The course of plasma alpha-1-microglobulin and haemolysis during cardiac surgery and the relationship to acute kidney injury, a pilot study.

Haemolysis occurring during cardiac surgery with cardiopulmonary bypass (CPB) is assumed to be a risk factor for postoperative acute kidney injury (AKI). Plasma alpha-1 microglobulin (A1M) may have a protective role as haem scavenger. The aim of this study was to evaluate the association between AKI and the degree of haemolysis and the course of A1M concentrations during cardiac surgery, respectively.

Effects of Recombinant α-Microglobulin on Early Proteomic Response in Risk Organs after Exposure to Lu-Octreotate.

Recombinant α-microglobulin (A1M) is proposed as a protector during Lu-octreotate treatment of neuroendocrine tumors, which is currently limited by bone marrow and renal toxicity. Co-administration of Lu-octreotate and A1M could result in a more effective treatment by protecting healthy tissue, but the radioprotective action of A1M is not fully understood. The aim of this study was to examine the proteomic response of kidneys and bone marrow early after Lu-octreotate and/or A1M administration.

Hematological and renal toxicity in mice after three cycles of high activity [Lu]Lu-PSMA-617 with or without human α-microglobulin.

Radioligand therapy with [Lu]Lu-PSMA-617 can be used to prolong life and reduce tumor burden in terminally ill castration resistant prostate cancer patients. Still, accumulation in healthy tissue limits the activity that can be administered. Therefore, fractionated therapy is used to lower toxicity.

Recombinant α-Microglobulin (rA1M) Protects against Hematopoietic and Renal Toxicity, Alone and in Combination with Amino Acids, in a Lu-DOTATATE Mouse Radiation Model.

Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) is used clinically to treat metastasized or unresectable neuroendocrine tumors (NETs). Although Lu-DOTATATE is mostly well tolerated in patients, bone marrow suppression and long-term renal toxicity are still side effects that should be considered. Amino acids are often used to minimize renal radiotoxicity, however, they are associated with nausea and vomiting in patients.

Co-administration with A1M does not influence apoptotic response of Lu-octreotate in GOT1 neuroendocrine tumors.

Recombinant α-microglobulin (A1M) is a proposed radioprotector during Lu-octreotate therapy of neuroendocrine tumors (NETs). To ensure a maintained therapeutic effect, we previously demonstrated that A1M does not affect the Lu-octreotate induced decrease in GOT1 tumor volume. However, the underlying biological events of these findings are still unknown.

Hematological Toxicity in Mice after High Activity Injections of Lu-PSMA-617.

Prostate cancer (PC) is one of the most common malignancies affecting men, with poor prognosis after progression to metastatic castration-resistant prostate cancer (mCRPC). Radioligand therapy (RLT) targeting the overexpressed PSMA on PC cells, with, e.g.

Kidney Protection with the Radical Scavenger α-Microglobulin (A1M) during Peptide Receptor Radionuclide and Radioligand Therapy.

α-Microglobulin (A1M) is an antioxidant found in all vertebrates, including humans. It has enzymatic reductase activity and can scavenge radicals and bind free heme groups. Infused recombinant A1M accumulates in the kidneys and has therefore been successful in protecting kidney injuries in different animal models.

Ferryl Hemoglobin and Heme Induce A-Microglobulin in Hemorrhaged Atherosclerotic Lesions with Inhibitory Function against Hemoglobin and Lipid Oxidation.

Infiltration of red blood cells into atheromatous plaques and oxidation of hemoglobin (Hb) and lipoproteins are implicated in the pathogenesis of atherosclerosis. α-microglobulin (A1M) is a radical-scavenging and heme-binding protein. In this work, we examined the origin and role of A1M in human atherosclerotic lesions.

Production of functional human fetal hemoglobin in Nicotiana benthamiana for development of hemoglobin-based oxygen carriers.

Hemoglobin-based oxygen carriers have long been pursued to meet clinical needs by using native hemoglobin (Hb) from human or animal blood, or recombinantly produced Hb, but the development has been impeded by safety and toxicity issues. Herewith we report the successful production of human fetal hemoglobin (HbF) in Nicotiana benthamiana through Agrobacterium tumefaciens-mediated transient expression. HbF is a heterotetrameric protein composed of two identical α- and two identical γ-subunits, held together by hydrophobic interactions, hydrogen bonds, and salt bridges.

It's About Time: Time-Dependent Tissue Damage in the Adult Porcine Retina After Enucleation.

The ex vivo large animal retina is extensively used in research ranging from discovery of disease mechanisms to future treatment paradigms. Due to limited standardization when harvesting the tissue, the time after enucleation is often extended for several hours, a factor that so far has not yet been fully characterized. The purpose of this study was to investigate the relationship between time after enucleation and retinal tissue damage.

Structure, Functions, and Physiological Roles of the Lipocalin α-Microglobulin (A1M).

α-microglobulin (A1M) is found in all vertebrates including humans. A1M was, together with retinol-binding protein and β-lactoglobulin, one of the three original lipocalins when the family first was proposed in 1985. A1M is described as an antioxidant and tissue cleaning protein with reductase, heme- and radical-binding activities.

Binding of the human antioxidation protein α-microglobulin (A1M) to heparin and heparan sulfate. Mapping of binding site, molecular and functional characterization, and co-localization in vivo and in vitro.

