Heparin and low-molecular-weight heparin (enoxaparin) significantly ameliorate experimental colitis in rats

Background and aims: The anticoagulants, unfractionated heparin and low-mol ecular-weight heparin, demonstrated anti-inflammatory effects in animal mod els and in humans. Because of its dual effects, high-dose heparin was propo sed as a therapeutic modality for ulcerative colitis. We investigated wheth er a low dose of low-molecular-weight heparin-enoxaparin (Clexane, Rhone-Po ulenc Rorer, France)-ameliorates the inflammatory response in two models of experimental colitis. Methods: Colitis was induced in rats by intrarectal administration of dinit robenzene sulphonic acid. Enoxaparin (40, 80 and 200 mug/kg) or unfractiona ted heparin (100, 200 and 400 U/kg) were administered subcutaneously immedi ately after the induction of damage. Enoxaparin, 80 mug/kg, was also admini stered after induction of colitis by intrarectal administration of iodoacet amide. Rats were sacrificed 1, 3 or 7 days after induction of injury. Colon ic damage was assessed macroscopically and histologically. Mucosal prostagl andin E-2 generation, myeloperoxidase and nitric oxide synthase activities and tumour necrosis factor-alpha levels in blood were determined. Results: Enoxaparin and heparin significantly ameliorated the severity of d initrobenzene sulphonic acid- and iodoacetamide-induced colitis as demonstr ated by a decrease in mucosal lesion area, colonic weight and mucosal myelo peroxidase and nitric oxide synthase activities. The dose-response curve ha d a bell-shaped configuration: enoxaparin, 80 mug/kg, and unfractionated he parin, 200 U/kg, were the optimal doses. Conclusions: Low-dose enoxaparin and unfractionated heparin ameliorate the severity of experimental colitis. This effect is related to their anti-infl ammatory rather than anticoagulant properties.