Chloroquine may induce endothelial injury through lysosomal dysfunction and oxidative stress.
Identifieur interne : 000634 ( Main/Exploration ); précédent : 000633; suivant : 000635Chloroquine may induce endothelial injury through lysosomal dysfunction and oxidative stress.
Auteurs : Pauloc Greg Rio [Brésil] ; Regiane S. Da Cunha [Brésil] ; Gilson Biagini [Brésil] ; Bruna Bosquetti [Brésil] ; Júlia Budag [Brésil] ; Alberto Ortiz [Espagne] ; Maria Dolores Sánchez-Ni O [Espagne] ; Fellype C. Barreto [Brésil] ; Andréa E M. Stinghen [Brésil]Source :
- Toxicology and applied pharmacology [ 1096-0333 ] ; 2021.
Descripteurs français
- KwdFr :
- Cellules cultivées (MeSH), Cellules endothéliales (anatomopathologie), Cellules endothéliales (effets des médicaments et des substances chimiques), Cellules endothéliales (métabolisme), Chloroquine (administration et posologie), Chloroquine (effets indésirables), Chloroquine (usage thérapeutique), Endothélium vasculaire (anatomopathologie), Endothélium vasculaire (effets des médicaments et des substances chimiques), Endothélium vasculaire (métabolisme), Espèces réactives de l'oxygène (MeSH), Humains (MeSH), Lysosomes (effets des médicaments et des substances chimiques), Maladie de Fabry (induit chimiquement), Pandémies (MeSH), Stress oxydatif (effets des médicaments et des substances chimiques), Survie cellulaire (effets des médicaments et des substances chimiques).
- MESH :
- administration et posologie : Chloroquine.
- anatomopathologie : Cellules endothéliales, Endothélium vasculaire.
- effets des médicaments et des substances chimiques : Cellules endothéliales, Endothélium vasculaire, Lysosomes, Stress oxydatif, Survie cellulaire.
- effets indésirables : Chloroquine.
- induit chimiquement : Maladie de Fabry.
- métabolisme : Cellules endothéliales, Endothélium vasculaire.
- usage thérapeutique : Chloroquine.
- Cellules cultivées, Espèces réactives de l'oxygène, Humains, Pandémies.
English descriptors
- KwdEn :
- COVID-19 (drug therapy), Cell Survival (drug effects), Cells, Cultured (MeSH), Chloroquine (administration & dosage), Chloroquine (adverse effects), Chloroquine (therapeutic use), Endothelial Cells (drug effects), Endothelial Cells (metabolism), Endothelial Cells (pathology), Endothelium, Vascular (drug effects), Endothelium, Vascular (metabolism), Endothelium, Vascular (pathology), Fabry Disease (chemically induced), Humans (MeSH), Lysosomes (drug effects), Oxidative Stress (drug effects), Pandemics (MeSH), Reactive Oxygen Species (MeSH), SARS-CoV-2 (MeSH).
- MESH :
- chemical , administration & dosage : Chloroquine.
- chemical , adverse effects : Chloroquine.
- chemically induced : Fabry Disease.
- drug effects : Cell Survival, Endothelial Cells, Endothelium, Vascular, Lysosomes, Oxidative Stress.
- drug therapy : COVID-19.
- metabolism : Endothelial Cells, Endothelium, Vascular.
- pathology : Endothelial Cells, Endothelium, Vascular.
- chemical , therapeutic use : Chloroquine.
- Cells, Cultured, Humans, Pandemics, Reactive Oxygen Species, SARS-CoV-2.
