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Oxidative Stress, Proton Fluxes, and Chloroquine/Hydroxychloroquine Treatment for COVID-19

Chloroquine (CQ) and hydroxychloroquine (HCQ) have been proposed as treatments for COVID-19. These drugs have been studied for many decades, primarily in the context of their use as antimalarials, where they induce oxidative stress-killing of the malarial parasite. Less appreciated, however, is evid...

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Autores principales: Klouda, Christina B., Stone, William L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555760/
https://www.ncbi.nlm.nih.gov/pubmed/32967165
http://dx.doi.org/10.3390/antiox9090894
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author Klouda, Christina B.
Stone, William L.
author_facet Klouda, Christina B.
Stone, William L.
author_sort Klouda, Christina B.
collection PubMed
description Chloroquine (CQ) and hydroxychloroquine (HCQ) have been proposed as treatments for COVID-19. These drugs have been studied for many decades, primarily in the context of their use as antimalarials, where they induce oxidative stress-killing of the malarial parasite. Less appreciated, however, is evidence showing that CQ/HCQ causes systemic oxidative stress. In vitro and observational data suggest that CQ/HCQ can be repurposed as potential antiviral medications. This review focuses on the potential health concerns of CQ/HCQ induced by oxidative stress, particularly in the hyperinflammatory stage of COVID-19 disease. The pathophysiological role of oxidative stress in acute respiratory distress syndrome (ARDS) has been well-documented. Additional oxidative stress caused by CQ/HCQ during ARDS could be problematic. In vitro data showing that CQ forms a complex with free-heme that promotes lipid peroxidation of phospholipid bilayers are also relevant to COVID-19. Free-heme induced oxidative stress is implicated as a systemic activator of coagulation, which is increasingly recognized as a contributor to COVID-19 morbidity. This review will also provide a brief overview of CQ/HCQ pharmacology with an emphasis on how these drugs alter proton fluxes in subcellular organelles. CQ/HCQ-induced alterations in proton fluxes influence the type and chemical reactivity of reactive oxygen species (ROS).
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spelling pubmed-75557602020-10-19 Oxidative Stress, Proton Fluxes, and Chloroquine/Hydroxychloroquine Treatment for COVID-19 Klouda, Christina B. Stone, William L. Antioxidants (Basel) Review Chloroquine (CQ) and hydroxychloroquine (HCQ) have been proposed as treatments for COVID-19. These drugs have been studied for many decades, primarily in the context of their use as antimalarials, where they induce oxidative stress-killing of the malarial parasite. Less appreciated, however, is evidence showing that CQ/HCQ causes systemic oxidative stress. In vitro and observational data suggest that CQ/HCQ can be repurposed as potential antiviral medications. This review focuses on the potential health concerns of CQ/HCQ induced by oxidative stress, particularly in the hyperinflammatory stage of COVID-19 disease. The pathophysiological role of oxidative stress in acute respiratory distress syndrome (ARDS) has been well-documented. Additional oxidative stress caused by CQ/HCQ during ARDS could be problematic. In vitro data showing that CQ forms a complex with free-heme that promotes lipid peroxidation of phospholipid bilayers are also relevant to COVID-19. Free-heme induced oxidative stress is implicated as a systemic activator of coagulation, which is increasingly recognized as a contributor to COVID-19 morbidity. This review will also provide a brief overview of CQ/HCQ pharmacology with an emphasis on how these drugs alter proton fluxes in subcellular organelles. CQ/HCQ-induced alterations in proton fluxes influence the type and chemical reactivity of reactive oxygen species (ROS). MDPI 2020-09-21 /pmc/articles/PMC7555760/ /pubmed/32967165 http://dx.doi.org/10.3390/antiox9090894 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Klouda, Christina B.
Stone, William L.
Oxidative Stress, Proton Fluxes, and Chloroquine/Hydroxychloroquine Treatment for COVID-19
title Oxidative Stress, Proton Fluxes, and Chloroquine/Hydroxychloroquine Treatment for COVID-19
title_full Oxidative Stress, Proton Fluxes, and Chloroquine/Hydroxychloroquine Treatment for COVID-19
title_fullStr Oxidative Stress, Proton Fluxes, and Chloroquine/Hydroxychloroquine Treatment for COVID-19
title_full_unstemmed Oxidative Stress, Proton Fluxes, and Chloroquine/Hydroxychloroquine Treatment for COVID-19
title_short Oxidative Stress, Proton Fluxes, and Chloroquine/Hydroxychloroquine Treatment for COVID-19
title_sort oxidative stress, proton fluxes, and chloroquine/hydroxychloroquine treatment for covid-19
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555760/
https://www.ncbi.nlm.nih.gov/pubmed/32967165
http://dx.doi.org/10.3390/antiox9090894
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