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Oxidation reactions of cellular and acellular hemoglobins: Implications for human health.
Front Med Technol
November 2022
Laboratory of Biochemistry and Vascular Biology (LBVB), Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, MD, United States.
Oxygen reversibly binds to the redox active iron, a transition metal in human Hemoglobin (Hb), which subsequently undergoes oxidation in air. This process is akin to iron rusting in non-biological systems. This results in the formation of non-oxygen carrying methemoglobin (ferric) (Fe) and reactive oxygen species (ROS).
View Article and Find Full Text PDFScalable manufacturing platform for the production of methemoglobin as a non-oxygen carrying control material in studies of cell-free hemoglobin solutions.
PLoS One
February 2022
William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, United States of America.
Methemoglobin (metHb) arises from the oxidation of ferrous hemoglobin (HbFe2+, Hb) to ferric hemoglobin (HbFe3+, metHb), which is unable to bind gaseous ligands such as oxygen (O2) and carbon monoxide (CO), and binds to nitric oxide (NO) significantly slower compared to Hb. Therefore, metHb does not elicit vasoconstriction and systemic hypertension in vivo due to its extremely slow NO scavenging rate in comparison to cell-free Hb, but will induce oxidative tissue injury, demonstrating the potential of using metHb as a control material when studying the toxicity of cell-free Hb. Hence, the goal of this work was to develop a novel manufacturing strategy for production of metHb that is amenable to scale-up.
View Article and Find Full Text PDFLethal methemoglobinemia in the invasive brown treesnake after acetaminophen ingestion.
Sci Rep
January 2020
United States Department of Agriculture, Animal and Plant Health Inspection Service, Wildlife Services, National Wildlife Research Center, 4101 Laporte Avenue, Fort Collins, Colorado, 80521, USA.
The invasive brown treesnake (Boiga irregularis) has extirpated much of Guam's native birdlife and poses significant threats to other parts of the western Pacific. Acetaminophen (APAP) is a proven lethal oral toxicant in reptiles but the physiological mechanism is unknown. The effects of a lethal APAP oral dose on methemoglobin (MetHb, non-oxygen carrying form) levels and other blood parameters were examined in brown treesnakes.
View Article and Find Full Text PDFMicrovascular and systemic responses to novel PEGylated carboxyhaemoglobin-based oxygen carrier in a rat model of vaso-occlusive crisis.
Artif Cells Nanomed Biotechnol
December 2019
a Song Biotechnologies , Baltimore , MD , USA.
Hypoxia drives sickle cell disease (SCD) by inducing sickle cell haemoglobin to polymerize and deform red blood cells (RBC) into the sickle shape. A novel carboxyhaemoglobin-based oxygen carrier (PEG-COHb; PP-007) promotes unsickling in vitro by relieving RBC hypoxia. An in vivo rat model of vaso-occlusive crisis (VOC) capable of accommodating a suite of physiological and microcirculatory measurements was used to compare treatment with PEG-COHb to a non-oxygen carrying control solution (lactated ringer's [LRS]).
View Article and Find Full Text PDFWhole blood and Hextend: Bookends of modern tactical combat casualty care field resuscitation and starting point for multifunctional resuscitation fluid development.
J Trauma Acute Care Surg
July 2018
From the Department of Trauma and Expeditionary Medicine, Naval Medical Research Unit San Antonio (F.R.S., A.R.M., D.M.F., L.J.S., K.M.O., J.J.G.), JBSA-Ft. Sam Houston; Department of Surgery, San Antonio Military Medical Center (T.A.M., J.J.G.), JBSA-Ft. Sam Houston, Texas; and Washington University in St. Louis (F.R.S.), St. Louis, Missouri.
Background: Hemorrhage is the leading cause of preventable death in traumatically injured civilian and military populations. Prehospital resuscitation largely relies on crystalloid and colloid intravascular expansion, as whole blood and component blood therapy are logistically arduous. In this experiment, we evaluated the bookends of Tactical Combat Casualty Care Guidelines recommendations of prehospital resuscitation with Hextend and whole blood in a controlled hemorrhagic shock model within non-human primates, as means of a multifunctional resuscitative fluid development.
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