Resveratrol Inhibits the Production of Reactive Oxygen Species in Phorbol Ester- and Toll-Like Receptor-Stimulated Granulocytes from Diabetic Patients

Abstract

Hyperglycemia of diabetes is associated with increase in the generation of reactive oxygen species (ROS) and vascular complications. Resveratrol (RSV) has been proposed as a therapeutic resource for human diseases such as type 2 diabetes mellitus (T2DM). However, the role of hyperglycemia on resveratrol action in cells from innate immunity is poorly studied.The aim of the present study was, to evaluate the effects of RSV on ROS production by granulocytes from T2DM patients “primed” by chronic hyperglycemia “in vivo”. The effects of RSV on ROS production in granulocytes were quantified using a luminol assay. The granulocyte activators were phorbol 12,13-dibutyrate (PDB;), andLPS or zymosan (TRL4- and TRL2-activators, respectively). In some experiments, calphostin C were compared with those of RSV. RSV suppressed ROS generation in granulocytes from T2DM patients and non- diabetic (ND) controls in a similar manner (p>0.05). Percentage inhibition values was 85% and 64% inresting cells, 69 and 77%in PDB-stimulated cells, 69 and 67%in TRL4-activated cells, and 76 and 59%in TRL2-activated cells in T2DM patients and ND controls, respectively. The profile of inhibition of ROS production by calphostin C was similar to that obtained with RSV. The effect of RSV is not affected by hyperglycemia. ROS production in granulocytes from T2DM patients and ND controls wasinhibited by the polyphenol in a similar manner (p>0.05) The inhibition of ROS generation by RSV was comparable with that observed with calphostin C. PKC and/or NADPH-oxidase are targets of RSV action. RSV could be considered a therapeutic option to control innate immune oxidizing response and inflammation in diabetic complications.