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Sailer, J.* ; Schmitt, S.* ; Zischka, H. ; Gnaiger, E.*

Direct effects of clinically relevant antibiotics on mitochondrial respiration.

Int. J. Mol. Sci. 26, 5379 - 5379 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Antibiotics are indispensable in medical patient care, yet they may elicit off-target effects, particularly by affecting mitochondrial function. This study investigates three commonly used antibiotics, gentamicin, ciprofloxacin, and amoxicillin, for their direct effects on mitochondrial respiration and membrane potential. Using high-resolution respirometry, we show that gentamicin and ciprofloxacin markedly increase mitochondrial leak respiration in permeabilized human embryonic kidney cells, suggesting alterations in the mitochondrial inner membrane. This is supported by a gentamicin-induced decrease in mitochondrial membrane potential. Especially gentamicin, but also ciprofloxacin, dose- and time-dependently inhibit oxidative phosphorylation and the mitochondrial electron transfer capacity, pronouncedly in the NADH-linked but also in the succinate-linked pathway. Furthermore, gentamicin decreases Complex IV (CIV) activity in a time-dependent fashion. In contrast, amoxicillin has no significant effect on mitochondrial respiration. These findings emphasize the importance of evaluating the potential direct toxicity of antibiotics on mitochondria, as they are most critical off-target sites. High-resolution respirometry provides a powerful approach to characterize such effects early in the drug development process.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Cellular Respiration; Acute-renal-failure; Antimicrobial Spectrum; Gentamicin; Pharmacokinetics; Ciprofloxacin; Mechanism; Liver; Amoxicillin; Dysfunction; Resistance
ISSN (print) / ISBN 1661-6596
e-ISSN 1422-0067
Zeitschrift International Journal of Molecular Sciences
Quellenangaben Band: 26, Heft: 11, Seiten: 5379 - 5379 Artikelnummer: , Supplement: ,
Verlag MDPI
Verlagsort Basel
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Toxicology and Pharmacology (TOX)
Förderungen European Union