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Cell‐permeable succ...
Cell‐permeable succinate rescues mitochondrial respiration in cellular models of amiodarone toxicity
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- Bețiu, Alina M. (författare)
- Victor Babes University of Medicine and Pharmacy
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- Chamkha, Imen (författare)
- Lund University,Lunds universitet,Klinisk neurofysiologi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Mitokondriell Medicin,Forskargrupper vid Lunds universitet,Clinical Neurophysiology,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Mitochondrial Medicine,Lund University Research Groups,Medicon Village
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- Gustafsson, Ellen (författare)
- Lund University
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- Meijer, Elna (författare)
- Lund University
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- Avram, Vlad F. (författare)
- Victor Babes University of Medicine and Pharmacy
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- Frostner, Eleonor Åsander (författare)
- Lund University,Lunds universitet,Klinisk neurofysiologi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Mitokondriell Medicin,Forskargrupper vid Lunds universitet,Clinical Neurophysiology,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Mitochondrial Medicine,Lund University Research Groups,Medicon Village
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- Ehinger, Johannes K. (författare)
- Lund University,Lunds universitet,Klinisk neurofysiologi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Mitokondriell Medicin,Forskargrupper vid Lunds universitet,Clinical Neurophysiology,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Mitochondrial Medicine,Lund University Research Groups
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- Petrescu, Lucian (författare)
- Victor Babes University of Medicine and Pharmacy
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- Muntean, Danina M. (författare)
- Victor Babes University of Medicine and Pharmacy
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- Elmér, Eskil (författare)
- Lund University,Lunds universitet,Klinisk neurofysiologi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Mitokondriell Medicin,Forskargrupper vid Lunds universitet,Clinical Neurophysiology,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Mitochondrial Medicine,Lund University Research Groups,Medicon Village
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(creator_code:org_t)
- 2021-10-29
- 2021
- Engelska.
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:21
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://www.mdpi.com...
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https://lup.lub.lu.s...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- Amiodarone is a potent antiarrhythmic drug and displays substantial liver toxicity in hu-mans. It has previously been demonstrated that amiodarone and its metabolite (desethylamioda-rone, DEA) can inhibit mitochondrial function, particularly complexes I (CI) and II (CII) of the elec-tron 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 con-centration‐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 in-creasing mitochondrial function using intracellular delivery of succinate.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- Amiodarone
- ATP
- Desethylamiodarone
- HepG2 cells
- Mito-chondria
- NV118
- PBMCs
- Platelets
- Respiration
- Sotalol
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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- Av författaren/redakt...
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Bețiu, Alina M.
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Chamkha, Imen
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Gustafsson, Elle ...
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Meijer, Elna
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Avram, Vlad F.
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Frostner, Eleono ...
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visa fler...
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Ehinger, Johanne ...
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Petrescu, Lucian
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Muntean, Danina ...
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Elmér, Eskil
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