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European Journal of Haematology May 2023Iron overload is a pathological condition resulting from a congenital impairment of its regulation, increased intestinal iron absorption secondary to bone marrow... (Review)
Review
Iron overload is a pathological condition resulting from a congenital impairment of its regulation, increased intestinal iron absorption secondary to bone marrow erythroid hyperplasia, or a chronic transfusional regimen. In normal conditions, intracellular and systemic mechanisms contribute to maintaining iron balance. When this complex homeostatic mechanism fails, an iron overload could be present. Detecting an iron overload is not easy. The gold standard remains the liver biopsy, even if it is invasive and dangerous. Identifying iron using noninvasive techniques allowed a better understanding of the rate of iron overload in different organs, with a low risk for the patient. Estimating serum ferritin (mg/L) is the easiest and, consequently, the most employed diagnostic tool for assessing body iron stores, even if it could be a not specific method. The most common hematological causes of iron overload are myelodysplastic syndromes, sickle cell disease, and thalassemia. In all of these conditions, three drugs have been approved for the treatment of iron overload: deferiprone, deferoxamine, and deferasirox. These chelators have been demonstrated to help lower tissue iron levels and prevent iron overload complications, improving event-free survival (EFS). Nowadays, the decision to start chelation and which chelator to choose remains the joint decision of the clinician and patient.
Topics: Humans; Chelation Therapy; Iron Chelating Agents; Deferasirox; Deferiprone; Deferoxamine; Pyridones; Benzoates; Triazoles; Iron Overload; Iron
PubMed: 36708354
DOI: 10.1111/ejh.13935 -
Pharmacological Research Sep 2020Ferroptosis is a new kind of regulated cell death that is characterized by highly iron-dependent lipid peroxidation. Ferroptosis involves various biology processes, such... (Review)
Review
Ferroptosis is a new kind of regulated cell death that is characterized by highly iron-dependent lipid peroxidation. Ferroptosis involves various biology processes, such as iron metabolism, lipid metabolism, oxidative stress and biosynthesis of nicotinamide adenine dinucleotide phosphate (NADPH), glutathione (GSH) and coenzyme Q10 (CoQ10). A growing body of evidence suggests that ferroptosis is associated with cancer and neurodegenerative diseases (Alzheimer's disease, Parkinson's disease and Huntington's disease). This finding has helped develop a novel cytoprotective strategy to protect cells in neurodegenerative, blood and heart diseases by inhibiting ferroptosis. Meanwhile, the selective induction of ferroptosis has been adopted as a potential treatment strategy in some kinds of cancer. This review aims to summarize the mechanism of ferroptosis regulation and relevance to pathological physiology.
Topics: Animals; Antineoplastic Agents; Ferroptosis; Humans; Iron; Lipid Peroxidation; Neoplasms; Neurodegenerative Diseases; Neuroprotective Agents; Reactive Oxygen Species
PubMed: 32464324
DOI: 10.1016/j.phrs.2020.104919 -
Life Sciences Feb 2023Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) caused by multiple factors. Studies have shown that epithelial cell damage was associated with...
AIMS
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) caused by multiple factors. Studies have shown that epithelial cell damage was associated with ferroptosis in UC. Therefore, our research focused on the effects and mechanism of iron chelator deferasirox in UC.
MAIN METHODS
The UC model was induced by 2.5 % dextran sulfate sodium salt (DSS) and administered with deferasirox (10 mg/kg) for 7 days. Histological pathologies, inflammatory response, ferrous iron contents, oxidative stress and ferroptosis regulators were determined. Intestinal microbiota alteration and short-chain fatty acids (SCFAs) production were analyzed through 16S rRNA gene sequencing and targeted metabolomics.
KEY FINDINGS
Deferasirox significantly relieved the DSS-induced UC in mice, as evidenced by weight loss, survival rate, colon length shortening disease activity index (DAI) score and histology score. Deferasirox treatment reduced the level of pro inflammatory cytokines (IL-1β, IL-6, TNF-α and INF-γ). Ferroptosis was induced in mice with UC, as evidenced by ferrous iron accumulation, increased ROS production, SOD and GSH depletion, decreased the expression of GPX-4 and FTH, accompanied by increased expression of TF. Deferasirox treatment strongly reversed the alterations caused by ferroptotic characteristics in DSS-induced mice. Moreover, deferasirox treatment reshaped the composition of intestinal microbiota. The results revealed the genera of norank_f__Muribaculaceae, Lachnospiraceae_NK4A136_group, Prevotellaceae_UCG-001, Odoribacter and Blautia were increased distinctly, while Escherichia-Shigella and Streptococcus were significantly decreased by deferasirox treatment. Targeted metabolomics analysis indicated the SCFAs production enhanced in deferasirox-treated mice.
SIGNIFICANCE
Our results suggested that deferasirox could treat DSS-induced UC in mice by inhibiting ferroptosis and improving intestinal microbiota.
