CONICET | Buscador de Institutos y Recursos Humanos

Our research group has recently started a new line of research focused on the study of natural compounds that neutralize the toxic effects caused by Gentamicin (GEN) that are associated with an oxidative stress increasing in human cells. Luteolin, a flavonoid isolated from fruits of Prosopis strombulifera var. strombulifera with antioxidant properties and scavenger capacity of free radicals, has demonstrated in previous studies of our group, a marked protective effect against the production of reactive oxygen species (ROS) induced by GEN in human leukocytes.Thus, these results motivated us to study the effect of Luteolin on the activity of this antibiotic, in order to determine if its protective action on human cells can modify the antibacterial activity of GEN in different strains of Escherichia coli and Staphylococcus aureus. For this, a reference strains of E. coli ATCC 25922 and a clinical strain of E. coli resistant to GEN, a reference strains of S. aureus ATCC 29213 and a clinical strain of S. aureus resistant to GEN were used. The tube dilution method was used to determine the Minimum Inhibitory Concentration (MIC) of Luteolin on all strains of E. coli and S. aureus, while the checkerboard method was used to determine the interaction between Luteolin and Gentamicin employing combinations of these compounds at different concentrations in Mueller-Hinton broth.This way, it was observed that Luteolin submitted a MIC at the maximum concentration tested (125µg/ml) in both reference strains, while in clinical strains of E. coli and S. aureus resistant to GEN, Luteolin didn?t show antibacterial activity. Furthermore, when GEN was combined with Luteolin for the inhibition of E. coli ATCC and S. aureus ATCC a synergistic effect was observed. In E. coli ATCC a synergism was observed (FICIL+G = 0.254) when the concentration of Luteolin was decreased 250 times below its MIC and of the antibiotic 4 times below its individual MIC, while in S. aureus ATCC the synergic effect was greater (FICIL+G = 0.133) than E. coli ATCC when the concentration of Luteolin decreased 125 times below its MIC and of the antibiotics 8 times below its individual MIC. Regarding the GEN resistant strains of E. coli and S. aureu the presence of Luteolin didn´t produce changes in the sensitivity of GEN.On this basis we can conclude that Luteolin significantly increase the antibacterial activity of GEN in ATCC strains of E. coli and S. aureus, while the combination of Luteolin with GEN did not alter the sensitivity of the resistant strains of E. coli and S. aureus. Therefore, and based on the results above, we can say that Luteolin proved to have a protective effect against oxidative stress induced by GEN in human leukocytes without modifying substantially the antibacterial effect of this drug against resistant strains and strengthening it against reference strains.