Investigations into the cardioprotective properties of resveratrol
In this study the ability of resveratrol to inhibit the activation of the monocyte respiratory burst was investigated.;Differentiated U937 (dU937) cells were pre-treated with resveratrol before stimulation with f-met-leu-phe (fMLP), phorbol 12-myristate-13-acetate (PMA) or arachidonic acid (AA). The extra-cellular and total production of reactive oxygen species (ROS) were measured by isoluminol and luminol chemiluminescence (CL). Superoxide production was measured using lucigenin. Resveratrol was found to inhibit ROS production induced by all three stimuli. Measurement of ROS production was also confirmed using with two used, 2',7'-dichlorofluorescein (DCF) and dihydrorhodamine (DHR). Again resveratrol inhibited both responses. There were significant between the inhibitory effects of resveratrol on peroxidase-dependent (isoluminol, luminol, DCF and DHR) and independent (lucigenin- ROS measuring principles. Moreover, resveratrol was found to be oxidised by the horseradish peroxidase/hydrogen peroxide system.;The cell signal transduction pathways activated by fMLP, PMA and AA were investigated. Only fMLP was found to activate phosphatidylinositol-3-kinase (PI3K) and Akt, using specific inhibitors of both kinases. Resveratrol inhibited PI3K activity with little direct effect on other kinases shown to regulate the respiratory burst, including Akt, extra-cellular regulated protein kinase (ERK); and protein kinase C (PKC). Akt and ERK were found to be activated by fMLP.;In conclusion, resveratrol was found to be a potent inhibitor of ROS production, particularly if a peroxidase-dependent measuring principle was used. Resveratrol can be oxidised by peroxidases, which inhibit the oxidation of the redox probe. Use of a detection method that did not require peroxidase revealed that resveratrol was still a potent inhibitor of fMLP-induced ROS. Moreover, this inhibitory dose of resveratrol correlated with its ability to inhibit the PI3K-Akt pathway, one of the major regulatory pathways of fMLP-induced ROS production. Modulation of these cell signalling intermediates by resveratrol might represent an important anti-inflammatory pathway and further add to its potential cardioprotective properties.