stilbenes and 10-10--dimethyl-9-9--biacridinium

The present study was designed to examine whether resveratrol, a potent antioxidant, protects against renal ischemia-reperfusion (I/R) injury.. Wistar albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 6 h of reperfusion. Resveratrol (RVT, 30 mg/kg, i.p.) or vehicle was administered twice, at 30 min prior to ischemia and immediately before the reperfusion period. At the end of the reperfusion period, rats were decapitated and kidney samples were taken for histological examination or determination of levels of renal malondialdehyde (MDA), an end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration. Formation of reactive oxygen species in hepatic tissue samples was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. Renal tissue collagen content as a fibrosis marker was also determined, while serum creatinine and urea concentrations were measured for the evaluation of renal function. Tumor necrosis factor-alpha (TNF-alpha ) and lactate dehydrogenase (LDH) were also assayed in serum samples.. Ischemia/reperfusion caused a significant decrease in tissue GSH level, which was accompanied by significant increases in the renal luminol and lucigenin CL values, MDA level, MPO activity and collagen content. Similarly, serum creatinine and BUN levels, as well as LDH and TNF-alpha, were elevated in the I/R group as compared to control group. On the other hand, resveratrol treatment reversed all these biochemical indices, as well as histopathological alterations that were induced by I/R.. Findings of the present study suggest that resveratrol exerts renoprotective effects via its radical scavenging and antioxidant activities, which appear to involve the inhibition of tissue neutrophil infiltration.

Topics: Acridines; Animals; Antioxidants; Blood Urea Nitrogen; Creatine; Glutathione; Kidney Diseases; L-Lactate Dehydrogenase; Luminol; Male; Malondialdehyde; Oxidative Stress; Peroxidase; Rats; Rats, Wistar; Reperfusion Injury; Resveratrol; Stilbenes

trans-Resveratrol (t-RVT) has been shown to have a wide range of anti-inflammatory properties, some of which have been suggested to contribute to the molecular explanation of the French Paradox, a possible reason for the low incidence of heart disease in France. The ability of t-RVT to inhibit the production of reactive oxygen species (ROS) from monocytes (differentiated U937) was investigated using isoluminol, luminol, lucigenin, and 2',7'-dichlorofluorescein (DCF). t-RVT (0.1-50 microM) was found to significantly inhibit cellular ROS production stimulated by f-Met-Leu-Phe (fMLP), 12-phorbol 13-myristate, and arachidonic acid after a 1-h preincubation. The efficacy of t-RVT could be increased if it was added directly into the assay. NADPH-dependent superoxide production was measured in cell homogenates and t-RVT (10-50 microM) was found to have no effect on this activity. The majority of these redox probes require a peroxidase to be oxidized; therefore, the inhibitory effect of t-RVT on ROS measured by these probes is complicated by its ability to be oxidized by peroxidase enzymes and thus compete with the probe. t-RVT, known to be oxidized by the horseradish peroxidase (HRP)/H(2)O(2) system, was found to inhibit the HRP-dependent oxidation of the fluorescent probe DCF and the chemiluminescent probe isoluminol. However, using a redox probe that did not require oxidation by a peroxidase (lucigenin), significant inhibition was still observed. Moreover, the inhibitory effects of t-RVT on fMLP-induced ROS production correlated with significant inhibitory effects on fMLP-induced phosphatidylinositol 3-kinase (PI3K) activity at 50 microM and Akt phosphorylation (10-50 microM). Other known inhibitors of both PI3K and Akt were also found to inhibit this response. Therefore, inhibition of signaling through the PI3K to NADPH oxidase by t-RVT might represent an important anti-inflammatory mechanism.

Topics: Acridines; Extracellular Signal-Regulated MAP Kinases; Fluorescent Dyes; Humans; Monocytes; N-Formylmethionine Leucyl-Phenylalanine; NADPH Oxidases; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Respiratory Burst; Resveratrol; Signal Transduction; Stilbenes; U937 Cells