The mitochondria targeted antioxidant MitoQ protects against fluoroquinolone-induced oxidative stress and mitochondrial membrane damage in human Achilles tendon cells.
Tendinitis and tendon rupture during treatment with fluoroquinolone antibiotics is thought to be mediated via oxidative stress. This study investigated whether ciprofloxacin and moxifloxacin cause oxidative stress and mitochondrial damage in cultured normal human Achilles' tendon cells and whether an antioxidant targeted to mitochondria (MitoQ) would protect against such damage better than a non-mitochondria targeted antioxidant. Human tendon cells from normal Achilles' tendons were exposed to 0-0.3 mM antibiotic for 24 h and 7 days in the presence of 1 microM MitoQ or an untargeted form, idebenone. Both moxifloxacin and ciprofloxacin resulted in up to a 3-fold increase in the rate of oxidation of dichlorodihydrofluorescein, a marker of general oxidative stress in tenocytes (p<0.0001) and loss of mitochondrial membrane permeability (p<0.001). In cells treated with MitoQ the oxidative stress was less and mitochondrial membrane potential was maintained. Mitochondrial damage to tenocytes during fluoroquinolone treatment may be involved in tendinitis and tendon rupture.
Lowes
Damon A
DA
Division of Applied Medicine, School of Medicine & Dentistry, University of Aberdeen, UK.
Wallace
Carol
C
Murphy
Michael P
MP
Webster
Nigel R
NR
Galley
Helen F
HF
D000125:Achilles Tendon / Q000166:cytology / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism*; D000890:Anti-Infective Agents / Q000633:toxicity; D000975:Antioxidants / Q000494:pharmacology*; D001372:Aza Compounds / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002939:Ciprofloxacin / Q000633:toxicity*; D024841:Fluoroquinolones; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D000077266:Moxifloxacin; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D011804:Quinolines / Q000633:toxicity*; D012421:Rupture / Q000209:etiology; D052256:Tendinopathy / Q000209:etiology; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
D000890:Anti-Infective Agents; D000975:Antioxidants; D001372:Aza Compounds; D024841:Fluoroquinolones; D009943:Organophosphorus Compounds; D011804:Quinolines; D014451:Ubiquinone; C429014:mitoquinone; D002939:Ciprofloxacin; D000077266:Moxifloxacin