Assessment of amiodarone toxicity by high-resolution respirometry in human platelets

Scope: Amiodarone is one of the most widely used antiarrhythmic agents, but several side effects have been associated with its use. Research carried out in different animal tissues/cells reported that amiodarone toxicity might occur via the dysfunction of mitochondrial res-piratory chain. Platelets have been recently recognized as a convenient tool to assess mitochondrial respiration as mirror of organ-specific mitochondrial dysfunction in various pathologies or drug-induced, respectively. The literature addressing the effects of cardiovascular drugs, including amiodarone, on platelet respiration is scarce. The purpose of this study was to characterize the dose-dependent effects of amiodarone on mitochondrial respiration in intact and permeabilized human platelets.

Methods: Peripheral blood platelets were isolated from healthy volunteers by differential centrifugations. Res-piratory capacities of intact and digitonin-permeabi-lized cells (200 x 1000000 cells/mL) were analyzed by high-resolution respirometry using the Oxygraph-2k (Oroboros Ltd.), according to the Substrate-Uncoupler-Inhibitor-Titration (SUIT) protocol adapted to measure both complex I (CI) and complex II (CII)-de-pendent respiration in the presence of increasing con-centrations (15-240 μM) of amiodarone.

Results: In both intact and permeabilized cells, amiodarone elicited a dose-dependent inhibition of both CI and CII-supported respiration, with the maximal decrease (more than 50%) for the highest concentration. Amiodarone was particularly toxic for Complex II-supported respiration starting at lower doses (60μM) as compared to Complex I-supported respiration where inhibition started from 120μM.

Conclusions: Amiodarone in acute administration induced a dose-dependent inhibition of respiration in human platelets. Whether the drug effect can be recapitulated in platelets isolated from patients chronically treated with amiodarone warrants further investigation.

ISSN – online: 2734 – 6382
ISSN-L 1220-658X
ISSN – print: 1220-658X
The Romanian Journal of Cardiology is indexed by:
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CODE: 379
CME Credits: 10 (Romanian College of Physicians)