Exploring unconventional attributes of red blood cells and their potential applications in biomedicine

Anastasiadi, Alkmini T; Arvaniti, Vasiliki-Zoi; Hudson, Krystalyn E; Kriebardis, Anastasios G; Stathopoulos, Constantinos; D’Alessandro, Angelo; Spitalnik, Steven L; Tzounakas, Vassilis L

doi:10.1093/procel/pwae001

Cited by 7 publications

(2 citation statements)

References 197 publications

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“…Alternative therapeutic schemes can also be tested based on these cells. Additionally, erythrocytes could be used as delivery systems with the potential to increase the bioavailability of the active drug agent (Anastasiadi et al, 2024).…”

Section: Resultsmentioning

confidence: 99%

Anaerobic glycolysis and oxidative stress interrelation in erythrocytes under administration of Cornus mas L. fruit extracts to rats with streptozotocin-induced diabetes mellitus

Moroz,

Brodyak,

Kucharska

et al. 2024

Biol. Stud.

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Background. In diabetes mellitus (DM), analysis of changes in the biochemical profile of erythrocytes is the important stage of complex scientific research to clarify the mechanism of action of medicinal products based on plant raw materials. The fruits of Cornus mas L. are widely known. The biologically active compounds of these fruits show multiple biological effects. However, the effect of the fruit extracts of cornelian cherry on the functional state of erythrocytes in diabetes has not been sufficiently studied. The high glucose concentration in erythrocytes induces various structural and functional changes, which lead to numerous disturbances in their metabolism. Glucose transported into erythrocytes by facilitated diffusion via GLUT2 undergoes catabolic breakdown in anaerobic glycolysis (90 % of all glucose) and pentose phosphate pathway (the rest 10 %). ATP and reduced coenzymes of NADH + H+ and NADPH + H+ formed due to metabolism participate in maintaining the structure of hemoglobin. Enzymes of the antioxidant defense system, which prevent hemoglobin oxidation into methemoglobin, are especially important. Hyperglycemia and the development of oxidative stress in diabetes are the cause of a decrease in the activity of antioxidant enzymes and the accumulation of ligand forms of hemoglobin (HbCO2, MetHb, HbA1c). Therefore, the work aimed to investigate the effect of extracts of red and yellow fruits of Cornus mas L. on the content of end products of the glycolytic breakdown of glucose in erythrocytes and biochemical markers of the antioxidant status of these blood cells in rats with streptozotocin-induced diabetes. Materials and Methods. DM 1 type in animals was induced by intraperitoneal injection of streptozotocin. Experiments were performed on male Wistar rats, who, from the 10th day after diabetes induction, were administered per os extracts of red and yellow fruits of the cornelian cherry and loganic acid obtained from yellow fruits at a dose of 20 mg/kg of body weight for 14 days. On the 24th day of the experiment, the rats were decapitated under ether anesthesia, and blood was taken. The content of pyruvate and lactate (as the end products of anaerobic glycolysis) and L-lactate dehydrogenase activity were determined in plasma and erythrocytes, as well as biochemical markers of the antioxidant status of erythrocytes (activity of superoxide dismutase, catalase and glutathione peroxidase, level of reduced glutathione, TBA-reactive substances, concentration of oxidative modifications of proteins and advanced oxidation protein products). Results. The activity of catalase, superoxide dismutase, glutathione peroxidase and the concentration of reduced glutathione significantly increased against the decrease in the content of oxidative modifications of proteins, advanced oxidation protein products, TBA-reactive substances, pyruvate, L-lactate, and lactate dehydrogenase in rats with DM after administration of the fruit extracts of the cornelian cherry. Noteworthy, these biochemical indicators made it possible to assess the intensity of anaerobic glycolysis and the antioxidant status of blood erythrocytes in streptozotocin diabetes. Conclusions. Extracts of Cornus mas L. fruits might be potential natural drugs for the treatment of metabolic disorders in diabetes, as they have a corrective effect on the catabolic breakdown of glucose and the antioxidant defense system of erythrocytes, preventing the development of oxidative stress. It should be pointed out that the extract of red fruits of cornelian cherry showed the best effect among the studied extracts in normalizing these indicators.

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Section: Resultsmentioning

confidence: 99%

Anaerobic glycolysis and oxidative stress interrelation in erythrocytes under administration of Cornus mas L. fruit extracts to rats with streptozotocin-induced diabetes mellitus

Moroz,

Brodyak,

Kucharska

et al. 2024

Biol. Stud.

