirox(DFX) against hepatocellular carcinoma(HCC) through basic and clinical studies.METHODS In the basic study, the effect of DFX was investigated in three hepatoma cell...AIM To evaluate the inhibitory effects of deferasirox(DFX) against hepatocellular carcinoma(HCC) through basic and clinical studies.METHODS In the basic study, the effect of DFX was investigated in three hepatoma cell lines(Hep G2, Hep3 B, and Huh7), as well as in an N-nitrosodiethylamine-induced murine HCC model. In the clinical study, six advanced HCC patients refractory to chemotherapy were enrolled. The initial dose of DFX was 10 mg/kg per day and was increased by 10 mg/kg per day every week, until the maximum dose of 30 mg/kg per day. The duration of a single course of DFX therapy was 28 consecutive days. In the event of dose-limiting toxicity(according to the Common Terminology Criteria for Adverse Events v.4.0), DFX dose was reduced.RESULTS Administration of DFX inhibited the proliferation of hepatoma cell lines and induced the activation of caspase-3 in a dose-dependent manner in vitro. In the murine model, DFX treatment significantly suppressed the development of liver tumors(P < 0.01), and significantly upregulated the mR NA expression levels of hepcidin(P < 0.05), transferrin receptor 1(P < 0.05), and hypoxia inducible factor-1α(P < 0.05) in both tumor and non-tumor tissues, compared with control mice. In the clinical study, anorexia and elevated serum creatinine were observed in four and all six patients, respectively. However, reduction in DFX dose led to decrease in serum creatinine levels in all patients. After the first course of DFX, one patient discontinued the therapy. We assessed the tumor response in the remaining five patients; one patient exhibited stable disease, while four patients exhibited progressive disease. The one-year survival rate of the six patients was 17%.CONCLUSION We demonstrated that DFX inhibited HCC in the basic study, but not in the clinical study due to dose-limiting toxicities.展开更多
文摘Iron overload in myelodysplastic syndrome (MDS) results from multiple RBC-transfusions and inappropriate increased iron absoption associated with ineffective erythropoiesis. Data from hereditary iron-loading anemias indicate long-term consequences of iron toxicity are preventable and potentially reversible by effective iron-chelation therapy (ICT). There is increasing interest in using ICT in persons with MDS because of the recent introduction of orally effective iron-chelators which are suitable for older persons, (1-4). Ideally, evidence supporting the benefit of ICT in MDS should be evidenced-based, especially data from randomized trials showing better survival and, in exceptional cases, improved heart function . Such data are lacking. Nevertheless, it is possible to rely on the extensive data from trials of ICT in persons with thalassemia and to use well-defined predictors of increased risks of life-threatening complications to identify persons with MDS most likely to benefit from iron-chelating therapy.
基金Supported by the Royal Golden Jubilee PhD Program.Thailand Research Fund(Grant No.PHD/0333/2551)
文摘Objective:To evaluate the iron—chelating properties and free—radical scavenging activities of1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methyIpyridin—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 hound 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.
基金Supported by Luzhou Municipal People’s Government and Southwest Medical University(No.2021LZXNYD-J03)Science and Technology Department of Sichuan Province Project(No.2022YFS0611).
文摘Iron is one of the necessary metal elements in the human body.There are numerous factors that control the balance of iron metabolism,and its storage and transportation mechanisms are intricate.As one of the most energyintensive tissues in the body,the retina is susceptible to iron imbalance.The occurrence of iron overload in the retina leads to the generation of a significant quantity of reactive oxygen species.This will aggravate local oxidative stress and inflammatory reactions and even lead to ferroptosis,eventually resulting in retinal dysfunction.The blood-retinaretinal barrier is eventually harmed by oxidative stress and elevated inflammation,which are characteristics of retinal vascular disorders.The pathophysiology of retinal vascular disorders may be significantly influenced by iron.Recently,iron-chelating agents have been found to have antioxidative and anti-inflammatory actions in addition to iron chelating.Therefore,iron neutralization is considered to be a new and potentially useful therapeutic strategy.This article reviews the iron overload in retinal vascular diseases and discusses the therapeutic potential of iron-chelating agents.
基金Supported by Grants-in-Aid for Scientific Research from the Japan Society for the Program of Science,No.23590978 and No.16H05287the Strategic Research Promotion Program from Yamaguchi University
文摘AIM To evaluate the inhibitory effects of deferasirox(DFX) against hepatocellular carcinoma(HCC) through basic and clinical studies.METHODS In the basic study, the effect of DFX was investigated in three hepatoma cell lines(Hep G2, Hep3 B, and Huh7), as well as in an N-nitrosodiethylamine-induced murine HCC model. In the clinical study, six advanced HCC patients refractory to chemotherapy were enrolled. The initial dose of DFX was 10 mg/kg per day and was increased by 10 mg/kg per day every week, until the maximum dose of 30 mg/kg per day. The duration of a single course of DFX therapy was 28 consecutive days. In the event of dose-limiting toxicity(according to the Common Terminology Criteria for Adverse Events v.4.0), DFX dose was reduced.RESULTS Administration of DFX inhibited the proliferation of hepatoma cell lines and induced the activation of caspase-3 in a dose-dependent manner in vitro. In the murine model, DFX treatment significantly suppressed the development of liver tumors(P < 0.01), and significantly upregulated the mR NA expression levels of hepcidin(P < 0.05), transferrin receptor 1(P < 0.05), and hypoxia inducible factor-1α(P < 0.05) in both tumor and non-tumor tissues, compared with control mice. In the clinical study, anorexia and elevated serum creatinine were observed in four and all six patients, respectively. However, reduction in DFX dose led to decrease in serum creatinine levels in all patients. After the first course of DFX, one patient discontinued the therapy. We assessed the tumor response in the remaining five patients; one patient exhibited stable disease, while four patients exhibited progressive disease. The one-year survival rate of the six patients was 17%.CONCLUSION We demonstrated that DFX inhibited HCC in the basic study, but not in the clinical study due to dose-limiting toxicities.