Determination of two fluoroquinolones and their combinations with hyaluronan effect inin vitrocanine cartilage explants

Abstract

Background Previous studies reported the effect of enrofloxacin (Enro) and marbofloxacin (Mar) on cell death and alteration of the key genes involved in catabolic and anabolic processes and demonstrated the beneficial effects of hyaluronan (HA) combined with fluoroquinolones (FQs) on primary canine chondrocytes. This study further determines the effects of these treatments on canine cartilage explants in both normal and interleukin-1 beta (IL-1β)-stimulated conditions. Methods We examined sulfate glycosaminoglycan (s-GAG) release, uronic acid (UA) content, and safranin-O staining, as well as the expression patterns of inflammatory, extracellular matrix (ECM) component and enzymes. Results Enro treatment alone effectively stimulated proteoglycan anabolism by increasing UA content and glycosaminoglycans (GAGs) in normal and pre-IL-1β-stimulated explant, whereas Mar showed opposite results. The combination of HA and FQs increased s-GAG release and UA content in normal explants in addition to effective down-regulated expression of MMP3. HA reduced the adverse effects of Mar by enhancing UA and GAG contents in both normal and pre-IL-1β-explants. Moreover, HA effectively induced HAS1and ACANup-regulation and reduced MMP9, TNF, PTGS2,and NFKB1 expression for a long term. Discussion Our results suggest the direct effects of Enro and Mar may selectively stimulate the conditioned explants to express MMP-codinggenes and promote gene expression involved in matrix production, pro-inflammatory cytokines, and cell degradation in different directions. HA successfully reduced the adverse effects of FQs by enhancing s-GAG and UA contents and down-regulated expression of MMPs.

Short-Term Exposure to Ciprofloxacin Reduces Proteoglycan Loss in Tendon Explants

“…Our results contradict these findings as we observed no significant effect of CPX on MMP-3 m RNA expression in equine SDFT explants after 4 days treatment. However, Siengdee, Pradit, Chomdej and Nganvongpanit [ 77 ] also reported MMP-9 downregulation by enrofloxacin (a metabolic precursor to CPX) and Corps, Harrall, Curry, Fenwick, Hazleman and Riley [ 17 ] observed downregulation of MMP-13, and our study corroborates these findings in whole tendon explants with both being downregulated by higher concentrations of CPX after 4 days treatment. The differences in molecular responses between this study and others may be due to the experimental systems used.…”

“…The differences in molecular responses between this study and others may be due to the experimental systems used. Notably, the findings in this study may not reflect the same tenocyte response to FQs than in cell culture models with cytokine-induced inflammation [ 17 , 36 , 77 ]. To our knowledge, this study is the first to investigate ADAMTS m RNA expression in tendon after treatment with FQs.…”

“…FQ-induced upregulation of IL-1B-potentiated MMP-3 expression by FQs has been reported in human tendon cell cultures [ 17 ] as well as canine cartilage explants [ 77 ]. Our results contradict these findings as we observed no significant effect of CPX on MMP-3 m RNA expression in equine SDFT explants after 4 days treatment.…”

Patient weight has diverse effects on the prescribing of different antibiotics to dogs

“…However, this is not the case for marbofloxacin which is a more costly fluroquinolone than enrofloxacin. Preferential use of marbofloxacin in larger animals may reflect the rarity of reported iatrogenic cartilage damage in large-breed dogs treated with this drug compared to others in the same class ( 16 , 50 ).…”