Abstract
COVID-19 is a pandemic with no end in sight. There is only one approved antiviral agent but global stocks are deemed insufficient. Despite in vitro antiviral activity, clinical trials of chloroquine and hydroxychloroquine were disappointing, and they may even impair outcomes. Chloroquine causes zebroid deposits reminiscent of Fabry disease (α-galactosidase A deficiency) and endothelial cells are key targets of COVID-19. We have explored the effect of chloroquine on cultured endothelial cells and its modulation by recombinant α-galactosidase A (agalsidase). Following dose-response studies, 0.5 μg/mL chloroquine was added to cultured human endothelial cells. Neutral red and Lysotracker were used to assess lysosomes. Cytotoxicity was evaluated by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) - MTT assay and cell stress by assessing reactive oxygen species (ROS) and nitric oxide (NO). In endothelial cells, chloroquine induced dose-dependent cytotoxicity at in vitro test concentrations for COVID-19 therapy. At a sublethal concentration, chloroquine significantly induced the accumulation of acid organelles (P < 0.05), increased ROS levels, and decreased NO production (P < 0.05). These adverse effects of chloroquine on endothelial cell biology were decreased by agalsidase-β (P < 0.05). Chloroquine-induced endothelial cell cytotoxicity and stress is attenuated by agalsidase-β treatment. This suggests that endothelial cell injury may contribute to the failure of chloroquine as therapy for COVID-19 and may be at least in part related to causing dysfunction of the lysosomal enzyme α-galactosidase A.
DOI: 10.1016/j.taap.2021.115412
PubMed: 33484708
PubMed Central: PMC7826090
Affiliations:
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Barreto</name><affiliation wicri:level="2"><nlm:affiliation>Department of Internal Medicine, Division of Nephrology, Universidade Federal do Paraná, Curitiba, PR, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Department of Internal Medicine, Division of Nephrology, Universidade Federal do Paraná, Curitiba, PR</wicri:regionArea><placeName><region type="state">Paraná (État)</region></placeName></affiliation></author><author><name sortKey="Stinghen, Andrea E M" sort="Stinghen, Andrea E M" uniqKey="Stinghen A" first="Andréa E M" last="Stinghen">Andréa E M. Stinghen</name><affiliation wicri:level="2"><nlm:affiliation>Experimental Nephrology Laboratory, Basic Pathology Department, Universidade Federal do Paraná, Curitiba, PR, Brazil. 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Da Cunha</name><affiliation wicri:level="2"><nlm:affiliation>Experimental Nephrology Laboratory, Basic Pathology Department, Universidade Federal do Paraná, Curitiba, PR, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Experimental Nephrology Laboratory, Basic Pathology Department, Universidade Federal do Paraná, Curitiba, PR</wicri:regionArea><placeName><region type="state">Paraná (État)</region></placeName></affiliation></author><author><name sortKey="Biagini, Gilson" sort="Biagini, Gilson" uniqKey="Biagini G" first="Gilson" last="Biagini">Gilson Biagini</name><affiliation wicri:level="2"><nlm:affiliation>Department of Internal Medicine, Universidade Federal do Paraná, Curitiba, PR, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Department of Internal Medicine, Universidade Federal do Paraná, Curitiba, PR</wicri:regionArea><placeName><region type="state">Paraná (État)</region></placeName></affiliation></author><author><name sortKey="Bosquetti, Bruna" sort="Bosquetti, Bruna" uniqKey="Bosquetti B" first="Bruna" last="Bosquetti">Bruna Bosquetti</name><affiliation wicri:level="2"><nlm:affiliation>Experimental Nephrology Laboratory, Basic Pathology Department, Universidade Federal do Paraná, Curitiba, PR, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Experimental Nephrology Laboratory, Basic Pathology Department, Universidade Federal do Paraná, Curitiba, PR</wicri:regionArea><placeName><region type="state">Paraná (État)</region></placeName></affiliation></author><author><name sortKey="Budag, Julia" sort="Budag, Julia" uniqKey="Budag J" first="Júlia" last="Budag">Júlia Budag</name><affiliation wicri:level="2"><nlm:affiliation>Experimental Nephrology Laboratory, Basic Pathology Department, Universidade Federal do