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Heparin and low‐molecular‐weight heparin (enoxaparin) significantly ameliorate experimental colitis in rats
Author(s) -
Dotan I.,
Hershkoviz R.,
Karmeli F.,
Brazowski E.,
Peled Y.,
Rachmilewitz D.,
Halpern Z.
Publication year - 2001
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1046/j.1365-2036.2001.01079.x
Subject(s) - medicine , heparin , low molecular weight heparin , colitis , myeloperoxidase , pharmacology , nitric oxide , anticoagulant , iodoacetamide , gastroenterology , inflammation , biochemistry , chemistry , enzyme , cysteine
Background and aims: The anticoagulants, unfractionated heparin and low‐molecular‐weight heparin, demonstrated anti‐inflammatory effects in animal models and in humans. Because of its dual effects, high‐dose heparin was proposed as a therapeutic modality for ulcerative colitis. We investigated whether a low dose of low‐molecular‐weight heparin—enoxaparin (Clexane, Rhône‐Poulenc Rorer, France)—ameliorates the inflammatory response in two models of experimental colitis. Methods: Colitis was induced in rats by intrarectal administration of dinitrobenzene sulphonic acid. Enoxaparin (40, 80 and 200 μg/kg) or unfractionated heparin (100, 200 and 400 U/kg) were administered subcutaneously immediately after the induction of damage. Enoxaparin, 80 μg/kg, was also administered after induction of colitis by intrarectal administration of iodoacetamide. Rats were sacrificed 1, 3 or 7 days after induction of injury. Colonic damage was assessed macroscopically and histologically. Mucosal prostaglandin E 2 generation, myeloperoxidase and nitric oxide synthase activities and tumour necrosis factor‐α levels in blood were determined. Results: Enoxaparin and heparin significantly ameliorated the severity of dinitrobenzene sulphonic acid‐ and iodoacetamide‐induced colitis as demonstrated by a decrease in mucosal lesion area, colonic weight and mucosal myeloperoxidase and nitric oxide synthase activities. The dose–response curve had a bell‐shaped configuration: enoxaparin, 80 μg/kg, and unfractionated heparin, 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‐inflammatory rather than anticoagulant properties.