Little in vitro effect of remdesivir on mitochondrial respiration and monoamine oxidase activity in isolated mitochondria

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F21%3A10432547" target="_blank" >RIV/00216208:11110/21:10432547 - isvavai.cz</a>

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=DwFzD7s~Ft" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=DwFzD7s~Ft</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.toxlet.2021.07.015" target="_blank" >10.1016/j.toxlet.2021.07.015</a>

Result language

angličtina

Original language name

Little in vitro effect of remdesivir on mitochondrial respiration and monoamine oxidase activity in isolated mitochondria

Original language description

Remdesivir (RDV) is a novel antiviral drug whose mitochondrial effects are not well known. In vitro effects of RDV on the mitochondrial respiration, individual respiratory complexes, and the activity of monoamine oxidase (MAO-A and MAO-B) were measured in isolated mitochondria. At micromolar RDV concentrations, minimal or no inhibitory effects on the studied mitochondrial enzymes were found. At very high concentrations of RDV, there was partial inhibition of complex I- (IC50 675 mmol/L, residual activity 39.4 %) and complex II-linked (IC50 81.8 mmol/L, residual activity 40.7 %) respiration, without inhibition of complex IV-linked respiration, and partial inhibition both of MAO-A (IC50 26.6 mmol/L, residual activity 35.2 %) and MAO-B (IC50 89.8 mmol/L, residual activity 34.0 %) activity. Individual respiratory complexes (I, II + III, and IV) were partially inhibited at a high drug concentration. The active metabolite of RDV (GS-4 43902) had very little effect on mitochondrial oxygen consumption rate with residual activity of 87.0 % for complex I-linked respiration, 90.3 % for complex II-linked respiration, and with no inhibition of complex IV-linked respiration. In conclusion, measurement of the effect of RDV and its active metabolite on isolated mitochondria shows that there is very little direct effect on mitochondrial respiration occurs at therapeutic drug concentration. (c) 2021 Elsevier B.V. All rights reserved.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30104 - Pharmacology and pharmacy

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Toxicology Letters

ISSN

0378-4274

e-ISSN

—

Volume of the periodical

350

Issue of the periodical within the volume

October

Country of publishing house

IE - IRELAND

Number of pages

9

Pages from-to

143-151

UT code for WoS article

000691222600015

EID of the result in the Scopus database

2-s2.0-85111263707