Effects of uremic solutes on reactive oxygen species in vitro model systems as a possibility of support the renal function management.

BACKGROUND: In view of the prevalence of oxidative stress in chronic kidney disease (CKD) patients, the loss of low-molecular-weight biomolecules by hemodialysis and the antioxidant potential of some uremic solutes that accumulate in CKD, we used in vitro model systems to test the antioxidant potential of the following uremic solutes: uric acid, hippuric acid, p-cresol, phenol, methylguanidine, L-arginine, L-tyrosine, creatinine and urea. METHODS: The in vitro antioxidant efficiencies of the uremic solutes, isolated or in mixtures, were tested with the following assays: i) ABTS radical cation decolorization assay; ii) hypochlorous acid (HOCl/OCl(-)) scavenging activity; iii) superoxide anion radical (O2(•-)) scavenging activity; iv) crocin bleaching assay (capture of peroxyl radical, ROO(•)); v) hydrogen peroxide (H2O2) scavenging activity. RESULTS: Four of the tested uremic solutes (p-cresol, phenol, L-tyrosine, uric acid) were effective antioxidants and their IC50 were found in three model systems: ABTS(•+), HOCl/OCl(-) and crocin bleaching assay. In the 4-solutes mixtures, each one of the solute captured 12.5% for the IC50 of the mixture to ABTS(•+) or HOCl/OCl(-), exhibiting a virtually exact additive effect. In the 2-solutes mixtures, for ROO(•) capture, it was observed the need of more mass of uremic solutes to reach an IC50 value that was higher than the projected IC50, obtained from the IC50 of single solutes (25% of each, in the binary mixtures) in the same assay. In model systems for O2(•-) and H2O2, none of the uremic solutes showed scavenging activity. CONCLUSIONS: The use of the IC50 as an analytical tool to prepare and analyze mixtures allows the determination of their scavenging capacities and may be useful for the assessment of the antioxidant status of biological samples under conditions of altered levels of the endogenous antioxidant network and/or in the employment and monitoring of exogenous antioxidant therapy.

Nicotine-enhanced oxidation of low-density lipoprotein and its components by myeloperoxidase/H2O2/Cl- system.

In this study, the effect of nicotine on the LDL oxidation by the MPO/H2O2/Cl- system and the effect of HOCl on LDL and some of its components, such as methyl linoleate, vitamin E and the amino acid tryptophan were explored. Nicotine, in micromolar concentrations, enhanced the tryptophan oxidation, either present in LDL or free, in solution. Nicotine also decreased the formation of conjugated dienes and oxygen consumption in a methyl linoleate / HOCl system, and there was evidence to suggest an increase in chlorohydrin formation. Acceleration of the vitamin E oxidation by HOCl was also observed in the presence of nicotine. These data show that the interaction of nicotine and HOCl can promote significant biochemical modifications in LDL particle and some of its components involved in the pathogenesis of cardiovascular and other diseases.

Chemical, enzymatic and cellular antioxidant activity studies of Agaricus blazei Murrill.

Mushrooms possess nutritional and medicinal properties that have long been used for human health preservation and that have been considered by researchers as possible sources of free radical scavengers. In this work, the antioxidant properties of water extracts from Agaricus blazei Murill, produced by maceration and decoction, are demonstrated in vitro. Resistance to oxidation is demonstrated through three mechanisms: i) inhibition of enzymatic oxidative process, with 100% inhibition of HRP (horseradish peroxidase) and MPO (myeloperoxidase); ii) inhibition of cellular oxidative stress, with 80% inhibition of the oxidative burst of polymorphonuclear neutrophils (PMNs); and iii) direct action over reactive species, with 62% and 87% suppression of HOCl and superoxide anion radical (O2• -), respectively. From the data, it was concluded that the aqueous extract of A. blazei has significant antioxidant activity, indicating its possible application for nutraceutical and medicinal purposes.