Paraná, Curitiba, PR, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Experimental Nephrology Laboratory, Basic Pathology Department, Universidade Federal do Paraná, Curitiba, PR</wicri:regionArea><placeName><region type="state">Paraná (État)</region></placeName></affiliation></author><author><name sortKey="Ortiz, Alberto" sort="Ortiz, Alberto" uniqKey="Ortiz A" first="Alberto" last="Ortiz">Alberto Ortiz</name><affiliation wicri:level="3"><nlm:affiliation>Nephrology and Hypertension, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain; IIS-Fundación Jimenez Diaz UAM, Madrid, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Nephrology and Hypertension, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain; IIS-Fundación Jimenez Diaz UAM, Madrid</wicri:regionArea><placeName><settlement type="city">Madrid</settlement><region nuts="2" type="region">Communauté de Madrid</region></placeName></affiliation></author><author><name sortKey="Sanchez Ni O, Maria Dolores" sort="Sanchez Ni O, Maria Dolores" uniqKey="Sanchez Ni O M" first="Maria Dolores" last="Sánchez-Ni O">Maria Dolores Sánchez-Ni O</name><affiliation wicri:level="3"><nlm:affiliation>IIS-Fundación Jimenez Diaz UAM, Madrid, Spain; Department of Pharmacology, School of Medicine, Universidad Autonoma de Madrid, Madrid, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>IIS-Fundación Jimenez Diaz UAM, Madrid, Spain; Department of Pharmacology, School of Medicine, Universidad Autonoma de Madrid, Madrid</wicri:regionArea><placeName><settlement type="city">Madrid</settlement><region nuts="2" type="region">Communauté de Madrid</region></placeName></affiliation></author><author><name sortKey="Barreto, Fellype C" sort="Barreto, Fellype C" uniqKey="Barreto F" first="Fellype C" last="Barreto">Fellype C. Barreto</name><affiliation wicri:level="2"><nlm:affiliation>Department of Internal Medicine, Division of Nephrology, Universidade Federal do Paraná, Curitiba, PR, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Department of Internal Medicine, Division of Nephrology, Universidade Federal do Paraná, Curitiba, PR</wicri:regionArea><placeName><region type="state">Paraná (État)</region></placeName></affiliation></author><author><name sortKey="Stinghen, Andrea E M" sort="Stinghen, Andrea E M" uniqKey="Stinghen A" first="Andréa E M" last="Stinghen">Andréa E M. Stinghen</name><affiliation wicri:level="2"><nlm:affiliation>Experimental Nephrology Laboratory, Basic Pathology Department, Universidade Federal do Paraná, Curitiba, PR, Brazil. Electronic address: andreastinghen@ufpr.br.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Experimental Nephrology Laboratory, Basic Pathology Department, Universidade Federal do Paraná, Curitiba, PR</wicri:regionArea><placeName><region type="state">Paraná (État)</region></placeName></affiliation></author></analytic><series><title level="j">Toxicology and applied pharmacology</title><idno type="eISSN">1096-0333</idno><imprint><date when="2021" type="published">2021</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>COVID-19 (drug therapy)</term><term>Cell Survival (drug effects)</term><term>Cells, Cultured (MeSH)</term><term>Chloroquine (administration & dosage)</term><term>Chloroquine (adverse effects)</term><term>Chloroquine (therapeutic use)</term><term>Endothelial Cells (drug effects)</term><term>Endothelial Cells (metabolism)</term><term>Endothelial Cells (pathology)</term><term>Endothelium, Vascular (drug effects)</term><term>Endothelium, Vascular (metabolism)</term><term>Endothelium, Vascular (pathology)</term><term>Fabry Disease (chemically induced)</term><term>Humans (MeSH)</term><term>Lysosomes (drug effects)</term><term>Oxidative Stress (drug effects)</term><term>Pandemics (MeSH)</term><term>Reactive Oxygen Species (MeSH)</term><term>SARS-CoV-2 (MeSH)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Cellules cultivées (MeSH)</term><term>Cellules endothéliales (anatomopathologie)</term><term>Cellules endothéliales (effets des médicaments et des substances chimiques)</term><term>Cellules endothéliales (métabolisme)</term><term>Chloroquine (administration et posologie)</term><term>Chloroquine (effets indésirables)</term><term>Chloroquine (usage thérapeutique)</term><term>Endothélium vasculaire (anatomopathologie)</term><term>Endothélium vasculaire (effets des médicaments et des