ArticleThe Journal of clinical investigation2009
Sequestration of extracellular hemoglobin within a haptoglobin complex decreases its hypertensive and oxidative effects in dogs and guinea pigs.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 194 citations in OpenAlex.
- Acetaminophen attenuates lipid peroxidation in children undergoing cardiopulmonary bypass.Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 2014Trial
- Suppression of haptoglobin and loss of striatal neurons in mice chronically exposed to chlorpyrifos-contaminated drinking water.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- CD163 at the crossroads: a viral-exploited immunomodulator.Virology journal · 2026Review
- Hemoglobin-Based Oxygen Carriers: Selected Advances and Challenges in the Design of Safe Oxygen Therapeutics (A Focused Review).International journal of molecular sciences · 2025Review
- Cell-free hemoglobin is associated with microcirculatory perfusion disturbances and acute kidney injury in rats on extracorporeal membrane oxygenation.BMC anesthesiology · 2025Article
- Microvascular Consequences of Methemoglobin Compared to Reduced Hemoglobin in the Microcirculation.Microcirculation (New York, N.Y. : 1994) · 2025Article
- Pilot study: In vitro reduction of hemoglobin from canine blood with hemoperfusion using the Cytosorb® adsorber.PloS one · 2025Article
- Signs of Hemolysis Predict Mortality and Ventilator Associated Pneumonia in Severe Acute Respiratory Distress Syndrome Patients Undergoing Veno-Venous Extracorporeal Membrane Oxygenation.ASAIO journal (American Society for Artificial Internal Organs : 1992) · 2025Article
- Cardiopulmonary bypass associated acute kidney injury: better understanding and better prevention.Renal failure · 2024Review
- Coadministration of PEGylated apohemoglobin and haptoglobin can limit vascular dysfunction in the microcirculation and prevent acute inflammation.Journal of applied physiology (Bethesda, Md. : 1985) · 2024Article
- Toxic side-effects of diaspirin cross-linked human hemoglobin are attenuated by the apohemoglobin-haptoglobin complex.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Acute Kidney Injury after Cardiac Surgery: Prediction, Prevention, and Management.Anesthesiology · 2023Review
- How Nitric Oxide Hindered the Search for Hemoglobin-Based Oxygen Carriers as Human Blood Substitutes.International journal of molecular sciences · 2023Review
- Polymerized human cord hemoglobin assisted with ascorbic acid as a red blood cell substitute alleviating oxidative stress for blood transfusion.Frontiers in bioengineering and biotechnology · 2023Article
- Transpulmonary generation of cell-free hemoglobin contributes to vascular dysfunction in pulmonary arterial hypertension via dysregulated clearance mechanisms.Pulmonary circulation · 2023Article
- Article
- Anti-inflammatory cytokines in sickle cell disease.Molecular biology reports · 2022Review
- Is hemolysis a novel therapeutic target in COVID-19?Frontiers in immunology · 2022Article
- Toxic effects of cell-free hemoglobin on the microvascular endothelium: implications for pulmonary and nonpulmonary organ dysfunction.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Haptoglobin treatment prevents cell-free hemoglobin exacerbated mortality in experimental rat sepsis.Intensive care medicine experimental · 2021Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Release of hemoglobin (Hb) into the circulation is a central pathophysiologic event that contributes to morbidity and mortality in chronic hemolytic anemias and severe malaria. These toxicities arise from Hb-mediated vasoactivity, possibly due to NO scavenging and localized tissue oxidative processes. Currently, there is no established treatment that targets circulating extracellular Hb. Here, we assessed the role of haptoglobin (Hp), the primary scavenger of Hb in the circulation, in limiting the toxicity of cell-free Hb infusion. Using a canine model, we found that glucocorticoid stimulation of endogenous Hp synthesis prevented Hb-induced hemodynamic responses. Furthermore, guinea pigs administered exogenous Hp displayed decreased Hb-induced hypertension and oxidative toxicity to extravascular environments, such as the proximal tubules of the kidney. The ability of Hp to both attenuate hypertensive responses during Hb exposure and prevent peroxidative toxicity in extravascular compartments was dependent on Hb-Hp complex formation, which likely acts through sequestration of Hb rather than modulation of its NO- and O2-binding characteristics. Our data therefore suggest that therapies involving supplementation of endogenous Hb scavengers may be able to treat complications of acute and chronic hemolysis, as well as counter the adverse effects associated with Hb-based oxygen therapeutics.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.