Ciprofloxacin-Induced Antibacterial Activity is Reversed by Vitamin E and Vitamin C

Abstract

In the present study, we investigated the possible involvement of oxidative stress in ciprofloxacin-induced cytotoxicity against several reference bacteria including Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 29213, and clinical isolate of methicillin-resistant Staphylococcus aureus (MRSA). Oxidative stress was assessed by measurement of hydrogen peroxide generation using a FACScan flow cytometer. The antibacterial activity of ciprofloxacin was assessed using the disk diffusion method and by measuring the minimum inhibitory concentration (MIC). Ciprofloxacin induced a dose-dependent antibacterial activity against all bacteria where the highest tested concentration was 100 ug/ml. Results revealed that E. coli cells were highly sensitive to ciprofloxacin (MIC = 0.21 μg/mL ± 0.087), P. aeruginosa and S. aureus cells were intermediately sensitive (MIC = 5.40 μg/mL ± 0.14; MIC = 3.42 μg/mL ± 0.377, respectively), and MRSA cells were highly resistant (MIC = 16.76 μg/mL ± 2.1). Pretreatment of E. coli cells with either vitamin E or vitamin C has significantly protected cells against ciprofloxacin-induced cytotoxicity. These results indicate the possible antagonistic properties for vitamins C or E when they are used concurrently with ciprofloxacin.

Vorinostat Pretreatment Enhanced Ciprofloxacin-Induced Antibacterial Activity

“…In agreement, ciprofloxacin susceptibility of these bacterial strains was previously shown [17,24,25]. Additionally, reactive oxygen species had essential role in the antibacterial effect of ciprofloxacin against bacteria such as P.…”

“…We have recently shown that vorinostat induce oxidative chromosomal damage leading its mutagenic effect in blood lymphocytes [19]. Given the importance of reactive oxygen species, energy metabolism, mitochondrial functions for the antibacterial action of floroquinolones [5][6][7]17], it is probable that these mechanisms has a role in the observed enhancement of ciprofloxacin antibacterial activity by vorinostat. Thus, a drug-drug interaction between vorinostat and ciprofloxacin is a possibility.…”

“…including vitamin E, vitamin C, vitamin B12 and other aniroxidants such as melatonin, tempol, and pentoxypheline were shown to reduce ciprofloxacin antibacterial activity [17]. During the course of its action against bacterial strains such as E. coli, Enterococcus faecalis, and S. aureus, ciprofloxacin systematically induced the production of reactive oxygen species [5].…”

“…aeruginosa, E. coli, and S. aureus [5][6][7]17]. Moreover, common scavengers of reactive oxygen species,…”

“…We have recently shown that vorinostat induce oxidative chromosomal damage leading its mutagenic effect in blood lymphocytes (ref). Recently, we showed that the antibacterial activity of ciprofloxacin is altered by major antioxidants, such as, vitamins E and C [17], tempol, pentoxifylline and melatonin [18]. Given that ciprofloxacin acts by inducement of bacterial oxidative damage [5,6], and the known oxidative cell-damaging activity of vorinostat [19], it is likely that vorinostat pretreatmnet enhances ciprofloxacin antibacterial activity.…”