New antioxidant C-glucosylxanthones from the stems of Arrabidaea samydoides

Three new C-glucosylxanthones, 2-(2'-O-trans-caffeoyl)-C-beta-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (1), 2-(2'-O-trans-cinnamoyl)-C-beta-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (2), and 2-(2'-O-trans-coumaroyl)-C-beta-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (3), were isolated from the stems of Arrabidaea samydoides, in addition to three known C-glucosylxanthones, mangiferin (4), 2-(2'-O-benzoyl)-C-beta-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (5), and muraxanthone (6). Their chemical structures were assigned on the basis of MS and 1D and 2D NMR experiments. Xanthones 1-6 showed moderate free radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) as well as antioxidant activity evidenced by redox properties measured on ElCD-HPLC.

A partial least squares regression study with antioxidant flavonoid compounds

The quantitative structure-activity relationship of a set of 19 flavonoid compounds presenting antioxidant activity was studied by means of PLS (Partial Least Squares) regression. The optimization of the structures and calculation of electronic properties were done by using the semiempirical method AMI. A reliable model (r(2) = 0.806 and q(2) = 0.730) was obtained and from this model it was possible to consider some aspects of the structure of the flavonoid compounds studied that are related with their free radical scavenging ability. The quality of the PLS model obtained in this work indicates that it can be used in order to design new flavonoid compounds that present ability to scavenge free radicals.

CLINICAL BIOCHEMICAL DETERMINATIONS IN THE MANGALARGA-PAULISTA HORSE - REFERENCE VALUES

Biochemical values are widely related with environmental agents, sex and age, and are used in disease diagnosis. Numerous reports have been published on the biochemical parameters of different breeds of horses. However, there is a paucity of information concerning Cu-Zn superoxide dismutase (SOD), ceruloplasmin, copper and zinc determinations in the serum. Blood samples from a total of 60 horses of the Mangalarga-Paulista breed, representing three age groups (0 to 4 months old, 6 to 18 months old and adult) were examined. Male horses have a higher mean value of SOD, ceruloplasmin and copper than do females. No significant sex-related difference was observed in serum zinc content of weaned and adult horses. SOD activity was significantly higher in adult animals. Since SOD has a protective effect against superoxide free radical toxicity and possesses anti-inflammatory activity, it is reasonable to assume that the increased activity of this enzyme may be due to an adaptation mechanism which protects the adult animal against oxygen toxicity.

INTRATRACHEAL INJECTION OF NICKEL CHLORIDE AND COPPER-ZINC SUPEROXIDE-DISMUTASE ACTIVITY IN LUNG OF RATS

Superoxide radical (O2-) is a free radical that may be involved in various toxic processes. Cu-Zn superoxide dismutase catalyses the dismutation of the superoxide free radical and protects cells from oxidative damage, and it has been used clinically. The concentration of Ni2+ and Cu-Zn superoxide dismutase activity were measured in lungs of rats at time intervals of 5, 12, 19, 26, 33, and 40 days following an intratracheal injection of 127 nmol of NiCl2. Nickel chloride increased nickel content and resulted in a significant increase of Cu-Zn superoxide dismutase activity in lungs. This elevation of Cu-Zn superoxide dismutase activity was highest on the 12th day (approximately threefold) and is at levels comparable to controls rats on day 40 onwards. Since Cu-Zn superoxide dismutase activity was increased in lung throughout our experimental period without corresponding increases of Cu2+ and Zn2+, we speculate that the elevation of Cu-Zn superoxide dismutase activity might be due to an increased half-life of the enzyme, induced by nickel.

Fmoc-POAC: [(9-fluorenylmethyloxycarbonyl)-2,2,5,5-tetramethylpyrrolidine-N-oxyl-3-amino-4-carboxylic acid]: A novel protected spin labeled beta-amino acid for peptide and protein chemistry

The stable free radical 2,2,6,6-tetramethylpiperidine-N-oxyl-4-amino-4-carboxylic acid (TOAC) is the only spin labeled amino acid that has been used to date to successfully label peptide sequences for structural studies. However, severe difficulty in coupling the subsequent amino acid has been the most serious shortcoming of this paramagnetic marker. This problem stems from the low nucleophilicity of TOAC's amine group towards the acylation reaction during peptide chain elongation. The present report introduces the alternative beta -amino acid 2,2,5,5-tetramethylpyrrolidine-N-oxyl-3-amino-4-carboxylic acid (POAC), potentially useful in peptide and protein chemistry. Investigations aimed at addressing the stereochemistry of this cyclic molecule through X-ray diffraction measurements of crystalline and bulk samples revealed that it consists only of the trans conformer. The 9-fluorenylmethyloxyearbonyl group (Fmoc) was chosen for temporary protection of the POAC amine function, allowing insertion of the probe at any position in a peptide sequence. The vasoactive octapeptide angiotensin II (AII, DRVYIHPF) was synthesized by replacing Pro(7) with POAC. The reaction of Fmoc-POAC with the peptidyl-resin occurred smoothly, and the coupling of the subsequent amino acid showed a much faster reaction when compared with TOAC. POAC(7)-AII was obtained in good yield, demonstrating that, in addition to TOAC, POAC is a convenient amino acid for the synthesis of spin labeled peptide analogues. The present findings open the possibility of a wide range of chemical and biological applications for this novel beta -amino acid derivative, including structural investigations involving its differentiated bend-inducing characteristics.

