TY - JOUR
T1 - An in vitro study on the interaction of the anti-Alzheimer drug rivastigmine with human erythrocytes
AU - Zambrano, Pablo
AU - Suwalsky, Mario
AU - Jemiola-Rzeminska, Malgorzata
AU - Strzalka, Kazimierz
AU - AGUILAR CAVALLO, LUIS FELIPE
N1 - Funding Information:
The authors thank to CONICYT-PFCHA (Beca Doctorado Nacional 21160337 to P. Zambrano) and FONDECYT (Project 1130043). All DSC measurements were carried out using the instrument purchased thanks to financial support of European Regional Development Fund (contract No. POIG.02.01.00-12-167/08 , Project Malopolska Centre of Biotechnology). The Jagiellonian University is a partner of the Leading National Research Center (KNOW) supported by the Ministry of Science and Higher Education (Poland) .
Funding Information:
The authors thank to CONICYT-PFCHA (Beca Doctorado Nacional 21160337 to P. Zambrano) and FONDECYT (Project 1130043). All DSC measurements were carried out using the instrument purchased thanks to financial support of European Regional Development Fund (contract No. POIG.02.01.00-12-167/08, Project Malopolska Centre of Biotechnology). The Jagiellonian University is a partner of the Leading National Research Center (KNOW) supported by the Ministry of Science and Higher Education (Poland).
Publisher Copyright:
© 2020 Elsevier B.V.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - The inhibition of the enzyme acetylcholinesterase (AChE) is a frequently used therapeutic option to treat Alzheimer's disease (AD). By decreasing the levels of acetylcholine degradation in the synaptic space, some cognitive functions of patients suffering from this disease are significantly improved. Rivastigmine is one of the most widely used AChE inhibitors. The objective of this work was to determine the effects of this drug on human erythrocytes, which have a type of AChE in the cell membrane. To that end, human erythrocytes and molecular models of its membrane constituted by dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE) were used. They correspond to classes of phospholipids present in the outer and inner monolayers of the human erythrocyte membrane, respectively. The experimental results obtained by X-ray diffraction and differential scanning calorimetry (DSC) indicated that rivastigmine molecules were able to interact with both phospholipids. Fluorescence spectroscopy results showed that rivastigmine produce a slight change in the acyl chain packing order and a weak displacement of the water molecules of the hydrophobic-hydrophilic membrane interface. On the other hand, observations by scanning electron microscopy (SEM) showed that the drug changed the normal biconcave shape of erythrocytes in stomatocytes (cup-shaped cells) and echinocytes (speculated shaped).
AB - The inhibition of the enzyme acetylcholinesterase (AChE) is a frequently used therapeutic option to treat Alzheimer's disease (AD). By decreasing the levels of acetylcholine degradation in the synaptic space, some cognitive functions of patients suffering from this disease are significantly improved. Rivastigmine is one of the most widely used AChE inhibitors. The objective of this work was to determine the effects of this drug on human erythrocytes, which have a type of AChE in the cell membrane. To that end, human erythrocytes and molecular models of its membrane constituted by dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE) were used. They correspond to classes of phospholipids present in the outer and inner monolayers of the human erythrocyte membrane, respectively. The experimental results obtained by X-ray diffraction and differential scanning calorimetry (DSC) indicated that rivastigmine molecules were able to interact with both phospholipids. Fluorescence spectroscopy results showed that rivastigmine produce a slight change in the acyl chain packing order and a weak displacement of the water molecules of the hydrophobic-hydrophilic membrane interface. On the other hand, observations by scanning electron microscopy (SEM) showed that the drug changed the normal biconcave shape of erythrocytes in stomatocytes (cup-shaped cells) and echinocytes (speculated shaped).
KW - Acethylcholinesterase
KW - Cell membrane
KW - Human erythrocyte
KW - Lipid bilayer
KW - Rivastigmine
UR - http://www.scopus.com/inward/record.url?scp=85079839352&partnerID=8YFLogxK
U2 - 10.1016/j.cbi.2020.109019
DO - 10.1016/j.cbi.2020.109019
M3 - Article
C2 - 32092302
AN - SCOPUS:85079839352
VL - 319
JO - Chemico-Biological Interactions
JF - Chemico-Biological Interactions
SN - 0009-2797
M1 - 109019
ER -