stilbenes and cumene-hydroperoxide

Plant polyphenols like flavonoids and hydroxystilbens have been found to possess radical scavenging/antioxidative activity, especially when studied in cell-free systems. A positive effect in such assays, however, does not necessarily indicate a protective activity against deleterious effects of oxidative stress in intact cells. In fact it has been shown that polyphenols can act as anti-oxidants as well as pro-oxidants. The aim of the present study was to investigate whether and with what potency selected polyphenols are able to inhibit cellular radical generation in C6 cells and whether they can induce oxidative stress themselves. Cumene hydroperoxide (CHP) was used as a model to induce radical generation which was measured by means of a fluorometric 2',7'-dichlorodihydro-fluorescein assay. CHP-induced, time and concentration dependent, a manifold increase of DCF fluorescence indicating intracellular radical generation. This process was inhibited by all the flavonoids and the hydroxystilben resveratrol, at low micromolar concentrations. The most potent compounds, luteolin and galangin, already at concentrations of 5 to 10 microM nearly completely abolished the radical generation in the presence of 500 microM CHP. The following ranking of anti-oxidative potency was obtained: luteolingalangin>kaempferol>quercetin>resveratrolgenisteintaxifolin. This ranking is completely different from that obtained by means of a trolox equivalent antioxidant capacity (TEAC) assay in a cell-free system, thus putting the biological relevance of the latter in question. Remarkably, one compound induced oxidative stress itself, namely genistein. This flavonoid inhibited the cellular radical generation in the presence of CHP while it significantly enhanced it in the absence of the peroxide.

Topics: Astrocytoma; Benzene Derivatives; Brain Neoplasms; Dose-Response Relationship, Drug; Flavonoids; Free Radical Scavengers; Free Radicals; Genistein; Luteolin; Oxidants; Oxidative Stress; Phenols; Plant Extracts; Polyphenols; Resveratrol; Stilbenes

Recent epidemiological studies proposed that the glutathione S-transferase (GST) M1-null genotype may contribute to diseases associated with oxidative stress. The genetic polymorphism exhibited by the GSTM1 may be an important factor in risk toward oxidant chemicals. In this study, we investigated the effect of GSTM1-null genotype in lymphocyte and oxidative stress-dependent inhibition of platelet aggregation. To determine whether GSTM1 deficiency is a genetic determinant of cell toxicity toward oxidant chemicals, lymphocytes were incubated in vitro with low levels of benzo(a)pyrene (BaP), cumene hydroperoxide (CumOOH), or trans-stilbene oxide that do not decrease cell viability, and were assessed for oxidative damage and for the lymphocyte-dependent inhibition of platelet response. Malondialdehyde and carbonyl levels, and the oxidation of cisparinaric acid, were used as biomarkers of oxidative stress in lymphocytes. Following stimulation by BaP or CumOOH, when peroxidation-dependent changes in these parameters were compared between the GSTM1-null genotype and the positive genotype, no significant differences were found between the two genotypes. On the other hand, preincubation of the lymphocytes with BaP or CumOOH attenuated their inhibitory action on ADP-induced platelet aggregation. However, our results indicate that lymphocytes of individuals with the GSTM1-null genotype have greater inhibitory activity on platelet function after exposure to BaP, but not CumOOH, although they are not more susceptible to in vitro oxidative stress.

Topics: Adult; Benzene Derivatives; Benzo(a)pyrene; Blood Platelets; Female; Glutathione Transferase; Humans; Leukocytes, Mononuclear; Lymphocytes; Male; Malondialdehyde; Oxidants; Oxidative Stress; Stilbenes

Chick liver glutathione peroxidase activity was separated into selenium-dependent and selenium-independent enzyme fractions and the effects of chemicals on the activities of each fraction were examined. Clofibrate induced the selenium-dependent enzyme, while phenobarbital, butylhydroxyanisole and trans-stilbene oxide elevated selenium-independent peroxidase activity. A third enzyme, which showed glutathione peroxidase activity toward both hydrogen peroxide and cumene hydroperoxide, was found.

Topics: Animals; Benzene Derivatives; Butylated Hydroxyanisole; Chickens; Chromatography, Gel; Clofibrate; Glutathione Peroxidase; Hydrogen Peroxide; Liver; Male; Methylcholanthrene; Phenobarbital; Stilbenes