substances chimiques)</term><term>Endothélium vasculaire (métabolisme)</term><term>Espèces réactives de l'oxygène (MeSH)</term><term>Humains (MeSH)</term><term>Lysosomes (effets des médicaments et des substances chimiques)</term><term>Maladie de Fabry (induit chimiquement)</term><term>Pandémies (MeSH)</term><term>Stress oxydatif (effets des médicaments et des substances chimiques)</term><term>Survie cellulaire (effets des médicaments et des substances chimiques)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Chloroquine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Chloroquine</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Chloroquine</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Cellules endothéliales</term><term>Endothélium vasculaire</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Fabry Disease</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Survival</term><term>Endothelial Cells</term><term>Endothelium, Vascular</term><term>Lysosomes</term><term>Oxidative Stress</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>COVID-19</term></keywords><keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Cellules endothéliales</term><term>Endothélium vasculaire</term><term>Lysosomes</term><term>Stress oxydatif</term><term>Survie cellulaire</term></keywords><keywords scheme="MESH" qualifier="effets indésirables" xml:lang="fr"><term>Chloroquine</term></keywords><keywords scheme="MESH" qualifier="induit chimiquement" xml:lang="fr"><term>Maladie de Fabry</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Endothelial Cells</term><term>Endothelium, Vascular</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cellules endothéliales</term><term>Endothélium vasculaire</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Endothelial Cells</term><term>Endothelium, Vascular</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Chloroquine</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Chloroquine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cells, Cultured</term><term>Humans</term><term>Pandemics</term><term>Reactive Oxygen Species</term><term>SARS-CoV-2</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Cellules cultivées</term><term>Espèces réactives de l'oxygène</term><term>Humains</term><term>Pandémies</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">COVID-19 is a pandemic with no end in sight. There is only one approved antiviral agent but global stocks are deemed insufficient. Despite in vitro antiviral activity, clinical trials of chloroquine and hydroxychloroquine were disappointing, and they may even impair outcomes. Chloroquine causes zebroid deposits reminiscent of Fabry disease (α-galactosidase A deficiency) and endothelial cells are key targets of COVID-19. We have explored the effect of chloroquine on cultured endothelial cells and its modulation by recombinant α-galactosidase A (agalsidase). Following dose-response studies, 0.5 μg/mL chloroquine was added to cultured human endothelial cells. Neutral red and Lysotracker were used to assess lysosomes. Cytotoxicity was evaluated by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) - MTT assay and cell stress by assessing reactive oxygen species (ROS) and nitric oxide (NO). In endothelial cells, chloroquine induced dose-dependent cytotoxicity at in vitro test concentrations for COVID-19 therapy. At a sublethal concentration, chloroquine significantly induced the accumulation of acid organelles (P < 0.05), increased ROS levels, and decreased NO production (P < 0.05). These adverse effects of chloroquine on endothelial cell biology were decreased by agalsidase-β (P < 0.05). Chloroquine-induced endothelial cell cytotoxicity and stress is attenuated by agalsidase-β treatment. This suggests that endothelial cell injury may contribute to the failure of chloroquine as therapy for COVID-19 and may be at least in part related to causing dysfunction of the lysosomal enzyme α-galactosidase A.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">33484708</PMID><DateCompleted><Year>2021</Year><Month>03</Month><Day>08</Day></DateCompleted><DateRevised><Year>2021</Year><Month>03</Month><Day>08</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1096-0333</ISSN><JournalIssue CitedMedium="Internet"><Volume>414</Volume><PubDate><Year>2021</Year><Month>03</Month><Day>01</Day></PubDate></JournalIssue><Title>Toxicology and applied pharmacology</Title><ISOAbbreviation>Toxicol Appl Pharmacol</ISOAbbreviation></Journal><ArticleTitle>Chloroquine may induce endothelial injury through lysosomal dysfunction and oxidative stress.