Stability of glutathione added as a supplement to parenteral nutrition

Abstract

Background: Most very premature newborns (<32 weeks of gestation) receive parenteral nutrition (PN) that is inherently contaminated with peroxides. Oxidative stress induced by PN is associated with bronchopulmonary dysplasia, a main pathological complication in these infants who have weak antioxidant capacity to detoxify peroxides because of their glutathione deficiency. In animals, glutathione supplementation of PN prevented oxidative stress and alveolar loss (the main characteristic of bronchopulmonary dysplasia). Of its two forms-oxidized glutathione (GSSG) and reduced glutathione (GSH)-GSSG was used because of its better stability. However, a 30% loss of GSSG in PN is observed. The potentially high therapeutic benefits of GSSG supplementation on the health of very premature infants make the study of its stability highly important.Methods: GSSG was incubated in combination with the following components of PN: dextrose, multivitamins, Primene, and Travasol, and with cysteine, cystine, and peroxides, for 24 h. Total glutathione in these solutions was measured 0-24 h after the addition of GSSG. Results:The combination of cysteine and multivitamins caused the maximum loss of glutathione. The stability of GSSG was not affected by multivitamins. The cysteine was responsible for ∼20% of the loss of GSSG; in the presence of multivitamins, the loss reached >70%. Removing the cysteine prevented the degradation of glutathione. Conclusion:GSSG reacts with cysteine to form cysteine-glutathione mixed disulfide, another suitable glutathione substrate for preterm neonates. The study confirms that GSSG added to PN can potentially provide a precursor to de novo synthesis of glutathione in vivo.

Dose–Response Effects of Glutathione Supplement in Parenteral Nutrition on Pulmonary Oxidative Stress and Alveolarization in Newborn Guinea Pig

“…GSSG was used rather than GSH due to its improved stability in PN [ 15 ] and similar affinity for γ-glutamyl transferase [ 16 ]. A recent article [ 17 ] demonstrated that the loss of GSSG in PN is caused by the presence of cysteine in PN. The reaction leads to the generation of a mixed disulfide cysteine–glutathione.…”

Glutathione Supplementation Prevents Neonatal Parenteral Nutrition-Induced Short- and Long-Term Epigenetic and Transcriptional Disruptions of Hepatic H2O2 Metabolism in Guinea Pigs

“…Whatever the mechanism, the fact that GSSG supplementation prevents Gpx1 hypermethylation is important. Indeed, GSSG supplementation is proposed for premature newborns who require PN [ 8 , 24 , 26 ].…”

“…Both GSSG and GSH are substrates for the gamma-glutamyl cycle, which promotes the intracellular transfer of cysteine from plasma glutathione (GSH or GSSG) with a view to the new cellular synthesis of glutathione [ 25 ]. GSSG is chosen because of its better stability in PN solutions than GSH [ 26 ]. In vivo, glutathione supplementation helps maintain optimal GPx activity to detoxify PN peroxides as they arrive.…”

Response of the Glutathione (GSH) Antioxidant Defense System to Oxidative Injury in Necrotizing Enterocolitis

“…Targeted supplementation with GSH, for example, as the principal antioxidant for premature infants with antioxidant deficiencies, is being investigated in literature for its therapeutic and preventative potential. Mode of supplementation is also imperative as GSH addition to nutritional modalities such as parenteral nutrition or infant formula has the potential for oxidation of the antioxidant leading to decreased availability [37].…”