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Hemolysis and free hemoglobin revisited: exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins.
TLDR
This perspective reviews the principal mechanisms of Hb and hemin toxicity in different disease states, updates how the natural scavengers efficiently control these toxic moieties, and explores critical issues in the development of human plasma-derived Hp and hemopexin as therapeutics for patients with excessive intravascular hemolysis. Expand
Blood-brain barrier disruption and oxidative stress in guinea pig after systemic exposure to modified cell-free hemoglobin.
TLDR
Systemic exposure to an extracellular Hb triggers blood-brain barrier disruption and oxidative stress, which may have important implications for the use of Hb-based therapeutics and may provide indirect insight on the central nervous system vasculopathies associated with excessive hemolysis. Expand
Haptoglobin, hemopexin, and related defense pathways—basic science, clinical perspectives, and drug development
TLDR
The present review discusses the components of physiologic Hb/heme detoxification and their potential therapeutic application in a wide range of hemolytic conditions. Expand
Comparison of Oral Absorption and Bioavailability of Drugs Between Monkey and Human
TLDR
Monkeys appear to be a good predictor of Fa in humans, however, a generally lower F makes monkeys a potentially poor predictor of human F. Expand
CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin.
TLDR
It is demonstrated that Hb interacts efficiently with CD163 in the absence of Hp, identifying CD163 as a scavenger receptor for native Hb and small-molecular-weight Hb-based blood substitutes after Hp depletion. Expand
Structural and functional characterization of glutaraldehyde-polymerized bovine hemoglobin and its isolated fractions.
TLDR
Structural modification imparted by glutaraldehyde resulted in nearly identical functional characteristics of PolyHbBv and its fractions with regard to oxygen equilibrium, ligand binding, and autoxidative kinetics. Expand
Evidence for structural protein damage and membrane lipid remodeling in red blood cells from COVID-19 patients
TLDR
A significant impact of SARS-CoV-2 infection on RBC structural membrane homeostasis at the protein and lipid levels is suggested. Expand
Structural Basis of Peroxide-mediated Changes in Human Hemoglobin
TLDR
The novel oxidative pathway of HbA0 modification detailed here may explain the diverse oxidative, toxic, and potentially immunogenic effects associated with the release of hemoglobin from red blood cells during hemolytic diseases and/or when cell-free Hb is used as a blood substitute. Expand
Hemoglobinuria-related acute kidney injury is driven by intrarenal oxidative reactions triggering a heme toxicity response
TLDR
In models of stored blood transfusion and hemoglobin (Hb) exposure in guinea pigs and beagle dogs, experiments confirmed that free heme is a likely trigger of tubule barrier deregulation and oxidative cell damage and reinforced the hypothesis that uncontrolledfree heme could trigger the UPR as an important pathway of renal injury during hemoglobinuria. Expand
Purification and chemical modifications of hemoglobin in developing hemoglobin based oxygen carriers.
TLDR
The efficacy of blood substitutes, as a whole, has been readily demonstrated, in animals as well as clinical studies, but the remaining issue seems to be the hypertensive response seen in many hemoglobin solutions. Expand
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