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

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.