In Vivo Accelerated Acetaldehyde Metabolism Using Acetaldehyde Dehydrogenase-Loaded Erythrocytes

Magnani, Mauro; Laguerre, M.; Rossi, Luigia; Bianchi, Marzia; Ninfali, Paolino; Mangani, Filippo; Ropars, C.

doi:10.1093/oxfordjournals.alcalc.a045059

Cited by 25 publications

(16 citation statements)

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“…The MCH and MCHC of alcocytes were decreased, probably due to a leakage of hemoglobin from cells during dialysis. Similar decreases in MCV and MCH were described in the literature [37, 38]. MCV, MCH, and MCHC of alcocytes were virtually independent of the number of dialysis steps and of osmolality of the dialysis solution at the second dialysis step.…”

Section: Resultssupporting

confidence: 86%

“…The cytosolic ratio for free NAD + /NADH in the erythrocytes is 471 ± 143 as estimated using the indirect method [40]. When the total nucleotides (free plus protein-bound) were directly measured, a physiological ratio NAD + /NADH in the erythrocytes was equal to 2.2–2.5 [30] but varied from 0.5–0.6 to 20–30 under various conditions [37]. To keep the cytosolic NAD + /NADH ratio in alcocytes supplemented with excess NAD + , and to compensate for possible loss of NADH from the cells during hypotonic dialysis, we tested how the addition of NADH to the dialysis solution could impact ethanol oxidation using the obtained alcocytes.…”

Section: Resultsmentioning

confidence: 99%

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Rapid Elimination of Blood Alcohol Using Erythrocytes: Mathematical Modeling and In Vitro Study

Alexandrovich

Kosenko

Sinauridze

et al. 2017

BioMed Research International

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Erythrocytes (RBCs) loaded with alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALD) can metabolize plasma ethanol and acetaldehyde but with low efficiency. We investigated the rate-limiting factors in ethanol oxidation by these enzymes loaded into RBCs. Mathematical modeling and in vitro experiments on human RBCs loaded simultaneously with ADH and ALD (by hypoosmotic dialysis) were performed. The simulation showed that the rate of nicotinamide-adenine dinucleotide (NAD+) generation in RBC glycolysis, but not the activities of the loaded enzymes, is the rate-limiting step in external ethanol oxidation. The rate of oxidation could be increased if RBCs are supplemented by NAD+ and pyruvate. Our experimental data verified this theoretical conclusion. RBCs loaded with the complete system of ADH, ALD, NAD+, and pyruvate metabolized ethanol 20–40 times faster than reported in previous studies. The one-step procedure of hypoosmotic dialysis is the optimal method to encapsulate ADH and ALD in RBCs after cell recovery, encapsulation yield, osmotic resistance, and RBC-indexes. Consequently, transfusion of the RBCs loaded with the complete metabolic system, including ADH, ALD, pyruvate, and NAD+ in the patients with alcohol intoxication, may be a promising method for rapid detoxification of blood alcohol based on metabolism.

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Section: Resultssupporting

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Rapid Elimination of Blood Alcohol Using Erythrocytes: Mathematical Modeling and In Vitro Study

Alexandrovich

Kosenko

Sinauridze

et al. 2017

BioMed Research International

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“…Figure 4 shows micrographs of erythrocyte samples before and after the loading procedure by , have been reported to be for human RBCs within the normal ranges, being about 110 days and 28 days, respectively (normal values: MCL 89-131 days, MHL 19-29 days) (Bax et al 1999). Treated murine RBCs show a slightly reduced MHL (6-11 days vs normal 12-14 days) (Magnani et al 1990;Bourgeaux et al 2012). The dialysis method to develop proteinloaded erythrocytes has been employed in several in vitro (Magnani et al 1988) and in vivo preclinical and clinical studies (Bax et al 2013;Bax et al 2007).…”

Section: Loading Proceduresmentioning

confidence: 82%

Erythrocyte‐mediated delivery of recombinant enzymes

Leuzzi

Rossi

Gabucci

et al. 2016

J of Inher Metab Disea

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The possibility to clone, express and purify recombinant enzymes have originated the opportunity to dispose of a virtually infinite array of proteins that could be used in the clinics to treat several inherited and acquired pathological conditions. However, the direct administration of these recombinant proteins faces some intrinsic difficulties, such as degradation by circulating proteases and/or inactivation by the patient immune system. The use of drug delivery systems may overcome these limitations. Concerning recombinant enzyme therapy, the present review will mainly focus on the exploitation of erythrocytes as a carrier system for enzymes removing potentially noxious metabolites from the circulation, either as limiting treatment strategy for auxotrophic tumours or as a detoxing approach for some intoxication type inherited metabolic disorders. Moreover, the possibility of using RBCs as a potential delivering system addressing the enzymes to the monocyte-macrophages of reticular endothelial system for the treatment of diseases associated with this cell lineage, e.g. lysosome storage diseases, will be briefly discussed.

