Dose-dependent effects of acetaminophen and ibuprofen on mitochondrial respiration of human platelets
Beţiu, Alina Maria ; Lighezan, Rodica ; Avram, Vlad Florian LU ; Muntean, Danina Mirela ; Elmér, Eskil LU
and Petrescu, Lucian
(2023)
In Molecular and Cellular Biochemistry
- Abstract
Acetaminophen and ibuprofen are widely used over-the-counter medications to reduce fever, pain, and inflammation. Although both drugs are safe in therapeutic concentrations, self-medication is practiced by millions of aged patients with comorbidities that decrease drug metabolism and/or excretion, thus raising the risk of overdosage. Mitochondrial dysfunction has emerged as an important pathomechanism underlying the organ toxicity of both drugs. Assessment of mitochondrial oxygen consumption in peripheral blood cells is a novel research field Cu several applications, including characterization of drug toxicity. The present study, conducted in human platelets isolated from blood donor-derived buffy coat, was aimed at assessing the acute,... (More)
Acetaminophen and ibuprofen are widely used over-the-counter medications to reduce fever, pain, and inflammation. Although both drugs are safe in therapeutic concentrations, self-medication is practiced by millions of aged patients with comorbidities that decrease drug metabolism and/or excretion, thus raising the risk of overdosage. Mitochondrial dysfunction has emerged as an important pathomechanism underlying the organ toxicity of both drugs. Assessment of mitochondrial oxygen consumption in peripheral blood cells is a novel research field Cu several applications, including characterization of drug toxicity. The present study, conducted in human platelets isolated from blood donor-derived buffy coat, was aimed at assessing the acute, concentration-dependent effects of each drug on mitochondrial respiration. Using the high-resolution respirometry technique, a concentration-dependent decrease of oxygen consumption in both intact and permeabilized platelets was found for either drug, mainly by inhibiting complex I-supported active respiration. Moreover, ibuprofen significantly decreased the maximal capacity of the electron transport system already from the lowest concentration. In conclusion, platelets from healthy donors represents a population of cells easily available, which can be routinely used in studies assessing mitochondrial drug toxicity. Whether these results can be recapitulated in patients treated with these medications is worth further investigation as potential peripheral biomarker of drug overdose.
(Less)
- author
- Beţiu, Alina Maria
; Lighezan, Rodica
; Avram, Vlad Florian
LU
; Muntean, Danina Mirela
; Elmér, Eskil
LU
and Petrescu, Lucian
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- epub
- subject
- keywords
- Acetaminophen, Buffy coat, Human platelets, Ibuprofen, Mitochondria, Respiration
- in
- Molecular and Cellular Biochemistry
- publisher
- Springer
- external identifiers
-
- pmid:37486451
- scopus:85165483089
- ISSN
- 0300-8177
- DOI
- 10.1007/s11010-023-04814-z
- language
- English
- LU publication?
- yes
- id
- 81394d14-8bcf-437d-b0d3-7f3b8f41660e
- date added to LUP
- 2023-09-19 11:01:16
- date last changed
- 2024-04-19 01:26:40
@article{81394d14-8bcf-437d-b0d3-7f3b8f41660e,
abstract = {{<p>Acetaminophen and ibuprofen are widely used over-the-counter medications to reduce fever, pain, and inflammation. Although both drugs are safe in therapeutic concentrations, self-medication is practiced by millions of aged patients with comorbidities that decrease drug metabolism and/or excretion, thus raising the risk of overdosage. Mitochondrial dysfunction has emerged as an important pathomechanism underlying the organ toxicity of both drugs. Assessment of mitochondrial oxygen consumption in peripheral blood cells is a novel research field Cu several applications, including characterization of drug toxicity. The present study, conducted in human platelets isolated from blood donor-derived buffy coat, was aimed at assessing the acute, concentration-dependent effects of each drug on mitochondrial respiration. Using the high-resolution respirometry technique, a concentration-dependent decrease of oxygen consumption in both intact and permeabilized platelets was found for either drug, mainly by inhibiting complex I-supported active respiration. Moreover, ibuprofen significantly decreased the maximal capacity of the electron transport system already from the lowest concentration. In conclusion, platelets from healthy donors represents a population of cells easily available, which can be routinely used in studies assessing mitochondrial drug toxicity. Whether these results can be recapitulated in patients treated with these medications is worth further investigation as potential peripheral biomarker of drug overdose.</p>}},
author = {{Beţiu, Alina Maria and Lighezan, Rodica and Avram, Vlad Florian and Muntean, Danina Mirela and Elmér, Eskil and Petrescu, Lucian}},
issn = {{0300-8177}},
keywords = {{Acetaminophen; Buffy coat; Human platelets; Ibuprofen; Mitochondria; Respiration}},
language = {{eng}},
publisher = {{Springer}},
series = {{Molecular and Cellular Biochemistry}},
title = {{Dose-dependent effects of acetaminophen and ibuprofen on mitochondrial respiration of human platelets}},
url = {{http://dx.doi.org/10.1007/s11010-023-04814-z}},
doi = {{10.1007/s11010-023-04814-z}},
year = {{2023}},
}