Deferoxamine produces nitric oxide under ferricyanide oxidation, blood incubation, and UV-irradiation

• Published in: Free radical biology & medicine Vol. 160; pp. 458 - 470
• Main Authors: Mukosera, George T., Liu, Taiming, Manaen, Meshach, Zhu, Lingchao, Power, Gordon, Schroeder, Hobe, Blood, Arlin B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.11.2020
• Subjects: Animals; Deferoxamine; Ferricyanide; Ferricyanides; Iron Chelating Agents; Iron nitrosyl hemoglobin; Nitric Oxide; Sheep; Ultraviolet Rays; Ferricyanide; Iron nitrosyl hemoglobin; Nitric oxide; Deferoxamine
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2020.08.004

Deferoxamine (DFO), an iron chelator, is used therapeutically for the removal of excess iron in multiple clinical conditions such as beta thalassemia and intracerebral hemorrhage. DFO is also used as an iron chelator and hypoxia-mimetic agent in in vivo and in vitro basic research. Here we unexpectedly discover DFO to be a nitric oxide (NO) precursor in experiments where it was intended to act as an iron chelator. Production of NO from aqueous solutions of DFO was directly observed by ozone-based chemiluminescence using a ferricyanide-based assay and was confirmed by electron paramagnetic resonance (EPR). DFO also produced NO following exposure to ultraviolet light, and its incubation with sheep adult and fetal blood resulted in considerable formation of iron nitrosyl hemoglobin, as confirmed by both visible spectroscopy and EPR. These results suggest that experiments using DFO can be confounded by concomitant production of NO, and offer new insight into some of DFO's unexplained clinical side effects such as hypotension. [Display omitted] •Deferoxamine (DFO), a commonly used iron chelator, releases nitric oxide (NO) under oxidative conditions as well as under UV light.•Iron nitrosyl hemoglobin (HbNO) is also significantly formed from DFO incubated with sheep blood.•NO release from DFO could confound experiments using DFO, and offer new insight into some of DFO's unexplained clinical side effects such as hypotension.