|
KMID : 1034820230190020333
|
|
Molecular & Cellular Toxicology
2023 Volume.19 No. 2 p.333 ~ p.342
|
|
|
Mitochondrial dysfunction is underlying fluoroquinolone toxicity: an integrated mitochondrial toxicity assessment
|
|
Tianyi Jiang
Stefan Kustermann
Xiaoqin Wu
Christine Zihlmann
Meifang Zhang
Yi Mao
Waikwong Wu
Jianxun Xie
|
|
|
Abstract
|
|
|
Background : Antibiotics bear an inherent risk of mitochondrial toxicity due to the structural similarities between mitochondria and bacteria. Drug-induced mitochondrial dysfunction can contribute to organ toxicity and has resulted in a considerable number of market withdrawals. Fluoroquinolones were alerted for hepatotoxicity liability and were recently given black box warnings by FDA for the potential disabling side effects including tendonitis, pain in extremities and joints, neuropathies associated with paraesthesia, depression, impairment of memory, hearing, vision, etc.
Objective : In this study, the potential involvement of mitochondrial impairment in the toxicity of four fluoroquinolones was investigated with a panel of mechanistic endpoints including ATP, mitochondrial respiration, as well as mitochondrial DNA and protein levels.
Results : Data revealed mitochondrial toxicity to different extents, induced by the tested fluoroquinolones and suggested mitochondrial protein synthesis as potential mechanism of action.
Conclusion : This study exemplifies an integrated/holistic approach with a selected battery/panel of in vitro assays/endpoints serving to identify mitochondrial toxicity early on in the development of drugs, in particular, antibiotics.
|
|
|
KEYWORD
|
|
|
Mitochondrial toxicity, Mitochondrial protein synthesis, Integrated approach, Fluoroquinolones, Antibiotics, Drug development
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|
|