An added value of azithromycin: mitigation of doxorubicin-associated oxidative damage and genotoxicity in normal human bronchial epithelium cells

Mutagenesis. 2025 Apr 24;40(2):126-136. doi: 10.1093/mutage/geae024.

Abstract

Doxorubicin, a well-known and widely used antineoplastic agent with direct ROS-accumulating activity, has proven effective in treating various cancer types. However, its non-specific cytotoxicity towards non-cancerous cells prompts concerns regarding potential adverse effects. Azithromycin is an antibiotic for treating bacterial infections and an anti-inflammatory agent, particularly beneficial in managing respiratory conditions like bronchitis and sinusitis. Despite azithromycin's well-documented antibacterial properties, its potential cellular/genomic protective effects remain unexplored. As an in vitro model, BEAS-2B cells (normal human bronchial epithelium cells) were employed in this study to assess whether azithromycin possesses any protective properties against doxorubicin-induced cellular toxicity. Cells in pretreatment culture were treated to various amounts of azithromycin (3.125, 6.25, 12.5, 25, and 50 μg/ml) in combination with doxorubicin at IC50 (0.08 μg/ml). Doxorubicin at 0.08 μg/ml highlighted cytotoxicity, oxidative stress, and genotoxicity. Azithromycin at 25 and 50 μg/ml markedly modulated oxidative stress and genomic damage by decreasing the ROS and LPO amounts and suppressing DNA fragmentation in the comet assay parameters. Consequently, azithromycin may be regarded as a cytomodulating, antigenotoxic, and antioxidant agent.

Keywords: Comet assay; azithromycin; cytomodulator; doxorubicin; genoprotective.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Antibiotics, Antineoplastic / toxicity
  • Antioxidants / pharmacology
  • Azithromycin* / pharmacology
  • Bronchi* / cytology
  • Bronchi* / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • DNA Damage* / drug effects
  • DNA Fragmentation / drug effects
  • Doxorubicin* / adverse effects
  • Doxorubicin* / pharmacology
  • Doxorubicin* / toxicity
  • Epithelial Cells* / drug effects
  • Epithelial Cells* / metabolism
  • Humans
  • Lipid Peroxidation / drug effects
  • Oxidative Stress* / drug effects
  • Reactive Oxygen Species / metabolism

Substances

  • Azithromycin
  • Doxorubicin
  • Reactive Oxygen Species
  • Anti-Bacterial Agents
  • Antioxidants
  • Antibiotics, Antineoplastic