Trophic enteral nutrition increases hepatic glutathione and protects against peroxidative damage after exposure to endotoxin.
BACKGROUND
During total parenteral nutrition (TPN), hepatic concentration of the important intracellular antioxidant glutathione (GSH) is decreased. This study sought to determine whether enteral trophic (small quantity) feeding of GSH precursors would increase hepatic GSH levels during TPN and result in decreased peroxidative injury after endotoxin exposure.


METHODS
Sprague-Dawley rats received full TPN for 7 days with postpyloric infusions of either (1) amino acid GSH precursors (cysteine, 60 mg/d; glycine, 86 mg/d; glutamate, 31 mg/d; F1); (2) iso-nitrogenous alanine (132 mg/d; F2); or (3) normal saline (SA). Hepatic GSH concentration was measured by gas chromatography/mass spectrometry. In a parallel study, animals were given TPN and either F1 or SA for 7 days, and endotoxin was administered intravenously before death. Hepatic lipid peroxidation and histology were assessed.


RESULTS
Hepatic GSH concentration measured 11.7 +/- 0.6 micromol/g in F1. This was significantly higher (P <.001) than in F2 (7.0 +/- 0.8 micromol/g) or SA (5.0 +/- 0.4 micromol/g). F2 and SA were not significantly different. Hepatic malondialdehyde concentration after exposure to endotoxin was significantly higher in SA (10.36 micromol/g +/- 0.65) than in F1 (7.38 micromol/g +/- 0.77; P <.01). All SA animals had histologic evidence of hepatic necrosis, whereas none of the F1 group showed these changes.


CONCLUSIONS
Targeted trophic feeding of GSH amino acid precursors during parenteral nutrition markedly increased hepatic GSH concentration. This was associated with decreased lipid peroxidation and enhanced hepatocellular protection after endotoxin challenge. Thus, targeted trophic feedings may aid in the prevention of TPN-related liver disease.
Dzakovic
Alexander
A
Children's Hospital, Boston, MA 02115, USA.
Kaviani
Amir
A
Eshach-Adiv
Orly
O
Perez-Atayde
Antonio
A
Ling
Pei-Ra
PR
Yu
Ming
M
Bistrian
Bruce
B
Jaksic
Tom
T
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004750:Enteral Nutrition / Q000379:methods*; D005978:Glutathione / Q000096:biosynthesis*; D015227:Lipid Peroxidation; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D010289:Parenteral Nutrition, Total; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D004731:Endotoxins; D005978:Glutathione