Evidence mapPaperPMID 34769217Full record

ArticleInternational journal of molecular sciences2021

Cell-Permeable Succinate Rescues Mitochondrial Respiration in Cellular Models of Amiodarone Toxicity.

Alina M Bețiu, Imen Chamkha, Ellen Gustafsson, Elna Meijer, Vlad F Avram, Eleonor Åsander Frostner, Johannes K Ehinger, Lucian Petrescu, Danina M Muntean, Eskil Elmér

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

  1. Article
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  5. Review
  6. Subcellular activation of β-adrenergic receptors using a spatially restricted antagonist.Proceedings of the National Academy of Sciences of the United States of America · 2024
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  7. Article
  8. Article
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  11. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Alina M BețiuDepartment of Functional Sciences-Pathophysiology, "Victor Babeș" University of Medicine and Pharmacy, Eftimie Murgu Sq. no. 2, 300041 Timișoara, Romania.
Imen ChamkhaMitochondrial Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, BMC A13, 221 84 Lund, Sweden.ORCID 0000-0002-6919-585X
Ellen GustafssonMitochondrial Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, BMC A13, 221 84 Lund, Sweden.
Elna MeijerMitochondrial Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, BMC A13, 221 84 Lund, Sweden.
Vlad F AvramCentre for Translational Research and Systems Medicine, "Victor Babeș" University of Medicine and Pharmacy, Eftimie Murgu Sq. no. 2, 300041 Timișoara, Romania.
Eleonor Åsander FrostnerMitochondrial Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, BMC A13, 221 84 Lund, Sweden.
Johannes K EhingerMitochondrial Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, BMC A13, 221 84 Lund, Sweden.ORCID 0000-0002-2417-5767
Lucian PetrescuInstitute of Cardiovascular Diseases, Doctoral School of "Victor Babeș" University of Medicine and Pharmacy, Eftimie Murgu Sq. no. 2, 300041 Timișoara, Romania.
Danina M MunteanDepartment of Functional Sciences-Pathophysiology, "Victor Babeș" University of Medicine and Pharmacy, Eftimie Murgu Sq. no. 2, 300041 Timișoara, Romania.
Eskil ElmérMitochondrial Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, BMC A13, 221 84 Lund, Sweden.ORCID 0000-0001-7901-1826

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Amiodarone is a potent antiarrhythmic drug and displays substantial liver toxicity in humans. It has previously been demonstrated that amiodarone and its metabolite (desethylamiodarone, DEA) can inhibit mitochondrial function, particularly complexes I (CI) and II (CII) of the electron transport system in various animal tissues and cell types. The present study, performed in human peripheral blood cells, and one liver-derived human cell line, is primarily aimed at assessing the concentration-dependent effects of these drugs on mitochondrial function (respiration and cellular ATP levels). Furthermore, we explore the efficacy of a novel cell-permeable succinate prodrug in alleviating the drug-induced acute mitochondrial dysfunction. Amiodarone and DEA elicit a concentration-dependent impairment of mitochondrial respiration in both intact and permeabilized platelets via the inhibition of both CI- and CII-supported respiration. The inhibitory effect seen in human platelets is also confirmed in mononuclear cells (PBMCs) and HepG2 cells. Additionally, amiodarone elicits a severe concentration-dependent ATP depletion in PBMCs, which cannot be explained solely by mitochondrial inhibition. The succinate prodrug NV118 alleviates the respiratory deficit in platelets and HepG2 cells acutely exposed to amiodarone. In conclusion, amiodarone severely inhibits metabolism in primary human mitochondria, which can be counteracted by increasing mitochondrial function using intracellular delivery of succinate.

Indexed as

Adenosine TriphosphateAmiodaroneAnti-Arrhythmia AgentsBlood PlateletsCell RespirationHep G2 CellsHumansMitochondriaProdrugsProtective AgentsSuccinic AcidAdenosine TriphosphateAmiodaroneAnti-Arrhythmia AgentsProdrugsProtective AgentsSuccinic AcidamiodaroneATPdesethylamiodaroneHepG2 cellsmitochondriaNV118PBMCsplateletsrespirationsotalol

Identifiers

PMID34769217
PMCPMC8583998

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.