The effects of enrofloxacin on decorin and glycosaminoglycans in avian tendon cell cultures

Abstract

Tendonitis and tendon rupture have been reported to occur during or following therapy with fluoroquinolone antibiotics. Though the pathogenesis is unknown, several studies suggest that fluoroquinolone antibiotics alter proteoglycan content in soft tissues, including tendons, and thereby alter collagen fibrillogenesis. To better understand the mechanism of action of fluoroquinolones, we studied the effects of enrofloxacin, a widely used fluoroquinolone in veterinary medicine, on avian tendon cell cultures established from gastrocnemius tendons from 18-day-old chicken embryos. We found that cell proliferation was progressively inhibited with increasing concentrations of enrofloxacin. This was accompanied by changes in morphology, extracellular matrix content and collagen fibril formation as detected by electron microscopy. We also observed a 35% decrease in the content of total monosaccharides in enrofloxacin-treated cells. The ratio of individual monosaccharides was also altered in enrofloxacin-treated cells. Enrofloxacin also induced the synthesis of small amounts of keratan sulfate in tendon cells. Moreover we observed enrofloxacin-induced changes in glycosylation of decorin, the most abundant tendon proteoglycan, resulting in the emergence of multiple lower molecular bands that were identifiable as decorin after chondroitinase ABC and N-glycanase treatment of extracts from enrofloxacin-treated cells. Medium conditioned by enrofloxacin-treated cells contained less decorin than did medium conditioned by control cells. We hypothesize that enrofloxacin induces either changes in the number of N-linked oligosaccharides attached to the core protein of decorin or changes in decorin degradation process. In conclusion, our data suggest that enrofloxacin affects cell proliferation and extracellular matrix through changes in glycosylation.

Two fluoroquinolones and their combinations with hyaluronan: comparison of effects on canine chondrocyte culture

“…Our data are consistent with other studies. Enro treatment has been reported to decrease the matrix components, such as collagens and proteoglycans, of chondrocytes and tendon cells in various species (Yoon et al ., ,b; Lim et al ., ).…”

“…The safety of Enro has been demonstrated through the high ability of human foreskin fibroblasts to defend themselves against protozoan parasite infection, without cell toxicity (Barbosa et al ., ). However, the effects of Enro on cell proliferation, DNA fragmentation, and apoptosis induction have been reported in canine tendon cells and chondrocytes (Lim et al ., ) and in avian and equine tenocytes (Yoon et al ., ,b). The mechanisms of FQ‐induced cell apoptosis remain incompletely understood.…”

Adverse Effects of Antimicrobials via Predictable or Idiosyncratic Inhibition of Host Mitochondrial Components

“…In vitro toxicity has been demonstrated in tenocytes and chondrocytes (11,84,101), and the chondrotoxicity has been associated with reactive oxygen species (51). Osteoblasts are also sensitive to fluoroquinolones, since these cells produce excess lactate in the presence of therapeutically relevant concentrations of the drug (13).…”

Proteomics Perspectives in Rotator Cuff Research: A Systematic Review of Gene Expression and Protein Composition in Human Tendinopathy

“…In our additional specific Medline search, we identified 13 proteomics studies, of which 5[87–91] had not been captured in the comprehensive searches. Altogether we identified 14 studies that applied proteomics technologies on tendon tissues/cells, but none of them were eligible for inclusion in the present review: 1 study was only presented as a conference abstract[92], 10 were conducted on animal tendons or cultured cells[88, 90, 91, 93–99], and 3 were conducted on human tendons to examine exercise-induced changes[100], drug concentrations[101], or laboratory procedures[102]. …”