Topics: Mice; Animals; Colitis, Ulcerative; Deferasirox; Gastrointestinal Microbiome; Ferroptosis; RNA, Ribosomal, 16S; Colon; Sodium Chloride; Sodium Chloride, Dietary; Iron; Dextran Sulfate; Mice, Inbred C57BL; Disease Models, Animal; Colitis
PubMed: 36563842
DOI: 10.1016/j.lfs.2022.121312 -
Hemoglobin Jan 2022The population of Cambodia (in 2019) was approximately 16 million with an annual growth rate of 1.4% in which the prevalence of hemoglobinopathies was estimated at about... (Review)
Review
The population of Cambodia (in 2019) was approximately 16 million with an annual growth rate of 1.4% in which the prevalence of hemoglobinopathies was estimated at about 40.0% (range 30.0-50.0%) to be carriers, and 2240 annual births for β-thalassemia major (β-TM). The overall prevalence of β-thalassemia (β-thal) and α-thalassemia (α-thal) were 40.9 and 39.6%, respectively. Currently, the specific epidemiological data regarding the abnormal gene frequency/mutations among different ethnic groups is unknown. In 2011, national guidelines for the Clinical Management of Patients with Thalassemia in Cambodia were developed and published by the Ministry of Health (MoH). Packed red cells (PRCs) are available at most referral hospitals (provincial hospitals). Oral iron chelators [deferiprone (DFP) and deferasirox (DFX)] are only available from a private pharmaceutical company. The future needs for Cambodia are to develop a national policy on the prevention or control of β-thal and α-thal, and a national registry of patients with thalassemia, to determine the gene frequency of α- and β-thal in different regions of the country, and to place the iron chelators on the list of essential medicines.
Topics: Cambodia; Hemoglobinopathies; Humans; Iron Chelating Agents; alpha-Thalassemia; beta-Thalassemia
PubMed: 35950584
DOI: 10.1080/03630269.2021.2008956 -
Revista Alergia Mexico (Tecamachalco,... Sep 2023Deferasirox is an active iron chelator, used in the treatment of iron overload such as hemochromatosis. Up to 28% may present adverse reactions to said drug. A...
BACKGROUND
Deferasirox is an active iron chelator, used in the treatment of iron overload such as hemochromatosis. Up to 28% may present adverse reactions to said drug. A desensitization protocol for this drug may be useful when there are no other therapeutic options.
CASE REPORT
A 52-year-old female with a diagnosis of hemochromatosis who began treatment with phlebotomy, poor response and tolerance, so it was decided to treat with deferasirox 500 mg daily, presenting symptoms of urticaria and angioedema on the third dose. Hospitalization was decided for a desensitization protocol with an initial dose of 0.6mg with a gradual increase in the dose, reaching a maintenance dose of 500 mg per day on the third day.
CONCLUSIONS
The rapid desensitization protocol for Deferasirox is useful when there is no response or therapeutic alternative.
Topics: Female; Humans; Middle Aged; Deferasirox; Hemochromatosis; Iron Chelating Agents
PubMed: 37933925
DOI: 10.29262/ram.v70i3.1256 -
Naunyn-Schmiedeberg's Archives of... Nov 2022Renal I/R injury is a severe medical condition contributing to acute kidney injury (AKI), leading to rapid kidney dysfunction and high mortality rates. It is generally... (Review)
Review
Renal I/R injury is a severe medical condition contributing to acute kidney injury (AKI), leading to rapid kidney dysfunction and high mortality rates. It is generally observed during renal transplantation, shock, trauma, and urologic and cardiovascular surgery, for which there is no effective treatment. Cell death and damage are commonly linked to I/R. Cell death triggered by iron-dependent lipid peroxidation, such as ferroptosis, has been demonstrated to have a significant detrimental effect in renal IRI models, making it a new type of cell death currently being researched. Ferroptosis is a nonapoptotic type of cell death that occurs when free iron enters the cell and is a critical component of many biological processes. In ferroptosis-induced renal I/R injury, iron chelators such as Deferasirox, Deferiprone, and lipophilic antioxidants are currently suppressed lipid peroxidation Liproxstatin-1 (Lip-1), Ferrostatin-1 along with antioxidants like vitamin and quercetin. Ferroptosis has been considered a potential target for pharmaceutical intervention to alleviate renal IRI-associated cell damage. Thus, this review emphasized the role of ferroptosis and its inhibition in renal IRI. Also, Pharmacological modulation of ferroptosis mechanism in renal I/R injury has been conferred. Graphical abstract.
Topics: Deferasirox; Deferiprone; Ferroptosis; Humans; Iron; Iron Chelating Agents; Ischemia; Kidney; Pharmaceutical Preparations; Quercetin; Reperfusion; Reperfusion Injury; Vitamins
PubMed: 35920897
DOI: 10.1007/s00210-022-02277-5 -
Annals of the New York Academy of... Nov 2023Combination chelation therapies are considered in transfusion-dependent thalassemia patients for whom monotherapy regimens have failed to achieve iron balance or... (Review)
Review
Combination chelation therapies are considered in transfusion-dependent thalassemia patients for whom monotherapy regimens have failed to achieve iron balance or intensification of iron chelation therapy is required for the rapid reduction of excess iron to avoid permanent organ damage. Combination chelation may provide a more flexible approach for individualizing chelation therapy, thereby improving tolerability, adherence, and quality of life. In principle, iron chelators can be combined with an infinite number of dosing regimens; these involve simultaneous or sequential exposure to the chelators on the same day or alternating the drugs on different days. Clinical studies have established the safety and efficacy of chelation combinations. However, real-life data with combination therapies indicate the significance of compliance for a meaningful reduction in iron overload compared to monotherapies.
Topics: Humans; Chelation Therapy; Deferasirox; Deferoxamine; Deferiprone; Quality of Life; Benzoates; Triazoles; Pyridones; Iron Chelating Agents; Iron Overload; Iron; Drug Therapy, Combination
PubMed: 37594980
DOI: 10.1111/nyas.15052