</ArticleTitle><Pagination><MedlinePgn>115412</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0041-008X(21)00019-3</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.taap.2021.115412</ELocationID><Abstract><AbstractText>COVID-19 is a pandemic with no end in sight. There is only one approved antiviral agent but global stocks are deemed insufficient. Despite in vitro antiviral activity, clinical trials of chloroquine and hydroxychloroquine were disappointing, and they may even impair outcomes. Chloroquine causes zebroid deposits reminiscent of Fabry disease (α-galactosidase A deficiency) and endothelial cells are key targets of COVID-19. We have explored the effect of chloroquine on cultured endothelial cells and its modulation by recombinant α-galactosidase A (agalsidase). Following dose-response studies, 0.5 μg/mL chloroquine was added to cultured human endothelial cells. Neutral red and Lysotracker were used to assess lysosomes. Cytotoxicity was evaluated by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) - MTT assay and cell stress by assessing reactive oxygen species (ROS) and nitric oxide (NO). In endothelial cells, chloroquine induced dose-dependent cytotoxicity at in vitro test concentrations for COVID-19 therapy. At a sublethal concentration, chloroquine significantly induced the accumulation of acid organelles (P < 0.05), increased ROS levels, and decreased NO production (P < 0.05). These adverse effects of chloroquine on endothelial cell biology were decreased by agalsidase-β (P < 0.05). Chloroquine-induced endothelial cell cytotoxicity and stress is attenuated by agalsidase-β treatment. This suggests that endothelial cell injury may contribute to the failure of chloroquine as therapy for COVID-19 and may be at least in part related to causing dysfunction of the lysosomal enzyme α-galactosidase A.</AbstractText><CopyrightInformation>Copyright © 2021 Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Gregório</LastName><ForeName>PauloC</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Experimental Nephrology Laboratory, Basic Pathology Department, Universidade Federal do Paraná, Curitiba, PR, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>da Cunha</LastName><ForeName>Regiane S</ForeName><Initials>RS</Initials><AffiliationInfo><Affiliation>Experimental Nephrology Laboratory, Basic Pathology Department, Universidade Federal do Paraná, Curitiba, PR, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Biagini</LastName><ForeName>Gilson</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, Universidade Federal do Paraná, Curitiba, PR, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bosquetti</LastName><ForeName>Bruna</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Experimental Nephrology Laboratory, Basic Pathology Department, Universidade Federal do Paraná, Curitiba, PR, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Budag</LastName><ForeName>Júlia</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Experimental Nephrology Laboratory, Basic Pathology Department, Universidade Federal do Paraná, Curitiba, PR, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ortiz</LastName><ForeName>Alberto</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Nephrology and Hypertension, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain; IIS-Fundación Jimenez Diaz UAM, Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sánchez-Niño</LastName><ForeName>Maria Dolores</ForeName><Initials>MD</Initials><AffiliationInfo><Affiliation>IIS-Fundación Jimenez Diaz UAM, Madrid, Spain; Department of Pharmacology, School of Medicine, Universidad Autonoma de Madrid, Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Barreto</LastName><ForeName>Fellype C</ForeName><Initials>FC</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, Division of Nephrology, Universidade Federal do Paraná, Curitiba, PR, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stinghen</LastName><ForeName>Andréa E M</ForeName><Initials>AEM</Initials><AffiliationInfo><Affiliation>Experimental Nephrology Laboratory, Basic Pathology Department, Universidade Federal do Paraná, Curitiba, PR, Brazil. Electronic address: andreastinghen@ufpr.br.