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Metals
Published in Frank A. Barile, Barile’s Clinical Toxicology, 2019
Anirudh J. Chintalapati, Frank A. Barile
Deferoxamine is an aluminum (Al) and iron (Fe(II)) chelator that is beneficial in the treatment of acute and chronic Fe poisoning and for Al overload. The compound is isolated from bacteria (Streptomyces pilosus) and is one of the few chelators recommended for the alleviation of secondary Fe overload. It is not effective orally and requires continuous subcutaneous administration to achieve efficient Fe elimination. Figure 26.4 illustrates the structure of deferoxamine with a chelated Fe moiety. It preferentially binds both free and bound Fe from hemosiderin and ferritin but not Fe contained in hemoglobin, transferrin, or cytochromes. Chemical structure of deferoxamine with Fe in the reduced form.
Iron Metabolism: Iron Transport and Cellular Uptake Mechanisms
Published in Bo Lönnerdal, Iron Metabolism in Infants, 2020
Iron chelation therapy was started some 20 years ago in patients with iron overload and anemia.2 At the present time, the ideal chelating agent (Table 4) has still to be found and only one drug has been judged to be clinically useful. Desferrioxamine B, a siderophore produced by Streptomyces pilosus, forms a very stable complex with iron but not with other metal ions, is effective in vivo, and has few side effects. The initial therapy with daily intramuscular bolus injections of desferrioxamine proved insufficient to prevent iron loading in the face of frequent repeated transfusions. Since the half-time of desferrioxamine in the circulation is only 5 to 10 min, it must be administered by continuous infusion to be effective. The required amount of desferrioxamine B (usually 2 to 4 g/d) is most conveniently given with a small portable infusion pump.286–288 If significant amounts are given over sufficient time, they have been shown to result in negative iron balance in patients with thalassemia with any level of iron loading (Table 5). Concomitant ascorbic acid treatment in ascorbate depleted individuals appears to render tissue more accessible to desferrioxamine, although the effect may be more limited when both urinary and stool iron excretion are taken into account. Unfortunately, ascorbic acid also appears to enchance the toxicity of tissue iron. Deterioration of heavily iron-loaded patients is well documented.2,279 For this reason, ascorbic acid should be given in limited amounts (100 to 200 mg/d) only to individuals who are ascorbic acid depleted.
SARS-CoV-2 Infection Dysregulates Host Iron (Fe)-Redox Homeostasis (Fe-R-H): Role of Fe-Redox Regulators, Ferroptosis Inhibitors, Anticoagulants, and Iron-Chelators in COVID-19 Control
Published in Journal of Dietary Supplements, 2023
Sreus A.G. Naidu, Roger A. Clemens, A. Satyanarayan Naidu
Deferoxamine B (DFOA) is a natural siderophore, a hydroxamic acid metabolite of the soil bacterium Streptomyces pilosus. The exquisite affinity of DFOA for Fe3+ identified its potential to remove excess iron from patients with transfusion dependent Hb disorders (313). DFOA binds to Fe3+ in the vascular space at 1:1 ratio and forms a water-soluble ferrioxamine (FOA) complex (314). In the hepatocytes, the FOA complex is excreted through bile and in plasma or tissue milieu, the FOA is filtered out by the kidneys. DFOA can remove Fe3+ only from storage proteins (ferritin and hemosiderin) and not from Hb, cytochromes, LF, and TF (23, 314). This selective iron-binding activity makes DFOA a physiologically relevant drug chelate for iron detoxification in many diseases and organ dysfunctions.
Enterobactin induces the chemokine, interleukin-8, from intestinal epithelia by chelating intracellular iron
Published in Gut Microbes, 2020
Piu Saha, Beng San Yeoh, Xia Xiao, Rachel M. Golonka, Ahmed A. Abokor, Camilla F. Wenceslau, Yatrik M. Shah, Bina Joe, Matam Vijay-Kumar
Enterobactin (Ent; from Escherichia coli) procured from Sigma-Aldrich (St. Louis, MO) is supplied free of iron and endotoxin (≥98% purity; HPLC). Iron-free Pyoverdine (from Pseudomonas fluorescens), ferrichrome (from Ustilago sphaerogena), Deferiprone, deferoxamine mesylate salt (DFO; from Streptomyces pilosus), 2,3 dihydroxybenzoic acid (2,3-DHBA), lipopolysaccharide (LPS) from E. coli 0128:B12, dimethyl sulfoxide (DMSO), ferric chloride (FeCl3, Fe3+), 2,2ʹ-dipyridyl, and cyclosporin H were purchased from Sigma-Aldrich (St. Louis, MO). Flagellin (FliC) from Salmonella enterica subsp. enterica serovar Typhimurium (SL3201, fljB-), a kind gift from Dr. Andrew Gewirtz, Georgia State University, was purified through sequential cation and anion-exchange chromatography as previously described.52 FITC Annexin-V apoptosis detection kit was purchased from Molecular Probes (Life Technologies, Columbus, OH). Chrome azurol S (CAS) was purchased from Acros Organics (Geel, Belgium). Recombinant mouse Lcn2 (alias neutrophil gelatinase-associated lipocalin) (rec-Lcn2; Cat# CM17) produced by a mammalian (human) expression system was procured from Novoprotein Scientific Inc. (Fremont, CA). Carrier-free rec-Lcn2 was supplied at a purity ≥95% as determined by reducing SDS-PAGE and free from endotoxin, siderophore, and iron.
Marine natural products with monoamine oxidase (MAO) inhibitory activity
Published in Pharmaceutical Biology, 2020
Ahreum Hong, Le Cam Tu, Inho Yang, Kyung-Min Lim, Sang-Jip Nam
Piloquinone (2, Figure 2) was reported in 1963 from the mycelium of Streptomyces pilosus (Connor et al. 1963). However, the inhibitory activities of 2 on recombinant human MAO were not studied until five decades later, with a derivative (3) from Streptomyces sp. CNQ-027 (Lee, Choi, et al. 2017). Interestingly, both piloquinones showed MAO-B selectivity over MAO-A, with a good selective index value of 0.19 (2, MAO-B IC50 1.21 μM), or no MAO-A inhibitory activity up to 80 μM (3, MAO-B IC50 14.5 μM). This finding was in conflict with a previous study which showed MAO-A selectivity with a dibenzopyrone frame fungal secondary metabolite (Lee, Kim, et al. 2017). The attached pentyl chain may be responsible for the selective conversion of piloquinones. Compound 3 showed potent inhibitory activity comparable with current Parkinson’s disease drugs, based on a MAO-B inhibitory mechanism. It is noteworthy that 3 is the most potent MAO-B inhibitor derived from microbial sources.