Could oxidative stress be involved in cellular damage generated by Linezolid?

MARTINEZ SR; ALBESA I; BECERRA M C

Cordoba

Otro; RICiFa 3° Reunión Internacional de Ciencias Farmacéuticas.; 2014

Dpto. Farmacia. Fac. Ciencias Químicas-UNC y la Univ. Nac. de Rosario.

Could oxidative stress be involved in cellular damage generated by Linezolid? Martínez SR a,b, Albesa Ia,b, Becerra MC a,b. a IMBIV-CONICET, Instituto Multidisciplinario de Biología Vegetal, Ciudad Universitaria, X5000HUA Córdoba, Argentina Martínez; E-mail: martinezsolr@gmail.com b Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, X5000HUA Córdoba, Argentina Keywords: Reactive oxygen species, reactive nitrogen species, Staphylococcus aureus, Linezolid. Antibiotics disturb the physiological homeostasis of bacterial cells by interfering with essential cellular functions or structures. This physiological response is specifically tailored to overcome the inflicted damage and, thus, closely linked to the antibiotic target and mechanism of action. Linezolid is an Oxazolidinone, its binds to the 50S subunit of the prokaryotic ribosome inhibiting protein synthesis. It has activity against Gram positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) as one of the last therapeutic option. The objective was to evaluate the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in S.aureus ATCC 29213 and S.aureus ATCC MRSA 43300 treated with LZD at different concentrations, as a tool to know if reactive species are involved in the mechanism of action of this antibiotic. ROS generation was evaluated by two different methods, the reduction of the Nitro Tetrazolium Blue (NBT) and by Fluorescent Microscopy using 2,7- dichlorodihydrofluorescein diacetate. On the other hand, RNS was measured by the Griess assay. Indeed, the Ferrying reducing antioxidative power (FRAP) was measured to investigate bacterial response to stress. The generation of ROS and RNS in the S.aureus ATCC 29213 was particularly higher than in the S.aureus ATCC 43300; ROS measurement was 23% and 17% respectively. Similar result was obtained by fluorescent microscopy. S.aureus ATCC 43300 was less affected by stress as demonstrated by FRAP assay. The results show that LZD produces oxidative stress in S.aureus strains as well as a methicillin resistant strain. This reactive species could be involved in the mechanism of action of this antibiotic which causes cellular damage.