title: Oral pretreatment with recombinant human lactoferrin limits trauma-hemorrhagic shock-induced gut injury and the biological activity of mesenteric lymph.
abstract: BACKGROUND
  Lactoferrin (LF) is a pleiotropic glycoprotein that is found in bodily secretions and is postulated to enhance the gastrointestinal barrier and promote mucosal immunity. Thus, the ability of talactoferrin, an oral recombinant form of human LF, to limit gut injury and the production of biologically active gut-derived products was tested using a rat model of trauma-hemorrhagic shock (T/HS).
  
  
  METHODS
  Male rats were orally dosed with vehicle or talactoferrin (1000 mg/kg, every day) for 5 d before being subjected to T/HS or trauma-sham shock (T/SS). Subsequently, rats were subjected to a laparotomy (trauma) and hemorrhagic shock (mean arterial pressure, 30-35 mm Hg × 90 min) or to T/SS, followed by resuscitation with their shed blood. Before inducing shock, the mesenteric lymphatic duct was catheterized for collection of mesenteric lymph. Four hours after the end of the shock or sham-shock period, rats were sacrificed, a segment of the distal ileum was collected for morphologic analysis, and lymph samples were processed and frozen. Subsequently, lymph samples were tested in several pharmacodynamic assays, including endothelial cell permeability, neutrophil respiratory burst activity, and red blood cell (RBC) deformability. Total white blood cell counts in lymph samples were also quantified.
  
  
  RESULTS
  Pretreatment with talactoferrin reduced the incidence of T/HS-induced morphologic injury of ileum to T/SS levels. Post-T/HS lymph from vehicle-treated rats increased endothelial monolayer permeability and neutrophil priming for an augmented respiratory burst, and induced loss of RBC deformability, compared with T/SS groups. Talactoferrin pretreatment significantly reduced the biological activity of T/HS lymph on respiratory burst activity and RBC deformability, but had no effect on the lymph cell count or endothelial cell permeability.
  
  
  CONCLUSIONS
  These results provide a proof of principle that prophylactic dosing of oral talactoferrin can potentially protect the gut in a T/HS model and limit the production of biologically active factors in rat gastrointestinal tissue subjected to ischemia-reperfusion-type injuries.
authors: Department of Surgery, New Jersey Medical School Rutgers, Newark, New Jersey.
authors: Julie Y
authors: JY
authors: Son
authors: Department of Surgery, New Jersey Medical School Rutgers, Newark, New Jersey.
authors: Benjamin
authors: B
authors: Chandler
authors: Department of Surgery, New Jersey Medical School Rutgers, Newark, New Jersey.
authors: Eleonora
authors: E
authors: Feketova
authors: Department of Surgery, New Jersey Medical School Rutgers, Newark, New Jersey.
authors: Yung
authors: Y
authors: Qin
authors: Agennix Inc., Princeton, New Jersey.
authors: Elizabeth J
authors: EJ
authors: Quackenbush
authors: Department of Surgery, New Jersey Medical School Rutgers, Newark, New Jersey. Electronic address: Edeitch@njms.rutgers.edu.
authors: Edwin A
authors: EA
authors: Deitch
mesh_terms: D000284:Administration, Oral; D000818:Animals; D007082:Ileum / Q000187:drug effects / Q000293:injuries*; D007781:Lactoferrin / Q000494:pharmacology*; D007813:Laparotomy / Q000009:adverse effects; D008196:Lymph / Q000187:drug effects / Q000502:physiology*; D008208:Lymphatic System / Q000187:drug effects / Q000502:physiology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D016897:Respiratory Burst / Q000187:drug effects; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000209:etiology; D014947:Wounds and Injuries / Q000150:complications
chemical_list: C490098:LTF protein, human; D011994:Recombinant Proteins; C515276:talactoferrin alfa; D007781:Lactoferrin
keywords: Hemorrhagic shock; Lactoferrin; Respiratory burst; Talactoferrin