Bifunctional 3-Hydroxy-4-Pyridinones as Potential Selective Iron(III) Chelators: Solution Studies and Comparison with Other Metals of Biological and Environmental Relevance

The binding ability of five bifunctional 3-hydroxy-4-pyridinones towards Cu2+ and Fe3+ was studied by means of potentiometric and UV–Vis spectrophotometric measurements carried out at I = 0.15 mol L−1 in NaCl(aq),T = 298.15 K and 310.15 K. The data treatments allowed us to determine speciation schemes featured by metal-ligand species with different stoichiometry and stability, owing to the various functional groups present in the 3-hydroxy-4-pyridinones structures, which could potentially participate in the metal complexation, and in the Cu2+ and Fe3+ behaviour in aqueous solution. Furthermore, the sequestering ability and metal chelating affinity of the ligands were investigated by the determination of pL0.5 and pM parameters at different pH conditions. Finally, a comparison between the Cu2+ and Fe3+/3-hydroxy-4-pyridinones data herein presented with those already reported in the literature on the interaction of Zn2+ and Al3+ with the same ligands showed that, from the thermodynamic point of view, the 3-hydroxy-4-pyridinones are particularly selective towards Fe3+ and could therefore be considered promising iron-chelating agents, also avoiding the possibility of competition, and eventually the depletion, of essential metal cations of biological and environmental relevance, such as Cu2+ and Zn2+.

Natural Iron Chelators as Potential Therapeutic Agents for the Treatment of Iron Overload Diseases

Iron overload disease is a group of heterogeneous disease, which is caused either due to hereditary or acquired condition. Excess of iron participate in redox reactions that catalyzes the generation of reactive oxygen species (ROS) and increases oxidative stress, which causes cellular damage and encourage the cell injury and cell death. The electronic databases of Scopus, PubMed and Google Scholar have been intensively searched for the research as well as review articles published with the full text available and with the key words such as natural iron chelating agent, synthetic iron chelating agents, iron overload disease, oxidative stress and antioxidant which were appearing in the title, abstract or keywords. In light of the literature review presented in this artial, based on meta-analyses, we suggest that iron chelating agents were used for the management of iron overload disease. These agents were having wide spectrum of activity, they were not only used for the management of iron overload disease but also used as anticancer and antioxidant in various oxidative stress mediated diseases. Last from many years Desferoxamine (DFO) was used as standard iron chelator but currently two new synthetic iron chelators such as Deferiprone (DFP) and Deferasirox (DFS) are available clinically. These clinically available synthetic iron chelators were having serious side effects and certain limitations. Phytochemicals such as flavonoids and polyphenols compounds were having iron chelating as well as antioxidant property with no or minimal side effects. Hence, this review provides an updates on natural iron chelation therapy for the safe and efficacious management of iron overload diseases.

Detection of endocrine disorders in young children with multi-transfused thalassemia major

Background Beta thalassemia major (TM) is the most common inherited genetic disorder worldwide. Patients are at risk of iron overload, which leads to various forms of tissue damage, including endocrinopathies. The aim of this study was to evaluate the prevalence and risk factors of endocrine disorders in young patients with multi-transfused TM receiving iron chelation therapy. Methods The inclusion criteria included all known cases of TM according to hemoglobin electrophoresis data, aged 12 years or younger, during the study period. The patient’s age, gender, parent’s consanguinity, clinical examination, and types of iron chelating agents used were recorded. Serum ferritin level, complete blood count (CBC), blood glucose homeostasis, thyroid, and parathyroid functions were determined. Results One hundred twenty patients met the inclusion criteria; 70% of them had malnutrition. The presence of endocrine disorders was observed in 28/120 (23.33%) patients. The most common endocrine disorders were thyroid disorders, either subclinical or clinical hypothyroidism in 11/120 (9.17%) patients, followed by abnormalities in glucose homeostasis 9/120 (7.5%). The prevalence of impaired glucose tolerance, impaired fasting glucose, and diabetes mellitus in the present study was 5 (4.17%), 4 (3.33%), and 0 (00%), respectively, while the least frequent endocrine disorder seen in our patients was hypoparathyroidism in 8/120 (6.66%). We noted that high serum ferritin levels and poor patient compliance to therapy were significantly associated with increased endocrine disorders (OR 0.98, 95% CI 0.96–0.99, P = 0.003 and OR 0.38, 95% CI 0.16:0.93, P = 0.03, respectively). Combined chelating iron agents significantly decreased the prevalence of endocrine disorders when compared with monotherapy (OR 0.40, 95% CI 0.16:0.97, P = 0.04). Conclusion Endocrine disorders could occur in TM patients early before or equal to 12 years of life in about one-fourth of the patients. A high serum ferritin level and poor patient compliance to therapy were significantly associated with increased endocrine disorders. Combined iron-chelating agents were associated with a decreased prevalence of endocrine disorders when compared with monotherapy.

Role of Flavonoids in the Treatment of Iron Overload

Iron overload, a high risk factor for many diseases, is seen in almost all human chronic and common diseases. Iron chelating agents are often used for treatment but, at present, most of these have a narrow scope of application, obvious side effects, and other disadvantages. Recent studies have shown that flavonoids can affect iron status, reduce iron deposition, and inhibit the lipid peroxidation process caused by iron overload. Therefore, flavonoids with iron chelating and antioxidant activities may become potential complementary therapies. In this study, we not only reviewed the research progress of iron overload and the regulation mechanism of flavonoids, but also studied the structural basis and potential mechanism of their function. In addition, the advantages and disadvantages of flavonoids as plant iron chelating agents are discussed to provide a foundation for the prevention and treatment of iron homeostasis disorders using flavonoids.

Protective Effects of Deferoxamine on Vestibulotoxicity in Gentamicin-Induced Bilateral Vestibulopathy Rat Model

Introduction: Administration of aminoglycoside (AG) antibiotics is one of the most common causes of ototoxicity. This study aimed to determine the protective effects of deferoxamine, an iron-chelating agent, on vestibulotoxicity using an intratympanic gentamicin injection (ITGM)-induced bilateral vestibulopathy rat model.Methods: Fifteen Sprague-Dawley rats were randomly assigned to the ITGM only (n = 5), the ITGM combined with intramuscular deferoxamine (DFO) injection (ITGM+DFO, n = 5), or the intratympanic normal saline (control, n = 5) group. The rats in the ITGM+DFO group received intramuscular injection of 150 mg/kg of deferoxamine at 30, 90, and 150 min after the ITGM. The vestibular function was evaluated using the rotarod and open field test every 3 days after the injection until Day 16 when the rats were subjected to histological changes.Results: The rats in the ITGM only group began to show significantly impaired vestibular function 2 days after ITGM into both ears. In contrast, the vestibular function was maintained in the control and ITGM+DFO groups without a difference throughout the experiments. The rats in the ITGM only group showed a near-complete loss of the type I and II hair cells and a collapse of the sensory epithelium in both the saccule and utricle. In contrast, the rats in the ITGM+DFO and control groups showed a relatively well-preserved sensory epithelium including the hair cells, cilia, and otolith layer.Conclusion: This study provides experimental evidence for preventive effects of iron-chelating agents on AG-induced vestibulotoxicity. Simultaneous administration of iron-chelating agents may be considered when using ototoxic agents, especially in those considered to be vulnerable to toxic damage of the inner ear.