Pyruvate Improves Neutrophilic Nitric Oxide Generation in Peritoneal Dialysis Solutions

Abstract

To investigate the effects of pyruvate (Pyr)-based peritoneal dialysis solutions (P-PDS) on neutrophilic nitric oxide (NO) generation, we incubated human peripheral neutrophils in dL-lactate (Lac, 40 mM)-based PDS and equimolar P-PDS, and Hanks' balanced salt solution at various pH and high glucose (HG) levels, respectively. The production of NO in various test solutions was determined based on the Griess reaction. Acidic pH, high Lac, and HG induced an acute and substantial inhibition of neutrophilic NO, whereas Pyr in PDS significantly improved the NO generation in both acidic pH and physiological pH, and also in HG conditions. The Pyr protection may be associated with the improvement of glucose metabolic pathways in addition to its alkalization.

Pyruvate: immunonutritional effects on neutrophil intracellular amino or alpha-keto acid profiles and reactive oxygen species production

“…used for glutathione, proline, purine and pyrimidine synthesis, export of glutamate in exchange for import of cystine and following conversion to cysteine, synthesis of glucosamines or NAD+, etc.) can all be modulated by pyruvate-enriched immunonutrition in PMN (Agam and Gutman 1972; Curi et al 1989, 1988; Fink 2008; Frei et al 1975; Fuchs et al 1994; Engel et al 2009a, b; Mühling et al 2010, 2005; Newsholme et al 1987; Serrano and Curi 1989; Wu et al 2005, 2003). …”

“…It primarily generates superoxide, a highly reactive free radical, by transferring electrons from NADPH inside the cell across the membrane and coupling these to molecular oxygen. In phagosomes or outside the cell, superoxide can spontaneously form hydrogen peroxide that will undergo further reactions to generate reactive oxygen species (ROS) (Newsholme et al 1987; Wu et al 2005, 2003; Zhou and Yu 1998). Superoxide is capable of killing bacteria and fungi by mechanisms that are not yet fully understood.…”

“…It also may inactivate critical metabolic enzymes, initiate lipid peroxidation and liberate redox active iron, which allows the generation of indiscriminate oxidants such as the hydroxyl radical. Superoxide probably kills bacteria directly as the virulence of many pathogens is dramatically attenuated when their superoxide dismutase (SOD) genes are deleted (Engel et al 2009a, b; Mühling et al 2010, 2006, 2005, 2004, 2002; Wu et al 2005, 2003). Therefore, superoxide is one of the main reactive oxygen species in neutrophils and as such, SOD plays a key antioxidant role.…”

“…protein unfolding and aggregation) (i.e. Cicalese et al 1996a, 1996b; Dahlgren and Karlsson 1999; Ing et al 1997, Huang et al 2009; Wu et al 2005, 2003). But regarding the “positive” or “desired” bacteriocidal nature of chlorine solutions induced by HOCl one should bear in mind that the diapedesis of immunonutritionally (i.e.…”

“…via glycolysis in which one molecule of glucose breaks down into two molecules of pyruvate or reversible transamination reactions, etc. ), but also unites several key metabolic processes (Agam and Gutman 1972; Curi et al 1989, 1988; Fauth et al 1993 and 1990; Frei et al 1975; Fuchs et al 1994; Homem de Bittencourt et al 1993; Ing et al 1997; Newsholme et al 1987; Wu et al 2005 and 2003). …”