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

Abstract

BackgroundIn 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.MethodsThe 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.ResultsFour 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.ConclusionsThe 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.

Bisphenol A is an exogenous toxin that promotes mitochondrial injury and death in tubular cells

“…Additionally, BPA increased oxidative stress dependent on NADPH oxidase‐generated ROS. Oxidative stress is a driver of sublethal and lethal tissue and kidney injury in CKD . ‐ Further evidence for the oxidative stress elicited by BPA is the strong induction of antioxidant defenses.…”

“…Oxidative stress is a driver of sublethal and lethal tissue and kidney injury in CKD. [37][38][39] Further evidence for the oxidative stress elicited by BPA is the strong induction of antioxidant defenses. This may limit BPA toxicity.…”

The molecular mechanisms of hemodialysis vascular access failure

“…91 ECs are essential regulators of WSS-induced vessel remodeling. 102 – 104 Numerous studies have addressed the effects of normal and pathological WSS on vascular biology and especially on the endothelium. EC morphology, gene and protein expression, as well as protein release are all strongly affected by different WSS patterns.…”

Free p-Cresol Alters Neutrophil Function in Dogs

“…The few studies that have evaluated the effect of p‐cresol on neutrophil function demonstrate that uremic toxins may contribute to immunosuppression in uremic patients, thus inhibiting oxidative metabolism without accelerating neutrophil apoptosis . Recent studies have demonstrated that p‐cresol promotes an increase of ROS production in mononuclear cells in vitro , besides presenting antioxidant activity . Hypoalbuminemia in patients with CRF favors an increase in the free portion of p‐cresol and this fact seems to be related to the high frequency of patients hospitalized for infectious conditions , probably due to immunosuppression.…”