Healing effects of heparin on acetic acid-induced gastric ulcers in rats.
OBJECTIVE
To investigate whether or not heparin can accelerate the healing process of acetic acid-induced gastric ulcers in rats and to identify the mechanisms for heparin to produce this effect, so that we can develop a new therapeutic application to heparin besides its traditional anticoagulant activity.


METHODS
Male Sprague-Dawley rats were used to produce acetic acid-induced gastric ulcers. Heparin in the doses of 100, 500, and 1000 U/kg were administered intravenously through the tail vein once daily, starting 1 day after ulcer induction for 7 days in the dose-response experiment or heparin 1000 U/kg at a time schedule of 3, 5, and 7 days in the time-response study, respectively. The gastric mucosal blood flow (GMBF) was measured using a laser Doppler flowmeter under ether anesthesia. The rats were then sacrificed and the ulcer areas were measured. The gastric mucosa was then scraped for the determinations of mucosal prostaglandin E2 (PGE2) level and myeloper-oxidase (MPO) activity.


RESULTS
Heparin in the doses of 500 and 1000 U/kg accelerated the healing of acetic acid ulcers in a dose-dependent manner. The highest dose of heparin also reduced the ulcer areas in a time-dependent fashion. The effect was accompanied by an increase in gastric mucosal PGE2 levels. The same dose of heparin not only decreased the gastric mucosal MPO activity but also increased the GMBF in a time-related manner.


CONCLUSIONS
Heparin with the doses used in the present study accelerated the healing of acetic acid-induced gastric ulcers in rats in a dose- and time-dependent manner, and this action was related to its effects to increase the levels of gastric mucosal PGE2 and GMBF as well as to decrease the gastric mucosal MPO activity.
D019342:Acetic Acid; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000098:blood supply / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D013276:Stomach Ulcer / Q000139:chemically induced / Q000503:physiopathology*