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

Abstract

Fluoroquinolone antibiotics are associated with increased risk of tendinopathy and tendon rupture, which can occur well after cessation of treatment. We have previously reported that the fluoroquinolone ciprofloxacin (CPX) reduced proteoglycan synthesis in equine tendon explants. This study aimed to determine the effects of CPX on proteoglycan catabolism and whether any observed effects are reversible. Equine superficial digital flexor tendon explant cultures were treated for 4 days with 1, 10, 100 or 300 µg/mL CPX followed by 8 days without CPX. The loss of [35S]-labelled proteoglycans and chemical pool of aggrecan and versican was studied as well as the gene expression levels of matrix-degrading enzymes responsible for proteoglycan catabolism. CPX suppressed [35S]-labelled proteoglycan and total aggrecan loss from the explants, although not in a dose-dependent manner, which coincided with downregulation of mRNA expression of MMP-9, -13, ADAMTS-4, -5. The suppressed loss of proteoglycans was reversed upon removal of the fluoroquinolone with concurrent recovery of MMP and ADAMTS mRNA expression, and downregulated TIMP-2 and upregulated TIMP-1 expression. No changes in MMP-3 expression by CPX was observed at any stage. These findings suggest that CPX suppresses proteoglycan catabolism in tendon, and this is partially attributable to downregulation of matrix-degrading enzymes.

Safety of fluoroquinolones

“…These clinical findings suggest a certain incapability to return to normal tendon homeostasis and a prolonged period of elevated risk of FQ-associated tendinopathy after discontinuation of FQ therapy. FQ-associated tendinopathy is associated with collagen disruption and degeneration, and a proteoglycan synthesis reduction, partially attributable to downregulation of matrix metalloproteinase (MMP)-degrading enzymes [ 13 , 15 ].…”

“…Estos hallazgos clínicos sugieren una falta de retorno a la homeostasis normal del tendón y un período prolongado de riesgo elevado de tendinopatía asociada a las FQs tras la interrupción del tratamiento con FQ. La tendinopatía asociada a las FQs se asocia a la alteración y degeneración del colágeno, y a una reducción de la síntesis de proteoglicanos atribuible en parte a la regulación a la baja de las enzimas degradadoras de la metaloproteinasa de matriz (MMP) [13,15].…”