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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Toxicology Letters

ISSN

0378-4274

e-ISSN

—

Svazek periodika

350

Číslo periodika v rámci svazku

October

Stát vydavatele periodika

IE - Irsko

Počet stran výsledku

9

Strana od-do

143-151

Kód UT WoS článku

000691222600015

EID výsledku v databázi Scopus

2-s2.0-85111263707