Uremic Toxins and Ciprofloxacin Affect Human Tenocytes In Vitro

Abstract

Tendinopathy is a rare but serious complication of quinolone therapy. Risk factors associated with quinolone-induced tendon disorders include chronic kidney disease accompanied by the accumulation of uremic toxins. Hence, the present study explored the effects of the representative uremic toxins phenylacetic acid (PAA) and quinolinic acid (QA), both alone and in combination with ciprofloxacin (CPX), on human tenocytes in vitro. Tenocytes incubated with uremic toxins +/- CPX were investigated for metabolic activity, vitality, expression of the dominant extracellular tendon matrix (ECM) protein type I collagen, cell-matrix receptor β1-integrin, proinflammatory interleukin (IL)-1β, and the ECM-degrading enzyme matrix metalloproteinase (MMP)-1. CPX, when administered at high concentrations (100 mM), suppressed tenocyte metabolism after 8 h exposure and at therapeutic concentrations after 72 h exposure. PAA reduced tenocyte metabolism only after 72 h exposure to very high doses and when combined with CPX. QA, when administered alone, led to scarcely any cytotoxic effect. Combinations of CPX with PAA or QA did not cause greater cytotoxicity than incubation with CPX alone. Gene expression of the pro-inflammatory cytokine IL-1β was reduced by CPX but up-regulated by PAA and QA. Protein levels of type I collagen decreased in response to high CPX doses, whereas PAA and QA did not affect its synthesis significantly. MMP-1 mRNA levels were increased by CPX. This effect became more pronounced in the form of a synergism following exposure to a combination of CPX and PAA. CPX was more tenotoxic than the uremic toxins PAA and QA, which showed only distinct suppressive effects.

Patellar tendon biomechanical and morphologic properties and their relationship to serum clinical variables in persons with prediabetes and type 2 diabetes

“…The correlations with creatine (positive) and GFR (negative) are interesting as they suggest that kidney function could be related to tendon properties regardless of the diabetic state of an individual. Interestingly, a recent study linked uremic toxins to dysfunction in tenocytes, 58 and tendinopathies are particularly high in hemodialysis patients, 59 thus providing a potential link between kidney function and changes in tendon properties.…”

Bilateral rupture of the quadricipital tendon in patients with chronic kidney disease: The peculiarities of management (case report)

“…Similarly, in 1991, Kurer et al [ 10 ] proposed that beta 2- microglobulin amyloidosis reduces tendon elasticity by its accumulation in the tendon system. Furthermore, Hofmann et al [ 11 ] proposed in 1990 that the accumulation of toxic uric acid inside the tendon system weakens it, Which was approved by a recent study [ 12 ], made to evaluate the direct effect of the uremic toxins on tendon metabolism in vitro. It objected that uremic Toxins such as phenylacetic acid suppressed tenocyte metabolic activity and increased the rate of cell death.…”

Editorial for Special Issue: Achilles Curse and Remedy: Tendon Diseases from Pathophysiology to Novel Therapeutic Approaches

“… Cross-talk with exogenous cells: e.g., with macrophages during inflammation by Vinhas et al [ 5 ] and myoblasts at the site of myotendinous junction by Strenzke et al [ 6 ]. Niche chemical composition: e.g., uremic toxins and antibiotics in pathological kidney conditions by Popowski et al [ 7 ]; tissue chemical changes during tendon aging by Yin et al [ 8 ]; and cartilage oligomeric matrix protein (COMP) fragmentation in tendon injury by Smith et al [ 9 ]. Tendon structural composition and biomechanical properties: e.g., alterations in elastic properties after tendon injury by Frankewycz et al [ 10 ] and in vitro and in vivo response of tenocytes to mechanical stimulation by Fleischhacker et al [ 11 ].…”

“…Niche chemical composition: e.g., uremic toxins and antibiotics in pathological kidney conditions by Popowski et al [ 7 ]; tissue chemical changes during tendon aging by Yin et al [ 8 ]; and cartilage oligomeric matrix protein (COMP) fragmentation in tendon injury by Smith et al [ 9 ].…”