Iridoids from the aerial parts of Verbena littoralis (Verbenaceae)

The iridoids, 6S-hydroxy-8S-methyl-4-methylene-hexahydro-cyclopenta[c]pyran-3-one and 6S,9S-dihydroxy-8S-methyl-4methylene-hexahydro-cyclopenta[c]pyran-3-one, were isolated from the aerial parts of Verbena littoralis. Their structures and stereochemistry were elucidated by means of NMR spectral data analysis. Both compounds showed moderate in vitro activity against gram positive and negative bacteria as well as moderate in vivo intestinal peristaltic action in mouse. The iridoids also showed moderate free radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) as well as antioxidant activity, the latter being evidenced by redox properties measured using EICD-HPLC. (C) 2004 Elsevier Ltd. All rights reserved.

Quercetin-PVP K25 solid dispersions: Preparation, thermal characterization and antioxidant activity

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Application of Polysaccharide Hydrogels in Adsorption and Controlled-Extended Release of Fertilizers Processes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of α-tocopherol, taurine and selenium on the attenuation of ischemia/reperfusion injury of splanchnic organs

Background: Splanchnic artery occlusion shock is caused by increased capillary permeability and cellular injury precipitated by oxygen derived free radicals following ischemia and reperfusion of splanchnic organs. The purpose of this study was to assess the role of several well-known oxygen- derived free radical scavengers in ameliorating or preventing this syndrome. Study design: Anesthetized rats were subjected to periods of occlusion of the visceral arteries and reperfusion. Tocopherol, taurine, selenium or a 'cocktail' of these three agents was injected subcutaneously for 4 consecutive days prior to operation. Mean arterial blood pressure was measured throughout the experimental period. Fluorometry and technetium-99m pyrophosphate counting of the visceral organs were performed as well as a histologic grading system for intestinal viability. Results: Final mean arterial blood pressure associated with the 'cocktail' and selenium groups was 79.1 ± 27.4 mmHg and 83.6 ± 17.8 mmHg, respectively. These values were significantly higher than the control group, 40.8 ± 11.4 mmHg (P < 0.05). Similar patterns of the benefit of selenium in contrast with the other groups were obtained with fluorescein perfusion, radioisotopic activity and histologic analysis. Conclusion: Pretreatment with selenium of splanchnic ischemia and reperfusion in the rat improves mean arterial blood pressure and microcirculatory visceral perfusion. Further analysis of the precise protective mechanism of selenium for reperfusion injury will enable visceral organs to withstand the consequences of increased capillary leakage and oxidant injury.

Effect of allopurinol in the course of adriamycin induced nephropathy

The role of superoxide in adriamycin-induced nephropathy (single dose; i.v. 3 mg/kg) has been studied by blocking superoxide synthesis through the administration of allopurinol (500 mg/L in drinking water). In Experiment I (EI), allopurinol administration was started 3 days prior to nephropathy induction and continued until day 14. In Experiment II (EII) allopurinol administration was started 2 weeks after nephropathy induction and was maintained until the end of the experiment (26 weeks). Affected glomeruli frequency and tubulointerstitial lesion index (TILI) were determined at Weeks 2 and 4 (EI) and Week 26 (EII). In EI, and 24 h mean proteinuria in the nephrotic control group (NCG-I) differed from that of the treated nephrotic group (TNG-I) at Week 1 (TNG = 33.3 ± 6.39 mg/24 h; NCG = 59.8 ± 6.3 mg/24 h; p < 0.05) and 2 (NCG-I = 80.0 ± 17.5 mg/24h; TNG-I = 49.1 ± 8.4 mg/24 h; p < 0.05). No glomerular alterations were observed and TILI medians were not different in both nephrotic groups at week 2 (NCG-I = 1+: TNG = 1+) and 4 (NCG = 4+; TNG = 4+). In EII, NCG-II and TNG-II presented different 24 h proteinuria values only at Week 6, (136.91 ± 22.23 mg/24 h ad 72.66 ± 10.72 mg/24 h, respectively; p < 0.05). Between nephrotic groups, there was no statistical difference in the median of affected glomeruli (CNG-II = 56%; TNG-II = 48% and TILI (NCG-II = 8+; TNG-II = 9+). Thus, allopurinol was associated with a transient reduction in proteinuria and it did not alter the progression of the nephropathy.

Toxic mechanism of nickel exposure on cardiac tissue

The incidence of cardiovascular disease has increased in the general population, and cardiac damage is indicated as one important cause of mortality. In addition, pollution and metal exposure have increased in recent years. For this reason, toxic effects of metals, such as nickel, and their relation to cardiac damage should be urgently established. Although free radical-mediated cellular damage and reactive oxygen species have been theorized as contributing to the nickel mechanism of toxicity, recent investigations have established that free radicals may be important contributors to cardiac dysfunction. However, there is little information on the effect of nickel exposure on markers of oxidative stress in cardiac tissue. Nickel exposure (Ni2+ 100 mg L-1 from NiSO4) significantly increased lipoperoxide and total lipid concentrations in cardiac tissue. We also observed increased serum levels of cholesterol (59%), lactate dehydrogenase (LDH-64%), and alanine transaminase (ALT-30%) in study animals. The biochemical parameters recovered to the control values with tocopherol intake (0.2 mg 200 g-1). Vitamin E alone significantly decreased the lipoperoxide concentration and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the heart. Since no alterations were observed in catalase and GSH-Px activities by nickel exposure while SOD activities were decreased, we conclude that superoxide radical (O2 -) generated by nickel exposure is of primary importance in the pathogenesis of cardiac damage. Tocopherol, by its antioxidant activity, decreased the toxic effects of nickel exposure on heart of rats.