Dextran sulphate sodium induces acute colitis and alters hepatic function in hamsters.
Dextran sulphate sodium (DSS)-induced colitis in rodents is an experimental model for human inflammatory bowel disease (IBD). The aim of this study was to characterize the effect of DSS in hamster colon and liver. DSS (2-5%) was administrated in the drinking water for 4-6 days. Clinical symptoms were recorded daily, inflammatory and fatty acid-related metabolic markers were assessed in plasma, colon and liver. Six days of 3 or 5% DSS induced a severe wasting disease, whereas 2.5% DSS induced a colonic inflammation without severe systemic adverse effects. The systemic inflammatory response was characterized by an inverse production of albumin and the acute phase protein haptoglobin. The colonic inflammatory response was confined to the proximal colon, manifested by a high macroscopic inflammatory score, increased colon weight and expression of IL-1beta, IL-6 and iNOS, infiltration of inflammatory cells and epithelial disruption. In contrast, only a low/mild inflammatory response was observed in the distal colon of DSS-exposed hamsters. Significant hepatic-related metabolic alterations were also observed, with elevation of plasma triglycerides and increased liver expression of lipoprotein lipase and reduced expression of acyl-CoA oxidase and cytochrome P450A. Although liver weight was significantly reduced, no histopathological signs of inflammation or tissue damage were observed. In summary, hamsters exposed to 2.5% DSS for 6 days develop acute colitis resembling murine DSS-induced colitis. In addition, DSS-exposed hamster showed alterations in hepatic fatty acids metabolism resembling human IBD, suggesting that the model can potentially be used for target discovery and validation of hepatic-related metabolic alterations.
Karlsson
Agneta
A
Department of Integrative Pharmacology, AstraZeneca R&D Mölndal, Sweden.
Jägervall
Ake
A
Pettersson
Madeleine
M
Andersson
Ann-Katrin
AK
Gillberg
Per-Göran
PG
Melgar
Silvia
S
D000208:Acute Disease; D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000473:pathology; D006224:Cricetinae; D016264:Dextran Sulfate / Q000008:administration & dosage*; D004195:Disease Models, Animal; D006801:Humans; D018836:Inflammation Mediators / Q000008:administration & dosage*; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D008111:Liver Function Tests; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010865:Pilot Projects
D018836:Inflammation Mediators; D016264:Dextran Sulfate