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“…Red blood cells (RBCs) are critically important for organismal biology by, for example, delivering oxygen to multiple tissues and removing carbon dioxide [ 1 ]. To transport oxygen, every human RBC contains ~250 million hemoglobin molecules [ 2 ], each of which contains four heme groups, with each of those containing one atom of the ferrous form of iron caged within a porphyrin ring.…”

Section: Introductionmentioning

confidence: 99%

The Role of Ergothioneine in Red Blood Cell Biology: A Review and Perspective

Thomas,

Francis,

Zimring

et al. 2024

Antioxidants

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Oxidative stress can damage tissues and cells, and their resilience or susceptibility depends on the robustness of their antioxidant mechanisms. The latter include small molecules, proteins, and enzymes, which are linked together in metabolic pathways. Red blood cells are particularly susceptible to oxidative stress due to their large number of hemoglobin molecules, which can undergo auto-oxidation. This yields reactive oxygen species that participate in Fenton chemistry, ultimately damaging their membranes and cytosolic constituents. Fortunately, red blood cells contain robust antioxidant systems to enable them to circulate and perform their physiological functions, particularly delivering oxygen and removing carbon dioxide. Nonetheless, if red blood cells have insufficient antioxidant reserves (e.g., due to genetics, diet, disease, or toxin exposure), this can induce hemolysis in vivo or enhance susceptibility to a “storage lesion” in vitro, when blood donations are refrigerator-stored for transfusion purposes. Ergothioneine, a small molecule not synthesized by mammals, is obtained only through the diet. It is absorbed from the gut and enters cells using a highly specific transporter (i.e., SLC22A4). Certain cells and tissues, particularly red blood cells, contain high ergothioneine levels. Although no deficiency-related disease has been identified, evidence suggests ergothioneine may be a beneficial “nutraceutical.” Given the requirements of red blood cells to resist oxidative stress and their high ergothioneine content, this review discusses ergothioneine’s potential importance in protecting these cells and identifies knowledge gaps regarding its relevance in enhancing red blood cell circulatory, storage, and transfusion quality.

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Therapeutic potential of red blood cell-derived extracellular vesicles in reducing neuroinflammation and protecting against retinal degeneration

Sekar,

Cioanca,

Yang

et al. 2024

Preprint

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Neuroinflammation is a pathological process mediated through immune cell activation and pro-inflammatory cytokine release, resulting in neuronal cell death. In the central nervous system (CNS), neuroinflammation is a characteristic feature underlying the onset and progression of retinal and neurodegenerative diseases. Targeting neuroinflammation to reduce neuronal cell death and protect against visual and cognitive declines is therefore a key therapeutic strategy. However, due to the complex and multi-faceted nature of these diseases, to date there has been little therapeutic success with single target approaches insufficient to tackle widespread and multi-pathway inflammatory cascades. Furthermore, as the retina and brain reside within immune-privileged environments, a major challenge in treating these diseases is producing and delivering a therapeutic that, in itself, does not exacerbate inflammation. Extracellular vesicles (EV), derived from red blood cells (RBC EV), present a promising solution to overcome these hurdles, due to their innate ability to cross blood-tissue barriers, biocompatible nature, and their broad anti-inflammatory properties to modulate complex neuroinflammatory pathways.This study therefore investigated the therapeutic potential of RBC EV in mediating neuroinflammation using anin-vivophoto-oxidative damage model of retinal degeneration as a model for CNS neuroinflammation. In this work, we developed a novel incubation pipeline using N1 medium supplement and superoxide dismutase (SOD) supplementation to promote the production of safe, neuroprotective, and anti-inflammatory RBC EV. Delivery of RBC EVin vivo, was shown to be safe with strong penetration across all retinal layers. Further, therapeutic administration of RBC EV via local intravitreal injection significantly reduced inflammation and cell death and preserved retinal function. Notably, strong safety and therapeutic efficacy was also demonstrated in the retina following systemic (intraperitoneal) administration, highlighting a potential game-changing approach for less-invasive therapeutic delivery to the CNS. Finally, multi-omic analyses andin vitrofindings supported an anti-inflammatory mechanism-of-action, with RBC EV modulating pro-inflammatory cytokine release, including those known to be involved in the pathogenesis of retinal and neurodegenerative diseases.Taken together, these findings highlight the broad applicability of RBC EV in treating neuroinflammation in the CNS, presenting a scalable and effective treatment approach for these currently untreatable diseases.

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Exploring unconventional attributes of red blood cells and their potential applications in biomedicine

Cited by 7 publications

References 197 publications

Anaerobic glycolysis and oxidative stress interrelation in erythrocytes under administration of Cornus mas L. fruit extracts to rats with streptozotocin-induced diabetes mellitus

Anaerobic glycolysis and oxidative stress interrelation in erythrocytes under administration of Cornus mas L. fruit extracts to rats with streptozotocin-induced diabetes mellitus

The Role of Ergothioneine in Red Blood Cell Biology: A Review and Perspective

Therapeutic potential of red blood cell-derived extracellular vesicles in reducing neuroinflammation and protecting against retinal degeneration

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