title: Starvation enhances hepatic free radical release following endotoxemia.
abstract: Although it is well known that malnourished patients who become septic have an increased risk of organ failure and death compared to normally nourished individuals, the pathological processe(s) underlying this observation are unknown. To evaluate one possible explanation for this finding, we tested the hypothesis that malnutrition depresses hepatic antioxidant stores and accelerates hepatic release of oxygen free radicals in an animal model of sepsis. Male rats were either fasted (n = 14) or fed (n = 14) for 3 days prior to receiving lipopolysaccharide (LPS, 17 mg/kg intraperitoneally). Animals were weighed daily and then sacrificed 6 and 24 hr after LPS administration to determine hepatic superoxide anion (an oxygen free radical) release and liver glutathione (GSH, an antioxidant) content. Fasted rats were severely malnourished as indicated by a 23% decrease in body weight compared to fed rats, which gained 11% (P < 0.05). Liver GSH was depressed by 30% (P < 0.05) and 20% (P = 0.066) in the fasted compared to fed animals 6 and 24 hr after LPS administration. In addition, hepatic superoxide anion release was 210 and 75% higher in the fasted animals 6 and 24 hr after LPS injection (P < 0.05 at both time points). Liver superoxide anion release and GSH content were negatively correlated (P < 0.001, R = - 0.73) indicating that superoxide anion release increased as GSH content fell. Malnutrition leads to depletion of liver antioxidant stores with accelerated release of hepatic oxygen free radicals. Oxidant-mediated organ damage may be one cause of increased morbidity and mortality in malnourished, systemically infected patients.
authors.affiliation: Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Robinson
authors.forename: R R
authors.initials: RR
authors.lastname: Rustum
authors.forename: E A
authors.initials: EA
authors.lastname: Chambers
authors.forename: J D
authors.initials: JD
authors.lastname: Rounds
authors.forename: D W
authors.initials: DW
authors.lastname: Wilmore
authors.forename: D O
authors.initials: DO
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D019446:Endotoxemia / Q000097:blood*; D004926:Escherichia coli; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000378:metabolism*; D008297:Male; D009748:Nutrition Disorders / Q000150:complications*; D051381:Rats; D017208:Rats, Wistar; D013217:Starvation / Q000150:complications*; D013481:Superoxides / Q000097:blood*
chemical_list: D005609:Free Radicals; D008070:Lipopolysaccharides; D013481:Superoxides; D005978:Glutathione