Sailer Judith, Schmitt Sabine, Zischka Hans, Gnaiger Erich
Institute of Toxicology and Environmental Hygiene, TUM School of Medicine and Health, Technical University Munich (TUM), 80802 Munich, Germany.
Oroboros Instruments, Schoepfstrasse 18, 6020 Innsbruck, Austria.
Int J Mol Sci. 2025 Jun 4;26(11):5379. doi: 10.3390/ijms26115379.
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.
抗生素在医疗患者护理中不可或缺，但它们可能会引发脱靶效应，尤其是通过影响线粒体功能。本研究调查了三种常用抗生素庆大霉素、环丙沙星和阿莫西林对线粒体呼吸和膜电位的直接影响。使用高分辨率呼吸测定法，我们发现庆大霉素和环丙沙星显著增加了通透化人胚肾细胞中的线粒体漏呼吸，这表明线粒体内膜发生了改变。庆大霉素诱导的线粒体膜电位降低支持了这一点。特别是庆大霉素，还有环丙沙星，剂量和时间依赖性地抑制氧化磷酸化和线粒体电子传递能力，在NADH连接途径中显著，在琥珀酸连接途径中也显著。此外，庆大霉素以时间依赖性方式降低细胞色素c氧化酶（CIV）活性。相比之下，阿莫西林对线粒体呼吸没有显著影响。这些发现强调了评估抗生素对线粒体潜在直接毒性的重要性，因为线粒体是最关键的脱靶位点。高分辨率呼吸测定法为在药物开发过程早期表征此类效应提供了一种强大的方法。
