Abstract
Ciprofloxacin works through interfering with replication and transcription of bacterial DNA, which leads to increased oxidative stress, and death of bacterial cells. Drugs with strong antioxidant such as tempol, melatonin and pentoxifylline might interfere with the antibacterial activity of ciprofloxacin. In the current study, the effect of these drugs on the cytotoxicity of ciprofloxacin was investigated against several reference bacteria. Standard bacterial strains included Escherichia coli ATCC 35218, Staphylococcus aureus ATCC29213, Pseudomonas aeruginosa ATCC 9027, Staphylococcus epidermidis ATCC 12228, Acinetobacter baumannii ATCC 17978, Proteus mirabilis ATCC 12459, Klebsiella pneumoniae ATCC 13883, methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43300), and Streptococcus pneumoniae (ATCC 25923). The antibacterial activity of ciprofloxacin with or without treatment of bacterial cells by tempol, melatonin or pentoxifylline was assessed using the disc diffusion method and by measuring the minimum inhibitory concentration (MIC) and zones of inhibition of bacterial growth. All of the tested bacterial strains were sensitive to ciprofloxacin. When treated with tempol, melatonin or pentoxifylline, all bacterial strains showed significantly smaller zones of inhibition and larger MIC values compared ciprofloxacin alone. In correlation, reactive oxygen species (ROS) generation induced by ciprofloxacin antibacterial action was diminished by treatment of bacterial cells with tempol, melatonin or pentoxifylline. In conclusion, results indicate the possible antagonistic properties for agents with antioxidant properties such as tempol, melatonin and pentoxifylline when they are used concurrently with flouroquinolones. This could be related to the ability of these agents to inhibit oxidative stress in bacterial cells.
Highlights
Ciprofloxacin antibiotic is active against Gram-positive and Gram-negative bacteria
The possible interactive effect of tempol, melatonin or pentoxifylline with ciprofloxacin antibacterial activity was investigated against different species of reference bacteria, namely, E. coli, S. aureus, P. aeruginosa, S. epidermidis, A. baumannii, P. mirabilis, and K. pneumoniae
When bacteria were treated with combination of ciprofloxacin and tempol, melatonin or pentoxifylline, the zones of inhibition of the combination were significantly lower than those of ciprofloxacin alone for all tested bacterial strains (Table 1)
Summary
Ciprofloxacin antibiotic is active against Gram-positive and Gram-negative bacteria It is commonly used in the treatment of various infections such as urinary tract infections, chronic bacterial prostatitis, and acute uncomplicated cystitis [1]. Ciprofloxacin mechanism of action is not totally understood, yet, it starts by interfering with bacterial DNA replication and transcription through inhibition of DNA gyrase/topoisomerase II and DNA topoisomerase IV [2]. This eventually leads to the formation of quinolone-enzyme-DNA complexes, and the generation of oxidative free radicals as singlet oxygen (1 O2 ) and superoxide anion (O2 ́ ) [3], and the subsequent cellular death [4,5]. Failure of ciprofloxacin treatment was reported in elderly patients taking supplement preparations [7]
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