Effect of Simvastatin, Coenzyme Q10, Resveratrol, Acetylcysteine and Acetylcarnitine on Mitochondrial Respiration
Language English Country Czech Republic Media print
Document type Journal Article
PubMed
27187037
DOI
10.14712/fb2016062020053
PII: file/5803/fb2016a0007.pdf
Knihovny.cz E-resources
- MeSH
- Acetylcysteine pharmacology MeSH
- Acetylcarnitine pharmacology MeSH
- Cell Respiration drug effects MeSH
- Mitochondria drug effects metabolism MeSH
- Brain drug effects MeSH
- Neuroprotective Agents pharmacology MeSH
- Swine MeSH
- Electron Transport Complex IV metabolism MeSH
- Resveratrol MeSH
- Simvastatin pharmacology MeSH
- Oxygen Consumption drug effects MeSH
- Stilbenes pharmacology MeSH
- Ubiquinone analogs & derivatives pharmacology MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Acetylcysteine MeSH
- Acetylcarnitine MeSH
- coenzyme Q10 MeSH Browser
- Neuroprotective Agents MeSH
- Electron Transport Complex IV MeSH
- Resveratrol MeSH
- Simvastatin MeSH
- Stilbenes MeSH
- Ubiquinone MeSH
Some therapeutic and/or adverse effects of drugs may be related to their effects on mitochondrial function. The 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 the calcium-induced decrease of the respiratory rate were also studied. We observed a significant inhibitory effect of simvastatin on mitochondrial respiration (IC50 = 24.0 μM for Complex I-linked respiration, IC50 = 31.3 μM for Complex II-linked respiration, and IC50 = 42.9 μM for Complex IV-linked respiration); the inhibitory effect of resveratrol was found at very high concentrations (IC50 = 162 μM for Complex I-linked respiration, IC50 = 564 μM for Complex II-linked respiration, and IC50 = 1454 μM for Complex IV-linked respiration). Concentrations required 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 partial inhibition of the Complex I+II-linked mitochondrial respiration, and all tested drugs counteracted this inhibition. None of the tested drugs showed mitochondrial toxicity (characterized by respiratory rate inhibition) at drug concentrations achieved at therapeutic drug intake. Resveratrol, simvastatin, and acetylcarnitine had the greatest neuroprotective potential (characterized by protective effects against calcium-induced reduction of the respiratory rate).
References provided by Crossref.org
CoQ10 and Mitochondrial Dysfunction in Alzheimer's Disease
In vitro effects of antipsychotics on mitochondrial respiration
