Xanthohumol prevents carbon tetrachloride-induced acute liver injury in rats.

Xanthohumol (XN), a prenyl flavonoid present in beer, prevents the acute hepatic injury induced by carbon tetrachloride (CCl4) in rats. Pre-treatment of rats with XN significantly reduced the increased liver weight observed in CCl4-intoxicated rats, normalised the increased values of plasma lactate dehydrogenase, glutamate oxaloacetate transaminase and glutamate pyruvate transaminase activities and reduced the incidence of histopathological alterations produced by CCl4. The oxidative stress induced by CCl4 administration elicited a significant decrease in the levels of reduced glutathione as well as an increase in thiobarbituric acid reactive substances (TBARS) and H2O2 concentrations. Pre-treatment of rats with XN resulted in a significant (p<0.05) increase in reduced glutathione (GSH) content and a reduction in TBARS and H2O2 concentrations to their normal values. XN pre-treatment also prevented the significant reductions of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase activities observed in CCl4-treated rats compared to control animals. Our results suggest that the hepatoprotective effect of XN is based on its antioxidant properties as well as it being an efficient inhibitor of lipid peroxidation and a protector against the degradation of antioxidant enzymes induced by CCl4 intoxication.

Fluorescence quenching study on the interaction between quercetin and lipoxygenase.

The interaction between quercetin and lipoxygenase was investigated by fluorescence spectroscopy. The analysis of the emission quenching at different temperatures revealed that the quenching mechanism correspond to a static process and, as consequence, a complex quercetin-lipoxygenase is formed. The thermodynamic parameters ΔG, ΔH and ΔS were calculated to be-32.57 kJ mol(-1),-3.21 kJ mol(-1) and 87.14 J mol(-1) K(-1) respectively, which suggest that hydrophobic forces plays a major role in the stabilization of the complex quercetin-lipoxygenase. The distance, r, between donor (lipoxygenase) and acceptor (quercetin) was calculated to be 3.84 nm based on Förster's non-radiative energy transfer theory. The results obtained from the evaluation of three dimensional florescence spectra suggest a conformational modification of the protein in the region of the coupling with quercetin.

Use of pegfilgrastim support on day 9 to maintain relative dose intensity of chemotherapy in breast cancer patients receiving a day 1 and 8 CMF regimen.

AIM: In several commonly used regimens, chemotherapy doses are split across different days of the cycle. We aimed to determine the feasibility of growth factor support with once-per-cycle pegfilgrastim in this setting. METHODS: This phase II study in breast cancer patients assessed the utility of a single 6 mg subcutaneous dose of pegfilgrastim administered on day 9 of an intravenous (IV) "split" CMF (cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2) and 5-fluorouracil 600 mg/m(2)) chemotherapy regimen administered on days 1 and 8 and repeated every 28 days for 6 cycles. RESULTS: Fifty-eight patients were enrolled, with 49 completing the study. For the primary endpoint, 48 patients (83%) received >or=85% of the relative dose intensity (RDI) of chemotherapy over all 6 cycles (95% confidence interval [CI], 71-91%). Across all chemotherapy cycles, 41 patients (71%) received all scheduled cycles on time and most patients (n=49, 84%) received >or=85% of the planned dose of all chemotherapy agents in all cycles. In total, 295/319 cycles (92%) were delivered on schedule and >or=85% of the planned dose of all chemotherapy agents were administered in 309/319 cycles (97%). Febrile neutropenia was reported in only 2 patients (3%). There were no grade 4 adverse events related to pegfilgrastim. DISCUSSION: Day 9 pegfilgrastim administration was well tolerated and provided effective protection against neutropenia in patients receiving IV CMF on days 1 and 8, allowing chemotherapy to be delivered on time and at the scheduled dose in most patients.

Determination of lipoxygenase activity in plant extracts using a modified ferrous oxidation-xylenol orange assay.

The ferrous oxidation-xylenol orange (FOX) assay method for determination of lipid hydroperoxides is based on that under acidic conditions Fe2+ is oxidized to Fe3+, which then oxidizes xylenol orange to a product that absorb at 550 nm. The procedure has been adapted for determination of lipoxygenase activity in plant extracts. This enzyme is responsible for generation of off-flavors in vegetal foods, bleaching of pigments, and a lot of oxidative degradations. It is of interest to check the initial lipoxygenase activity in vegetal foods before the processing, using an assay that is rapid, reproducible, and easily adaptable to high throughput format. The enzymatic assay is based on a discontinuous determination of lipoxygenase activity using the FOX reagent for colorimetric determination of hydroperoxides accumulated in the medium by a period of incubation that is established by the addition of the extract (start of the reaction) and the addition of FOX reagent (finish of the reaction). The procedure is capable of detecting lipoxygenase activity in a number of vegetable homogenates, being especially useful for a rapid visual evaluation of this enzymatic activity.