Propranolol does not affect the oxidative burst of rat neutrophils or complement serum opsonizing capacity in in vivo and in vitro experiments

Propranolol is a ß-adrenergic antagonist used for the treatment of a variety of cardiac conditions and has a palliative value when used in situations in which adrenergic signals and symptoms are involved. It is used as a co-adjuvant in hyperthyroidism to decrease heart rate and output, as well as the tremor. The aim of this work was to study the effect of propranolol treatment on the oxidative burst of rat peripheral blood neutrophils and on the complement system.In the in vivo study, Wistar male rats were treated with propranolol by gavage for 16 days with 220 or 440 μg/animal/day. These doses are equivalent to 80 or 160 mg/adult human (~70 day/kg), respectively. Neutrophils were obtained and stimulated with opsonized immune complexes (opIC). The oxidative burst of control (from water treated rats) or propranolol-treated rat cells was measured by luminol- and lucigenin-dependent chemiluminescence (CL). The CL of treated rat neutrophils was not affected by any of the propranolol doses studied when compared to the control responses.In the in vitro study whole blood and serum from Wistar male rats were incubated for 1 h at 37C° with propranolol at three different concentrations (17.5, 35 and 70 μg/mL). After incubation, neutrophils were isolated from whole blood and stimulated with opIC while treated sera were used to opsonize IC. IC opsonized with treated sera were used to stimulate neutrophils from normal rats. In both cases oxidative burst was measured by luminol- and lucigenin-dependent CL. No differences in responses or activities were detected between in vitro treated neutrophils or sera and their respective controls.These results suggest that this drug, at the concentrations studied and with the experimental approach used, had no effect on the oxidative burst during phagocytosis of opIC or on the complement opsonization capacity of the sera

Assessment of Antioxidant Activity of Spray Dried Extracts of Psidium guajava Leaves by DPPH and Chemiluminescence Inhibition in Human Neutrophils

This work evaluated the physicochemical properties and antioxidant activity of spray dried extracts (SDE) from Psidium guajava L. leaves. Different drying carriers, namely, maltodextrin, colloidal silicon dioxide, Arabic gum, and β-cyclodextrin at concentrations of 40 and 80% relative to solids content, were added to drying composition. SDE were characterized through determination of the total phenolic, tannins, and flavonoid content. Antioxidant potential of the SDE was assessed by two assays: cellular test that measures the luminol-enhanced chemiluminescence (LumCL) produced by neutrophils stimulated with phorbol myristate acetate (PMA) and the DPPH radical scavenging (DPPH* method). In both assays the antioxidant activity of the SDE occurred in a concentration-dependent manner and showed no toxicity to the cells. Using the CLlum method, the IC50 ranged from 5.42 to 6.50 µg/mL. The IC50 of the SDE ranged from 7.96 to 8.11 µg/mL using the DPPH• method. Psidium guajava SDE presented significant antioxidant activity; thus they show high potential as an active phytopharmaceutical ingredient. Our findings in human neutrophils are pharmacologically relevant since they indicate that P. guajava SDE is a potential antioxidant and anti-inflammatory agent in human cells

The role of seasonality on the inhibitory effect of Brazilian green propolis on the oxidative metabolism of neutrophils

The reactive oxygen species (ROS) produced by neutrophils are involved in the pathogenesis of several diseases, for which the intake of antioxidants could benefit patients either as a prophylactic or therapeutic treatment. Propolis is among the known antioxidants, and its chemical composition may vary under the influence of seasonality, which may interfere in its biological properties. This work evaluates the role of seasonality on the production of some important compounds of propolis samples produced monthly from November 2001 through October 2002 as well as the effect of these samples on the oxidative metabolism of stimulated neutrophils, by using both luminol and lucigenin to produce chemiluminescence (CLlum and CLluc, respectively). The cytotoxicity of the most active extracts to neutrophils was also investigated. The inhibitory effect of the propolis samples varied significantly during the studied period for both assays (3.4 +/- 1.1 to 16.0 +/- 1.1 mu g/mL for CLlum and 6.2 +/- 2.0 to 30.0 +/- 5.0 mu g/mL for CLluc), which was also observed in the quantitative profile of the main analyzed compounds (aromadendrin-4`-methyl ether, artepillin C, and baccharin). This effect started to become more prominent during the fall and, among all the studied extracts, the one obtained in May displayed the highest inhibitory effect on CL production (3.4 +/- 1.1 mu g/mL for alum and 6.2 +/- 2.0 mu g/mL for CLluc). The HPLC qualitative profiles of the extracts of propolis samples were quite similar, but there was a huge variation in terms of quantitative profile. It seems that aromadendrin-4`-methyl ether and baccharin play an essential role in the antioxidant activity, while artepillin C is not very important for this effect. The extracts presenting the highest antioxidant activity were produced in May, June, and August, and they did not display cytotoxicity at 25 mu g/mL; quercetin, used as control, was not toxic to neutrophils at 8.5 mu g/mL (C) 2010 Elsevier B.V. All rights reserved.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[02/11469-5]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[01/14219-7]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[06/59893-0

Patients with systemic sclerosis present increased DNA damage differentially associated with DNA repair gene polymorphisms

Patients with systemic sclerosis (SSc) exhibit increased toxicity when exposed to genotoxic agents. In our study, we evaluated DNA damage and polymorphic sites in 2 DNA repair genes (XRCC1 Arg399Gln and XRCC4 Ile401Thr) in patients with SSc. A total of 177 patients were studied for DNA repair gene polymorphisms. Fifty-six of them were also evaluated for DNA damage in peripheral blood cells using the comet assay. Compared to controls, the patients as a whole or stratified into major clinical variants (limited or diffuse skin involvement), irrespective of the underlying treatment schedule, exhibited increased DNA damage. XRCC1 (rs: 25487) and XRCC4 (rs: 28360135) allele and genotype frequencies observed in patients with SSc were not significantly different from those observed in controls; however, the XRCC1 Arg399Gln allele was associated with increased DNA damage only in healthy controls and the XRCC4 Ile401Thr allele was associated with increased DNA damage in both patients and controls. Further, the XRCC1 Arg399Gln allele was associated with the presence of antinuclear antibody and anticentromere antibody. No association was observed between these DNA repair gene polymorphic sites and clinical features of patients with SSc. These results corroborate the presence of genomic instability in SSc peripheral blood cells, as evaluated by increased DNA damage, and show that polymorphic sites of the XRCC1 and XRCC4 DNA repair genes may differentially influence DNA damage and the development of auto-antibodies413458465FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPES