Pyruvate Preserves Neutrophilic Superoxide Production in Acidic, High Glucose‐Enriched Peritoneal Dialysis Solutions

Abstract

Py in PDS effectively protected neutrophils from HG-induced inhibition of O2- production, even at a physiological pH. The Py cytoprotection may be associated with the preservation of carbohydrate 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.…”

“…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). …”

Pyruvate in the Correction of Intracellular Acidosis: A Metabolic Basis as a Novel Superior Buffer

“…The impact of Pyr on systemic acidosis, however, at present has not been well appreciated [31], and potential mechanisms whereby Pyr preferably corrected severe acidosis have not been fully elucidated either [6, 34]. There are several likely biochemical sites on which the metabolism of exogenous Pyr consumes intracellular protons, indicating that Pyr is of particular significance in the pHi modulation [32,35,36,37] (fig. 1):…”

“…In addition, Pyr might be also a promising buffer to correct uremic acidosis in patients undergoing peritoneal dialysis (PD), which markedly improves the biocompatibility of PD solutions [5, 36]. It may efficiently correct chronic acidotic status in hemodialysis patients as well, which is not satisfactorily treated at present [60].…”