A 3.0-kDa low molecular weight heparin promotes gastric ulcer healing in rats.
BACKGROUND
Previous studies have shown that intragastric administration of unfractionated heparin enhances gastric ulcer healing in rats. As the large molecule of heparin may be partially degraded in the upper gastrointestinal tract, it is likely that fragments of heparin, derived from the unfractionated parent compound, are involved in the anti-ulcer action in the stomach. Therefore, it is possible that low molecular weight heparin may have a similar ulcer healing effect.


METHODS
Male Sprague-Dawley rats with acetic acid-induced gastric ulcers were given a 3.0-kDa low molecular weight heparin (0.6-6.0 mg/kg) intravenously or intragastrically once daily for 4 days. Ulcer healing, mucosal histological changes, angiogenesis and gastric mucus production both in vivo and in vitro were determined. The bleeding time was measured to indicate the anticoagulation activity.


RESULTS
Both intravenous and intragastric low molecular weight heparin dose dependently accelerated gastric ulcer healing, which was accompanied by a significant increase in mucosal regeneration and proliferation, angiogenesis and mucus content in the stomach. The drug also stimulated the mucus production in MKN-28 cells. Drug administration by either route did not alter the bleeding time in rats.


CONCLUSIONS
A 3.0-kDa low molecular weight heparin possesses an ulcer healing effect similar to that of unfractionated heparin in the stomach of the rat. This smaller molecular drug is superior to the unfractionated form, does not affect the coagulation activity and may show better absorption in the gastrointestinal tract.
Li
Y
Y
Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Shin
V Y
VY
Cheuk
C Y
CY
Liu
E S
ES
Cho
C H
CH
D000818:Animals; D000925:Anticoagulants / Q000097:blood / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D006495:Heparin, Low-Molecular-Weight / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008970:Molecular Weight; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D014945:Wound Healing / Q000187:drug effects*
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight