Related Experiment Video
Updated: Jun 16, 2025
Working with Auditory HEI-OC1 Cells
Published on: September 3, 2016
Antibiotic-induced mitochondrial dysfunction: Exploring tissue-specific effects on HEI-OC1 cells and peripheral blood
Tianshi Liu1, Imen Chamkha1, Eskil Elmér2
1Mitochondrial Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
Abstract:
Antibiotics are crucial in treating infectious diseases, particularly in intensive care unit patients, but they can lead to side effects such as ototoxicity. A mechanism for this is antibiotics targeting mitochondrial components in eucaryotic cells, due to their resemblance of those in bacteria. Here we investigate how five classes of antibiotics (carbapenems, fluoroquinolones, aminoglycosides, glycopeptides, and oxazolidinones) affect mitochondrial respiratory function, ATP levels, mitochondrial membrane potential and levels of reactive oxygen species in an inner-ear derived epithelial cell line (HEI-OC1) and human primary blood cells (PBMCs) at clinically relevant concentrations. Mitochondrial respiration in intact HEI-OC1 cells was suppressed in response to the majority of the tested antibiotics. This effect was lost when the HEI-OC1 cells were permeabilized and substrate supply controlled. Further in these cells, ROS levels were increased and ATP levels reduced. In contrast, no measure of mitochondrial function of PBMCs was affected by any antibiotics at the same concentration. We show that HEI-OC1 cells are sensitive to a broad range of antibiotics, and that the mechanism of toxicity to mitochondrial respiration is upstream of the mitochondrial respiratory chain, with downstream effects on mitochondrial respiration, ATP levels and ROS levels.
Insights
Antibiotics can harm inner ear cells by disrupting mitochondrial function, leading to reduced ATP and increased reactive oxygen species (ROS). However, human blood cells showed no such antibiotic-induced mitochondrial toxicity.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Antibiotics are vital for treating infections, especially in intensive care units.
- Antibiotic-induced ototoxicity is a significant concern, potentially linked to mitochondrial damage due to similarities between bacterial and mitochondrial components.
- Understanding the specific mechanisms of antibiotic toxicity on mitochondria is crucial for patient safety.
Purpose of the Study:
- To investigate the effects of five major antibiotic classes on mitochondrial function in inner ear epithelial cells and human blood cells.
- To determine if antibiotics impact mitochondrial respiration, ATP production, membrane potential, and reactive oxygen species (ROS) generation.
- To elucidate the mechanism of antibiotic-induced mitochondrial dysfunction.
Main Methods:
- Utilized HEI-OC1 (inner ear epithelial) and PBMCs (human primary blood) cell lines.
- Assessed mitochondrial respiration, ATP production, mitochondrial membrane potential, and ROS generation.
- Tested carbapenems, fluoroquinolones, aminoglycosides, glycopeptides, and oxazolidinones at clinically relevant concentrations.
Main Results:
- Most tested antibiotics suppressed mitochondrial respiration in intact HEI-OC1 cells.
- This suppression was not observed in permeabilized cells, indicating the effect is upstream of the respiratory chain.
- HEI-OC1 cells exhibited increased ROS production and reduced ATP levels, while PBMCs showed no mitochondrial dysfunction.
- The mechanism of toxicity involves effects upstream of the mitochondrial respiratory chain.
Conclusions:
- HEI-OC1 cells are sensitive to a wide range of antibiotics, showing significant mitochondrial dysfunction.
- Antibiotic toxicity in these cells affects mitochondrial respiration, ATP levels, and ROS generation.
- Human blood cells (PBMCs) are not affected by the same antibiotic concentrations, suggesting cell-specific sensitivity.
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