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>01</Month><Day>21</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Toxicol Appl Pharmacol</MedlineTA><NlmUniqueID>0416575</NlmUniqueID><ISSNLinking>0041-008X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D017382">Reactive Oxygen Species</NameOfSubstance></Chemical><Chemical><RegistryNumber>886U3H6UFF</RegistryNumber><NameOfSubstance UI="D002738">Chloroquine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000086382" MajorTopicYN="N">COVID-19</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002470" MajorTopicYN="N">Cell Survival</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002738" MajorTopicYN="N">Chloroquine</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D042783" MajorTopicYN="N">Endothelial Cells</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004730" MajorTopicYN="N">Endothelium, Vascular</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000795" MajorTopicYN="N">Fabry Disease</DescriptorName><QualifierName UI="Q000139" MajorTopicYN="N">chemically induced</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008247" MajorTopicYN="N">Lysosomes</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018384" MajorTopicYN="N">Oxidative Stress</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D058873" MajorTopicYN="N">Pandemics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017382" MajorTopicYN="N">Reactive Oxygen Species</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000086402" MajorTopicYN="N">SARS-CoV-2</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">Agalsidase-β</Keyword><Keyword MajorTopicYN="Y">COVID-19</Keyword><Keyword MajorTopicYN="Y">Endothelial cells</Keyword><Keyword MajorTopicYN="Y">Fabry disease</Keyword><Keyword MajorTopicYN="Y">Oxidative stress</Keyword><Keyword MajorTopicYN="Y">Therapy</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>10</Month><Day>26</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>12</Month><Day>23</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2021</Year><Month>01</Month><Day>11</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>1</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>3</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>1</Month><Day>23</Day><Hour>20</Hour><Minute>8</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">33484708</ArticleId><ArticleId IdType="pii">S0041-008X(21)00019-3</ArticleId><ArticleId IdType="doi">10.1016/j.taap.2021.115412</ArticleId><ArticleId IdType="pmc">PMC7826090</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Brésil</li><li>Espagne</li></country><region><li>Communauté de Madrid</li><li>Paraná (État)</li></region><settlement><li>Madrid</li></settlement></list><tree><country name="Brésil"><region name="Paraná (État)"><name sortKey="Greg Rio, Pauloc" sort="Greg Rio, Pauloc" uniqKey="Greg Rio P" first="Pauloc" last="Greg Rio">Pauloc Greg Rio</name></region><name sortKey="Barreto, Fellype C" sort="Barreto, Fellype C" uniqKey="Barreto F" first="Fellype C" last="Barreto">Fellype C. Barreto</name><name sortKey="Biagini, Gilson" sort="Biagini, Gilson" uniqKey="Biagini G" first="Gilson" last="Biagini">Gilson Biagini</name><name sortKey="Bosquetti, Bruna" sort="Bosquetti, Bruna" uniqKey="Bosquetti B" first="Bruna" last="Bosquetti">Bruna Bosquetti</name><name sortKey="Budag, Julia" sort="Budag, Julia" uniqKey="Budag J" first="Júlia" last="Budag">Júlia Budag</name><name sortKey="Da Cunha, Regiane S" sort="Da Cunha, Regiane S" uniqKey="Da Cunha R" first="Regiane S" last="Da Cunha">Regiane S. Da Cunha</name><name sortKey="Stinghen, Andrea E M" sort="Stinghen, Andrea E M" uniqKey="Stinghen A" first="Andréa E M" last="Stinghen">Andréa E M. Stinghen</name></country><country name="Espagne"><region name="Communauté de Madrid"><name sortKey="Ortiz, Alberto" sort="Ortiz, Alberto" uniqKey="Ortiz A" first="Alberto" last="Ortiz">Alberto Ortiz</name></region><name sortKey="Sanchez Ni O, Maria Dolores" sort="Sanchez Ni O, Maria Dolores" uniqKey="Sanchez Ni O M" first="Maria Dolores" last="Sánchez-Ni O">Maria Dolores Sánchez-Ni O</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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