Rapid Elimination of Blood Alcohol Using Erythrocytes: Mathematical Modeling and In Vitro Study
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 ex...
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doaj-604bfe897d334a93bdffcf338d22e5712020-11-24T22:08:55ZengHindawi LimitedBioMed Research International2314-61332314-61412017-01-01201710.1155/2017/58495935849593Rapid Elimination of Blood Alcohol Using Erythrocytes: Mathematical Modeling and In Vitro StudyYuliya G. Alexandrovich0Elena A. Kosenko1Elena I. Sinauridze2Sergey I. Obydennyi3Igor I. Kireev4Fazoil I. Ataullakhanov5Yuriy G. Kaminsky6Laboratory of Biophysics and Physiology of the Cell, Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Kosygin Street 4, Moscow 119334, RussiaLaboratory of Modeling and Bioinformatics, Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Institutskaya Street 3, Pyshchino, Moscow Region 142290, RussiaLaboratory of Biophysics and Physiology of the Cell, Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Kosygin Street 4, Moscow 119334, RussiaLaboratory of Biophysics and Physiology of the Cell, Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Kosygin Street 4, Moscow 119334, RussiaDepartment of Electron Microscopy, Moscow State University, Belozersky Institute of Physico-Chemical Biology, Leninskie Gory 1, Building 40, Moscow 119992, RussiaLaboratory of Biophysics and Physiology of the Cell, Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Kosygin Street 4, Moscow 119334, RussiaLaboratory of Modeling and Bioinformatics, Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Institutskaya Street 3, Pyshchino, Moscow Region 142290, RussiaErythrocytes (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.http://dx.doi.org/10.1155/2017/5849593 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yuliya G. Alexandrovich Elena A. Kosenko Elena I. Sinauridze Sergey I. Obydennyi Igor I. Kireev Fazoil I. Ataullakhanov Yuriy G. Kaminsky |
spellingShingle |
Yuliya G. Alexandrovich Elena A. Kosenko Elena I. Sinauridze Sergey I. Obydennyi Igor I. Kireev Fazoil I. Ataullakhanov Yuriy G. Kaminsky Rapid Elimination of Blood Alcohol Using Erythrocytes: Mathematical Modeling and In Vitro Study BioMed Research International |
author_facet |
Yuliya G. Alexandrovich Elena A. Kosenko Elena I. Sinauridze Sergey I. Obydennyi Igor I. Kireev Fazoil I. Ataullakhanov Yuriy G. Kaminsky |
author_sort |
Yuliya G. Alexandrovich |
title |
Rapid Elimination of Blood Alcohol Using Erythrocytes: Mathematical Modeling and In Vitro Study |
title_short |
Rapid Elimination of Blood Alcohol Using Erythrocytes: Mathematical Modeling and In Vitro Study |
title_full |
Rapid Elimination of Blood Alcohol Using Erythrocytes: Mathematical Modeling and In Vitro Study |
title_fullStr |
Rapid Elimination of Blood Alcohol Using Erythrocytes: Mathematical Modeling and In Vitro Study |
title_full_unstemmed |
Rapid Elimination of Blood Alcohol Using Erythrocytes: Mathematical Modeling and In Vitro Study |
title_sort |
rapid elimination of blood alcohol using erythrocytes: mathematical modeling and in vitro study |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6133 2314-6141 |
publishDate |
2017-01-01 |
description |
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. |
url |
http://dx.doi.org/10.1155/2017/5849593 |
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