- MeSH
- Transplantation, Autologous standards MeSH
- Iron Chelating Agents MeSH
- Bone Marrow Purging methods standards MeSH
- Deferoxamine pharmacology MeSH
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Neuroblastoma therapy MeSH
- Child, Preschool MeSH
- In Vitro Techniques MeSH
- Hematopoietic Stem Cell Transplantation MeSH
- Bone Marrow Transplantation MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Child, Preschool MeSH
The purpose of the present study was to compare the activity of two different clinically available iron chelators on the development of acute liver injury after administration of the bacterial endotoxin (lipopolysaccharide [LPS]) in rats. Lipopolysaccharide was administered either alone or after pretreatment with dexrazoxane (DEX) or deferoxamine (DFO). Control groups received only saline or its combination with either chelator. After 8 h, untreated LPS rats developed liver injury, with signs of inflammation and oxidative stress. Lipopolysaccharide reduced plasma iron concentrations in association with increased production of hepcidin and the reduced liver expression of ferroportin. Administration of chelating agents to LPS animals showed distinct effects. Although both drugs were able to reduce liver iron content, together with corresponding changes in hepcidin and ferroportin expressions, only DFO showed a protective effect against liver injury despite relatively small liver concentrations. In sharp contrast, DEX failed to improve any hallmark of liver injury and even worsened the GSH/GSSG ratio, the indicator of oxidative stress in the tissue. High-performance liquid chromatography-mass spectrometry analysis showed marked liver accumulation of iron-chelating metabolite of DEX (ADR-925), whereas the parent compound was undetectable. Further downregulation of transporters involved in bile formation was observed after DFO in the LPS group as well as in healthy animals. Neither chelator imposed significant liver injury in healthy animals. In conclusion, we demonstrated marked differences in the modulation of endotoxemic liver impairment between two iron chelators, implicating that particular qualities of chelating agents may be of crucial importance.
- MeSH
- Iron Chelating Agents therapeutic use MeSH
- Deferoxamine therapeutic use MeSH
- Dexrazoxane therapeutic use MeSH
- Endotoxemia complications MeSH
- Rats MeSH
- Liver Diseases drug therapy etiology MeSH
- Rats, Wistar MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
There is scarce evidence regarding the use of iron chelators in patients with hereditary hemochromatosis who are intolerant of phlebotomy or erythrocytapheresis. A 52-year-old man with genetically confirmed HFE hemochromatosis presented with liver disease and heart failure with severe left ventricular systolic dysfunction. Because of anemia after initial treatment, we added intravenous deferoxamine followed by oral deferiprone to less frequent erythrocytapheresis, which normalized systolic function within 1 year. Repeated cardiac magnetic resonance imaging revealed improvement of the T2* relaxation time. This report illustrates the beneficial effect of iron chelators in individuals with HFE hemochromatosis and poor tolerance of erythrocytapheresis.
- MeSH
- Iron Chelating Agents administration & dosage MeSH
- Deferoxamine administration & dosage MeSH
- Ventricular Dysfunction, Left diagnosis etiology MeSH
- Ferritins analysis MeSH
- Hemochromatosis * blood diagnosis drug therapy physiopathology MeSH
- Cardiomyopathies * diagnosis etiology physiopathology therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging, Cine methods MeSH
- Liver Diseases diagnosis etiology MeSH
- Iron Overload blood complications MeSH
- Hemochromatosis Protein genetics MeSH
- Pyridones administration & dosage MeSH
- Heart Failure * diagnosis drug therapy etiology MeSH
- Severity of Illness Index MeSH
- Stroke Volume MeSH
- Transferrin analysis MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- MeSH
- Chelation Therapy MeSH
- Deferiprone administration & dosage MeSH
- Deferoxamine administration & dosage MeSH
- Phlebotomy MeSH
- Drug Therapy, Combination MeSH
- Humans MeSH
- Young Adult MeSH
- Iron Overload drug therapy MeSH
- Anemia, Sideroblastic * drug therapy therapy MeSH
- Bone Marrow Transplantation MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
- MeSH
- Iron Chelating Agents administration & dosage pharmacology MeSH
- Chelation Therapy * trends MeSH
- Deferasirox administration & dosage pharmacology MeSH
- Deferiprone administration & dosage pharmacology MeSH
- Deferoxamine administration & dosage pharmacology MeSH
- Drug Therapy, Combination MeSH
- Humans MeSH
- Thalassemia drug therapy MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
