title: Effects of dehydroepiandrosterone administration on rat hepatic metabolism following thermal injury.
abstract: BACKGROUND
  Severe burns cause dramatic alterations in liver and whole-body metabolism. Recently, there has been interest in using dehydroepiandrosterone (DHEA) as a treatment for trauma patients, and enhanced survival and immune function have been reported using DHEA in animal trauma models. The specific effects of DHEA on hepatic metabolism following burn injury have not been explored.
  
  
  METHODS
  Male rats received either (1) a burn covering approximately 20% of the total body surface area or a sham burn or (2) burn injury followed by two intraperitoneal injections of DHEA or vehicle. After 4 days, the livers were isolated and perfused in vitro, and 28 metabolite fluxes were measured. Metabolic flux analysis was used to obtain the intracellular metabolic flux distribution and provide an overview of the metabolic state of the livers in each experimental group.
  
  
  RESULTS
  Burn injury decreased the uptake of lactate and the production of beta-hydroxybutyrate and increased the deamination of glutamine to glutamate and asparagine to aspartate. DHEA, compared to vehicle treatment, decreased pentose phosphate pathway (PPP) fluxes and the uptake of several amino acids in burned rats. Furthermore, DHEA treatment restored liver metabolism in burned rats to a state that was very similar to that of the sham control group.
  
  
  CONCLUSIONS
  DHEA administration appears to normalize hepatocellular metabolism in burned rats but also decreases the PPP flux, which may impair the liver's ability to recycle endogenous antioxidants. DHEA treatment combined with exogenous antioxidants should receive further consideration in the management of burn and trauma patients.
authors.affiliation: Center for Engineering in Medicine/Surgical Services, Shriners Hospital, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Banta
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Yokoyama
authors.forename: François
authors.initials: F
authors.lastname: Berthiaume
authors.forename: Martin L
authors.initials: ML
authors.lastname: Yarmush
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002056:Burns / Q000378:metabolism* / Q000473:pathology; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000276:Adjuvants, Immunologic; D000596:Amino Acids; D003687:Dehydroepiandrosterone