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“…EBRs for removal of low molecular metabolites (ethanol, methanol, cyanide, glucose or ammonium) from bloodstream have been described. These EBRs were based on alcohol dehydrogenase [11,59,60], alcohol oxidase [61], acetaldehyde dehydrogenase [11,62] or alcohol-and acetaldehyde dehydrogenase together [63] in cases of ethanol, methanol and acetaldehyde removal.…”

Section: Erythrocytes-bioreactors For Low Molecular Metabolites Utilimentioning

confidence: 99%

“…Alcohol and methanol intoxication [59,60] Alcohol oxidase [61] Acetaldehyde dehydrogenase [62] Alcohol dehydrogenase + acetaldehyde dehydrogenase [11,63]…”

Section: Active Substance Application Referencesmentioning

confidence: 99%

Erythrocytes as Carriers: From Drug Delivery to Biosensors

et al. 2020

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Drug delivery using natural biological carriers, especially erythrocytes, is a rapidly developing field. Such erythrocytes can act as carriers that prolong the drug's action due to its gradual release from the carrier; as bioreactors with encapsulated enzymes performing the necessary reactions, while remaining inaccessible to the immune system and plasma proteases; or as a tool for targeted drug delivery to target organs, primarily to cells of the reticuloendothelial system, liver and spleen. To date, erythrocytes have been studied as carriers for a wide range of drugs, such as enzymes, antibiotics, anti-inflammatory, antiviral drugs, etc., and for diagnostic purposes (e.g., magnetic resonance imaging). The review focuses only on drugs loaded inside erythrocytes, defines the main lines of research for erythrocytes with bioactive substances, as well as the advantages and limitations of their application. Particular attention is paid to in vivo studies, opening-up the potential for the clinical use of drugs encapsulated into erythrocytes.Pharmaceutics 2020, 12, 276 2 of 44 property of RBCs allows to load them with biologically active substances of different molecular weights. For these reasons, erythrocytes are promising biocompatible cells for drug delivery.The methods for incorporating various substances into red blood cells differ in the way that substances penetrate the cells. The cause of permeability may be the pores' formation in the cell membrane due to a physical exposure (high voltage electric pulse [10,11] or ultrasound [12]). Drug molecules can also enter the RBCs by endocytosis in the presence of certain chemical compounds (for example, primaquine [13], vinblastine, chlorpromazine, hydrocortisone or tetracaine [14,15]), or using the cell-penetrating peptides bounded to the compound that should be encapsulated [16]. However, the most popular are different variants of osmotic methods.In some cases, RBCs are first exposed to a hyperosmotic pulse of a low molecular weight substance that penetrates very well through the cell membrane (for example, dimethyl sulfoxide (DMSO) [17,18] or glucose [19,20]). After washing the cells, which decreases the external concentration of these compounds and creates a gradient of their concentration between both sides of the RBC membrane, the target drug is introduced into the external volume. Water with this drug begins to enter into the cells to decrease the osmotic pressure there. The process ends when the gradient of DMSO or glucose disappears. The pores close and part of the drug remains into RBCs. Other, the most popular of the osmotic methods are hypoosmotic. These methods are based on creating a hypotonic environment around RBCs, which causes swelling of the cells and opening pores in the cellular membrane, through which therapeutic compounds can penetrate RBCs. Then, a hypertonic solution is introduced into the cell suspension. The pores close, the cells restore their original size, trapping the drug molecules inside the cell. Osmotic methods are divided into severa...

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In Vivo Accelerated Acetaldehyde Metabolism Using Acetaldehyde Dehydrogenase-Loaded Erythrocytes

Cited by 25 publications

References 0 publications

Rapid Elimination of Blood Alcohol Using Erythrocytes: Mathematical Modeling and In Vitro Study

Rapid Elimination of Blood Alcohol Using Erythrocytes: Mathematical Modeling and In Vitro Study

Erythrocyte‐mediated delivery of recombinant enzymes

Erythrocytes as Carriers: From Drug Delivery to Biosensors

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