Bactericidal antibiotics promote oxidative damage and programmed cell death in sinonasal epithelial cells

Michael A. Kohanski, Anuj Tharakan, Nyall London, Andrew P Lane, Murugappan Ramanathan

Research output: Contribution to journalArticle

Abstract

Background: Antibiotics are widely and heavily used in the treatment of chronic sinusitis. Bactericidal antibiotics can stimulate reactive oxygen species (ROS) formation, a proinflammatory response, and cell death in cultured human sinonasal epithelial cells (SNECs). Sulforaphane (SFN) is a potent stimulator of the antioxidant nuclear factor erythroid 2-related factor 2 (Nrf-2) system and a suppressor of inflammation. In this study we utilized SFN to further explore the relationship between levofloxacin treatment, ROS formation, and the cell death response. Methods: SNECs were collected from patients during endoscopic sinus surgery and grown in culture at the air-liquid interface. Differentiated SNECs were stimulated with levofloxacin with or without SFN pretreatment. ROS were quantified. Apoptosis markers of caspase-3 activity and DNA fragmentation were quantified. Results: Cultured SNECs treated with levofloxacin resulted in a significant increase in activity of the proapoptotic caspase-3 protease (5.9-fold, p = 0.01). The increase in activity was suppressed by pretreatment with SFN (1.9-fold). ROS levels increased with levofloxacin treatment (range, 1.2-fold to 1.8-fold), but were not significantly suppressed by pretreatment with SFN (range, 1.0-fold to 1.3-fold). Conclusion: In this study, we demonstrate that treatment of cultured SNECs with levofloxacin leads to an increase in caspase-3 activity. SFN pretreatment suppresses the increased apoptotic response possibly through its antioxidant stimulating properties. Our results suggest that levofloxacin treatment stimulates a potent proapoptotic possibly through an ROS-dependent mechanism. Future studies will explore if this antibiotic-induced response is harmful to recovery of function in those with sinusitis.

Original languageEnglish (US)
Pages (from-to)359-364
Number of pages6
JournalInternational Forum of Allergy and Rhinology
Volume7
Issue number4
DOIs
StatePublished - Apr 1 2017

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Keywords

  • antibiotics
  • apoptosis
  • innate immunity
  • rhinosinusitis
  • ROS
  • sulforaphane

ASJC Scopus subject areas

  • Immunology and Allergy
  • Otorhinolaryngology

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