Stability of the Glutathione Supplementation into Parenteral Nutrition to Protect Very Preterm Babies from Oxidative Stress

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 babies 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 - disulfide (GSSG) and free thiol (GSH) - GSSG was used because of its better stability in PN. However, a 30% loss of GSSG in PN is observed. The potentially high therapeutic benefits of GSSG supplementation on the health of very premature babies makes the study of its stability highly important. Thus, GSSG was incubated in combination with the following components of PN: dextrose, multivitamins, Primene, Travasol, as well as with cysteine, cystine and peroxides for 24h. Total glutathione in these solutions was measured 0-24h after the addition of GSSG. The combination of cysteine and multivitamins caused the maximum loss of glutathione. Removing the cysteine prevented the degradation of glutathione. GSSG reacts with cysteine to form cysteine-glutathione disulfide, another suitable glutathione substrate for preterm neonates.