title: Hepatocyte growth factor, hepatocyte growth factor activator and arginine in a rat fulminant colitis model.
abstract: BACKGROUND
  Dextran sodium sulfate (DSS) is commonly used to induce a murine fulminant colitis model. Hepatocyte growth factor (HGF) has been shown to decrease the symptoms of inflammatory bowel disease (IBD) but the effect of its activator, HGFA, is not well characterized. Arginine reduces effects of oxidative stress but its effect on IBD is not well known. The primary aim is to determine whether HGF and HGFA, or arginine will decrease IBD symptoms such as pain and diarrhea in a DSS-induced fulminant colitis murine model.
  
  
  METHODS
  A severe colitis was induced in young, male Fischer 344 rats with 4% (w/v) DSS oral solution for seven days; rats were sacrificed on day 10. Rats were divided into five groups of 8 animals: control, HGF (700 mcg/kg/dose), HGF and HGFA (10 mcg/dose), HGF and arginine, and high dose HGF (2800 mcg/kg/dose). Main clinical outcomes were pain, diarrhea and weight loss. Blinded pathologists scored the terminal ileum and distal colon.
  
  
  RESULTS
  DSS reliably induced severe active colitis in 90% of animals (n = 36/40). There were no differences in injury scores between control and treatment animals. HGF led to 1.38 fewer days in pain (p = 0.036), while arginine led to 1.88 fewer days of diarrhea (P = 0.017) compared to controls. 88% of HGFA-treated rats started regaining weight (P < 0.001).
  
  
  CONCLUSIONS
  Although treatment was unable to reverse fulminant disease, HGF and arginine were associated with decreased days of pain and diarrhea. These clinical interventions may reduce associated symptoms for severe IBD patients, even when urgent surgical intervention remains the only viable option.
authors.affiliation: Department of Surgery, Madigan Army Medical Center, Tacoma, WA, USA.
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Zwintscher
authors.affiliation: Department of Surgery, University of Virginia, Charlottesville, VA, USA.
authors.forename: Puja M
authors.initials: PM
authors.lastname: Shah
authors.affiliation: Department of Clinical Investigation, Madigan Army Medical Center, Tacoma, WA, USA.
authors.forename: Shashikumar K
authors.initials: SK
authors.lastname: Salgar
authors.affiliation: Department of Surgery, Madigan Army Medical Center, Tacoma, WA, USA; Department of Surgery, Children's Hospital & Research Center Oakland, Oakland, CA, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Newton
authors.affiliation: Department of Surgery, UMass Memorial Medical Center, Worcester, MA, USA.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Maykel
authors.affiliation: Division of Colon and Rectal Surgery, University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Samy
authors.affiliation: Division of Colon and Rectal Surgery, University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: Murad
authors.initials: M
authors.lastname: Jabir
authors.affiliation: Division of Colon and Rectal Surgery, University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Steele
keywords: Fulminant colitis; Inflammatory bowel disease