RESUMEN
Helicobacter pylori infection is marked by intense production of reactive oxygen species (ROS) through the activation of neutrophils that are constantly attracted to the infected gastric mucosa. Here, gallic acid and its alkyl esters were evaluated as compounds able to act as antimicrobial agents and inhibitors of ROS released by H. pylori-activated neutrophils simultaneously. We found that the higher hydrophobicity caused by esterification of gallic acid led to a significant increase in its ability as a cytotoxic agent against H. pylori, a scavenger of ROS and an inhibitor of NADPH oxidase in neutrophils. Octyl gallate, a widely used food additive, showed the highest antimicrobial activity against H. pylori, with a minimum inhibitory concentration (MIC) value of 125 µg mL-1, whereas gallic acid had a MIC value higher than 1000 µg mL-1. The production of superoxide anion radicals was almost 100% abolished by the addition of 10 µM (2.82 µg mL-1) octyl gallate, whereas gallic acid inhibited around 20%. A similar tendency was also found when measuring the production of hypochlorous acid. The protective effect of the esters was cytochemically confirmed. In conclusion, this study showed that hydrophobicity is a crucial factor to obtain a significant anti-ROS and anti-H. pylori activity. Finally, it highlights octyl gallate, a food additive widely used in the food industry, as a promising molecule in the treatment of H. pylori infection.
Asunto(s)
Aditivos Alimentarios/farmacología , Ácido Gálico/análogos & derivados , Infecciones por Helicobacter/microbiología , Helicobacter pylori/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Ácido Gálico/farmacología , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiología , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/enzimología , Infecciones por Helicobacter/metabolismo , Helicobacter pylori/crecimiento & desarrollo , Humanos , NADPH Oxidasas/antagonistas & inhibidores , NADPH Oxidasas/metabolismo , Neutrófilos/efectos de los fármacos , Neutrófilos/enzimología , Neutrófilos/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
This work aims to demonstrate that the gallic acid structure modification to the decyl gallate (G14) compound contributed to increase the antifungal activity against several species of pathogenic fungi, mainly, Candida spp., Cryptococcus spp., Paracoccidioides spp., and Histoplasma capsulatum, according to standardized microdilution method described by Clinical Laboratory Standard Institute (CLSI) documents. Moreover this compound has a particularly good selectivity index value, which makes it an excellent candidate for broad-spectrum antifungal prototype and encourages the continuation of subsequent studies for the discovery of its mechanism of action.