The effects of enrofloxacin on canine tendon cells and chondrocytes proliferation in vitro

Abstract

Enrofloxacin, a fluoroquinolone antibiotic has been used widely in humans and domestic animals, including dogs, because of its broad-spectrum activity and relative safety. The side effects of fluoroquinolone, induced tendinopathy, tendonitis, spontaneous tendon rupture and cartilage damage, remain incompletely understood. In the present study, we investigated the in vitro effects of enrofloxacin on cell proliferation and induction of apoptosis in canine Achilles tendon cells and chondrocytes. Cell growth and proliferation after treating with enrofloxacin for 2-6 days was quantified by a colorimetric 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxyanilide inner salt (XTT) assay. The results showed that enrofloxacin could inhibit the proliferation of canine tendon cells and chondrocytes at increasing concentrations (10-200 microg/ml). The inhibition of proliferation of canine tendon cells and chondrocytes after exposure to enrofloxacin were associated with induction of apoptosis, as evidenced by the typical nuclear apoptotic condensed nuclei found using Hoechst 33258 staining. It was demonstrated that canine tendon cells and chondrocytes treated with 200 microg/ml enrofloxacin for 4 days exhibited apoptotic features and fragmentation of DNA. Enrofloxacin also increased the apoptosis of canine tendon cells and chondrocytes in a dose and time-dependent manner. The results indicate that enrofloxacin inhibits cell proliferation, induces apoptosis and DNA fragmentation, which might explain enrofloxacin-induced tendinopathy and cartilage damage.

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

“…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.…”

Fluoroquinolone-Mediated Inhibition of Cell Growth, S-G2/M Cell Cycle Arrest, and Apoptosis in Canine Osteosarcoma Cell Lines

“…Several studies have demonstrated the cytotoxic and apoptosis-inducing effects of FQ antibiotics on tendon cells, chondrocytes, and a variety of human cancer cell lines [8], [25]–[29]. However, previous studies used a wide range of concentrations, and multiple mechanisms of action have been implicated.…”

“…While post-operative limb-spare infections are quite common in the dog, multiple studies have found such infections to be associated with improved survival when compared with similarly treated dogs without infection [3]–[5]. One such study reported that 24 out of 32 dogs experiencing post-operative allograft infections were treated with fluoroquinolone antibiotics [3], a class of drugs known to have independent activity against several tissue and cancer cell lines in vitro and in vivo [6]–[8]. Fluoroquinolones (FQs), such as ciprofloxacin (CPFX) and enrofloxacin (ENFX), target topoisomerase enzymes and in this way share a similar mechanism to traditional anti-neoplastic agents such as doxorubicin, irinotecan, and etoposide [6], [7], [9].…”

Fluoroquinolone-Induced Tendinopathy: Etiology and Preventive Measures

“…Myxomatous degeneration can be observed in ciprofloxacin and pefloxacin treated rats (Olcay et al 2011). Following exposure to pefloxacin, ofloxacin (Kato et al 1995) or enrofloxacin (Lim et al 2008), nuclei of tenocytes became pyknotic and fragmented. Such degenerative ultrastructural changes observed in the Achilles tendon samples from rats treated with gemifloxacin, ofloxacin or ciprofloxa- The quinolone core is shown at top.…”