Cytofluorometric analysis of chondrotoxicity of fluoroquinolone antimicrobial agents.
To better understand quinolone-related arthropathy, we conceived an experimental ex vivo model using cell cultures of articular chondrocytes issued from pretreated New Zealand White rabbits (NZW). Juvenile (4- to 5-week-old) NZW were orally dosed with ofloxacin or pefloxacin (300 mg/kg of body weight for 1 day) or with pefloxacin (300 mg/kg for 7 days). Adult (5-month-old) NZW were treated with pefloxacin (300 mg/kg for 1 day). Chondrocytes were enzymatically recovered from cartilage and were analyzed by cytofluorometry using 2',7'-dichlorofluorescein diacetate (DCFH-DA) and dihydrorhodamine 123 (DHR), reflecting cellular respiratory-burst activity, and rhodamine 123 (Rh123) and 10-N-nonyl-acridine orange (NAO), specific for the mitochondrial activity and mass, respectively. A significant increase in the respiratory burst was detected by DCFH-DA and DHR in all treated groups of young animals, compared with untreated control groups. No significant increase of respiratory burst was noted in older treated rabbits. The 7-day treatment resulted in a decrease in mitochondrial uptake of Rh123 and an increase in NAO uptake. Fluoroquinolone arthrotoxicity seems to involve in its early phase the respiratory burst of immature articular chondrocytes.
Hayem
G
G
Unité 13, Institut National de la Santé et de la Recherche Médicale, Hôpital Claude Bernard, Paris, France.
Petit
P X
PX
Levacher
M
M
Gaudin
C
C
Kahn
M F
MF
Pocidalo
J J
JJ
D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D002357:Cartilage Diseases / Q000139:chemically induced*; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D005470:Fluorometry / Q000379:methods; D008853:Microscopy; D008928:Mitochondria / Q000187:drug effects; D015242:Ofloxacin / Q000633:toxicity*; D015366:Pefloxacin / Q000633:toxicity*; D011817:Rabbits; D016897:Respiratory Burst / Q000187:drug effects; D012680:Sensitivity and Specificity
D000890:Anti-Infective Agents; D005456:Fluorescent Dyes; D015366:Pefloxacin; D015242:Ofloxacin