Antimutagenic Effects of Vitamin C Against Oxidative Changes Induced by Quinolones
Myriam Arriaga-Alba1, Roberto Rivera-Sánchez1, Rocio Flores-Paz1, Yessica Dorin Torres-Ramos2, Ivonne María Olivares-Corichi3 and Juan José Hicks2*
1Laboratorio de Investigación Microbiológica, Hospital Juárez de México, Av. Instituto Politécnico Nacional No. 5160, C.P. 07760, México, DF, México
2Departamento de Bioquímica y Medicina Ambiental, Instituto Nacional de Enfermedades Respiratorias, Calzada de Tlalpan 4502, C.P. 14080, México, DF, México
3Sección de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México
Article history:
Received March 29, 2006
Accepted October 17, 2007
Key words:
ascorbic acid, vitamin C, norfloxacin, nalidixic acid, antioxidant, antimutagenesis, prooxidant
Summary:
Quinolones are broad-spectrum antibiotics effective against both Gram-positive and Gram-negative bacteria. Reactive oxygen species (ROS) generated by quinolones may damage cell structures and could be a risk to health. The use of vitamin C to reduce such risks may have the opposite effects: vitamin C in the presence of divalent metal ions can induce the Fenton reaction, leading to hydroxyl radical (HO·) generation and oxidative damage. The purpose of this study is to evaluate the antioxidant and prooxidant properties of vitamin C by measuring its effects on both lipid peroxidation and mutagenesis induced by quinolones nalidixic acid (NLX) or norfloxacin (NOR) in Salmonella typhimurium TA102. Mutagenicity was evaluated by the Ames test and the results were expressed as (histidine+ revertants/ng of quinolone), while lipoperoxidation was measured as thiobarbituric acid reactive substances (μmol malondialdehyde/(mL ⋅ h)). The effects of different concentrations of nalidixic acid (10–1000 ng) or norfloxacin (7–700 ng) on S. typhimurium TA102 were studied, employing the S9 mix (liver homogenate from rats pre-treated with Arochlor 1254) in the presence of 10–1000 μg of ascorbic acid (AA) with 0.1 mM FeCl3 or EDTA. Minimal inhibitory concentrations of NOR and NLX against 25 uropathogenic Escherichia coli strains were obtained using the plate dilution method in the presence of vitamin C. Vitamin C (1 mg) together with 0.1 mM FeCl3 showed a prooxidant effect in the S9 mix and enhanced the lipoperoxidation induced by either NOR or NLX. Mutagenic potency was also increased for both NOR and NLX. When metal ions were chelated with EDTA, ascorbate showed both antimutagenic and antioxidant properties. Mutagenic potency and lipoperoxidation were reduced for both NOR and NLX. The addition of vitamin C did not change the minimal in vitro inhibitory concentrations of NLX or NOR against the 25 uropathogenic E. coli strains. The antimutagenic and antioxidant effects of vitamin C were especially marked when the Salmonella strain was exposed to NOR or NLX in the presence of EDTA. In contrast, the vitamin C in the presence of FeCl3 increased ROS generation, enhancing both the mutagenic effect of the quinolones and malondialdehyde production from lipoperoxidation induced in the bacterial membranes. Therapeutic use of quinolones together with vitamin C and divalent cations might induce the Fenton reaction involving norfloxacin and nalidixic acid. However, our results suggest that vitamin C could be a good alternative for reducing the genotoxic risk of these therapeutic drugs if it is carefully handled.
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