Heparin and heparan sulfate (HS) are linear sulfated disaccharide polymers. Heparin is found mainly in mast cells, while heparan sulfate is found in connective tissue, extracellular matrix and on cell membranes in most tissues. α-microglobulin (A1M) is a ubiquitous protein with thiol-dependent antioxidant properties, protecting cells and matrix against oxidative damage due to its reductase activities and radical- and heme-binding properties.

Lu-PSMA-617 Therapy in Mice, with or without the Antioxidant α-Microglobulin (A1M), Including Kidney Damage Assessment Using Tc-MAG3 Imaging.

Anti-prostate specific membrane antigen (PSMA) radioligand therapy is promising but not curative in castration resistant prostate cancer. One way to broaden the therapeutic index could be to administer higher doses in combination with radioprotectors, since administered radioactivity is kept low today in order to avoid side-effects from a high absorbed dose to healthy tissue. Here, we investigated the human radical scavenger α-microglobulin (A1M) together with 177-Lutetium (Lu) labeled PSMA-617 in preclinical models with respect to therapeutic efficacy and kidney toxicity.

Expression, Purification and Initial Characterization of Functional α-Microglobulin (A1M) in .

α-Microglobulin (A1M) is a small glycoprotein that belongs to the lipocalin protein family. A major biological role of A1M is to protect cells and tissues against oxidative damage by clearing free heme and reactive oxygen species. Because of this, the protein has attracted great interest as a potential pharmaceutical candidate for treatment of acute kidney injury and preeclampsia.

Pregnant alpha-1-microglobulin (A1M) knockout mice exhibit features of kidney and placental damage, hemodynamic changes and intrauterine growth restriction.

Alpha-1-microglobulin (A1M) is an antioxidant previously shown to be elevated in maternal blood during pregnancies complicated by preeclampsia and suggested to be important in the endogenous defense against oxidative stress. A knockout mouse model of A1M (A1Mko) was used in the present study to assess the importance of A1M during pregnancy in relation to the kidney, heart and placenta function. Systolic blood pressure (SBP) and heart rate (HR) were determined before and throughout gestation.

Heme-Induced Oxidation of Cysteine Groups of Myofilament Proteins Leads to Contractile Dysfunction of Permeabilized Human Skeletal Muscle Fibres.

Heme released from red blood cells targets a number of cell components including the cytoskeleton. The purpose of the present study was to determine the impact of free heme (20-300 µM) on human skeletal muscle fibres made available during orthopedic surgery. Isometric force production and oxidative protein modifications were monitored in permeabilized skeletal muscle fibre segments.

The Role of α-Microglobulin (A1M) in Erythropoiesis and Erythrocyte Homeostasis-Therapeutic Opportunities in Hemolytic Conditions.

α-microglobulin (A1M) is a small protein present in vertebrates including humans. It has several physiologically relevant properties, including binding of heme and radicals as well as enzymatic reduction, that are used in the protection of cells and tissue. Research has revealed that A1M can ameliorate heme and ROS-induced injuries in cell cultures, organs, explants and animal models.

Hemopexin and α1-microglobulin heme scavengers with differential involvement in preeclampsia and fetal growth restriction.

Hemopexin and α1-microglobulin act as scavengers to eliminate free heme-groups responsible for hemoglobin-induced oxidative stress. The present study evaluated maternal and fetal plasma concentrations of these scavengers in the different phenotypes of placenta-mediated disorders. Singleton pregnancies with normotensive fetal growth restriction [FGR] (n = 47), preeclampsia without FGR (n = 45) and preeclampsia with FGR (n = 51) were included prospectively as well as uncomplicated pregnancies (n = 49).

α-Microglobulin (A1M) Protects Human Proximal Tubule Epithelial Cells from Heme-Induced Damage In Vitro.

Oxidative stress is associated with many renal disorders, both acute and chronic, and has also been described to contribute to the disease progression. Therefore, oxidative stress is a potential therapeutic target. The human antioxidant α-microglobulin (A1M) is a plasma and tissue protein with heme-binding, radical-scavenging and reductase activities.

α-Microglobulin Binds Illuminated Flavins and Has a Protective Effect Against Sublethal Riboflavin-Induced Damage in Retinal Epithelial Cells.

Riboflavin (vitamin B2) is an important constituent of the prosthetic groups flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), which are utilized as electron-carriers in energy metabolism. Excitation by UV-light leads to the generation of riboflavin radicals and reactive oxygen species (ROS), which can oxidize a wide range of biomolecules. The human protein α-microglobulin (A1M) is a reductase and a radical scavenger, which can protect cells and matrix against oxidative damage.

Correction: The Human Endogenous Protection System against Cell-Free Hemoglobin and Heme Is Overwhelmed in Preeclampsia and Provides Potential Biomarkers and Clinical Indicators.

[This corrects the article DOI: 10.1371/journal.pone.

Human radical scavenger α-microglobulin protects against hemolysis in vitro and α-microglobulin knockout mice exhibit a macrocytic anemia phenotype.

During red blood cell (RBC) lysis hemoglobin and heme leak out of the cells and cause damage to the endothelium and nearby tissue. Protective mechanisms exist; however, these systems are not sufficient in diseases with increased extravascular hemolysis e.g.