Effect of Simvastatin, Coenzyme Q10, Resveratrol, Acetylcysteine and Acetylcarnitine on Mitochondrial Respiration

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F44555601%3A13440%2F16%3A43887662" target="_blank" >RIV/44555601:13440/16:43887662 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/16:10327271

Výsledek na webu

<a href="http://fb.cuni.cz/file/5803/fb2016a0007.pdf" target="_blank" >http://fb.cuni.cz/file/5803/fb2016a0007.pdf</a>

DOI - Digital Object Identifier

—

Jazyk výsledku

angličtina

Název v původním jazyce

Effect of Simvastatin, Coenzyme Q10, Resveratrol, Acetylcysteine and Acetylcarnitine on Mitochondrial Respiration

Popis výsledku v původním jazyce

Some therapeutic and/or adverse effects of drugs may be related to their effects on mitochondrial function. Effects of simvastatin, resveratrol, coenzyme Q10, acetylcysteine, and acetylcarnitine on Complex I-, Complex II-, or Complex IV-linked respiratory rate were determined in isolated brain mitochondria. The protective effects of these biologically active compounds on calcium induced decrease of the respiratory rate were also studied. We observed significant inhibitory effect of simvastatin on mitochondrial respiration (IC50 = 24.0 ?M for Complex I-linked respiration, IC50 = 31.3 ?M for Complex II-linked respiration, and IC50 = 42.9 ?M for Complex IV-linked respiration); the inhibitory effect of resveratrol was found at very high concentrations (IC50 =162 ?M for Complex I-linked respiration, IC50 = 564 ?M for Complex II-linked respiration, and IC50 = 1454 ?M for Complex IV-linked respiration). Concentrations necessary for effective simvastatin- or resveratrol-induced inhibition of mitochondrial respiration were found much higher than concentrations achieved under standard dosing of these drugs. Acetylcysteine and acetylcarnitine did not affect the oxygen consumption rate of mitochondria. Coenzyme Q10 induced an increase of Complex I-linked respiration. The increase of free calcium ions induced a partial inhibition of the Complex I+II-linked mitochondrial respiration, and all tested drugs counteracted this inhibition. None of tested drugs showed mitochondrial toxicity (characterized by respiratory rate inhibition) at drug concentrations achieved at therapeutic drug intake. Resveratrol, simvastatin, and acetylcarnitine have larges neuroprotective potential (characterized by protective effects against calcium-induced reduction of the respiratory rate).

Název v anglickém jazyce

Effect of Simvastatin, Coenzyme Q10, Resveratrol, Acetylcysteine and Acetylcarnitine on Mitochondrial Respiration

Popis výsledku anglicky

Some therapeutic and/or adverse effects of drugs may be related to their effects on mitochondrial function. Effects of simvastatin, resveratrol, coenzyme Q10, acetylcysteine, and acetylcarnitine on Complex I-, Complex II-, or Complex IV-linked respiratory rate were determined in isolated brain mitochondria. The protective effects of these biologically active compounds on calcium induced decrease of the respiratory rate were also studied. We observed significant inhibitory effect of simvastatin on mitochondrial respiration (IC50 = 24.0 ?M for Complex I-linked respiration, IC50 = 31.3 ?M for Complex II-linked respiration, and IC50 = 42.9 ?M for Complex IV-linked respiration); the inhibitory effect of resveratrol was found at very high concentrations (IC50 =162 ?M for Complex I-linked respiration, IC50 = 564 ?M for Complex II-linked respiration, and IC50 = 1454 ?M for Complex IV-linked respiration). Concentrations necessary for effective simvastatin- or resveratrol-induced inhibition of mitochondrial respiration were found much higher than concentrations achieved under standard dosing of these drugs. Acetylcysteine and acetylcarnitine did not affect the oxygen consumption rate of mitochondria. Coenzyme Q10 induced an increase of Complex I-linked respiration. The increase of free calcium ions induced a partial inhibition of the Complex I+II-linked mitochondrial respiration, and all tested drugs counteracted this inhibition. None of tested drugs showed mitochondrial toxicity (characterized by respiratory rate inhibition) at drug concentrations achieved at therapeutic drug intake. Resveratrol, simvastatin, and acetylcarnitine have larges neuroprotective potential (characterized by protective effects against calcium-induced reduction of the respiratory rate).

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FL - Psychiatrie, sexuologie

OECD FORD obor

—

Projekt

<a href="/cs/project/NV15-28967A" target="_blank" >NV15-28967A: Modulátory mitochondriálních enzymů k léčbě neurodegenerativních onemocnění</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

Folia Biologica

ISSN

0015-5500

e-ISSN

—

Svazek periodika

62

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

14

Strana od-do

53-66

Kód UT WoS článku

—

EID výsledku v databázi Scopus

—