Direct Effects of Clinically Relevant Antibiotics on Mitochondrial Respiration

Area of Science:

• Biochemistry
• Pharmacology
• Cell Biology

Background:

• Antibiotics are crucial for treating infections but can cause unintended side effects.
• Mitochondria are vital for cellular energy production and are potential targets for antibiotic toxicity.

Purpose of the Study:

• To investigate the direct impact of gentamicin, ciprofloxacin, and amoxicillin on mitochondrial respiration and membrane potential.
• To assess the potential of these antibiotics to cause off-target mitochondrial toxicity.

Main Methods:

• High-resolution respirometry was used to measure mitochondrial function in permeabilized human embryonic kidney cells.
• Mitochondrial respiration, membrane potential, and specific enzyme activities (Complex IV) were analyzed.

Main Results:

• Gentamicin and ciprofloxacin increased mitochondrial leak respiration and inhibited oxidative phosphorylation and electron transfer capacity.
• Gentamicin decreased mitochondrial membrane potential and Complex IV activity.
• Amoxicillin demonstrated no significant effects on mitochondrial respiration.

Conclusions:

• Gentamicin and ciprofloxacin exhibit direct mitochondrial toxicity, impacting key respiratory functions.
• Mitochondrial dysfunction represents a critical off-target effect of certain antibiotics.
• High-resolution respirometry is a valuable tool for early detection of antibiotic-induced mitochondrial toxicity.