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The arthropathogenic effects of quinolones have been described in juvenile animals of multiple species such as dogs, rats, non-human primates, rabbits and guinea pigs. Several studies have been performed to clarify the exact mechanism leading to cartilage damage. In these studies, the investigators focused on the inhibitory effects of quinolones on DNA, collagen and proteoglycan synthesis and on the formation of oxygen-derived reactive molecules. Recently, it was suggested that quinolone-induced arthropathy is possibly associated with the magnesium-chelating properties of quinolones. However, the exact mechanism of quinolone-induced arthropathy is still unkown. This article reviews and summarizes several possible mechanisms for quinolone-induced arthropathy.
Enrofloxacin is a synthetic chemotherapeutic agent from the class of the fluoroquinolones that is widely used to treat bacterial infections in animals. Fluoroquinolones cause severe lesions in articular-epiphyseal cartilage complexes of growing mammals. The aim of the present study was to determine whether enrofloxacin has chondrotoxic, dose- and time-dependent effects on avian articular cartilage. 21-day-old male broiler chickens were treated orally with a single or five doses of 10, 50, 100, 300 and 600 mg/kg/day of enrofloxacin. 24 hours after the last dose the animals were killed and femoral head with condyles and tibial condyles were subject to a gross and histopathological investigation. The lesion scoring system was used to determine the progression of lesions. The mean score in birds treated with a single dose of 300 and 600 mg/kg of enrofloxacin was significantly increased when compared to the control group, while the administration of one dose of 10, 50 and 100 mg/kg of the drug did not cause substantial changes in the examined articular cartilages. The mean score was significantly greater in birds dosed for 5 days with 50, 100, 300 or 600 mg/kg/day of enrofloxacin when compared to the control group. Histologic changes included, among others, occurrence of chondrocytes with shrunken cytoplasm and pyknotic nuclei, spindle-shaped cells, clusters of chondrocytes and loss of proteoglycan. In conclusions, our results indicate that the use of enrofloxacin in growing chickens at recommended dosage is safe from the point of view of possibility of chondrotoxic effect. Only very high dosage of enrofloxacin, significantly exceeding the therapeutically applied doses, can induce toxic effects in articular cartilage and intensity of chondrotoxicity is dose- and time-dependent. Moreover, our findings suggest that quinolone-induced arthropathy is considerably less expressed in birds than in mammals.
Quinolone-induced arthropathy has been observed after a single very large dose, or after several moderately large doses in juvenile animals of multiple species. The purpose of the present study was to determine whether long-term treatment with therapeutic doses of enrofloxacin has a detrimental effect on chicken articular cartilage. 21-day-old broiler chickens were treated orally with 10 mg/kg/day of enrofloxacin for 10, 20 and 35 days. 24 hours after the last dose, the animals were killed and the femoral head with condyles and tibial condyles were subjected to a gross and histopathological investigation. The necropsy did not reveal macroscopic visible pathological changes in the articular cartilage surface, as well as in soft tissues surrounding joints in any of the animals from this study. Also, light microscopy evaluation did not show significant histopathological changes in any of the specimens from either experimental and control animals. In conclusion, our results indicate that treatment with a therapeutic dose of enrofloxacin for a period exceeding the recommended duration of therapy does not cause arthropathy in growing chickens. Moreover, the results obtained seem to indicate that chondrotoxicity of quinolones does not have a cumulative nature.
A capillary electrophoresis (CE) method for the simultaneous determination of residues of six quinolones (enrofloxacin, ciprofloxacin, ofloxacin, lomefloxacin, norfloxacin, cinoxacin) in chicken, hen, and swine tissue samples were developed and validated. The sample preparation consisted of a solid phase extraction on C-18 cartridges prior to the analysis by CE with UV detection. The method was validated in terms of selectivity, linearity, precision, accuracy, recovery, and stability. The calibration curves were linear to at least 10-1 000 ng/g for all quinolones with r² > 0.999. The values of decision limits (CCα) and detection capabilities (CCβ) for the analysed substances were between 3.2-16.9 and 3.5-20.3 ng/g, respectively. The CE method was robust and specific, allowing reliable quantification of quinolone residues in animal tissues and should also be useful for clinical and biomedical investigations.
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