Uremic Toxins and Ciprofloxacin Affect Human Tenocytes In Vitro

Erman Popowski, Benjamin Kohl, Tobias Schneider, Joachim Jankowski, Gundula Schulze-Tanzil*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Web of Science)

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 beta 1-integrin, proinflammatory interleukin (IL)-1 beta, 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-1 beta 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.

Original languageEnglish
Article number4241
Number of pages18
JournalInternational journal of molecular sciences
Volume21
Issue number12
DOIs
Publication statusPublished - Jun 2020

Keywords

  • ciprofloxacin
  • tenocytes
  • uremic toxins
  • phenylacetic acid
  • quinolinic acid
  • integrin
  • interleukin-1beta
  • matrix metalloproteinase-1
  • QUADRICEPS TENDON-RUPTURE
  • PHENYLACETIC ACID
  • ACHILLES-TENDON
  • BILATERAL QUADRICEPS
  • INDUCED TENDINOPATHY
  • QUINOLINIC ACID
  • FLUOROQUINOLONE ANTIBIOTICS
  • TRYPTOPHAN-METABOLISM
  • CELL-PROLIFERATION
  • HEMODIALYSIS

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