Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells
Sci Transl Med
3 July 2013:
Vol. 5,
Issue 192,
p.
192ra85
Sci. Transl. Med. DOI:
10.1126/scitranslmed.3006055
ABSTRACT: Prolonged
antibiotic treatment can lead to detrimental side effects in patients,
including ototoxicity, nephrotoxicity, and
tendinopathy, yet the mechanisms underlying the
effects of antibiotics in mammalian systems remain unclear. It has been
suggested
that bactericidal antibiotics induce the
formation of toxic reactive oxygen species (ROS) in bacteria. We show
that clinically
relevant doses of bactericidal
antibiotics—quinolones, aminoglycosides, and β-lactams—cause
mitochondrial dysfunction and
ROS overproduction in mammalian cells. We
demonstrate that these bactericidal antibiotic–induced effects lead to
oxidative
damage to DNA, proteins, and membrane lipids.
Mice treated with bactericidal antibiotics exhibited elevated oxidative
stress
markers in the blood, oxidative tissue damage,
and up-regulated expression of key genes involved in antioxidant defense
mechanisms,
which points to the potential physiological
relevance of these antibiotic effects. The deleterious effects of
bactericidal
antibiotics were alleviated in cell culture and
in mice by the administration of the antioxidant N-acetyl-l-cysteine
or prevented by preferential use of bacteriostatic antibiotics. This
work highlights the role of antibiotics in
the production of oxidative tissue damage in
mammalian cells and presents strategies to mitigate or prevent the
resulting
damage, with the goal of improving the safety of
antibiotic treatment in people.
- Copyright © 2013, American Association for the Advancement of Science
Citation: S. Kalghatgi, C. S. Spina, J. C. Costello, M. Liesa, J. R. Morones-Ramirez, S. Slomovic, A. Molina, O. S. Shirihai, J. J.
Collins, Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells. Sci. Transl. Med. 5, 192ra85 (2013).