New Quinolones: In Vitro Effects as a Potential Source of Clinical Toxicity

Research output: Contribution to journalArticle

Abstract

4-Quinolones affect mammalian cellular functions in vitro in several ways. High concentrations inhibit DNA replication, but individual genes are perhaps sensitive to lower concentrations of drug. Inhibition of cell proliferation differs widely among 4-quinolones. Ciprofloxacin and norfloxacin are the most antiproliferative, inhibiting cell growth by -30% at 20 mg/L. Genotoxicity tests with 4-quinolones are probably “false-positive” as a result of increased [3H]thymidine uptake that is not related to DNA damage. Ciprofloxacin at ≥ 10 mg/L causes significant strand breaks in DNA, which seemingly are quickly repaired and do not cause mutations or cancer. Production of immunoglobulin is inhibited by ciprofloxacin at a concentration of 5 mg/L, but production of the growth factor interleukin 2 (IL-2) is increased by 4-quinolones at the same concentration and is hyperinduced at higher concentrations. Thus the effects are very contradictory. Increased production of IL-2 may contribute to central nervous system adverse effects. 4-Quinolones in combination with theophylline or antiinflammatory drugs may inhibit γ-aminobutyric acid receptor binding and thereby have adverse effects on the central nervous system. Some 4-quinolones induce crystalluria, which may be nephropathic.

Details

Authors
Organisations
External organisations
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Microbiology in the medical area
Original languageEnglish
Pages (from-to)S1382-S1389
JournalReviews of Infectious Diseases
Volume11
Publication statusPublished - 1989 Jan 1
Publication categoryResearch
Peer-reviewedYes