Introduction: 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 ¼ 36/40). There were no differences
in injury scores between control and treatment animals. HGF led to 1.38 fewer days in pain
(p ¼ 0.036), while arginine led to 1.88 fewer days of diarrhea (P ¼ 0.017) compared to controls. 88% of
HGFA-treated rats started regaining weight (P < 0.001).
Discussion/Conclusion: 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.