title: Hexapeptides from human milk prevent the induction of oxidative stress from parenteral nutrition in the newborn guinea pig.
abstract: BACKGROUND
  In preterm neonates, peroxides contaminating total parenteral nutrition (TPN) contribute to oxidative stress, which is suspected to be a strong inducer of hepatic complications related to prematurity. Recently, others reported that hexapeptides derived from human milk (HM) exerted free radical-scavenging activities in vitro. Therefore, the aim of this study was to assess the capacity of these hexapeptides to limit the generation of peroxides in TPN and to prevent TPN-induced hepatic oxidative stress.
  
  
  METHODS
  At 3 d of life, guinea pigs were infused, through a catheter in jugular vein, with TPN containing or not peptide-A (YGYTGA) or peptide-B (ISELGW). Peroxide concentrations were measured in TPN solutions, whereas glutathione, glutathionyl-1,4-dihydroxynonenal (GS-HNE) and mRNA levels of interleukin-1 (IL-1) and tumor necrosis factor-α (TNFα) were determined in liver after 4 d of infusion.
  
  
  RESULTS
  The addition of peptide-A to TPN allowed a reduction in peroxide contamination by half. In vivo, peptide-A or peptide-B corrected the hepatic oxidative status induced by TPN. Indeed, both peptides lowered the hepatic redox potential of glutathione and the level of GS-HNE, a marker of lipid peroxidation. As compared with animals infused with TPN without peptide, the hepatic mRNA levels of IL-1 and TNFα were lower in animals infused with TPN containing peptide-A or peptide-B.
  
  
  CONCLUSIONS
  These results suggest that the addition of YGYTGA or ISELGW to TPN will reduce oxidative stress in newborns. The reduction in mRNA of two proinflammatory cytokines could be important for the incidence of hepatic complications related to TPN.
authors.affiliation: Department of Pediatrics, University of Montreal, Montréal, Quebec, Canada.
authors.forename: Khalil
authors.initials: K
authors.lastname: Miloudi
authors.forename: Apollinaire
authors.initials: A
authors.lastname: Tsopmo
authors.forename: James K
authors.initials: JK
authors.lastname: Friel
authors.forename: Thérèse
authors.initials: T
authors.lastname: Rouleau
authors.forename: Blandine
authors.initials: B
authors.lastname: Comte
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lavoie
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D004745:Enkephalins / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008895:Milk, Human; D023421:Models, Animal; D015688:Oncogene Protein pp60(v-src) / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010288:Parenteral Nutrition / Q000009:adverse effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D010545:Peroxides / Q000378:metabolism; D011498:Protein Precursors / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004745:Enkephalins; D016166:Free Radical Scavengers; D007375:Interleukin-1; D010446:Peptide Fragments; D010545:Peroxides; D011498:Protein Precursors; D014409:Tumor Necrosis Factor-alpha; C098708:peptide A; C056943:peptide B; D015688:Oncogene Protein pp60(v-src); D005978:Glutathione