title: Short-term effect of ascorbate on bacterial content, plasminogen activator inhibitor-1, and myeloperoxidase in septic mice.
abstract: BACKGROUND
  Sepsis, a potential risk associated with surgery, leads to a systemic inflammatory response including the plugging of capillary beds. This plugging may precipitate organ failure and subsequent death. We have shown that capillary plugging can be reversed rapidly within 1 h by intravenous injection of ascorbate in mouse skeletal muscle. It is unknown whether, in parallel with this effect, ascorbate negatively affects the protective responses to sepsis involving the fibrinolytic and immune systems. We hypothesized that treatment with ascorbate for 1 h does not alter bacterial content, plasminogen activator inhibitor 1 (PAI-1), and neutrophil infiltration in lung, kidney, spleen, and liver (organs with high immune response) of septic mice.
  
  
  METHODS
  Sepsis was induced by feces injection into the peritoneum. Mice were injected intravenously with ascorbate at 6 h (10 mg/kg), and samples of peritoneal fluid, arterial blood, and organs collected at 7 h were subjected to analyses of bacterial content, PAI-1 messenger RNA and enzymatic activity, and myeloperoxidase (MPO) (a measure of neutrophil infiltration).
  
  
  RESULTS
  Sepsis increased bacterial content in all fluids and organs and increased PAI-1 messenger RNA and enzymatic activity in the lung and liver. Sepsis increased the myeloperoxidase level in the lung and liver, and lowered it in the spleen. Except for decreasing the bacterial content in blood, these responses to sepsis were not altered by ascorbate.
  
  
  CONCLUSIONS
  The rapid effect of ascorbate against capillary plugging in the septic mouse skeletal muscle is not accompanied by alterations in PAI-1 or myeloperoxidase responses in the organs with high immune response.
authors.affiliation: Critical Illness Research Program, Lawson Health Research Institute, London, Ontario, Canada; Department of Physiology and Pharmacology, University of Western Ontario, London, Canada.
authors.forename: Scott B
authors.initials: SB
authors.lastname: Swarbreck
authors.affiliation: Critical Illness Research Program, Lawson Health Research Institute, London, Ontario, Canada; Department of Physiology and Pharmacology, University of Western Ontario, London, Canada.
authors.forename: Dan
authors.initials: D
authors.lastname: Secor
authors.affiliation: Critical Illness Research Program, Lawson Health Research Institute, London, Ontario, Canada; Department of Medical Biophysics, University of Western Ontario, London, Canada.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Ellis
authors.affiliation: Department of Anesthesia and Perioperative Medicine, Critical Care Western, University of Western Ontario, London, Canada.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Sharpe
authors.affiliation: Department of Exercise and Nutrition Sciences, University at Buffalo, Buffalo, New York.
authors.forename: John X
authors.initials: JX
authors.lastname: Wilson
authors.affiliation: Critical Illness Research Program, Lawson Health Research Institute, London, Ontario, Canada; Department of Physiology and Pharmacology, University of Western Ontario, London, Canada; Department of Medical Biophysics, University of Western Ontario, London, Canada. Electronic address: ktyml@lhsc.on.ca.
authors.forename: Karel
authors.initials: K
authors.lastname: Tyml
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001419:Bacteria / Q000302:isolation & purification*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D009195:Peroxidase / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D009195:Peroxidase; D001205:Ascorbic Acid
keywords: Bacteria; Fibrinolysis; Neutrophil; Sepsis; Vitamin C