Effect of coadministration of parenteral multivitamins with lipid emulsion on lung remodeling in an animal model of total parenteral nutrition

Abstract

Exposure of parenteral multivitamin solutions (MVP) to ambient light generates peroxides and vitamin loss, and induces initiation of fibrosis and a reduced alveolar count in an animal model of total parenteral nutrition (TPN). Adding MVP to the lipid moiety of TPN prevents lipid peroxidation and vitamin loss. The aim of the study was to compare modes of delivery of MVP on lung procollagen mRNA and alveolar counts. Three-day-old guinea pig pups were infused continuously with one of three intravenous solutions: 1) control = dextrose; 2) AA + MVP = MVP given with the dextrose + amino-acid moiety, in a "piggyback" setup with a lipid emulsion mixed close to the infusion site; and 3) LIP + MVP = same as AA + MVP, except that MVP is given with the lipid emulsion. After 4 days, lungs were prepared for alveolar count (intercept technique) and for quantification of the procollagen/beta-actin mRNA ratio (initial step of fibrosis). Data were compared by ANOVA. The procollagen mRNA was lower (P < 0.05) in animals receiving LIP + MVP than those with AA + MVP. But the two modes of admixture of MVP had the same effect on the alveolar counts, which were lower (P < 0.01) than controls. The mode of delivery of TPN affects lung remodeling. Although LIP + MVP protects against the initiation of lung fibrosis, the absence of a beneficial effect on alveolar counts suggests that these features of lung remodeling are not caused by a unique component of TPN. Specific roles of peroxides, components of MVP, and light exposure on lung remodeling need to be explored before LIP + MVP can be recommended as an alternative mode of parenteral vitamin delivery.

Influence of the calcium concentration in the presence of organic phosphorus on the physicochemical compatibility and stability of all-in-one admixtures for neonatal use

“…The infusion of oxidized lipids and secondary peroxidation products can be extremely cytotoxic, and may cause many disorders, such as hepatic steatosis [ 36 ], hyper triglyceridemia [ 37 ], increase in vascular resistance in the lung [ 17 , 38 ], lung remodeling [ 39 ] and chronic lung diseases of prematurity [ 40 , 41 ]. TPN is a potential source of oxidants and this is particularly dangerous in preterm infants who are vulnerable to oxidative stress [ 42 , 43 ].…”

“…This bag has low oxygen permeation and could be collapsed to eliminate, as much as possible, the oxygen in the bag. Moreover, the presence of amino acids [ 42 , 48 ] in formulations containing trace elements, lipids and vitamins [ 23 ] decrease the peroxide formation and its clinical complications [ 39 , 42 ]. Lavoie et al [ 42 ] showed that during the 6 hours after TPN preparation the balance between generation and consumption of peroxides is positive, and after this time they presume that the balance changed in favor of the consumption, during their transformation into free radicals via the Fenton-like reaction induced by trace elements present in the PN solution [ 49 ].…”

Lung Diseases - Selected State of the Art Reviews

“…Lung samples from premature baboons with BPD (Das et al, 2004) showed a large number of apoptotic events. In newborn guinea pigs given parenteral nutrition for 4 days, the alveolar count was 20% lower when the nutritive solution was infused without light protection, peroxide concentration being higher in light-exposed solutions (Section 5.2 below) (Lavoie et al, , 2005(Lavoie et al, , 2008. On histology, 30% of alveolar cells were in an apoptotic state .…”

“…Since glutathione levels are low in preterm infants , these molecules can conceivably overwhelm the glutathione system, allowing the redox potential to shift toward an oxidized state. Infusion of parenteral nutrition without light protection for 4 days in newborn guinea pigs was associated with: 1) a loss of glutathione , 2) a more oxidized glutathione redox potential (Lavoie et al, 2008), and 3) a lower alveolar count (Lavoie et al, , 2005(Lavoie et al, , 2008, as compared to animals infused with a fully photoprotected solution. A recent study demonstrated that the blood glutathione redox potential measured in 7-day-old preterm infants (26  1 weeks' gestation) was correlated with the severity of BPD; a more oxidized status was measured in the most severe cases .…”

“…Various factors may contribute to a shift in redox potential to a more oxidized state ( Figure 3, dashed line). An induced or sustained oxidized status favours the apoptosis process, leading to a loss of tissue such as observed in BPD (Das et al, 2004;Lavoie et al, , 2005Lavoie et al, , 2008. In preterm infants, these factors are oxygen supplementation, parenteral nutrition (containing peroxides), and inflammation.…”