Fisar 2016b Folia Biol (Praha)

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Fisar Z, Hroudova J, Singh N, Koprivova A, Maceckova D (2016) Effect of simvastatin, coenzyme Q10, resveratrol, acetylcysteine and acetylcarnitine on mitochondrial respiration. Folia Biol (Praha) 62:53-66.

Β» PMID: 27187037

Fisar Z, Hroudova J, Singh N, Koprivova A, Maceckova D (2016) Folia Biol (Praha)

Abstract: 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 ΞΌM for Complex I-linked respiration, IC50 = 31.3 ΞΌM for Complex II-linked respiration, and IC50 = 42.9 ΞΌM for Complex IV-linked respiration); the inhibitory effect of resveratrol was found at very high concentrations (IC50 = 162 ΞΌM for Complex I-linked respiration, IC50 = 564 ΞΌM for Complex II-linked respiration, and IC50 = 1454 ΞΌM 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).

β€’ Bioblast editor: Kandolf G β€’ O2k-Network Lab: CZ Prague Fisar Z

Labels: MiParea: Respiration, Pharmacology;toxicology 

Organism: Pig  Tissue;cell: Nervous system  Preparation: Isolated mitochondria 

Coupling state: OXPHOS, ET  Pathway: N, S, CIV, NS, ROX  HRR: Oxygraph-2k 

2017-11, Resveratrol 

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